45 Skin and subcutaneous tissue

Acquired
Acquired
Campbell de Morgan spots These are arteriovenous fistulae at the dermal capillary level in - sun-exposed skin of  older patients ( Figure 45.45 ). Spider naevi These are angiomata that appear (and may disappear) sponta neously at puberty or in two-thirds of  pregnant women, usually disappearing in the puerperium ( Figure 45.46 ). Spider naevi are also associated with c hronic liver disease. They can be treated with intense pulsed light or pulsed-dye laser. Pyogenic granuloma These share many histological characteristics of  haemangio mata and are probably a subtype thereof  ( Figure 45.47 are small (0.5–1.5 /uni00A0 cm), raised, pedunculated, soft, red nodular lesions showing superficial ulceration and a tendency to bleed after trivial trauma. They should be excised with a minimal margin. Glomus tumour This arises from a subcutaneous arteriovenous shunt (Sucquet– Hoyer canals), especially in the corium of  the nail bed. Typically , JP Sucquet , 1840–1870, anatomist, Paris, France. Heinrich Hoyer , 1834–1907, Professor of  Histology , Embryology and Anatomy , Central Medical School, The Polish University , Warsaw , Poland. - it is a small, purple nodule measuring a few millimetres in size, which is disproportionately painful in response to insignificant stimuli, including cold exposure ( Figure 45.48 ). Subungual - varieties may be invisible causes of  paroxysmal digital pain. ). Most Angiosarcoma (‘malignant angioendothelioma’) A rare, highly malignant tumour arising from the endothelial cells ( Figure 45.49 ). The lymphangiosarcoma variant arises from lymphatic endothelium and can develop in lymphoedem - atous tissue, particularly an extremity . Proliferation is rapid with early systemic spread.
Figure 45.44
‘Port-wine’ stain (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.45
Campbell de Morgan spot (courtesy of Mr AR Green
baum).
Figure 45.46
Spider naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.47
Pyogenic granuloma (courtesy of St John’s Institute for
Dermatology, London, UK).
Kaposi’s sarcoma Kaposi’s sarcoma is a malignant, proliferative tumour of vascular endothelial cells, which was first described in elderly Jewish men but is now most commonly associated with immune compromise after transplantation or HIV infection ( Figure 45.50 ). There appears to be a causal link with infection by human herpesvirus 8. Kaposi’s sarcoma usually starts as a red-brown, indurated, plaque-like skin lesion that becomes nodular and then ulcerates. Treatment is with radiotherapy .
Figure 45.48
Glomus tumour (courtesy of St John’s Institute for
Dermatology, London, UK).
Acquired
Pressure sores These begin with tissue necrosis at a pressure point and develop into a cone-shaped volume of  necrotic loss. As many as 10% of  acute hospital inpatients will have some degree of  pressure sore. The majority a ff ect the elderly and patients with spinal injury or decreased sensibility; 80% of  paraplegics will get a pressure sore and 8% die as a result. The pathogenesis of  pressure sores revolves around unre lieved pressure: an increase in local tissue pressure above that of  perfusion pressure produces ischaemic necrosis that is directly proportional to the duration and degree of  pressure and inver sely proportional to the area over which it is applied. Muscle and fat are more susceptible to pressure than skin. In a patient who has no predisposing factors management is aimed at debridement and repair of  the defect, on the assump tion that recurrence will not occur once normal function and sensibility returns. In the paraplegic patient, recurrence is likely so management should involve a multidisciplinary approach. Primary treatment involves relieving pressure (special mattress, nursing care, relief  of  muscle spasm and contractures), opti mising nutrition, correcting anaemia and preventing infection. Surgery involves thorough debridement to promote healing and plastic surgery to reconstruct the defect. Ulcers An ulcer is a discontinuity of  an epithelial surface. It is characterised by destruction of  the surface epithelium and a granulating base. Ulcers can be classified as non-specific, specific and malignant ( Figure 45.51 ). Sinus A sinus is a blind-ending tract connecting a cavity lined with granulation tissue (often an abscess cavity) to an epithelial (a) (b) (c) (d ) ( e) Burrill Bernard Crohn , 1884–1983, gastroenterologist, Mount Sinai Hospital, New Y ork, NY , USA, described regional ileitis in 1932. - - surface ( Figure 45.52a ). Sinuses may be congenital or acquired. Congenital sinuses arise from the remnants of persistent embryonic ducts. Acquired sinuses can result from: a retained foreign body (ingrown hair or suture material); chronic infection (tuberculosis, osteomyelitis or actinomycosis); chronic - inflammation (Crohn’s disease); malignancy; or inadequate surgical drainage of  a cavity . , Treatment of  a sinus is directed at removing the underlying cause. Biopsies should always be taken from the wall of  a sinus to exclude malignancy or specific infection. For specific man - - agement of  the disease conditions, please refer to the appro - priate chapter. Fistula A fistula is an abnormal communication between two epithelium-lined surfaces ( Figure 45.52b ). This commu - nication or tract is usually lined by granulation tissue, but may become epithelialised in chronic cases. Fistulae may be congenital (e.g. tracheo-oesophageal and branchial fistulae) or acquired (e.g. enterocutaneous complicating Crohn’ s disease or surgery , or arteriovenous). Management of  a fistula is directed at the underlying aetiology (see the appropriate chapters).
Figure 45.51
Some characteristic shapes of the edges of ulcers.
/uni00A0
(a)
Non-speci
/f_i
c ulcer: note the shelving edge.
(b)
Tuberculous ulcer:
note the undermined edge.
(c)
Basal cell carcinoma (rodent ulcer):
note the rolled edge, which may exhibit small blood vessels.
thelioma: note the heaped-up, everted edge and irregular thickened
base.
(e)
Syphilis: note the punched-out edge and thin base, which
may be covered with a ‘wash-leather’ slough.
Figure 45.52
A sinus
(a)
and a
/f_i
stula
(b)
; both usually arise from a
preceding abscess.
(a)
This is a blind track, in this case a pilonidal
abscess.
(b)
This is a track connecting two epithelium-lined surfaces,
in this case a colocutaneous
/f_i
stula from colon to skin.
Acquired
Campbell de Morgan spots These are arteriovenous fistulae at the dermal capillary level in - sun-exposed skin of  older patients ( Figure 45.45 ). Spider naevi These are angiomata that appear (and may disappear) sponta neously at puberty or in two-thirds of  pregnant women, usually disappearing in the puerperium ( Figure 45.46 ). Spider naevi are also associated with c hronic liver disease. They can be treated with intense pulsed light or pulsed-dye laser. Pyogenic granuloma These share many histological characteristics of  haemangio mata and are probably a subtype thereof  ( Figure 45.47 are small (0.5–1.5 /uni00A0 cm), raised, pedunculated, soft, red nodular lesions showing superficial ulceration and a tendency to bleed after trivial trauma. They should be excised with a minimal margin. Glomus tumour This arises from a subcutaneous arteriovenous shunt (Sucquet– Hoyer canals), especially in the corium of  the nail bed. Typically , JP Sucquet , 1840–1870, anatomist, Paris, France. Heinrich Hoyer , 1834–1907, Professor of  Histology , Embryology and Anatomy , Central Medical School, The Polish University , Warsaw , Poland. - it is a small, purple nodule measuring a few millimetres in size, which is disproportionately painful in response to insignificant stimuli, including cold exposure ( Figure 45.48 ). Subungual - varieties may be invisible causes of  paroxysmal digital pain. ). Most Angiosarcoma (‘malignant angioendothelioma’) A rare, highly malignant tumour arising from the endothelial cells ( Figure 45.49 ). The lymphangiosarcoma variant arises from lymphatic endothelium and can develop in lymphoedem - atous tissue, particularly an extremity . Proliferation is rapid with early systemic spread.
Figure 45.44
‘Port-wine’ stain (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.45
Campbell de Morgan spot (courtesy of Mr AR Green
baum).
Figure 45.46
Spider naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.47
Pyogenic granuloma (courtesy of St John’s Institute for
Dermatology, London, UK).
Kaposi’s sarcoma Kaposi’s sarcoma is a malignant, proliferative tumour of vascular endothelial cells, which was first described in elderly Jewish men but is now most commonly associated with immune compromise after transplantation or HIV infection ( Figure 45.50 ). There appears to be a causal link with infection by human herpesvirus 8. Kaposi’s sarcoma usually starts as a red-brown, indurated, plaque-like skin lesion that becomes nodular and then ulcerates. Treatment is with radiotherapy .
Figure 45.48
Glomus tumour (courtesy of St John’s Institute for
Dermatology, London, UK).
Acquired
Pressure sores These begin with tissue necrosis at a pressure point and develop into a cone-shaped volume of  necrotic loss. As many as 10% of  acute hospital inpatients will have some degree of  pressure sore. The majority a ff ect the elderly and patients with spinal injury or decreased sensibility; 80% of  paraplegics will get a pressure sore and 8% die as a result. The pathogenesis of  pressure sores revolves around unre lieved pressure: an increase in local tissue pressure above that of  perfusion pressure produces ischaemic necrosis that is directly proportional to the duration and degree of  pressure and inver sely proportional to the area over which it is applied. Muscle and fat are more susceptible to pressure than skin. In a patient who has no predisposing factors management is aimed at debridement and repair of  the defect, on the assump tion that recurrence will not occur once normal function and sensibility returns. In the paraplegic patient, recurrence is likely so management should involve a multidisciplinary approach. Primary treatment involves relieving pressure (special mattress, nursing care, relief  of  muscle spasm and contractures), opti mising nutrition, correcting anaemia and preventing infection. Surgery involves thorough debridement to promote healing and plastic surgery to reconstruct the defect. Ulcers An ulcer is a discontinuity of  an epithelial surface. It is characterised by destruction of  the surface epithelium and a granulating base. Ulcers can be classified as non-specific, specific and malignant ( Figure 45.51 ). Sinus A sinus is a blind-ending tract connecting a cavity lined with granulation tissue (often an abscess cavity) to an epithelial (a) (b) (c) (d ) ( e) Burrill Bernard Crohn , 1884–1983, gastroenterologist, Mount Sinai Hospital, New Y ork, NY , USA, described regional ileitis in 1932. - - surface ( Figure 45.52a ). Sinuses may be congenital or acquired. Congenital sinuses arise from the remnants of persistent embryonic ducts. Acquired sinuses can result from: a retained foreign body (ingrown hair or suture material); chronic infection (tuberculosis, osteomyelitis or actinomycosis); chronic - inflammation (Crohn’s disease); malignancy; or inadequate surgical drainage of  a cavity . , Treatment of  a sinus is directed at removing the underlying cause. Biopsies should always be taken from the wall of  a sinus to exclude malignancy or specific infection. For specific man - - agement of  the disease conditions, please refer to the appro - priate chapter. Fistula A fistula is an abnormal communication between two epithelium-lined surfaces ( Figure 45.52b ). This commu - nication or tract is usually lined by granulation tissue, but may become epithelialised in chronic cases. Fistulae may be congenital (e.g. tracheo-oesophageal and branchial fistulae) or acquired (e.g. enterocutaneous complicating Crohn’ s disease or surgery , or arteriovenous). Management of  a fistula is directed at the underlying aetiology (see the appropriate chapters).
Figure 45.51
Some characteristic shapes of the edges of ulcers.
/uni00A0
(a)
Non-speci
/f_i
c ulcer: note the shelving edge.
(b)
Tuberculous ulcer:
note the undermined edge.
(c)
Basal cell carcinoma (rodent ulcer):
note the rolled edge, which may exhibit small blood vessels.
thelioma: note the heaped-up, everted edge and irregular thickened
base.
(e)
Syphilis: note the punched-out edge and thin base, which
may be covered with a ‘wash-leather’ slough.
Figure 45.52
A sinus
(a)
and a
/f_i
stula
(b)
; both usually arise from a
preceding abscess.
(a)
This is a blind track, in this case a pilonidal
abscess.
(b)
This is a track connecting two epithelium-lined surfaces,
in this case a colocutaneous
/f_i
stula from colon to skin.
Acquired
Campbell de Morgan spots These are arteriovenous fistulae at the dermal capillary level in - sun-exposed skin of  older patients ( Figure 45.45 ). Spider naevi These are angiomata that appear (and may disappear) sponta neously at puberty or in two-thirds of  pregnant women, usually disappearing in the puerperium ( Figure 45.46 ). Spider naevi are also associated with c hronic liver disease. They can be treated with intense pulsed light or pulsed-dye laser. Pyogenic granuloma These share many histological characteristics of  haemangio mata and are probably a subtype thereof  ( Figure 45.47 are small (0.5–1.5 /uni00A0 cm), raised, pedunculated, soft, red nodular lesions showing superficial ulceration and a tendency to bleed after trivial trauma. They should be excised with a minimal margin. Glomus tumour This arises from a subcutaneous arteriovenous shunt (Sucquet– Hoyer canals), especially in the corium of  the nail bed. Typically , JP Sucquet , 1840–1870, anatomist, Paris, France. Heinrich Hoyer , 1834–1907, Professor of  Histology , Embryology and Anatomy , Central Medical School, The Polish University , Warsaw , Poland. - it is a small, purple nodule measuring a few millimetres in size, which is disproportionately painful in response to insignificant stimuli, including cold exposure ( Figure 45.48 ). Subungual - varieties may be invisible causes of  paroxysmal digital pain. ). Most Angiosarcoma (‘malignant angioendothelioma’) A rare, highly malignant tumour arising from the endothelial cells ( Figure 45.49 ). The lymphangiosarcoma variant arises from lymphatic endothelium and can develop in lymphoedem - atous tissue, particularly an extremity . Proliferation is rapid with early systemic spread.
Figure 45.44
‘Port-wine’ stain (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.45
Campbell de Morgan spot (courtesy of Mr AR Green
baum).
Figure 45.46
Spider naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.47
Pyogenic granuloma (courtesy of St John’s Institute for
Dermatology, London, UK).
Kaposi’s sarcoma Kaposi’s sarcoma is a malignant, proliferative tumour of vascular endothelial cells, which was first described in elderly Jewish men but is now most commonly associated with immune compromise after transplantation or HIV infection ( Figure 45.50 ). There appears to be a causal link with infection by human herpesvirus 8. Kaposi’s sarcoma usually starts as a red-brown, indurated, plaque-like skin lesion that becomes nodular and then ulcerates. Treatment is with radiotherapy .
Figure 45.48
Glomus tumour (courtesy of St John’s Institute for
Dermatology, London, UK).
Acquired
Pressure sores These begin with tissue necrosis at a pressure point and develop into a cone-shaped volume of  necrotic loss. As many as 10% of  acute hospital inpatients will have some degree of  pressure sore. The majority a ff ect the elderly and patients with spinal injury or decreased sensibility; 80% of  paraplegics will get a pressure sore and 8% die as a result. The pathogenesis of  pressure sores revolves around unre lieved pressure: an increase in local tissue pressure above that of  perfusion pressure produces ischaemic necrosis that is directly proportional to the duration and degree of  pressure and inver sely proportional to the area over which it is applied. Muscle and fat are more susceptible to pressure than skin. In a patient who has no predisposing factors management is aimed at debridement and repair of  the defect, on the assump tion that recurrence will not occur once normal function and sensibility returns. In the paraplegic patient, recurrence is likely so management should involve a multidisciplinary approach. Primary treatment involves relieving pressure (special mattress, nursing care, relief  of  muscle spasm and contractures), opti mising nutrition, correcting anaemia and preventing infection. Surgery involves thorough debridement to promote healing and plastic surgery to reconstruct the defect. Ulcers An ulcer is a discontinuity of  an epithelial surface. It is characterised by destruction of  the surface epithelium and a granulating base. Ulcers can be classified as non-specific, specific and malignant ( Figure 45.51 ). Sinus A sinus is a blind-ending tract connecting a cavity lined with granulation tissue (often an abscess cavity) to an epithelial (a) (b) (c) (d ) ( e) Burrill Bernard Crohn , 1884–1983, gastroenterologist, Mount Sinai Hospital, New Y ork, NY , USA, described regional ileitis in 1932. - - surface ( Figure 45.52a ). Sinuses may be congenital or acquired. Congenital sinuses arise from the remnants of persistent embryonic ducts. Acquired sinuses can result from: a retained foreign body (ingrown hair or suture material); chronic infection (tuberculosis, osteomyelitis or actinomycosis); chronic - inflammation (Crohn’s disease); malignancy; or inadequate surgical drainage of  a cavity . , Treatment of  a sinus is directed at removing the underlying cause. Biopsies should always be taken from the wall of  a sinus to exclude malignancy or specific infection. For specific man - - agement of  the disease conditions, please refer to the appro - priate chapter. Fistula A fistula is an abnormal communication between two epithelium-lined surfaces ( Figure 45.52b ). This commu - nication or tract is usually lined by granulation tissue, but may become epithelialised in chronic cases. Fistulae may be congenital (e.g. tracheo-oesophageal and branchial fistulae) or acquired (e.g. enterocutaneous complicating Crohn’ s disease or surgery , or arteriovenous). Management of  a fistula is directed at the underlying aetiology (see the appropriate chapters).
Figure 45.51
Some characteristic shapes of the edges of ulcers.
/uni00A0
(a)
Non-speci
/f_i
c ulcer: note the shelving edge.
(b)
Tuberculous ulcer:
note the undermined edge.
(c)
Basal cell carcinoma (rodent ulcer):
note the rolled edge, which may exhibit small blood vessels.
thelioma: note the heaped-up, everted edge and irregular thickened
base.
(e)
Syphilis: note the punched-out edge and thin base, which
may be covered with a ‘wash-leather’ slough.
Figure 45.52
A sinus
(a)
and a
/f_i
stula
(b)
; both usually arise from a
preceding abscess.
(a)
This is a blind track, in this case a pilonidal
abscess.
(b)
This is a track connecting two epithelium-lined surfaces,
in this case a colocutaneous
/f_i
stula from colon to skin.

Anomalies of skin metabolism
Anomalies of skin metabolism
Skin has the potential for a blood supply 20–100 times greater than its metabolic and thermoregulatory requirements. This apparent excess enables restitution of  mechanical integrity after the myriad of  trivial injuries (scratching, stretching, compressing, thermal) to which skin is subjected; however, blood supply is inadequate to support full-thickness wound healing, which requires primary closure or granulation tissue. Skin functions optimally at temperatures below body core temperature and can tolerate long periods of  ischaemia, allow ing it to be both grafted and/or expanded for use in recon struction. Anomalies of skin metabolism
Skin has the potential for a blood supply 20–100 times greater than its metabolic and thermoregulatory requirements. This apparent excess enables restitution of  mechanical integrity after the myriad of  trivial injuries (scratching, stretching, compressing, thermal) to which skin is subjected; however, blood supply is inadequate to support full-thickness wound healing, which requires primary closure or granulation tissue. Skin functions optimally at temperatures below body core temperature and can tolerate long periods of  ischaemia, allow ing it to be both grafted and/or expanded for use in recon struction. Anomalies of skin metabolism
Skin has the potential for a blood supply 20–100 times greater than its metabolic and thermoregulatory requirements. This apparent excess enables restitution of  mechanical integrity after the myriad of  trivial injuries (scratching, stretching, compressing, thermal) to which skin is subjected; however, blood supply is inadequate to support full-thickness wound healing, which requires primary closure or granulation tissue. Skin functions optimally at temperatures below body core temperature and can tolerate long periods of  ischaemia, allow ing it to be both grafted and/or expanded for use in recon struction.

Atypical (dysplastic) naevus
Atypical (dysplastic) naevus
To be ‘atypical naevi’, lesions must have three of the following in situ characteristics: variegated pigmentation; ill-defined borders; undulating irregular surfaces; or size >5 /uni00A0 mm. Terminology is confused because, although the terms ‘dysplastic’ and ‘atypical’ are often used interchangeably , dysplasia is a histological diag nosis with findings of  irregular proliferations of  melanocytes at the basal layer of  the epidermis. In fact, a small proportion of  clinically ‘atypical naevi’ are actually dysplastic when exam . ined microscopically Atypical naevi can be sporadic or familial (familial atypical multiple mole–melanoma [FAMMM] syndrome). Possession of  more than five lesions confers a relative risk of  melanoma six times greater than usual; within FAMMM syndrome confer a 100% risk of  malignant melanoma and patients with FAMMM syndrome should be screened for melanoma 6-monthly , lifelong ( Figure 45.29 ). Data from the World Health Organization suggest that both non-melanoma and melanoma skin cancers continue to increase in incidence, despite educational programmes and wide-ranging changes in uptake of  sun protective measures and improvements in sunscreens. Skin cancer is the common - est malignancy in white-skinned people, constituting 33% of all recorded malignancies annually , with 2–3 million new non-melanoma skin cancers and 132 /uni00A0 000 new malignant mela - e melanomas) diagnosed nomas (4.5% of  all new cancers ar each year.
Figure 45.28
Giant congenital pigmented naevus (courtesy of St
John’s Institute for Dermatology, London, UK).
Figure 45.29
Dysplastic naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Atypical (dysplastic) naevus
To be ‘atypical naevi’, lesions must have three of the following in situ characteristics: variegated pigmentation; ill-defined borders; undulating irregular surfaces; or size >5 /uni00A0 mm. Terminology is confused because, although the terms ‘dysplastic’ and ‘atypical’ are often used interchangeably , dysplasia is a histological diag nosis with findings of  irregular proliferations of  melanocytes at the basal layer of  the epidermis. In fact, a small proportion of  clinically ‘atypical naevi’ are actually dysplastic when exam . ined microscopically Atypical naevi can be sporadic or familial (familial atypical multiple mole–melanoma [FAMMM] syndrome). Possession of  more than five lesions confers a relative risk of  melanoma six times greater than usual; within FAMMM syndrome confer a 100% risk of  malignant melanoma and patients with FAMMM syndrome should be screened for melanoma 6-monthly , lifelong ( Figure 45.29 ). Data from the World Health Organization suggest that both non-melanoma and melanoma skin cancers continue to increase in incidence, despite educational programmes and wide-ranging changes in uptake of  sun protective measures and improvements in sunscreens. Skin cancer is the common - est malignancy in white-skinned people, constituting 33% of all recorded malignancies annually , with 2–3 million new non-melanoma skin cancers and 132 /uni00A0 000 new malignant mela - e melanomas) diagnosed nomas (4.5% of  all new cancers ar each year.
Figure 45.28
Giant congenital pigmented naevus (courtesy of St
John’s Institute for Dermatology, London, UK).
Figure 45.29
Dysplastic naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Atypical (dysplastic) naevus
To be ‘atypical naevi’, lesions must have three of the following in situ characteristics: variegated pigmentation; ill-defined borders; undulating irregular surfaces; or size >5 /uni00A0 mm. Terminology is confused because, although the terms ‘dysplastic’ and ‘atypical’ are often used interchangeably , dysplasia is a histological diag nosis with findings of  irregular proliferations of  melanocytes at the basal layer of  the epidermis. In fact, a small proportion of  clinically ‘atypical naevi’ are actually dysplastic when exam . ined microscopically Atypical naevi can be sporadic or familial (familial atypical multiple mole–melanoma [FAMMM] syndrome). Possession of  more than five lesions confers a relative risk of  melanoma six times greater than usual; within FAMMM syndrome confer a 100% risk of  malignant melanoma and patients with FAMMM syndrome should be screened for melanoma 6-monthly , lifelong ( Figure 45.29 ). Data from the World Health Organization suggest that both non-melanoma and melanoma skin cancers continue to increase in incidence, despite educational programmes and wide-ranging changes in uptake of  sun protective measures and improvements in sunscreens. Skin cancer is the common - est malignancy in white-skinned people, constituting 33% of all recorded malignancies annually , with 2–3 million new non-melanoma skin cancers and 132 /uni00A0 000 new malignant mela - e melanomas) diagnosed nomas (4.5% of  all new cancers ar each year.
Figure 45.28
Giant congenital pigmented naevus (courtesy of St
John’s Institute for Dermatology, London, UK).
Figure 45.29
Dysplastic naevus (courtesy of St John’s Institute for
Dermatology, London, UK).

Basal cell carcinoma
Basal cell carcinoma
This is usually a slow-growing, locally invasive, malignant tumour of  pluripotential epithelial cells arising from basal epidermis and hair follicles; hence, it a ff ects the pilosebaceous skin. Summary box 45.2 Basal cell carcinoma /uni25CF /uni25CF /uni25CF /uni25CF - Epidemiology The strongest predisposing factor to BCC is UVR. It occurs in the elderly or the middle-aged after excessive sun exposure, - with 95% occurring between the ages of 40 and 80 years. The incidence of BCC rises with proximity to the equator, although 33% arise in parts of  the body not usually exposed to the sun. Other predisposing factors include exposure to arsenical compounds, coal tar, aromatic hydrocarbons and IR , they and genetic skin cancer syndromes. White-skinned people are almost exclusively a ff ected. BCC is more common in men than in women. Pathogenesis BCCs have no apparent precursor lesions and their develop - ment is proportional to the initial dose of the carcinogen, but not duration of  exposure. The most likely model of  patho - mal factors as intrinsic genesis for BCCs involves mesoder promoters coupled with an initiation step. BCCs metastasise extremely rarely . Macroscopic BCCs can be divided into localised (nodular, nodulocystic, cystic, pigmented and naevoid) and generalised (superficial: multifocal and superficial spreading; or infiltrative: morphoeic, ice pick and cicatrising). Nodular and nodulocystic variants account for 90% of  BCCs. Microscopic Twenty-six histological subtypes have been described. The characteristic finding is of  ovoid cells in nests with a single
Slow growing
Risk factor – UVR
90% nodular/nodular cystic
High- and low-risk BCC
divide, explaining why tumour growth rates are slower than their cell cycle speed would suggest and why incompletely excised lesions are more aggressive. Morphoeic BCCs synthe sise type 4 collagenase and so spread rapidly ( Figure 45.30 Frederic E Mohs , 1910–2002, American physician and general surgeon, University of  Wisconsin, Madison, WI, USA, developed Mohs’ micrographic surgical technique in 1938 for cutaneous malignant lesions. Jean-Nicolas Marjolin , 1780–1850, surgeon, Paris, France, described the development of  carcinomatous ulcers in scars in 1828. There are ‘high-risk’ and ‘low-risk’ BCCs. High-risk BCCs: are large (>2 /uni00A0 cm); are located at sites where direct invasion - gives access to the cranium (near the eye, nose and ear); are ). recurrent tumours; are tumours forming in the presence of immunosuppression; or have micronodular or infiltrating histological subtypes. Management Treatment can be surgical or non-surgical. Tumour and surrounding surgical margins should always be assessed and marked under loupe magnification, the latter varying between 2 and 15 /uni00A0 mm depending on the macroscopic variant. Where margins are ill-defined or tissue is at a premium (nose, eyes), either a two-stage surgical approach with subsequent recon - struction after confirmation of  clear margins or Mohs’ micro - graphic surgery is advisable. The histological sample must be orientated and marked for pathological examination. Mohs’ micrographic sur gery is a method used by derma - tological surgeons (dermatologists who have undergone extra training in techniques of  cutaneous surgery and histopathol - ogy) to excise skin cancer under microscopic control. In elderly or infirm patients, radiotherapy produces simi - lar recurrence rates to surgery , but with the risk of  generating further malignancy after one to two decades. Biopsy-proven, superficial tumours can be treated with topical treatments (5-fluorouracil, imiquimod). Unless excision of  a BCC is complete, there is a 67% recur - r ence rate if  margins are grossly involved and a 33% recur - rence rate within 2 years with microscopic involvement or when reported ‘close’. Patients with uncomplicated, completely excised lesions can be discharged. Follow-up is reserved for patients with tumours in high-risk ar eas; for those with globally sun-damaged skin; for those with syndr omes; and for those who decline further surgery after incomplete excisions.
(a)
(b)
(c)
Figure 45.30
(a)
A nodulocystic basal carcinoma (BCC). Note the
characteristic pearly surface with telangiectasia.
(b)
An ulcerating
BCC on the lower eyelid.
(c)
A recurrent morphoeic BCC. (
courtesy of Mr AR Greenbaum;
(c)
courtesy of St John’s Institute for
Dermatology, London, UK.)
Basal cell carcinoma
This is usually a slow-growing, locally invasive, malignant tumour of  pluripotential epithelial cells arising from basal epidermis and hair follicles; hence, it a ff ects the pilosebaceous skin. Summary box 45.2 Basal cell carcinoma /uni25CF /uni25CF /uni25CF /uni25CF - Epidemiology The strongest predisposing factor to BCC is UVR. It occurs in the elderly or the middle-aged after excessive sun exposure, - with 95% occurring between the ages of 40 and 80 years. The incidence of BCC rises with proximity to the equator, although 33% arise in parts of  the body not usually exposed to the sun. Other predisposing factors include exposure to arsenical compounds, coal tar, aromatic hydrocarbons and IR , they and genetic skin cancer syndromes. White-skinned people are almost exclusively a ff ected. BCC is more common in men than in women. Pathogenesis BCCs have no apparent precursor lesions and their develop - ment is proportional to the initial dose of the carcinogen, but not duration of  exposure. The most likely model of  patho - mal factors as intrinsic genesis for BCCs involves mesoder promoters coupled with an initiation step. BCCs metastasise extremely rarely . Macroscopic BCCs can be divided into localised (nodular, nodulocystic, cystic, pigmented and naevoid) and generalised (superficial: multifocal and superficial spreading; or infiltrative: morphoeic, ice pick and cicatrising). Nodular and nodulocystic variants account for 90% of  BCCs. Microscopic Twenty-six histological subtypes have been described. The characteristic finding is of  ovoid cells in nests with a single
Slow growing
Risk factor – UVR
90% nodular/nodular cystic
High- and low-risk BCC
divide, explaining why tumour growth rates are slower than their cell cycle speed would suggest and why incompletely excised lesions are more aggressive. Morphoeic BCCs synthe sise type 4 collagenase and so spread rapidly ( Figure 45.30 Frederic E Mohs , 1910–2002, American physician and general surgeon, University of  Wisconsin, Madison, WI, USA, developed Mohs’ micrographic surgical technique in 1938 for cutaneous malignant lesions. Jean-Nicolas Marjolin , 1780–1850, surgeon, Paris, France, described the development of  carcinomatous ulcers in scars in 1828. There are ‘high-risk’ and ‘low-risk’ BCCs. High-risk BCCs: are large (>2 /uni00A0 cm); are located at sites where direct invasion - gives access to the cranium (near the eye, nose and ear); are ). recurrent tumours; are tumours forming in the presence of immunosuppression; or have micronodular or infiltrating histological subtypes. Management Treatment can be surgical or non-surgical. Tumour and surrounding surgical margins should always be assessed and marked under loupe magnification, the latter varying between 2 and 15 /uni00A0 mm depending on the macroscopic variant. Where margins are ill-defined or tissue is at a premium (nose, eyes), either a two-stage surgical approach with subsequent recon - struction after confirmation of  clear margins or Mohs’ micro - graphic surgery is advisable. The histological sample must be orientated and marked for pathological examination. Mohs’ micrographic sur gery is a method used by derma - tological surgeons (dermatologists who have undergone extra training in techniques of  cutaneous surgery and histopathol - ogy) to excise skin cancer under microscopic control. In elderly or infirm patients, radiotherapy produces simi - lar recurrence rates to surgery , but with the risk of  generating further malignancy after one to two decades. Biopsy-proven, superficial tumours can be treated with topical treatments (5-fluorouracil, imiquimod). Unless excision of  a BCC is complete, there is a 67% recur - r ence rate if  margins are grossly involved and a 33% recur - rence rate within 2 years with microscopic involvement or when reported ‘close’. Patients with uncomplicated, completely excised lesions can be discharged. Follow-up is reserved for patients with tumours in high-risk ar eas; for those with globally sun-damaged skin; for those with syndr omes; and for those who decline further surgery after incomplete excisions.
(a)
(b)
(c)
Figure 45.30
(a)
A nodulocystic basal carcinoma (BCC). Note the
characteristic pearly surface with telangiectasia.
(b)
An ulcerating
BCC on the lower eyelid.
(c)
A recurrent morphoeic BCC. (
courtesy of Mr AR Greenbaum;
(c)
courtesy of St John’s Institute for
Dermatology, London, UK.)
Basal cell carcinoma
This is usually a slow-growing, locally invasive, malignant tumour of  pluripotential epithelial cells arising from basal epidermis and hair follicles; hence, it a ff ects the pilosebaceous skin. Summary box 45.2 Basal cell carcinoma /uni25CF /uni25CF /uni25CF /uni25CF - Epidemiology The strongest predisposing factor to BCC is UVR. It occurs in the elderly or the middle-aged after excessive sun exposure, - with 95% occurring between the ages of 40 and 80 years. The incidence of BCC rises with proximity to the equator, although 33% arise in parts of  the body not usually exposed to the sun. Other predisposing factors include exposure to arsenical compounds, coal tar, aromatic hydrocarbons and IR , they and genetic skin cancer syndromes. White-skinned people are almost exclusively a ff ected. BCC is more common in men than in women. Pathogenesis BCCs have no apparent precursor lesions and their develop - ment is proportional to the initial dose of the carcinogen, but not duration of  exposure. The most likely model of  patho - mal factors as intrinsic genesis for BCCs involves mesoder promoters coupled with an initiation step. BCCs metastasise extremely rarely . Macroscopic BCCs can be divided into localised (nodular, nodulocystic, cystic, pigmented and naevoid) and generalised (superficial: multifocal and superficial spreading; or infiltrative: morphoeic, ice pick and cicatrising). Nodular and nodulocystic variants account for 90% of  BCCs. Microscopic Twenty-six histological subtypes have been described. The characteristic finding is of  ovoid cells in nests with a single
Slow growing
Risk factor – UVR
90% nodular/nodular cystic
High- and low-risk BCC
divide, explaining why tumour growth rates are slower than their cell cycle speed would suggest and why incompletely excised lesions are more aggressive. Morphoeic BCCs synthe sise type 4 collagenase and so spread rapidly ( Figure 45.30 Frederic E Mohs , 1910–2002, American physician and general surgeon, University of  Wisconsin, Madison, WI, USA, developed Mohs’ micrographic surgical technique in 1938 for cutaneous malignant lesions. Jean-Nicolas Marjolin , 1780–1850, surgeon, Paris, France, described the development of  carcinomatous ulcers in scars in 1828. There are ‘high-risk’ and ‘low-risk’ BCCs. High-risk BCCs: are large (>2 /uni00A0 cm); are located at sites where direct invasion - gives access to the cranium (near the eye, nose and ear); are ). recurrent tumours; are tumours forming in the presence of immunosuppression; or have micronodular or infiltrating histological subtypes. Management Treatment can be surgical or non-surgical. Tumour and surrounding surgical margins should always be assessed and marked under loupe magnification, the latter varying between 2 and 15 /uni00A0 mm depending on the macroscopic variant. Where margins are ill-defined or tissue is at a premium (nose, eyes), either a two-stage surgical approach with subsequent recon - struction after confirmation of  clear margins or Mohs’ micro - graphic surgery is advisable. The histological sample must be orientated and marked for pathological examination. Mohs’ micrographic sur gery is a method used by derma - tological surgeons (dermatologists who have undergone extra training in techniques of  cutaneous surgery and histopathol - ogy) to excise skin cancer under microscopic control. In elderly or infirm patients, radiotherapy produces simi - lar recurrence rates to surgery , but with the risk of  generating further malignancy after one to two decades. Biopsy-proven, superficial tumours can be treated with topical treatments (5-fluorouracil, imiquimod). Unless excision of  a BCC is complete, there is a 67% recur - r ence rate if  margins are grossly involved and a 33% recur - rence rate within 2 years with microscopic involvement or when reported ‘close’. Patients with uncomplicated, completely excised lesions can be discharged. Follow-up is reserved for patients with tumours in high-risk ar eas; for those with globally sun-damaged skin; for those with syndr omes; and for those who decline further surgery after incomplete excisions.
(a)
(b)
(c)
Figure 45.30
(a)
A nodulocystic basal carcinoma (BCC). Note the
characteristic pearly surface with telangiectasia.
(b)
An ulcerating
BCC on the lower eyelid.
(c)
A recurrent morphoeic BCC. (
courtesy of Mr AR Greenbaum;
(c)
courtesy of St John’s Institute for
Dermatology, London, UK.)

Blood supply of the skin
Blood supply of the skin
The body can be envisaged as three-dimensional segments of  tissue called angiosomes, each with an arterial supply and a venous drainage. Blood equilibrates and flows between neighbouring angiosomes via ‘choke’ vessels, which tend to be situated within muscles. Cutaneous arteries, direct branches of segmental arteries (concentrated at the dorsoventral axes and intermuscular septae), perforate the underlying muscles or run directly within fascial layers to the skin from the deep tissues ( Figure 45.2 ). The blood supply to the skin anastomoses in subfascial, fas - cial, subdermal, dermal and subepidermal plexi. The epider - - mis contains no blood vessels so cells there derive nourishment by di ff usion.
Sweat gland
Subcutaneous fat
Angiosome A Angiosome B
Epidermis
Subcutaneous
fat
Musculocutaneous
perforator
Fasciocutaneous
perforator
Muscle
Fascia and
epimysium
Choke vessels between
angiosomes A and B
within muscle
Named
artery and
Major vein
vein
Major artery
Figure 45.2
Schematic showing two neighbouring angiosomes. Note
the choke vessels within the muscle spanning the two cutaneous
territories of angiosomes A and B; two common examples of myocu
taneous
/f_l
aps that utilise this physiology include the rectus abdominis
and the latissimus dorsi
/f_l
aps.
unvalved veins. Unvalved veins allow oscillating flow in the subdermal plexus between cutaneous territories, equilibrating flow and pressure. The valved cutaneous veins drain via plexi to the deep veins. Blood supply of the skin
The body can be envisaged as three-dimensional segments of  tissue called angiosomes, each with an arterial supply and a venous drainage. Blood equilibrates and flows between neighbouring angiosomes via ‘choke’ vessels, which tend to be situated within muscles. Cutaneous arteries, direct branches of segmental arteries (concentrated at the dorsoventral axes and intermuscular septae), perforate the underlying muscles or run directly within fascial layers to the skin from the deep tissues ( Figure 45.2 ). The blood supply to the skin anastomoses in subfascial, fas - cial, subdermal, dermal and subepidermal plexi. The epider - - mis contains no blood vessels so cells there derive nourishment by di ff usion.
Sweat gland
Subcutaneous fat
Angiosome A Angiosome B
Epidermis
Subcutaneous
fat
Musculocutaneous
perforator
Fasciocutaneous
perforator
Muscle
Fascia and
epimysium
Choke vessels between
angiosomes A and B
within muscle
Named
artery and
Major vein
vein
Major artery
Figure 45.2
Schematic showing two neighbouring angiosomes. Note
the choke vessels within the muscle spanning the two cutaneous
territories of angiosomes A and B; two common examples of myocu
taneous
/f_l
aps that utilise this physiology include the rectus abdominis
and the latissimus dorsi
/f_l
aps.
unvalved veins. Unvalved veins allow oscillating flow in the subdermal plexus between cutaneous territories, equilibrating flow and pressure. The valved cutaneous veins drain via plexi to the deep veins. Blood supply of the skin
The body can be envisaged as three-dimensional segments of  tissue called angiosomes, each with an arterial supply and a venous drainage. Blood equilibrates and flows between neighbouring angiosomes via ‘choke’ vessels, which tend to be situated within muscles. Cutaneous arteries, direct branches of segmental arteries (concentrated at the dorsoventral axes and intermuscular septae), perforate the underlying muscles or run directly within fascial layers to the skin from the deep tissues ( Figure 45.2 ). The blood supply to the skin anastomoses in subfascial, fas - cial, subdermal, dermal and subepidermal plexi. The epider - - mis contains no blood vessels so cells there derive nourishment by di ff usion.
Sweat gland
Subcutaneous fat
Angiosome A Angiosome B
Epidermis
Subcutaneous
fat
Musculocutaneous
perforator
Fasciocutaneous
perforator
Muscle
Fascia and
epimysium
Choke vessels between
angiosomes A and B
within muscle
Named
artery and
Major vein
vein
Major artery
Figure 45.2
Schematic showing two neighbouring angiosomes. Note
the choke vessels within the muscle spanning the two cutaneous
territories of angiosomes A and B; two common examples of myocu
taneous
/f_l
aps that utilise this physiology include the rectus abdominis
and the latissimus dorsi
/f_l
aps.
unvalved veins. Unvalved veins allow oscillating flow in the subdermal plexus between cutaneous territories, equilibrating flow and pressure. The valved cutaneous veins drain via plexi to the deep veins.

Common vascular birthmarks
Common vascular birthmarks
Salmon patch A salmon patch is a vascular malformation that presents as a pinkish macule, usually at the nape of  neck ( Figure 45.42 is caused by an area of  persistent fetal dermal circulation that usually disappears at 1 year. Capillary haemangioma (strawberry naevus) This is the commonest ‘birthmark’, occurring most frequently on the head and neck ( Figure 45.43 ). Ninety per cent are present at birth; as a consequence of  intravascular thrombosis, fibrosis and mast cell infiltration, 10% resolve each subsequent year, with 70% resolved by 7 years old. White skin is a ff ected most commonly and girls are a ff ected three times more than boys. Capillary vascular malformations (’port-wine’ stains) Capillary vascular malformations (‘port-wine stains’ [PWSs]) are 20 times less common than capillary haemangiomata and result from defective maturation of  the cutaneous sympathetic innervation during embryogenesis, leading to localised intra dermal capillary vasodilatation ( Figure 45.44 ). They appear Campbell Greig de Morgan , 1811–1876, surgeon, Middlesex Hospital, London, UK. First to propose that cancer started locally and then spread first to lymph nodes and beyond. - ). It at birth as flat, smooth, intensely purple-stained areas, most frequently on the head and neck, often within the maxillary and mandibular dermatomes of  the trigeminal nerve. Treatment with intense pulsed light and pulsed-dye laser is successful. PWSs may be associated with various syndromes.
Figure 45.42
Salmon patch (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.43
Capillary haemangioma (courtesy of St John’s Institute
for Dermatology, London, UK).
Common vascular birthmarks
Salmon patch A salmon patch is a vascular malformation that presents as a pinkish macule, usually at the nape of  neck ( Figure 45.42 is caused by an area of  persistent fetal dermal circulation that usually disappears at 1 year. Capillary haemangioma (strawberry naevus) This is the commonest ‘birthmark’, occurring most frequently on the head and neck ( Figure 45.43 ). Ninety per cent are present at birth; as a consequence of  intravascular thrombosis, fibrosis and mast cell infiltration, 10% resolve each subsequent year, with 70% resolved by 7 years old. White skin is a ff ected most commonly and girls are a ff ected three times more than boys. Capillary vascular malformations (’port-wine’ stains) Capillary vascular malformations (‘port-wine stains’ [PWSs]) are 20 times less common than capillary haemangiomata and result from defective maturation of  the cutaneous sympathetic innervation during embryogenesis, leading to localised intra dermal capillary vasodilatation ( Figure 45.44 ). They appear Campbell Greig de Morgan , 1811–1876, surgeon, Middlesex Hospital, London, UK. First to propose that cancer started locally and then spread first to lymph nodes and beyond. - ). It at birth as flat, smooth, intensely purple-stained areas, most frequently on the head and neck, often within the maxillary and mandibular dermatomes of  the trigeminal nerve. Treatment with intense pulsed light and pulsed-dye laser is successful. PWSs may be associated with various syndromes.
Figure 45.42
Salmon patch (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.43
Capillary haemangioma (courtesy of St John’s Institute
for Dermatology, London, UK).
Common vascular birthmarks
Salmon patch A salmon patch is a vascular malformation that presents as a pinkish macule, usually at the nape of  neck ( Figure 45.42 is caused by an area of  persistent fetal dermal circulation that usually disappears at 1 year. Capillary haemangioma (strawberry naevus) This is the commonest ‘birthmark’, occurring most frequently on the head and neck ( Figure 45.43 ). Ninety per cent are present at birth; as a consequence of  intravascular thrombosis, fibrosis and mast cell infiltration, 10% resolve each subsequent year, with 70% resolved by 7 years old. White skin is a ff ected most commonly and girls are a ff ected three times more than boys. Capillary vascular malformations (’port-wine’ stains) Capillary vascular malformations (‘port-wine stains’ [PWSs]) are 20 times less common than capillary haemangiomata and result from defective maturation of  the cutaneous sympathetic innervation during embryogenesis, leading to localised intra dermal capillary vasodilatation ( Figure 45.44 ). They appear Campbell Greig de Morgan , 1811–1876, surgeon, Middlesex Hospital, London, UK. First to propose that cancer started locally and then spread first to lymph nodes and beyond. - ). It at birth as flat, smooth, intensely purple-stained areas, most frequently on the head and neck, often within the maxillary and mandibular dermatomes of  the trigeminal nerve. Treatment with intense pulsed light and pulsed-dye laser is successful. PWSs may be associated with various syndromes.
Figure 45.42
Salmon patch (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.43
Capillary haemangioma (courtesy of St John’s Institute
for Dermatology, London, UK).

Congenital genetic disorders
Congenital/genetic disorders
Neurofibromatosis There are two distinct neurofibromatosis (NF) syndromes, in which Schwann cells form tumours ( Figure 45.3 ). Each is caused by di ff erent genes on di ff erent chromosomes: 70% are autosomal dominant and 30% arise from sporadic mutations. NF-1 (V on Recklinghausen’s disease) is the commoner variant, mutation on chromosome 17. Skin manifestations appear in early life, with the development of  more than five smooth- surfaced café-au-lait spots, subcutaneous neurofibromata, armpit or groin freckling and Lisch nodules. NF-2 produces multiple central nervous system tumours. Naevoid basal cell carcinoma (Gorlin’s) syndrome This is an autosomal dominant inherited condition caused by an abnormal tumour suppressor gene on chromosome 9q 22–31 coding the ‘patched’ protein; 90% of patients develop multiple basal cell carcinomas (BCCs). Patients may exhibit specific phenotypical characteristics, including overdeveloped supraorbital ridges; broad nasal roots; hypertelorism; bifid ribs; scoliosis; brachymetacarpalism; palmar pits; and molar odontogenic cysts; patients are also prone to other tumours. Xeroderma pigmentosum This syndrome is caused by an abnormality on the ‘patched’ gene of  chromosome 9q, resulting in aberrant nucleotide repair during cellular DNA maintenance. It confers a >2000-fold increase in skin cancer risk and has autosomal recessive inher itance. Su ff erers are intolerant of  UVR, leading to premature skin ageing and development of  multiple neoplasms. Most a ff ected individuals die in early adulthood from metastatic disease (60% mortality by 20 years of  age). Gardner’s syndrome This syndrome is an autosomal dominant disease variant of familial adenomatous polyposis (FAP), which is caused by gene mutations on chromosome 5q 22. Gardner’s syndrome can cause the development of  cutaneous pathology , such as multiple epidermoid cysts and lipomata. Ferguson-Smith syndrome A rare autosomal dominant inherited abnormality on chro mosome 9q in which a ff ected individuals develop multiple self-healing squamous cell carcinomas (SCCs) without relation to sun exposure. Congenital/genetic disorders
Neurofibromatosis There are two distinct neurofibromatosis (NF) syndromes, in which Schwann cells form tumours ( Figure 45.3 ). Each is caused by di ff erent genes on di ff erent chromosomes: 70% are autosomal dominant and 30% arise from sporadic mutations. NF-1 (V on Recklinghausen’s disease) is the commoner variant, mutation on chromosome 17. Skin manifestations appear in early life, with the development of  more than five smooth- surfaced café-au-lait spots, subcutaneous neurofibromata, armpit or groin freckling and Lisch nodules. NF-2 produces multiple central nervous system tumours. Naevoid basal cell carcinoma (Gorlin’s) syndrome This is an autosomal dominant inherited condition caused by an abnormal tumour suppressor gene on chromosome 9q 22–31 coding the ‘patched’ protein; 90% of patients develop multiple basal cell carcinomas (BCCs). Patients may exhibit specific phenotypical characteristics, including overdeveloped supraorbital ridges; broad nasal roots; hypertelorism; bifid ribs; scoliosis; brachymetacarpalism; palmar pits; and molar odontogenic cysts; patients are also prone to other tumours. Xeroderma pigmentosum This syndrome is caused by an abnormality on the ‘patched’ gene of  chromosome 9q, resulting in aberrant nucleotide repair during cellular DNA maintenance. It confers a >2000-fold increase in skin cancer risk and has autosomal recessive inher itance. Su ff erers are intolerant of  UVR, leading to premature skin ageing and development of  multiple neoplasms. Most a ff ected individuals die in early adulthood from metastatic disease (60% mortality by 20 years of  age). Gardner’s syndrome This syndrome is an autosomal dominant disease variant of familial adenomatous polyposis (FAP), which is caused by gene mutations on chromosome 5q 22. Gardner’s syndrome can cause the development of  cutaneous pathology , such as multiple epidermoid cysts and lipomata. Ferguson-Smith syndrome A rare autosomal dominant inherited abnormality on chro mosome 9q in which a ff ected individuals develop multiple self-healing squamous cell carcinomas (SCCs) without relation to sun exposure. Congenital/genetic disorders
Neurofibromatosis There are two distinct neurofibromatosis (NF) syndromes, in which Schwann cells form tumours ( Figure 45.3 ). Each is caused by di ff erent genes on di ff erent chromosomes: 70% are autosomal dominant and 30% arise from sporadic mutations. NF-1 (V on Recklinghausen’s disease) is the commoner variant, mutation on chromosome 17. Skin manifestations appear in early life, with the development of  more than five smooth- surfaced café-au-lait spots, subcutaneous neurofibromata, armpit or groin freckling and Lisch nodules. NF-2 produces multiple central nervous system tumours. Naevoid basal cell carcinoma (Gorlin’s) syndrome This is an autosomal dominant inherited condition caused by an abnormal tumour suppressor gene on chromosome 9q 22–31 coding the ‘patched’ protein; 90% of patients develop multiple basal cell carcinomas (BCCs). Patients may exhibit specific phenotypical characteristics, including overdeveloped supraorbital ridges; broad nasal roots; hypertelorism; bifid ribs; scoliosis; brachymetacarpalism; palmar pits; and molar odontogenic cysts; patients are also prone to other tumours. Xeroderma pigmentosum This syndrome is caused by an abnormality on the ‘patched’ gene of  chromosome 9q, resulting in aberrant nucleotide repair during cellular DNA maintenance. It confers a >2000-fold increase in skin cancer risk and has autosomal recessive inher itance. Su ff erers are intolerant of  UVR, leading to premature skin ageing and development of  multiple neoplasms. Most a ff ected individuals die in early adulthood from metastatic disease (60% mortality by 20 years of  age). Gardner’s syndrome This syndrome is an autosomal dominant disease variant of familial adenomatous polyposis (FAP), which is caused by gene mutations on chromosome 5q 22. Gardner’s syndrome can cause the development of  cutaneous pathology , such as multiple epidermoid cysts and lipomata. Ferguson-Smith syndrome A rare autosomal dominant inherited abnormality on chro mosome 9q in which a ff ected individuals develop multiple self-healing squamous cell carcinomas (SCCs) without relation to sun exposure.

Cutaneous manifestations of generalised disease
Cutaneous manifestations of generalised disease
Many diseases have cutaneous manifestations that present in surgical practice. These include: necrobiosis lipoidica, granu loma annulare in diabetes mellitus and pyoderma gangreno sum in inflammatory bowel disease. Their management should be sought in appropriate texts. Hyperhidrosis This involves excessive eccrine sweating of the palms, soles of  the feet, axillae and groins, causing functional and social Karl Lisch , 1907–1999, ophthalmologist, Wörgl, Austria. Robert J Gorlin , 1923–2006, American dentist and Professor of  Oral Pathology , published over 400 articles on craniofacial syndromes. Eldon John Gardner , 1909–1989, geneticist, The University of  Utah, Salt Lake City , UT , USA, described this syndrome in 1950. John Ferguson-Smith , 1888–1978, Glaswegian dermatologist. - problems. It can be treated with antiperspirants or periodic local injections with botulinum toxin A. More resistant cases are treated by transthoracic endoscopic sympathectomy . APC Lipodystrophy Lipodystrophy (lipoatrophy) is a localised or generalised loss of  fatty tissue, which can be primary or secondary . It can be a complication of  long-term administration of  insulin, follow - ing treatment of  human immunodeficiency virus (HIV) with - protease inhibitors or in transplant recipients. It can be treated in selected cases by autologous fat grafting, injections of  poly-l-lactic acid and free tissue transfer. Inflammatory conditions Hidradenitis suppurativa Characterised by follicular occlusion, folliculitis and secondary infection (usually with Staphylococcus aureus and Propionibacte - rium acnes ), hidradenitis suppurativa culminates in chronic - suppurative, painful skin abscesses, sinus tracts and scarring. It - a ff ects apocrine gland-bearing skin in the axillae, groins and, less often, scalp, breast, chest and perineum ( Figure 45.4 ). A ff ecting four women for every man, it has a genetic predispo - sition, but variable penetrance, and is strongly associated with obesity , smoking and sex hormones (it starts at puberty and often resolves at menopause).
Figure 45.4
Hidradenitis suppurativa affecting the axilla (courtesy of
St John’s Institute for Dermatology, London, UK).
weight. Symptoms can be reduced by the use of  antiseptic soaps, tea tree oil and wearing non-compressive and aerated underwear. Medical treatments include topical and oral antibiotics and antiandrogen drugs. In selected cases, patients require radical excision of the a ff ected skin and subcutaneous tissue. Reconstruction after excision avoids contracture and functional impairment. Pyoderma gangrenosum Characterised by rapid onset and painful cutaneous ulceration with purple undermined edges, pyoderma gangrenosum is secondary to heightened immunological reactivity , usually from another disease process, such as inflammatory bowel disease, rheumatoid arthritis, non-Hodgkin’s lymphoma or granulomatosis with polyangiitis ( Figure 45.5 ). Ulcers gener ally respond to steroids; surgery is rarely indicated and may exacerbate the condition. Cutaneous manifestations of generalised disease
Many diseases have cutaneous manifestations that present in surgical practice. These include: necrobiosis lipoidica, granu loma annulare in diabetes mellitus and pyoderma gangreno sum in inflammatory bowel disease. Their management should be sought in appropriate texts. Hyperhidrosis This involves excessive eccrine sweating of the palms, soles of  the feet, axillae and groins, causing functional and social Karl Lisch , 1907–1999, ophthalmologist, Wörgl, Austria. Robert J Gorlin , 1923–2006, American dentist and Professor of  Oral Pathology , published over 400 articles on craniofacial syndromes. Eldon John Gardner , 1909–1989, geneticist, The University of  Utah, Salt Lake City , UT , USA, described this syndrome in 1950. John Ferguson-Smith , 1888–1978, Glaswegian dermatologist. - problems. It can be treated with antiperspirants or periodic local injections with botulinum toxin A. More resistant cases are treated by transthoracic endoscopic sympathectomy . APC Lipodystrophy Lipodystrophy (lipoatrophy) is a localised or generalised loss of  fatty tissue, which can be primary or secondary . It can be a complication of  long-term administration of  insulin, follow - ing treatment of  human immunodeficiency virus (HIV) with - protease inhibitors or in transplant recipients. It can be treated in selected cases by autologous fat grafting, injections of  poly-l-lactic acid and free tissue transfer. Inflammatory conditions Hidradenitis suppurativa Characterised by follicular occlusion, folliculitis and secondary infection (usually with Staphylococcus aureus and Propionibacte - rium acnes ), hidradenitis suppurativa culminates in chronic - suppurative, painful skin abscesses, sinus tracts and scarring. It - a ff ects apocrine gland-bearing skin in the axillae, groins and, less often, scalp, breast, chest and perineum ( Figure 45.4 ). A ff ecting four women for every man, it has a genetic predispo - sition, but variable penetrance, and is strongly associated with obesity , smoking and sex hormones (it starts at puberty and often resolves at menopause).
Figure 45.4
Hidradenitis suppurativa affecting the axilla (courtesy of
St John’s Institute for Dermatology, London, UK).
weight. Symptoms can be reduced by the use of  antiseptic soaps, tea tree oil and wearing non-compressive and aerated underwear. Medical treatments include topical and oral antibiotics and antiandrogen drugs. In selected cases, patients require radical excision of the a ff ected skin and subcutaneous tissue. Reconstruction after excision avoids contracture and functional impairment. Pyoderma gangrenosum Characterised by rapid onset and painful cutaneous ulceration with purple undermined edges, pyoderma gangrenosum is secondary to heightened immunological reactivity , usually from another disease process, such as inflammatory bowel disease, rheumatoid arthritis, non-Hodgkin’s lymphoma or granulomatosis with polyangiitis ( Figure 45.5 ). Ulcers gener ally respond to steroids; surgery is rarely indicated and may exacerbate the condition. Cutaneous manifestations of generalised disease
Many diseases have cutaneous manifestations that present in surgical practice. These include: necrobiosis lipoidica, granu loma annulare in diabetes mellitus and pyoderma gangreno sum in inflammatory bowel disease. Their management should be sought in appropriate texts. Hyperhidrosis This involves excessive eccrine sweating of the palms, soles of  the feet, axillae and groins, causing functional and social Karl Lisch , 1907–1999, ophthalmologist, Wörgl, Austria. Robert J Gorlin , 1923–2006, American dentist and Professor of  Oral Pathology , published over 400 articles on craniofacial syndromes. Eldon John Gardner , 1909–1989, geneticist, The University of  Utah, Salt Lake City , UT , USA, described this syndrome in 1950. John Ferguson-Smith , 1888–1978, Glaswegian dermatologist. - problems. It can be treated with antiperspirants or periodic local injections with botulinum toxin A. More resistant cases are treated by transthoracic endoscopic sympathectomy . APC Lipodystrophy Lipodystrophy (lipoatrophy) is a localised or generalised loss of  fatty tissue, which can be primary or secondary . It can be a complication of  long-term administration of  insulin, follow - ing treatment of  human immunodeficiency virus (HIV) with - protease inhibitors or in transplant recipients. It can be treated in selected cases by autologous fat grafting, injections of  poly-l-lactic acid and free tissue transfer. Inflammatory conditions Hidradenitis suppurativa Characterised by follicular occlusion, folliculitis and secondary infection (usually with Staphylococcus aureus and Propionibacte - rium acnes ), hidradenitis suppurativa culminates in chronic - suppurative, painful skin abscesses, sinus tracts and scarring. It - a ff ects apocrine gland-bearing skin in the axillae, groins and, less often, scalp, breast, chest and perineum ( Figure 45.4 ). A ff ecting four women for every man, it has a genetic predispo - sition, but variable penetrance, and is strongly associated with obesity , smoking and sex hormones (it starts at puberty and often resolves at menopause).
Figure 45.4
Hidradenitis suppurativa affecting the axilla (courtesy of
St John’s Institute for Dermatology, London, UK).
weight. Symptoms can be reduced by the use of  antiseptic soaps, tea tree oil and wearing non-compressive and aerated underwear. Medical treatments include topical and oral antibiotics and antiandrogen drugs. In selected cases, patients require radical excision of the a ff ected skin and subcutaneous tissue. Reconstruction after excision avoids contracture and functional impairment. Pyoderma gangrenosum Characterised by rapid onset and painful cutaneous ulceration with purple undermined edges, pyoderma gangrenosum is secondary to heightened immunological reactivity , usually from another disease process, such as inflammatory bowel disease, rheumatoid arthritis, non-Hodgkin’s lymphoma or granulomatosis with polyangiitis ( Figure 45.5 ). Ulcers gener ally respond to steroids; surgery is rarely indicated and may exacerbate the condition.

Cutaneous squamous cell carcinoma
Cutaneous squamous cell carcinoma
SCC is a malignant tumour of  keratinising cells of  the epider - mis or its appendages. It arises from the stratum basalis of  the epidermis and expresses cytokeratins 1 and 10. Epidemiology Four BCCs occur for every SCC, which is the second most common form of  skin cancer. It is strongly related to cumu - lative sun exposure and damage, especially in white-skinned individuals living nearer the equator. In the northern hemi - sphere it a ff ects the elderly , whereas it is not uncommon in sun-damaged, middle-aged white people in the souther n hemisphere. Everywhere, it is more common in men than in women. SCC is also associa ted with chronic inflammation (chronic sinus tracts, pre-existing scars, osteomyelitis, burns, vaccination points) and immunosuppression. When a SCC appears in a scar it is known as a Marjolin’s ulcer.
(a, b)
Squamous cell carcinoma /uni25CF /uni25CF /uni25CF IR causes SCC, as do chemical carcinogens (arsenicals, tar) and infection with HPV subtypes 5 and 16. There is also evidence that current and previous tobacco use doubles the relative risk of  SCC. In the past, actinic (solar) keratoses (AKs), i.e. cutaneous horns and keratoacanthomas, were considered to be prema lignant lesions leading to SCC. Current thinking is to classify these lesions on a continuum of  lesions, some of  which can impro ve, as with other squamous cell tumours suc h as cervical intraepithelial neoplasia. AKs are areas of  permanent sun damage in which there is dyskeratosis, partial-thickness cellular atypia and subep idermal inflammation, but an intact basement membrane ( Figure 45.31 ). They ‘wax and wane’ macroscopically between macular and papular, with and without keratinous surfaces. Most improve after moisturisation and remain as erythema tous macules; however, up to 20% form SCC. When an AK has a keratinous surface with a height greater than its base diameter, it is termed a keratin horn; 10% will have an underlying SCC ( Figure 45.32 ). Keratoacanthomas are rapidly growing, nodular tumour exhibiting symmetry around a central keratin-filled crater. John T Bowen , 1857–1941, Professor of  Dermatology , Harvard University Medical School, Boston, MA, USA, described this condition in 1912. August Queyrat , 1856–1933, dermatologist, Paris, France, described this condition in 1911. - Current thinking is that, rather than being separate pre - malignant entities, they are better considered as self-healing - SCCs and, as such, are often reported by pathologists as ‘keratoacanthoma-like SCCs’ ( Figure 45.33 ). Keratoacantho - mas are twice as common in men as in women and are usually found on the face or limbs of chronically sun-damaged 50- to - 70-year-old white-skinned individuals. T hey may be caused by HPV in a hair follicle during the growth phase and are also associated with smoking and chemical carcinogen exposure. Excision is recommended, rather than observation, as the dif - ferential diagnosis includes anaplastic SCC and the excision s scar is often better than that which remains after resolution. in situ and often develops as Bowen’s disease is SCC full-thickness dysplasia in hypertrophic AKs ( Figure 45.34 ). SCC in situ usually presents as a slowly enlarging erythematous scaly plaque and may occur anywhere on the mucocutaneous surface of the body . On the glans penis, it is called erythroplasia of  Queyrat ( Figure 45.35 ). Topical therapy with 5-fluorouracil or imiquimod is an e ff ective treatment. Alternatives include surgical excision with a 4-mm margin or Mohs’ micrographic surgery for larger or recurrent lesions.
Associated with UVR, chronic in
/f_l
ammation,
immunosuppression and chemical carcinogens
High- and low-risk SCC
Metastasis in 2% of low-risk and up to 30% of high-risk cases
Figure 45.31
Actinic keratosis (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.32
Cutaneous horn (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.33
Keratoacanthoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Macroscopic The appearance of  SCC may vary from smooth nodular, verrucous, papillomatous to ulcerating lesions. All ulcerate eventually as they grow . The ulcers have a characteristic everted edge and are surrounded by inflamed, indurated skin. Di ff erential diagnoses of  SCC include: AK; BCC; pyoderma gangrenosum; warts; and lichen simplex chronicus ( Figure 45.36 ). Albert Compton Broders , 1885–1964, American pathologist, MN, USA, and Chairman of  the Department of  Surgical Patholog MN, USA; for 1 year in 1935 Professor of  Surgical Pathology and Director of  Cancer Research, University of  V graded rectal cancer in the USA in a similar manner to the one that Cuthbert Dukes used to classify it in the UK. A combination of  Broders’ grading and Dukes’ classification gave a more accurate prognosis for rectal carcinoma than either method alone. Microscopic Characteristic irregular masses of  squamous epithelium are noted to proliferate and invade the dermis from the basal layer. The tumour stains positive for cytokeratins 1 and 10. SCC can be graded histologically according to Broders’ grading, which describes the proportion of  dedi ff erentiated cells in the tumour. Table 45.1 presents tumour classification and staging. Prognosis There are several independent prognostic variables for SCC: /uni25CF Depth: the deeper the lesion, the worse the prognosis. For SCC <2 /uni00A0 mm, metastasis is highly unlikely; if  SCC >6 /uni00A0 mm, 15% will have metastasised. y,  M a y o Clinic, Rochester, irginia, Charlottesville, V A, USA. Broders also
Figure 45.34
Bowen’s
disease – squamous cell
carcinoma
in situ
(courtesy
of St John’s Institute for
Dermatology, London, UK).
TABLE 45.1
Tumour–node–metastasis (TNM) classi
/f_i
cation and staging of squamous cell carcinoma.
Size
Nodes
NX
TX
Nodal involvement cannot be
Primary tumour cannot be
assessed
assessed
T0
N0
No evidence of primary tumour
No regional nodes
N1
Tis
Spread to 1 ipsilateral nearby node
In situ
(con
/f_i
ned to full-thickness
that is <3
/uni00A0
cm in diameter
epidermal) disease
T1
N2a
Primary <2
/uni00A0
cm
Spread to 1 ipsilateral nearby node
that is 3–6
/uni00A0
cm in diameter
T2
N2b
Primary >2
/uni00A0
cm
Spread to >1 ipsilateral nearby
nodes but none >6
/uni00A0
cm in diameter
T3
N2c
Primary invasion of a facial bone
Spread to contralateral node(s) but
none are >6
/uni00A0
cm in diameter
N3
T4
Spread to any node >6
/uni00A0
cm in
Invasion of muscle, base of skull
diameter
or other bones
Figure 45.35
Erythroplasia of Queyrat – squamous cell carcinoma
in situ
on the glans penis; also called Paget’s disease of the penis
(courtesy of St John’s Institute for Dermatology, London, UK).
Metastases
Stages
M0
Stage 0
No metastatic disease
Tis, N0, M0
M1
Stage I
Metastatic disease present
T1, N0, M0
Stage II
T2, N0, M0
Stage III
T3, N0, M0 or T1–T3, N1, M0
Stage IV
T1–T3, N2, M0 or any disease
that is N3, or T4 or M1
/uni25CF Surface size: lesions >2 /uni00A0 cm have a worse prognosis than smaller ones. /uni25CF Histological grade: the higher the Broders’ grade, the worse the prognosis. /uni25CF Microscopic invasion of  lymphovascular spaces or nerve tissue carries a high risk of  metastatic disease. Therefore, as well as information on pathological pattern, cellular morphology and Broders’ grade, any histopathology report for SCC should include the depth of  invasion, the pres ence of perineural or lymphovascular invasion and the deep and peripheral margin clearance. /uni25CF Site: SCCs on the lips and ears have higher local recur rence rates than lesions elsewhere, and tumours at the extremities fare worse than those on the trunk. /uni25CF Aetiology: SCCs that arise in burn scars, osteomyelitis skin sinuses, chronic ulcers and areas of  skin that have been irradiated have a higher metastatic potential. /uni25CF Immunosuppression: SCCs will invade further in those with impaired immune response. The overall rate of  metastasis varies between 2% and 30% for SCC (usually to regional nodes) with a local recurrence rate of  20%. Management SCC is a heterogeneous tumour with a malignant potential that varies between subtypes. Management must address the tumour’s tendency for lymphatic metastasis and the possibility of  in-transit metastasis. Surgical excision is the only means of  providing accurate information on histology and clearance. The margins for pri - mary excision should be tailored to surface size in the first instance. This should ideally be assessed using surgical loupe - magnification. A 4-mm clearance margin should be achieved and a 1-cm clearance if  the SCC measures <2 /uni00A0 cm across, margin if  the SCC measures >2 /uni00A0 cm; 95% of  local recurrence and regional metastases occur within 5 years, thus follow-up - beyond this period is not indicated. Cutaneous malignant melanoma Melanoma is a cancer of  melanocytes and can, therefore, arise in skin, mucosa, retina and the leptomeninges. Epidemiology Observational data suggest that cutaneous melanoma is caused by exposure to UVR, but this general observation, which is a generally reliable fact, may hide some of  the nuanced variables that contribute to melanoma formation.
(c)
Figure 45.36
(a)
A squamous cell carcinoma (SCC) on the face.
/uni00A0
(c)
SCC arising on the dorsum of the hand in a renal transplant recipient on immunosuppressive therapy.
who worked outside on a farm. (
(a–c)
courtesy of Mr AR Greenbaum;
(d)
(b)
A recurrent SCC arising in a previously skin-grafted area of the scalp.
(d)
SCC arising on the lip of a smoker
(d)
courtesy of St John’s Institute for Dermatology, London, UK.)
recreational activity in the sun and emigration among white- skinned people not suited to sun exposure. Although it accounts for less than 5% of  skin malignancy (and 1.6% of  all malignancy worldwide), it is responsible for over 75% of  skin malignancy-related deaths. It is the commonest cancer in young adults (20–39 years) and the most likely cause of  cancer-related death. Distribution between the sexes varies around the world and reflects occupational and recreational exposure to sunlight. Likewise, geographical distribution reflects e xposure of  white- skinned individuals to sunlight: Australia and New Zealand, countries with a predominantly white-skinned, immigrant population, have an incidence of  33.6 per 100 /uni00A0 000. Five per cent of  all patients with malignant melanoma will develop a second primary melanoma; 7% of  malignant melanomas pres ent as occult metastasis from an unknown primary . What is less clear within data on cutaneous melanoma is the contribution by variables such as serum vitamin D levels and vitamin receptor genotypes, because thinner melanomas and low er recurrence rates have been linked to higher serum vitamin D levels, and why some forms of  melanoma seem more attributable to cumulative sun exposure (superficial spreading) than others (nodular). Studies exploring whether there may be benefit from a degree of  sun exposure that avoids ‘sunbathing’ and burning and whether sun-related vitamin D production in skin, rather than supplemental vitamin D, is beneficial are ongoing, but our best information still bases sun avoidance at the centre of  melanoma prevention. Pathophysiology Cumulative UV exposure favours the development of  lentigo maligna melanoma (LMM) and later onset of  disease, whereas ‘flash fry’ exposure, typical of  rapidly acquired holiday tans, favours the other morphological variants and early onset of disease. A small proportion of malignant melanoma is genetically mediated and develops at an earlier age. People at most risk of developing malignant melanoma include: those with genetic syndromes; those with a past history of  malignant melanoma or with a first-degree rela tive who has malignant melanoma; those who have more than 30 sun-acquired naevi or a history of  five significant sunburns before the age of  16; fair-skinned/ red-haired people living close to the equator; anyone with excessive UVR exposure (environmental or salon-delivered); Summary box 45.4 Malignant melanoma /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Alexander Breslow , 1928–1980, pathologist, George Washington University , Washington, DC, USA, first reported in 1970 that the prognosis depends upon the thickness of  the tumour. nant melanoma incidence 20- to 30-fold). Male gender and solitary living are both associated with thicker melanomas at diagnosis. In women, higher socioeconomic status is positively correlated with developing melanoma. Macroscopic Only 10–20% of malignant melanomas form in pre-existing naevi, with the remainder arising de novo in previously normally pigmented skin. The most likely naevi to form malignant mela - noma are atypical naevi, atypical junctional lentiginous naevi (usually facial) and giant pigmented congenital naevi. Macroscopic features in a pre-existing naevus that suggest malignant change are listed in Summary box 45.5 . There are four common macroscopic variants of  malig - nant melanoma and several other notable, but rarer, forms, - as follows. This is the most common presentation (70%); usually arises in a pre-existing naevus after several years of  slow c hange, followed by rapid g rowth in the months before presentation ( Figure 45.37 ) . Nodularity within SSM heralds the onset of  the vertical growth phase. NM accounts for 15% of  all malignant melanoma and tends to be more aggressive than SSM, with a shorter clinical onset. These lesions often arise de novo in skin and are more common in men than in women, often presenting in middle age and usually on the trunk, head or neck ( Figure 45.38 ) . They typically appear as blue/black papules, 1–2 /uni00A0 cm in diameter, and because they lack the hori - zontal growth phase they tend to be sharply demarcated. Up to 5% are amelanotic.
Rising incidence
Genetic and acquired risk factors
Super
/f_i
cial spreading form the most common
Breslow thickness is the most important prognostic indicator
Sentinel node biopsy (SNB) is useful for staging
Super
/f_i
cial spreading melanoma (SSM).
Nodular melanoma (NM).
Figure 45.37
Super
/f_i
cial spreading melanoma (courtesy of St John’s
Institute for Dermatology, London, UK).
LMM was previously also known as Hutchinson’s melanotic freckle. This variant presents as a slow-growing, variegated brown macule on the face, neck or hands of the elderly ( Figure 45.39 ) . They are positively correlated with prolonged, intense sun exposure and a ff ect women more than men. They account for between 5% and 10% of  malignant melanomas. LMMs are thought to have less metastatic potential than other variants as they take longer to enter a vertical growth phase. Nonetheless, when they have entered the vertical growth phase their metasta tic potential is the same as any other mel anoma. ALM a ff ects the soles and palms. It is rare in white-skinned individuals (2–8% of malignant melanoma) but more common in Afro-Caribbean, Hispanic and Asian populations (35–60%). It usually presents as a flat, irregular macule in later life; 25% are amelanotic and may mimic a fungal infection or py ogenic granuloma. Sir Jonathan Hutchinson , 1828–1913, surgeon, St Bartholomew’s Hospital, London, UK. Malignant melanomas under the fingernail are usually SSM rather than ALM. For finger- or toenail lesions it is vital to biopsy the nail matrix rather than just the pigment on the nail plate. A classical feature of  a subungual melanoma is Hutchin - son’s sign: nail fold pigmentation that widens progressively to produce a triangular pigmented macule with associated nail dystrophy . The di ff erential diagnosis is ‘benign racial melanon - ychia’, which produces a linear dark streak under a nail in a - individual. Malignancy is unlikely if the nail fold dark-skinned is uninvolved ( Figure 45.40 ). /uni25CF Amelanotic melanoma may present as a flesh-coloured skin lesion; as a metastasis from an unknown skin primary; or in the gastrointestinal tract, with obstruction or intus - susception.
Figure 45.38
Nodular melanoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Lentigo maligna melanoma.
Acral lentiginous melanoma (ALM).
(a)
Figure 45.40
(a)
Acral lentiginous melanoma on the sole of the foot.
Note the swelling proximal to the nailfold.
(c)
Benign racial melanonychia. (
Institute for Dermatology, London, UK.)
Figure 45.39
Lentigo maligna melanoma (courtesy of St John’s Insti
tute for Dermatology, London, UK).
Miscellaneous
(b)
(c)
(b)
Subungual melanoma – probably a super
/f_i
cial spreading melanoma.
(a)
courtesy of Mr AR Greenbaum;
(b, c)
courtesy of St John’s
neck region. It has a propensity for perineural infiltration and often recurs locally if  not widely excised. It may be amelanotic clinically . Summary box 45.5 Macroscopic features in naevi suggestive of malignant melanoma /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Microscopic Malignant change occurs in the melanocytes in the basal epidermis, while in situ atypical melanocytes are limited to the dermoepidermal junction and show no evidence of dermal involvement. During the horizontal growth phase, cells spread along the dermoepidermal junction; although they may breach the dermis, their migration is predominantly radial. During the vertical growth phase, the dermis may be invaded. The greater the depth of  invasion, the greater the metastatic potential of the tumour. Management History and clinical examination should be directed at discov ering the primary lesion and identification of  local, regional or distant spread. An excision biopsy with a 2- to 3-mm margin of  skin and a cu ff of  subdermal fat is acceptable. Incision biopsy is occasion ally indicated: for instance, in large lesions on the face where an excision biopsy of  the whole lesion would be disfiguring. In experienced hands, observation and review every 2 /uni00A0 months may avoid biopsies in equivocal cases, but serial clin ical and dermoscopic photography by a clinician with exper tise in dermoscopy is mandatory when observ ation is chosen, rather than excision biopsy for definitive histopathological diagnosis. Dermoscopy coupled to computers with learning capability may soon outperform clinicians in melanoma diag nosis to the point where screening becomes m uch easier. Biopsy and pathological examination provide the first step towards staging melanoma. The Breslow thickness of  a mel anoma (measured to the nearest 0.1 /uni00A0 mm from the granular layer to the base of  the tumour) is the most important prog nostic indica tor in the absence of  lymph node metastases. The American Joint Committee on Cancer (AJCC) staging system takes lymph node involvement, distant metastases and evidence-based prognostic factors into account; these can then be used to guide optimum care and inclusion in researc studies for adjuvant or other treatments where applicable. The detail of  the AJCC melanoma staging system has become too specialised for the ambit of  this text; most spe cialists look up its detail as they assign a stage to a patient ( Table 45.2 ). Guidelines for staging are controversial. The author suggests that investigations should be directed towards detecting occult disease, so as to upstage patients and treat them accurately and appropriately , the only cure for malignant melanoma currently being appropriate surgery . Thus, o ff ering SNB to patients with T2a disease and greater is critical and investigations for T3a disease and greater should be directed to individual clinical presentation. Local treatment The treatment for melanoma is surgery . Lentigo maligna (melanoma in situ ) should be excised completely in most clin - ical situations because of  the risk of  it entering the vertical growth phase to become LMM. A complete excision requires no further treatment. For melanoma in situ a wide excision of  5 /uni00A0 mm is su ffi cient; for melanoma <1 /uni00A0 mm deep, a 1-cm margin is su ffi cient; and for deeper lesions, a 2-cm only margin is recommended, as there is no evidence that wider margins make a di ff erence. Regional lymph nodes The likelihood of metastatic spread to regional lymph nodes is proportional to the Breslow thickness of  the melanoma. Management of  regional lymph nodes has been a contentious topic for well over a century . Some advocated simultaneous elective lymph node clearance at the time of  wide excision of the primary melanoma. Others favoured a therapeutic lymphadenectomy if  regional metastases became clinically evident. Ideally , one would like to be able to select for treatment - those patients with the highest risk of  metastatic spread. SNB, an investigation based on the fact that lymphatic metastases proceed in an orderly fashion and can be predicted by mapping the lymphatic drainage from a primary tumour to the first or - ‘sentinel’ node in the regional lymphatic basin, o ff ered that potential, but prospective controlled studies have shown no survival benefit from lymphadenectomy after positive SNB involving micrometastasis <0.2 /uni00A0 mm in a single node. This may - be because most patients have been treated by removing the - sentinel node, which was the only node involved at that stage. However, completion lymphadenectomy after positive SNB remains, on current evidence, the optimum method for regional control, if patients accept the morbidity associated - with regional lymphadenectomy . Adjuvant therapy - When mutation locks BRAF protein signalling to ‘on’, it a ff ects the mitogen-activated protein kinase (MAPK) cellular - pathway , promoting initiation, malignant transformation, tumour progression and metastasis in the 50% of  malignant melanomas with BRAF V600 mutations. Targeted therapy in stage IV melanoma using dabrafenib or vemurafenib, which block BRAF action, has shown promising results with h metastatic melanoma. Trametinib has a di ff erent action on the MAPK pathway: stopping cell growth and promoting apoptosis. Combined use with dabrafenib to counter acquired - tumour resistance via MAPK pathway reactivation shows promising results in stage IV disease. Also, the selective immune
Change in size
Shape
Colour
Thickness (elevation/nodularity or ulceration)
Satellite lesions (pigment spreading into surrounding area)
Tingling/itching/serosanguineous discharge (usually late signs)
checkpoint inhibitors ipilimumab and nivolumab demonstrate benefit in metastatic or unresectable melanoma. Over the last 5 years, five randomised prospective trials of adjuvant therapy have reported findings in the treatment of patients with stage II to IV disease. While all five trials showed a significant impro vement in relapse-free survival, only two of the trials were mature enough to report on overall survival. Prognosis The Breslow thickness of  the primary tumour o ff ers the best correlation with survival in stage I disease. The higher the mitotic index, the poorer the prognosis of  the primary tumour. This has greater significance than the presence or absence of ulceration. The presence of  lymph node metastases is the single most important prognostic index in melanoma, outweighing both tumour and host factors. The number of  a ff ected nodes and the presence of  extranodal extension are also significant outcome predictors. Once regional nodes are clinically involved, 70–85% of  patients will have occult distant metastases. Merkel cell (dermal mechanoreceptor) tumour This is an aggressive malignant tumour of  Merkel cells and usually a ff ects the elderly . It is four times more common in Haig H Kasabach , 1898–1943, radiologist, Presbyterian Hospital, New Y ork, NY , USA. Katharine K Merritt , 1886–1986, pediatrician, Babies Hospital, Columbia University College of  Physicians and Surgeons, New Y ork, NY , USA. Kasabach and Merritt described the condition as a joint paper in 1940. women than in men ( Figure 45.41 ). Treatment is with wide local excision, aiming for a 25- to 30-mm margin, followed by radiotherapy .
Primary tumour
Regional nodes
NX
TX
Patients in whom nodes cannot be assessed
Primary tumour cannot be assessed (has
(e.g.
previous excision)
been curettage or has severely regressed)
T0
N0
No evidence of primary tumour
No node involvement
Tis
Melanoma
in situ
N1
a:
<0.8
/uni00A0
mm, no ulceration
T1
1 node
b:
0.8–1.0
/uni00A0
mm, no
<1.0
/uni00A0
mm
ulceration; or <1.0
/uni00A0
mm with
ulceration
a:
No ulceration
N2
T2
b:
With ulceration
2 or 3 nodes
1.01–2.0
/uni00A0
mm
a:
No ulceration
N3
T3
b:
With ulceration
2.01–4.0
/uni00A0
mm
a:
No ulceration
T4
b:
With ulceration
4
/uni00A0
mm
Clinical staging of melanoma
Stage IIa: T2b or T3a, N0, M0
Stage 0: Tis, N0, M0
Stage IIb: T3b or T4a, N0, M0
Stage Ia: T1a, N0, M0
Stage IIc: T4b, N0, M0
Stage Ib: T1b or T2a, N0, M0
LDH, lactate dehydrogenase; MSI denotes the presence of satellite lesions, in-transit lesions or local recurrence.
Distant metastases
M0
No detected distant metastases
M1a
a:
Micrometastasis (no MSI)
Skin, subcutaneous or distant lymph node
b:
Macrometastasis (no MSI)
metastases (normal serum LDH levels)
c:
MSI present
M1b
a:
Micrometastasis (no MSI)
Lung metastases (normal serum LDH
b:
Macrometastasis (no MSI)
levels)
c:
MSI present
M1c
a:
Micrometastasis, >3 nodes
All other visceral metastases or any distant
(no MSI)
metastases with elevated serum LDH
b:
Micrometastasis, >3 nodes
levels
or matted or 1 clinical node
(no MSI)
c:
1 clinical or occult node
with MSI present
M1d
Brain metastases
Stage III: any T, >N1, M0
Stage IV: any T, any N1, M1
Cutaneous squamous cell carcinoma
SCC is a malignant tumour of  keratinising cells of  the epider - mis or its appendages. It arises from the stratum basalis of  the epidermis and expresses cytokeratins 1 and 10. Epidemiology Four BCCs occur for every SCC, which is the second most common form of  skin cancer. It is strongly related to cumu - lative sun exposure and damage, especially in white-skinned individuals living nearer the equator. In the northern hemi - sphere it a ff ects the elderly , whereas it is not uncommon in sun-damaged, middle-aged white people in the souther n hemisphere. Everywhere, it is more common in men than in women. SCC is also associa ted with chronic inflammation (chronic sinus tracts, pre-existing scars, osteomyelitis, burns, vaccination points) and immunosuppression. When a SCC appears in a scar it is known as a Marjolin’s ulcer.
(a, b)
Squamous cell carcinoma /uni25CF /uni25CF /uni25CF IR causes SCC, as do chemical carcinogens (arsenicals, tar) and infection with HPV subtypes 5 and 16. There is also evidence that current and previous tobacco use doubles the relative risk of  SCC. In the past, actinic (solar) keratoses (AKs), i.e. cutaneous horns and keratoacanthomas, were considered to be prema lignant lesions leading to SCC. Current thinking is to classify these lesions on a continuum of  lesions, some of  which can impro ve, as with other squamous cell tumours suc h as cervical intraepithelial neoplasia. AKs are areas of  permanent sun damage in which there is dyskeratosis, partial-thickness cellular atypia and subep idermal inflammation, but an intact basement membrane ( Figure 45.31 ). They ‘wax and wane’ macroscopically between macular and papular, with and without keratinous surfaces. Most improve after moisturisation and remain as erythema tous macules; however, up to 20% form SCC. When an AK has a keratinous surface with a height greater than its base diameter, it is termed a keratin horn; 10% will have an underlying SCC ( Figure 45.32 ). Keratoacanthomas are rapidly growing, nodular tumour exhibiting symmetry around a central keratin-filled crater. John T Bowen , 1857–1941, Professor of  Dermatology , Harvard University Medical School, Boston, MA, USA, described this condition in 1912. August Queyrat , 1856–1933, dermatologist, Paris, France, described this condition in 1911. - Current thinking is that, rather than being separate pre - malignant entities, they are better considered as self-healing - SCCs and, as such, are often reported by pathologists as ‘keratoacanthoma-like SCCs’ ( Figure 45.33 ). Keratoacantho - mas are twice as common in men as in women and are usually found on the face or limbs of chronically sun-damaged 50- to - 70-year-old white-skinned individuals. T hey may be caused by HPV in a hair follicle during the growth phase and are also associated with smoking and chemical carcinogen exposure. Excision is recommended, rather than observation, as the dif - ferential diagnosis includes anaplastic SCC and the excision s scar is often better than that which remains after resolution. in situ and often develops as Bowen’s disease is SCC full-thickness dysplasia in hypertrophic AKs ( Figure 45.34 ). SCC in situ usually presents as a slowly enlarging erythematous scaly plaque and may occur anywhere on the mucocutaneous surface of the body . On the glans penis, it is called erythroplasia of  Queyrat ( Figure 45.35 ). Topical therapy with 5-fluorouracil or imiquimod is an e ff ective treatment. Alternatives include surgical excision with a 4-mm margin or Mohs’ micrographic surgery for larger or recurrent lesions.
Associated with UVR, chronic in
/f_l
ammation,
immunosuppression and chemical carcinogens
High- and low-risk SCC
Metastasis in 2% of low-risk and up to 30% of high-risk cases
Figure 45.31
Actinic keratosis (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.32
Cutaneous horn (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.33
Keratoacanthoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Macroscopic The appearance of  SCC may vary from smooth nodular, verrucous, papillomatous to ulcerating lesions. All ulcerate eventually as they grow . The ulcers have a characteristic everted edge and are surrounded by inflamed, indurated skin. Di ff erential diagnoses of  SCC include: AK; BCC; pyoderma gangrenosum; warts; and lichen simplex chronicus ( Figure 45.36 ). Albert Compton Broders , 1885–1964, American pathologist, MN, USA, and Chairman of  the Department of  Surgical Patholog MN, USA; for 1 year in 1935 Professor of  Surgical Pathology and Director of  Cancer Research, University of  V graded rectal cancer in the USA in a similar manner to the one that Cuthbert Dukes used to classify it in the UK. A combination of  Broders’ grading and Dukes’ classification gave a more accurate prognosis for rectal carcinoma than either method alone. Microscopic Characteristic irregular masses of  squamous epithelium are noted to proliferate and invade the dermis from the basal layer. The tumour stains positive for cytokeratins 1 and 10. SCC can be graded histologically according to Broders’ grading, which describes the proportion of  dedi ff erentiated cells in the tumour. Table 45.1 presents tumour classification and staging. Prognosis There are several independent prognostic variables for SCC: /uni25CF Depth: the deeper the lesion, the worse the prognosis. For SCC <2 /uni00A0 mm, metastasis is highly unlikely; if  SCC >6 /uni00A0 mm, 15% will have metastasised. y,  M a y o Clinic, Rochester, irginia, Charlottesville, V A, USA. Broders also
Figure 45.34
Bowen’s
disease – squamous cell
carcinoma
in situ
(courtesy
of St John’s Institute for
Dermatology, London, UK).
TABLE 45.1
Tumour–node–metastasis (TNM) classi
/f_i
cation and staging of squamous cell carcinoma.
Size
Nodes
NX
TX
Nodal involvement cannot be
Primary tumour cannot be
assessed
assessed
T0
N0
No evidence of primary tumour
No regional nodes
N1
Tis
Spread to 1 ipsilateral nearby node
In situ
(con
/f_i
ned to full-thickness
that is <3
/uni00A0
cm in diameter
epidermal) disease
T1
N2a
Primary <2
/uni00A0
cm
Spread to 1 ipsilateral nearby node
that is 3–6
/uni00A0
cm in diameter
T2
N2b
Primary >2
/uni00A0
cm
Spread to >1 ipsilateral nearby
nodes but none >6
/uni00A0
cm in diameter
T3
N2c
Primary invasion of a facial bone
Spread to contralateral node(s) but
none are >6
/uni00A0
cm in diameter
N3
T4
Spread to any node >6
/uni00A0
cm in
Invasion of muscle, base of skull
diameter
or other bones
Figure 45.35
Erythroplasia of Queyrat – squamous cell carcinoma
in situ
on the glans penis; also called Paget’s disease of the penis
(courtesy of St John’s Institute for Dermatology, London, UK).
Metastases
Stages
M0
Stage 0
No metastatic disease
Tis, N0, M0
M1
Stage I
Metastatic disease present
T1, N0, M0
Stage II
T2, N0, M0
Stage III
T3, N0, M0 or T1–T3, N1, M0
Stage IV
T1–T3, N2, M0 or any disease
that is N3, or T4 or M1
/uni25CF Surface size: lesions >2 /uni00A0 cm have a worse prognosis than smaller ones. /uni25CF Histological grade: the higher the Broders’ grade, the worse the prognosis. /uni25CF Microscopic invasion of  lymphovascular spaces or nerve tissue carries a high risk of  metastatic disease. Therefore, as well as information on pathological pattern, cellular morphology and Broders’ grade, any histopathology report for SCC should include the depth of  invasion, the pres ence of perineural or lymphovascular invasion and the deep and peripheral margin clearance. /uni25CF Site: SCCs on the lips and ears have higher local recur rence rates than lesions elsewhere, and tumours at the extremities fare worse than those on the trunk. /uni25CF Aetiology: SCCs that arise in burn scars, osteomyelitis skin sinuses, chronic ulcers and areas of  skin that have been irradiated have a higher metastatic potential. /uni25CF Immunosuppression: SCCs will invade further in those with impaired immune response. The overall rate of  metastasis varies between 2% and 30% for SCC (usually to regional nodes) with a local recurrence rate of  20%. Management SCC is a heterogeneous tumour with a malignant potential that varies between subtypes. Management must address the tumour’s tendency for lymphatic metastasis and the possibility of  in-transit metastasis. Surgical excision is the only means of  providing accurate information on histology and clearance. The margins for pri - mary excision should be tailored to surface size in the first instance. This should ideally be assessed using surgical loupe - magnification. A 4-mm clearance margin should be achieved and a 1-cm clearance if  the SCC measures <2 /uni00A0 cm across, margin if  the SCC measures >2 /uni00A0 cm; 95% of  local recurrence and regional metastases occur within 5 years, thus follow-up - beyond this period is not indicated. Cutaneous malignant melanoma Melanoma is a cancer of  melanocytes and can, therefore, arise in skin, mucosa, retina and the leptomeninges. Epidemiology Observational data suggest that cutaneous melanoma is caused by exposure to UVR, but this general observation, which is a generally reliable fact, may hide some of  the nuanced variables that contribute to melanoma formation.
(c)
Figure 45.36
(a)
A squamous cell carcinoma (SCC) on the face.
/uni00A0
(c)
SCC arising on the dorsum of the hand in a renal transplant recipient on immunosuppressive therapy.
who worked outside on a farm. (
(a–c)
courtesy of Mr AR Greenbaum;
(d)
(b)
A recurrent SCC arising in a previously skin-grafted area of the scalp.
(d)
SCC arising on the lip of a smoker
(d)
courtesy of St John’s Institute for Dermatology, London, UK.)
recreational activity in the sun and emigration among white- skinned people not suited to sun exposure. Although it accounts for less than 5% of  skin malignancy (and 1.6% of  all malignancy worldwide), it is responsible for over 75% of  skin malignancy-related deaths. It is the commonest cancer in young adults (20–39 years) and the most likely cause of  cancer-related death. Distribution between the sexes varies around the world and reflects occupational and recreational exposure to sunlight. Likewise, geographical distribution reflects e xposure of  white- skinned individuals to sunlight: Australia and New Zealand, countries with a predominantly white-skinned, immigrant population, have an incidence of  33.6 per 100 /uni00A0 000. Five per cent of  all patients with malignant melanoma will develop a second primary melanoma; 7% of  malignant melanomas pres ent as occult metastasis from an unknown primary . What is less clear within data on cutaneous melanoma is the contribution by variables such as serum vitamin D levels and vitamin receptor genotypes, because thinner melanomas and low er recurrence rates have been linked to higher serum vitamin D levels, and why some forms of  melanoma seem more attributable to cumulative sun exposure (superficial spreading) than others (nodular). Studies exploring whether there may be benefit from a degree of  sun exposure that avoids ‘sunbathing’ and burning and whether sun-related vitamin D production in skin, rather than supplemental vitamin D, is beneficial are ongoing, but our best information still bases sun avoidance at the centre of  melanoma prevention. Pathophysiology Cumulative UV exposure favours the development of  lentigo maligna melanoma (LMM) and later onset of  disease, whereas ‘flash fry’ exposure, typical of  rapidly acquired holiday tans, favours the other morphological variants and early onset of disease. A small proportion of malignant melanoma is genetically mediated and develops at an earlier age. People at most risk of developing malignant melanoma include: those with genetic syndromes; those with a past history of  malignant melanoma or with a first-degree rela tive who has malignant melanoma; those who have more than 30 sun-acquired naevi or a history of  five significant sunburns before the age of  16; fair-skinned/ red-haired people living close to the equator; anyone with excessive UVR exposure (environmental or salon-delivered); Summary box 45.4 Malignant melanoma /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Alexander Breslow , 1928–1980, pathologist, George Washington University , Washington, DC, USA, first reported in 1970 that the prognosis depends upon the thickness of  the tumour. nant melanoma incidence 20- to 30-fold). Male gender and solitary living are both associated with thicker melanomas at diagnosis. In women, higher socioeconomic status is positively correlated with developing melanoma. Macroscopic Only 10–20% of malignant melanomas form in pre-existing naevi, with the remainder arising de novo in previously normally pigmented skin. The most likely naevi to form malignant mela - noma are atypical naevi, atypical junctional lentiginous naevi (usually facial) and giant pigmented congenital naevi. Macroscopic features in a pre-existing naevus that suggest malignant change are listed in Summary box 45.5 . There are four common macroscopic variants of  malig - nant melanoma and several other notable, but rarer, forms, - as follows. This is the most common presentation (70%); usually arises in a pre-existing naevus after several years of  slow c hange, followed by rapid g rowth in the months before presentation ( Figure 45.37 ) . Nodularity within SSM heralds the onset of  the vertical growth phase. NM accounts for 15% of  all malignant melanoma and tends to be more aggressive than SSM, with a shorter clinical onset. These lesions often arise de novo in skin and are more common in men than in women, often presenting in middle age and usually on the trunk, head or neck ( Figure 45.38 ) . They typically appear as blue/black papules, 1–2 /uni00A0 cm in diameter, and because they lack the hori - zontal growth phase they tend to be sharply demarcated. Up to 5% are amelanotic.
Rising incidence
Genetic and acquired risk factors
Super
/f_i
cial spreading form the most common
Breslow thickness is the most important prognostic indicator
Sentinel node biopsy (SNB) is useful for staging
Super
/f_i
cial spreading melanoma (SSM).
Nodular melanoma (NM).
Figure 45.37
Super
/f_i
cial spreading melanoma (courtesy of St John’s
Institute for Dermatology, London, UK).
LMM was previously also known as Hutchinson’s melanotic freckle. This variant presents as a slow-growing, variegated brown macule on the face, neck or hands of the elderly ( Figure 45.39 ) . They are positively correlated with prolonged, intense sun exposure and a ff ect women more than men. They account for between 5% and 10% of  malignant melanomas. LMMs are thought to have less metastatic potential than other variants as they take longer to enter a vertical growth phase. Nonetheless, when they have entered the vertical growth phase their metasta tic potential is the same as any other mel anoma. ALM a ff ects the soles and palms. It is rare in white-skinned individuals (2–8% of malignant melanoma) but more common in Afro-Caribbean, Hispanic and Asian populations (35–60%). It usually presents as a flat, irregular macule in later life; 25% are amelanotic and may mimic a fungal infection or py ogenic granuloma. Sir Jonathan Hutchinson , 1828–1913, surgeon, St Bartholomew’s Hospital, London, UK. Malignant melanomas under the fingernail are usually SSM rather than ALM. For finger- or toenail lesions it is vital to biopsy the nail matrix rather than just the pigment on the nail plate. A classical feature of  a subungual melanoma is Hutchin - son’s sign: nail fold pigmentation that widens progressively to produce a triangular pigmented macule with associated nail dystrophy . The di ff erential diagnosis is ‘benign racial melanon - ychia’, which produces a linear dark streak under a nail in a - individual. Malignancy is unlikely if the nail fold dark-skinned is uninvolved ( Figure 45.40 ). /uni25CF Amelanotic melanoma may present as a flesh-coloured skin lesion; as a metastasis from an unknown skin primary; or in the gastrointestinal tract, with obstruction or intus - susception.
Figure 45.38
Nodular melanoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Lentigo maligna melanoma.
Acral lentiginous melanoma (ALM).
(a)
Figure 45.40
(a)
Acral lentiginous melanoma on the sole of the foot.
Note the swelling proximal to the nailfold.
(c)
Benign racial melanonychia. (
Institute for Dermatology, London, UK.)
Figure 45.39
Lentigo maligna melanoma (courtesy of St John’s Insti
tute for Dermatology, London, UK).
Miscellaneous
(b)
(c)
(b)
Subungual melanoma – probably a super
/f_i
cial spreading melanoma.
(a)
courtesy of Mr AR Greenbaum;
(b, c)
courtesy of St John’s
neck region. It has a propensity for perineural infiltration and often recurs locally if  not widely excised. It may be amelanotic clinically . Summary box 45.5 Macroscopic features in naevi suggestive of malignant melanoma /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Microscopic Malignant change occurs in the melanocytes in the basal epidermis, while in situ atypical melanocytes are limited to the dermoepidermal junction and show no evidence of dermal involvement. During the horizontal growth phase, cells spread along the dermoepidermal junction; although they may breach the dermis, their migration is predominantly radial. During the vertical growth phase, the dermis may be invaded. The greater the depth of  invasion, the greater the metastatic potential of the tumour. Management History and clinical examination should be directed at discov ering the primary lesion and identification of  local, regional or distant spread. An excision biopsy with a 2- to 3-mm margin of  skin and a cu ff of  subdermal fat is acceptable. Incision biopsy is occasion ally indicated: for instance, in large lesions on the face where an excision biopsy of  the whole lesion would be disfiguring. In experienced hands, observation and review every 2 /uni00A0 months may avoid biopsies in equivocal cases, but serial clin ical and dermoscopic photography by a clinician with exper tise in dermoscopy is mandatory when observ ation is chosen, rather than excision biopsy for definitive histopathological diagnosis. Dermoscopy coupled to computers with learning capability may soon outperform clinicians in melanoma diag nosis to the point where screening becomes m uch easier. Biopsy and pathological examination provide the first step towards staging melanoma. The Breslow thickness of  a mel anoma (measured to the nearest 0.1 /uni00A0 mm from the granular layer to the base of  the tumour) is the most important prog nostic indica tor in the absence of  lymph node metastases. The American Joint Committee on Cancer (AJCC) staging system takes lymph node involvement, distant metastases and evidence-based prognostic factors into account; these can then be used to guide optimum care and inclusion in researc studies for adjuvant or other treatments where applicable. The detail of  the AJCC melanoma staging system has become too specialised for the ambit of  this text; most spe cialists look up its detail as they assign a stage to a patient ( Table 45.2 ). Guidelines for staging are controversial. The author suggests that investigations should be directed towards detecting occult disease, so as to upstage patients and treat them accurately and appropriately , the only cure for malignant melanoma currently being appropriate surgery . Thus, o ff ering SNB to patients with T2a disease and greater is critical and investigations for T3a disease and greater should be directed to individual clinical presentation. Local treatment The treatment for melanoma is surgery . Lentigo maligna (melanoma in situ ) should be excised completely in most clin - ical situations because of  the risk of  it entering the vertical growth phase to become LMM. A complete excision requires no further treatment. For melanoma in situ a wide excision of  5 /uni00A0 mm is su ffi cient; for melanoma <1 /uni00A0 mm deep, a 1-cm margin is su ffi cient; and for deeper lesions, a 2-cm only margin is recommended, as there is no evidence that wider margins make a di ff erence. Regional lymph nodes The likelihood of metastatic spread to regional lymph nodes is proportional to the Breslow thickness of  the melanoma. Management of  regional lymph nodes has been a contentious topic for well over a century . Some advocated simultaneous elective lymph node clearance at the time of  wide excision of the primary melanoma. Others favoured a therapeutic lymphadenectomy if  regional metastases became clinically evident. Ideally , one would like to be able to select for treatment - those patients with the highest risk of  metastatic spread. SNB, an investigation based on the fact that lymphatic metastases proceed in an orderly fashion and can be predicted by mapping the lymphatic drainage from a primary tumour to the first or - ‘sentinel’ node in the regional lymphatic basin, o ff ered that potential, but prospective controlled studies have shown no survival benefit from lymphadenectomy after positive SNB involving micrometastasis <0.2 /uni00A0 mm in a single node. This may - be because most patients have been treated by removing the - sentinel node, which was the only node involved at that stage. However, completion lymphadenectomy after positive SNB remains, on current evidence, the optimum method for regional control, if patients accept the morbidity associated - with regional lymphadenectomy . Adjuvant therapy - When mutation locks BRAF protein signalling to ‘on’, it a ff ects the mitogen-activated protein kinase (MAPK) cellular - pathway , promoting initiation, malignant transformation, tumour progression and metastasis in the 50% of  malignant melanomas with BRAF V600 mutations. Targeted therapy in stage IV melanoma using dabrafenib or vemurafenib, which block BRAF action, has shown promising results with h metastatic melanoma. Trametinib has a di ff erent action on the MAPK pathway: stopping cell growth and promoting apoptosis. Combined use with dabrafenib to counter acquired - tumour resistance via MAPK pathway reactivation shows promising results in stage IV disease. Also, the selective immune
Change in size
Shape
Colour
Thickness (elevation/nodularity or ulceration)
Satellite lesions (pigment spreading into surrounding area)
Tingling/itching/serosanguineous discharge (usually late signs)
checkpoint inhibitors ipilimumab and nivolumab demonstrate benefit in metastatic or unresectable melanoma. Over the last 5 years, five randomised prospective trials of adjuvant therapy have reported findings in the treatment of patients with stage II to IV disease. While all five trials showed a significant impro vement in relapse-free survival, only two of the trials were mature enough to report on overall survival. Prognosis The Breslow thickness of  the primary tumour o ff ers the best correlation with survival in stage I disease. The higher the mitotic index, the poorer the prognosis of  the primary tumour. This has greater significance than the presence or absence of ulceration. The presence of  lymph node metastases is the single most important prognostic index in melanoma, outweighing both tumour and host factors. The number of  a ff ected nodes and the presence of  extranodal extension are also significant outcome predictors. Once regional nodes are clinically involved, 70–85% of  patients will have occult distant metastases. Merkel cell (dermal mechanoreceptor) tumour This is an aggressive malignant tumour of  Merkel cells and usually a ff ects the elderly . It is four times more common in Haig H Kasabach , 1898–1943, radiologist, Presbyterian Hospital, New Y ork, NY , USA. Katharine K Merritt , 1886–1986, pediatrician, Babies Hospital, Columbia University College of  Physicians and Surgeons, New Y ork, NY , USA. Kasabach and Merritt described the condition as a joint paper in 1940. women than in men ( Figure 45.41 ). Treatment is with wide local excision, aiming for a 25- to 30-mm margin, followed by radiotherapy .
Primary tumour
Regional nodes
NX
TX
Patients in whom nodes cannot be assessed
Primary tumour cannot be assessed (has
(e.g.
previous excision)
been curettage or has severely regressed)
T0
N0
No evidence of primary tumour
No node involvement
Tis
Melanoma
in situ
N1
a:
<0.8
/uni00A0
mm, no ulceration
T1
1 node
b:
0.8–1.0
/uni00A0
mm, no
<1.0
/uni00A0
mm
ulceration; or <1.0
/uni00A0
mm with
ulceration
a:
No ulceration
N2
T2
b:
With ulceration
2 or 3 nodes
1.01–2.0
/uni00A0
mm
a:
No ulceration
N3
T3
b:
With ulceration
2.01–4.0
/uni00A0
mm
a:
No ulceration
T4
b:
With ulceration
4
/uni00A0
mm
Clinical staging of melanoma
Stage IIa: T2b or T3a, N0, M0
Stage 0: Tis, N0, M0
Stage IIb: T3b or T4a, N0, M0
Stage Ia: T1a, N0, M0
Stage IIc: T4b, N0, M0
Stage Ib: T1b or T2a, N0, M0
LDH, lactate dehydrogenase; MSI denotes the presence of satellite lesions, in-transit lesions or local recurrence.
Distant metastases
M0
No detected distant metastases
M1a
a:
Micrometastasis (no MSI)
Skin, subcutaneous or distant lymph node
b:
Macrometastasis (no MSI)
metastases (normal serum LDH levels)
c:
MSI present
M1b
a:
Micrometastasis (no MSI)
Lung metastases (normal serum LDH
b:
Macrometastasis (no MSI)
levels)
c:
MSI present
M1c
a:
Micrometastasis, >3 nodes
All other visceral metastases or any distant
(no MSI)
metastases with elevated serum LDH
b:
Micrometastasis, >3 nodes
levels
or matted or 1 clinical node
(no MSI)
c:
1 clinical or occult node
with MSI present
M1d
Brain metastases
Stage III: any T, >N1, M0
Stage IV: any T, any N1, M1
Cutaneous squamous cell carcinoma
SCC is a malignant tumour of  keratinising cells of  the epider - mis or its appendages. It arises from the stratum basalis of  the epidermis and expresses cytokeratins 1 and 10. Epidemiology Four BCCs occur for every SCC, which is the second most common form of  skin cancer. It is strongly related to cumu - lative sun exposure and damage, especially in white-skinned individuals living nearer the equator. In the northern hemi - sphere it a ff ects the elderly , whereas it is not uncommon in sun-damaged, middle-aged white people in the souther n hemisphere. Everywhere, it is more common in men than in women. SCC is also associa ted with chronic inflammation (chronic sinus tracts, pre-existing scars, osteomyelitis, burns, vaccination points) and immunosuppression. When a SCC appears in a scar it is known as a Marjolin’s ulcer.
(a, b)
Squamous cell carcinoma /uni25CF /uni25CF /uni25CF IR causes SCC, as do chemical carcinogens (arsenicals, tar) and infection with HPV subtypes 5 and 16. There is also evidence that current and previous tobacco use doubles the relative risk of  SCC. In the past, actinic (solar) keratoses (AKs), i.e. cutaneous horns and keratoacanthomas, were considered to be prema lignant lesions leading to SCC. Current thinking is to classify these lesions on a continuum of  lesions, some of  which can impro ve, as with other squamous cell tumours suc h as cervical intraepithelial neoplasia. AKs are areas of  permanent sun damage in which there is dyskeratosis, partial-thickness cellular atypia and subep idermal inflammation, but an intact basement membrane ( Figure 45.31 ). They ‘wax and wane’ macroscopically between macular and papular, with and without keratinous surfaces. Most improve after moisturisation and remain as erythema tous macules; however, up to 20% form SCC. When an AK has a keratinous surface with a height greater than its base diameter, it is termed a keratin horn; 10% will have an underlying SCC ( Figure 45.32 ). Keratoacanthomas are rapidly growing, nodular tumour exhibiting symmetry around a central keratin-filled crater. John T Bowen , 1857–1941, Professor of  Dermatology , Harvard University Medical School, Boston, MA, USA, described this condition in 1912. August Queyrat , 1856–1933, dermatologist, Paris, France, described this condition in 1911. - Current thinking is that, rather than being separate pre - malignant entities, they are better considered as self-healing - SCCs and, as such, are often reported by pathologists as ‘keratoacanthoma-like SCCs’ ( Figure 45.33 ). Keratoacantho - mas are twice as common in men as in women and are usually found on the face or limbs of chronically sun-damaged 50- to - 70-year-old white-skinned individuals. T hey may be caused by HPV in a hair follicle during the growth phase and are also associated with smoking and chemical carcinogen exposure. Excision is recommended, rather than observation, as the dif - ferential diagnosis includes anaplastic SCC and the excision s scar is often better than that which remains after resolution. in situ and often develops as Bowen’s disease is SCC full-thickness dysplasia in hypertrophic AKs ( Figure 45.34 ). SCC in situ usually presents as a slowly enlarging erythematous scaly plaque and may occur anywhere on the mucocutaneous surface of the body . On the glans penis, it is called erythroplasia of  Queyrat ( Figure 45.35 ). Topical therapy with 5-fluorouracil or imiquimod is an e ff ective treatment. Alternatives include surgical excision with a 4-mm margin or Mohs’ micrographic surgery for larger or recurrent lesions.
Associated with UVR, chronic in
/f_l
ammation,
immunosuppression and chemical carcinogens
High- and low-risk SCC
Metastasis in 2% of low-risk and up to 30% of high-risk cases
Figure 45.31
Actinic keratosis (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.32
Cutaneous horn (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.33
Keratoacanthoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Macroscopic The appearance of  SCC may vary from smooth nodular, verrucous, papillomatous to ulcerating lesions. All ulcerate eventually as they grow . The ulcers have a characteristic everted edge and are surrounded by inflamed, indurated skin. Di ff erential diagnoses of  SCC include: AK; BCC; pyoderma gangrenosum; warts; and lichen simplex chronicus ( Figure 45.36 ). Albert Compton Broders , 1885–1964, American pathologist, MN, USA, and Chairman of  the Department of  Surgical Patholog MN, USA; for 1 year in 1935 Professor of  Surgical Pathology and Director of  Cancer Research, University of  V graded rectal cancer in the USA in a similar manner to the one that Cuthbert Dukes used to classify it in the UK. A combination of  Broders’ grading and Dukes’ classification gave a more accurate prognosis for rectal carcinoma than either method alone. Microscopic Characteristic irregular masses of  squamous epithelium are noted to proliferate and invade the dermis from the basal layer. The tumour stains positive for cytokeratins 1 and 10. SCC can be graded histologically according to Broders’ grading, which describes the proportion of  dedi ff erentiated cells in the tumour. Table 45.1 presents tumour classification and staging. Prognosis There are several independent prognostic variables for SCC: /uni25CF Depth: the deeper the lesion, the worse the prognosis. For SCC <2 /uni00A0 mm, metastasis is highly unlikely; if  SCC >6 /uni00A0 mm, 15% will have metastasised. y,  M a y o Clinic, Rochester, irginia, Charlottesville, V A, USA. Broders also
Figure 45.34
Bowen’s
disease – squamous cell
carcinoma
in situ
(courtesy
of St John’s Institute for
Dermatology, London, UK).
TABLE 45.1
Tumour–node–metastasis (TNM) classi
/f_i
cation and staging of squamous cell carcinoma.
Size
Nodes
NX
TX
Nodal involvement cannot be
Primary tumour cannot be
assessed
assessed
T0
N0
No evidence of primary tumour
No regional nodes
N1
Tis
Spread to 1 ipsilateral nearby node
In situ
(con
/f_i
ned to full-thickness
that is <3
/uni00A0
cm in diameter
epidermal) disease
T1
N2a
Primary <2
/uni00A0
cm
Spread to 1 ipsilateral nearby node
that is 3–6
/uni00A0
cm in diameter
T2
N2b
Primary >2
/uni00A0
cm
Spread to >1 ipsilateral nearby
nodes but none >6
/uni00A0
cm in diameter
T3
N2c
Primary invasion of a facial bone
Spread to contralateral node(s) but
none are >6
/uni00A0
cm in diameter
N3
T4
Spread to any node >6
/uni00A0
cm in
Invasion of muscle, base of skull
diameter
or other bones
Figure 45.35
Erythroplasia of Queyrat – squamous cell carcinoma
in situ
on the glans penis; also called Paget’s disease of the penis
(courtesy of St John’s Institute for Dermatology, London, UK).
Metastases
Stages
M0
Stage 0
No metastatic disease
Tis, N0, M0
M1
Stage I
Metastatic disease present
T1, N0, M0
Stage II
T2, N0, M0
Stage III
T3, N0, M0 or T1–T3, N1, M0
Stage IV
T1–T3, N2, M0 or any disease
that is N3, or T4 or M1
/uni25CF Surface size: lesions >2 /uni00A0 cm have a worse prognosis than smaller ones. /uni25CF Histological grade: the higher the Broders’ grade, the worse the prognosis. /uni25CF Microscopic invasion of  lymphovascular spaces or nerve tissue carries a high risk of  metastatic disease. Therefore, as well as information on pathological pattern, cellular morphology and Broders’ grade, any histopathology report for SCC should include the depth of  invasion, the pres ence of perineural or lymphovascular invasion and the deep and peripheral margin clearance. /uni25CF Site: SCCs on the lips and ears have higher local recur rence rates than lesions elsewhere, and tumours at the extremities fare worse than those on the trunk. /uni25CF Aetiology: SCCs that arise in burn scars, osteomyelitis skin sinuses, chronic ulcers and areas of  skin that have been irradiated have a higher metastatic potential. /uni25CF Immunosuppression: SCCs will invade further in those with impaired immune response. The overall rate of  metastasis varies between 2% and 30% for SCC (usually to regional nodes) with a local recurrence rate of  20%. Management SCC is a heterogeneous tumour with a malignant potential that varies between subtypes. Management must address the tumour’s tendency for lymphatic metastasis and the possibility of  in-transit metastasis. Surgical excision is the only means of  providing accurate information on histology and clearance. The margins for pri - mary excision should be tailored to surface size in the first instance. This should ideally be assessed using surgical loupe - magnification. A 4-mm clearance margin should be achieved and a 1-cm clearance if  the SCC measures <2 /uni00A0 cm across, margin if  the SCC measures >2 /uni00A0 cm; 95% of  local recurrence and regional metastases occur within 5 years, thus follow-up - beyond this period is not indicated. Cutaneous malignant melanoma Melanoma is a cancer of  melanocytes and can, therefore, arise in skin, mucosa, retina and the leptomeninges. Epidemiology Observational data suggest that cutaneous melanoma is caused by exposure to UVR, but this general observation, which is a generally reliable fact, may hide some of  the nuanced variables that contribute to melanoma formation.
(c)
Figure 45.36
(a)
A squamous cell carcinoma (SCC) on the face.
/uni00A0
(c)
SCC arising on the dorsum of the hand in a renal transplant recipient on immunosuppressive therapy.
who worked outside on a farm. (
(a–c)
courtesy of Mr AR Greenbaum;
(d)
(b)
A recurrent SCC arising in a previously skin-grafted area of the scalp.
(d)
SCC arising on the lip of a smoker
(d)
courtesy of St John’s Institute for Dermatology, London, UK.)
recreational activity in the sun and emigration among white- skinned people not suited to sun exposure. Although it accounts for less than 5% of  skin malignancy (and 1.6% of  all malignancy worldwide), it is responsible for over 75% of  skin malignancy-related deaths. It is the commonest cancer in young adults (20–39 years) and the most likely cause of  cancer-related death. Distribution between the sexes varies around the world and reflects occupational and recreational exposure to sunlight. Likewise, geographical distribution reflects e xposure of  white- skinned individuals to sunlight: Australia and New Zealand, countries with a predominantly white-skinned, immigrant population, have an incidence of  33.6 per 100 /uni00A0 000. Five per cent of  all patients with malignant melanoma will develop a second primary melanoma; 7% of  malignant melanomas pres ent as occult metastasis from an unknown primary . What is less clear within data on cutaneous melanoma is the contribution by variables such as serum vitamin D levels and vitamin receptor genotypes, because thinner melanomas and low er recurrence rates have been linked to higher serum vitamin D levels, and why some forms of  melanoma seem more attributable to cumulative sun exposure (superficial spreading) than others (nodular). Studies exploring whether there may be benefit from a degree of  sun exposure that avoids ‘sunbathing’ and burning and whether sun-related vitamin D production in skin, rather than supplemental vitamin D, is beneficial are ongoing, but our best information still bases sun avoidance at the centre of  melanoma prevention. Pathophysiology Cumulative UV exposure favours the development of  lentigo maligna melanoma (LMM) and later onset of  disease, whereas ‘flash fry’ exposure, typical of  rapidly acquired holiday tans, favours the other morphological variants and early onset of disease. A small proportion of malignant melanoma is genetically mediated and develops at an earlier age. People at most risk of developing malignant melanoma include: those with genetic syndromes; those with a past history of  malignant melanoma or with a first-degree rela tive who has malignant melanoma; those who have more than 30 sun-acquired naevi or a history of  five significant sunburns before the age of  16; fair-skinned/ red-haired people living close to the equator; anyone with excessive UVR exposure (environmental or salon-delivered); Summary box 45.4 Malignant melanoma /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Alexander Breslow , 1928–1980, pathologist, George Washington University , Washington, DC, USA, first reported in 1970 that the prognosis depends upon the thickness of  the tumour. nant melanoma incidence 20- to 30-fold). Male gender and solitary living are both associated with thicker melanomas at diagnosis. In women, higher socioeconomic status is positively correlated with developing melanoma. Macroscopic Only 10–20% of malignant melanomas form in pre-existing naevi, with the remainder arising de novo in previously normally pigmented skin. The most likely naevi to form malignant mela - noma are atypical naevi, atypical junctional lentiginous naevi (usually facial) and giant pigmented congenital naevi. Macroscopic features in a pre-existing naevus that suggest malignant change are listed in Summary box 45.5 . There are four common macroscopic variants of  malig - nant melanoma and several other notable, but rarer, forms, - as follows. This is the most common presentation (70%); usually arises in a pre-existing naevus after several years of  slow c hange, followed by rapid g rowth in the months before presentation ( Figure 45.37 ) . Nodularity within SSM heralds the onset of  the vertical growth phase. NM accounts for 15% of  all malignant melanoma and tends to be more aggressive than SSM, with a shorter clinical onset. These lesions often arise de novo in skin and are more common in men than in women, often presenting in middle age and usually on the trunk, head or neck ( Figure 45.38 ) . They typically appear as blue/black papules, 1–2 /uni00A0 cm in diameter, and because they lack the hori - zontal growth phase they tend to be sharply demarcated. Up to 5% are amelanotic.
Rising incidence
Genetic and acquired risk factors
Super
/f_i
cial spreading form the most common
Breslow thickness is the most important prognostic indicator
Sentinel node biopsy (SNB) is useful for staging
Super
/f_i
cial spreading melanoma (SSM).
Nodular melanoma (NM).
Figure 45.37
Super
/f_i
cial spreading melanoma (courtesy of St John’s
Institute for Dermatology, London, UK).
LMM was previously also known as Hutchinson’s melanotic freckle. This variant presents as a slow-growing, variegated brown macule on the face, neck or hands of the elderly ( Figure 45.39 ) . They are positively correlated with prolonged, intense sun exposure and a ff ect women more than men. They account for between 5% and 10% of  malignant melanomas. LMMs are thought to have less metastatic potential than other variants as they take longer to enter a vertical growth phase. Nonetheless, when they have entered the vertical growth phase their metasta tic potential is the same as any other mel anoma. ALM a ff ects the soles and palms. It is rare in white-skinned individuals (2–8% of malignant melanoma) but more common in Afro-Caribbean, Hispanic and Asian populations (35–60%). It usually presents as a flat, irregular macule in later life; 25% are amelanotic and may mimic a fungal infection or py ogenic granuloma. Sir Jonathan Hutchinson , 1828–1913, surgeon, St Bartholomew’s Hospital, London, UK. Malignant melanomas under the fingernail are usually SSM rather than ALM. For finger- or toenail lesions it is vital to biopsy the nail matrix rather than just the pigment on the nail plate. A classical feature of  a subungual melanoma is Hutchin - son’s sign: nail fold pigmentation that widens progressively to produce a triangular pigmented macule with associated nail dystrophy . The di ff erential diagnosis is ‘benign racial melanon - ychia’, which produces a linear dark streak under a nail in a - individual. Malignancy is unlikely if the nail fold dark-skinned is uninvolved ( Figure 45.40 ). /uni25CF Amelanotic melanoma may present as a flesh-coloured skin lesion; as a metastasis from an unknown skin primary; or in the gastrointestinal tract, with obstruction or intus - susception.
Figure 45.38
Nodular melanoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Lentigo maligna melanoma.
Acral lentiginous melanoma (ALM).
(a)
Figure 45.40
(a)
Acral lentiginous melanoma on the sole of the foot.
Note the swelling proximal to the nailfold.
(c)
Benign racial melanonychia. (
Institute for Dermatology, London, UK.)
Figure 45.39
Lentigo maligna melanoma (courtesy of St John’s Insti
tute for Dermatology, London, UK).
Miscellaneous
(b)
(c)
(b)
Subungual melanoma – probably a super
/f_i
cial spreading melanoma.
(a)
courtesy of Mr AR Greenbaum;
(b, c)
courtesy of St John’s
neck region. It has a propensity for perineural infiltration and often recurs locally if  not widely excised. It may be amelanotic clinically . Summary box 45.5 Macroscopic features in naevi suggestive of malignant melanoma /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Microscopic Malignant change occurs in the melanocytes in the basal epidermis, while in situ atypical melanocytes are limited to the dermoepidermal junction and show no evidence of dermal involvement. During the horizontal growth phase, cells spread along the dermoepidermal junction; although they may breach the dermis, their migration is predominantly radial. During the vertical growth phase, the dermis may be invaded. The greater the depth of  invasion, the greater the metastatic potential of the tumour. Management History and clinical examination should be directed at discov ering the primary lesion and identification of  local, regional or distant spread. An excision biopsy with a 2- to 3-mm margin of  skin and a cu ff of  subdermal fat is acceptable. Incision biopsy is occasion ally indicated: for instance, in large lesions on the face where an excision biopsy of  the whole lesion would be disfiguring. In experienced hands, observation and review every 2 /uni00A0 months may avoid biopsies in equivocal cases, but serial clin ical and dermoscopic photography by a clinician with exper tise in dermoscopy is mandatory when observ ation is chosen, rather than excision biopsy for definitive histopathological diagnosis. Dermoscopy coupled to computers with learning capability may soon outperform clinicians in melanoma diag nosis to the point where screening becomes m uch easier. Biopsy and pathological examination provide the first step towards staging melanoma. The Breslow thickness of  a mel anoma (measured to the nearest 0.1 /uni00A0 mm from the granular layer to the base of  the tumour) is the most important prog nostic indica tor in the absence of  lymph node metastases. The American Joint Committee on Cancer (AJCC) staging system takes lymph node involvement, distant metastases and evidence-based prognostic factors into account; these can then be used to guide optimum care and inclusion in researc studies for adjuvant or other treatments where applicable. The detail of  the AJCC melanoma staging system has become too specialised for the ambit of  this text; most spe cialists look up its detail as they assign a stage to a patient ( Table 45.2 ). Guidelines for staging are controversial. The author suggests that investigations should be directed towards detecting occult disease, so as to upstage patients and treat them accurately and appropriately , the only cure for malignant melanoma currently being appropriate surgery . Thus, o ff ering SNB to patients with T2a disease and greater is critical and investigations for T3a disease and greater should be directed to individual clinical presentation. Local treatment The treatment for melanoma is surgery . Lentigo maligna (melanoma in situ ) should be excised completely in most clin - ical situations because of  the risk of  it entering the vertical growth phase to become LMM. A complete excision requires no further treatment. For melanoma in situ a wide excision of  5 /uni00A0 mm is su ffi cient; for melanoma <1 /uni00A0 mm deep, a 1-cm margin is su ffi cient; and for deeper lesions, a 2-cm only margin is recommended, as there is no evidence that wider margins make a di ff erence. Regional lymph nodes The likelihood of metastatic spread to regional lymph nodes is proportional to the Breslow thickness of  the melanoma. Management of  regional lymph nodes has been a contentious topic for well over a century . Some advocated simultaneous elective lymph node clearance at the time of  wide excision of the primary melanoma. Others favoured a therapeutic lymphadenectomy if  regional metastases became clinically evident. Ideally , one would like to be able to select for treatment - those patients with the highest risk of  metastatic spread. SNB, an investigation based on the fact that lymphatic metastases proceed in an orderly fashion and can be predicted by mapping the lymphatic drainage from a primary tumour to the first or - ‘sentinel’ node in the regional lymphatic basin, o ff ered that potential, but prospective controlled studies have shown no survival benefit from lymphadenectomy after positive SNB involving micrometastasis <0.2 /uni00A0 mm in a single node. This may - be because most patients have been treated by removing the - sentinel node, which was the only node involved at that stage. However, completion lymphadenectomy after positive SNB remains, on current evidence, the optimum method for regional control, if patients accept the morbidity associated - with regional lymphadenectomy . Adjuvant therapy - When mutation locks BRAF protein signalling to ‘on’, it a ff ects the mitogen-activated protein kinase (MAPK) cellular - pathway , promoting initiation, malignant transformation, tumour progression and metastasis in the 50% of  malignant melanomas with BRAF V600 mutations. Targeted therapy in stage IV melanoma using dabrafenib or vemurafenib, which block BRAF action, has shown promising results with h metastatic melanoma. Trametinib has a di ff erent action on the MAPK pathway: stopping cell growth and promoting apoptosis. Combined use with dabrafenib to counter acquired - tumour resistance via MAPK pathway reactivation shows promising results in stage IV disease. Also, the selective immune
Change in size
Shape
Colour
Thickness (elevation/nodularity or ulceration)
Satellite lesions (pigment spreading into surrounding area)
Tingling/itching/serosanguineous discharge (usually late signs)
checkpoint inhibitors ipilimumab and nivolumab demonstrate benefit in metastatic or unresectable melanoma. Over the last 5 years, five randomised prospective trials of adjuvant therapy have reported findings in the treatment of patients with stage II to IV disease. While all five trials showed a significant impro vement in relapse-free survival, only two of the trials were mature enough to report on overall survival. Prognosis The Breslow thickness of  the primary tumour o ff ers the best correlation with survival in stage I disease. The higher the mitotic index, the poorer the prognosis of  the primary tumour. This has greater significance than the presence or absence of ulceration. The presence of  lymph node metastases is the single most important prognostic index in melanoma, outweighing both tumour and host factors. The number of  a ff ected nodes and the presence of  extranodal extension are also significant outcome predictors. Once regional nodes are clinically involved, 70–85% of  patients will have occult distant metastases. Merkel cell (dermal mechanoreceptor) tumour This is an aggressive malignant tumour of  Merkel cells and usually a ff ects the elderly . It is four times more common in Haig H Kasabach , 1898–1943, radiologist, Presbyterian Hospital, New Y ork, NY , USA. Katharine K Merritt , 1886–1986, pediatrician, Babies Hospital, Columbia University College of  Physicians and Surgeons, New Y ork, NY , USA. Kasabach and Merritt described the condition as a joint paper in 1940. women than in men ( Figure 45.41 ). Treatment is with wide local excision, aiming for a 25- to 30-mm margin, followed by radiotherapy .
Primary tumour
Regional nodes
NX
TX
Patients in whom nodes cannot be assessed
Primary tumour cannot be assessed (has
(e.g.
previous excision)
been curettage or has severely regressed)
T0
N0
No evidence of primary tumour
No node involvement
Tis
Melanoma
in situ
N1
a:
<0.8
/uni00A0
mm, no ulceration
T1
1 node
b:
0.8–1.0
/uni00A0
mm, no
<1.0
/uni00A0
mm
ulceration; or <1.0
/uni00A0
mm with
ulceration
a:
No ulceration
N2
T2
b:
With ulceration
2 or 3 nodes
1.01–2.0
/uni00A0
mm
a:
No ulceration
N3
T3
b:
With ulceration
2.01–4.0
/uni00A0
mm
a:
No ulceration
T4
b:
With ulceration
4
/uni00A0
mm
Clinical staging of melanoma
Stage IIa: T2b or T3a, N0, M0
Stage 0: Tis, N0, M0
Stage IIb: T3b or T4a, N0, M0
Stage Ia: T1a, N0, M0
Stage IIc: T4b, N0, M0
Stage Ib: T1b or T2a, N0, M0
LDH, lactate dehydrogenase; MSI denotes the presence of satellite lesions, in-transit lesions or local recurrence.
Distant metastases
M0
No detected distant metastases
M1a
a:
Micrometastasis (no MSI)
Skin, subcutaneous or distant lymph node
b:
Macrometastasis (no MSI)
metastases (normal serum LDH levels)
c:
MSI present
M1b
a:
Micrometastasis (no MSI)
Lung metastases (normal serum LDH
b:
Macrometastasis (no MSI)
levels)
c:
MSI present
M1c
a:
Micrometastasis, >3 nodes
All other visceral metastases or any distant
(no MSI)
metastases with elevated serum LDH
b:
Micrometastasis, >3 nodes
levels
or matted or 1 clinical node
(no MSI)
c:
1 clinical or occult node
with MSI present
M1d
Brain metastases
Stage III: any T, >N1, M0
Stage IV: any T, any N1, M1

Cylindroma (turban tumour)
Cylindroma (turban tumour)
A variant of  eccrine spiradenoma that coalesce when multiple on the scalp, forming a ‘turban tumour’. Cylindroma (turban tumour)
A variant of  eccrine spiradenoma that coalesce when multiple on the scalp, forming a ‘turban tumour’. Cylindroma (turban tumour)
A variant of  eccrine spiradenoma that coalesce when multiple on the scalp, forming a ‘turban tumour’.

Dermis
Dermis
The dermis constitutes 95% of  the skin and is structurally divided into a superficial papillary layer, which is composed of delicate collagen and elastin fibres in ground substance, into which a capillary and lymphatic network ramifies, and a deeper reticular layer, which is composed of  coarse branching collagen, layered parallel to the skin surface ( Figure 45.1 ). - The epidermis and dermis meet at the dermoepidermal junction in a three-dimensional wave-like arrangement in - which epidermal rete ridges project down, inter digitating with the upward-pointing, dermal papillae containing vascular and lymphatic plexi. m - The skin also contains specialised cells such as Langerhans cells, whose role is to engulf  antigens and present them to T cells. Merkel cells, and Meissner’s and Pacinian corpuscles have roles in mechanosensation. - Dermis
The dermis constitutes 95% of  the skin and is structurally divided into a superficial papillary layer, which is composed of delicate collagen and elastin fibres in ground substance, into which a capillary and lymphatic network ramifies, and a deeper reticular layer, which is composed of  coarse branching collagen, layered parallel to the skin surface ( Figure 45.1 ). - The epidermis and dermis meet at the dermoepidermal junction in a three-dimensional wave-like arrangement in - which epidermal rete ridges project down, inter digitating with the upward-pointing, dermal papillae containing vascular and lymphatic plexi. m - The skin also contains specialised cells such as Langerhans cells, whose role is to engulf  antigens and present them to T cells. Merkel cells, and Meissner’s and Pacinian corpuscles have roles in mechanosensation. - Dermis
The dermis constitutes 95% of  the skin and is structurally divided into a superficial papillary layer, which is composed of delicate collagen and elastin fibres in ground substance, into which a capillary and lymphatic network ramifies, and a deeper reticular layer, which is composed of  coarse branching collagen, layered parallel to the skin surface ( Figure 45.1 ). - The epidermis and dermis meet at the dermoepidermal junction in a three-dimensional wave-like arrangement in - which epidermal rete ridges project down, inter digitating with the upward-pointing, dermal papillae containing vascular and lymphatic plexi. m - The skin also contains specialised cells such as Langerhans cells, whose role is to engulf  antigens and present them to T cells. Merkel cells, and Meissner’s and Pacinian corpuscles have roles in mechanosensation. -

Eccrine poroma (papillary syringoma)
Eccrine poroma (papillary syringoma)
These are single raised or pedicled lesions found most often on the palm or sole. Eccrine poroma (papillary syringoma)
These are single raised or pedicled lesions found most often on the palm or sole. Eccrine poroma (papillary syringoma)
These are single raised or pedicled lesions found most often on the palm or sole.

Epidermis
Epidermis
The epidermis constitutes 5% of  the skin and is composed of five layers of  keratinised, stratified squamous epithelium – the strata: basalis (deep), spinosum, granulosum, lucidum and corneum (superficial). Most epidermal cells are keratinocytes arranged in layers. The basal epidermis (stratum basalis) also contains melano cytes. Keratinocytes are classified according to their depth in the epidermis and their degree of  di ff erentia tion. Kerati nocytes grow and are replaced via mitosis in the cells of stratum granulosum as they progress from deep to superficial, losing their nuclei and organelles as they ascend, before for ing the stratum corneum. The other keratinocyte layers in the skin (strata lucidum, granulosum and spinosum) are variably thick according to body site; for instance, all three are thick in the glabrous skin of the palms and soles of the feet and almost absent in eyelid skin. Melanocytes are dendritic cells of  neural crest origin, usu ally located in the basal epidermis. Each melanocyte synthe sises melanin, a brown-black pigment, which is transferred via membrane processes to the keratinocytes in the strata gran ulosum and spinosum. Melanin provides protection against ultra violet radiation (UVR). Ethnic di ff erences in skin colour are determined by variations in the amount, combination and Paul Langerhans , 1847–1888, Professor of  Pathological Anatomy , Freiberg, Germany . Friedrich Sigmund Merkel , 1845–1919, Professor of  Anatomy , successively at Rostock, Königsberg (now Kaliningrad in Russia) and Göttingen, Germany . George Meissner , 1829–1905, Professor of  Physiology , Göttingen, Germany . Filippo Pacini , 1812–1883, Professor of  Anatomy and Physiology , Florence, Italy . distribution of  melanin within the keratinocytes, not by di ff er - ences in the number of  melanocytes. The surface of  the epidermis is coated with a mixture of secreted molecules and microorganisms and generally has an acid pH, which is protective against harmful flora.
The classi
/f_i
cation of benign skin tumours
•
The management of malignant skin tumours
•
Epidermis
The epidermis constitutes 5% of  the skin and is composed of five layers of  keratinised, stratified squamous epithelium – the strata: basalis (deep), spinosum, granulosum, lucidum and corneum (superficial). Most epidermal cells are keratinocytes arranged in layers. The basal epidermis (stratum basalis) also contains melano cytes. Keratinocytes are classified according to their depth in the epidermis and their degree of  di ff erentia tion. Kerati nocytes grow and are replaced via mitosis in the cells of stratum granulosum as they progress from deep to superficial, losing their nuclei and organelles as they ascend, before for ing the stratum corneum. The other keratinocyte layers in the skin (strata lucidum, granulosum and spinosum) are variably thick according to body site; for instance, all three are thick in the glabrous skin of the palms and soles of the feet and almost absent in eyelid skin. Melanocytes are dendritic cells of  neural crest origin, usu ally located in the basal epidermis. Each melanocyte synthe sises melanin, a brown-black pigment, which is transferred via membrane processes to the keratinocytes in the strata gran ulosum and spinosum. Melanin provides protection against ultra violet radiation (UVR). Ethnic di ff erences in skin colour are determined by variations in the amount, combination and Paul Langerhans , 1847–1888, Professor of  Pathological Anatomy , Freiberg, Germany . Friedrich Sigmund Merkel , 1845–1919, Professor of  Anatomy , successively at Rostock, Königsberg (now Kaliningrad in Russia) and Göttingen, Germany . George Meissner , 1829–1905, Professor of  Physiology , Göttingen, Germany . Filippo Pacini , 1812–1883, Professor of  Anatomy and Physiology , Florence, Italy . distribution of  melanin within the keratinocytes, not by di ff er - ences in the number of  melanocytes. The surface of  the epidermis is coated with a mixture of secreted molecules and microorganisms and generally has an acid pH, which is protective against harmful flora.
The classi
/f_i
cation of benign skin tumours
•
The management of malignant skin tumours
•
Epidermis
The epidermis constitutes 5% of  the skin and is composed of five layers of  keratinised, stratified squamous epithelium – the strata: basalis (deep), spinosum, granulosum, lucidum and corneum (superficial). Most epidermal cells are keratinocytes arranged in layers. The basal epidermis (stratum basalis) also contains melano cytes. Keratinocytes are classified according to their depth in the epidermis and their degree of  di ff erentia tion. Kerati nocytes grow and are replaced via mitosis in the cells of stratum granulosum as they progress from deep to superficial, losing their nuclei and organelles as they ascend, before for ing the stratum corneum. The other keratinocyte layers in the skin (strata lucidum, granulosum and spinosum) are variably thick according to body site; for instance, all three are thick in the glabrous skin of the palms and soles of the feet and almost absent in eyelid skin. Melanocytes are dendritic cells of  neural crest origin, usu ally located in the basal epidermis. Each melanocyte synthe sises melanin, a brown-black pigment, which is transferred via membrane processes to the keratinocytes in the strata gran ulosum and spinosum. Melanin provides protection against ultra violet radiation (UVR). Ethnic di ff erences in skin colour are determined by variations in the amount, combination and Paul Langerhans , 1847–1888, Professor of  Pathological Anatomy , Freiberg, Germany . Friedrich Sigmund Merkel , 1845–1919, Professor of  Anatomy , successively at Rostock, Königsberg (now Kaliningrad in Russia) and Göttingen, Germany . George Meissner , 1829–1905, Professor of  Physiology , Göttingen, Germany . Filippo Pacini , 1812–1883, Professor of  Anatomy and Physiology , Florence, Italy . distribution of  melanin within the keratinocytes, not by di ff er - ences in the number of  melanocytes. The surface of  the epidermis is coated with a mixture of secreted molecules and microorganisms and generally has an acid pH, which is protective against harmful flora.
The classi
/f_i
cation of benign skin tumours
•
The management of malignant skin tumours
•

FUNCTION OF THE SKIN
FUNCTION OF THE SKIN
Skin and subcutaneous tissue have several important functions: /uni25CF Barrier to the environment enveloping the body and pro tecting against trauma, radiation and pathogens. Secreted sebum and sweat mix to form a microscopic acidic film across the epidermis – ‘the acid mantle’ – which is protec tive against microorg anisms and toxic substances. /uni25CF Regulates temperature and water homeostasis. /uni25CF Organ of  excretion for urea, sodium chloride, potassium and water, as well as sulphur-containing metabolites from drugs (e.g. dimethyl sulphoxide) or food (garlic, cumin). /uni25CF The skin has significant endocrine and metabolic functions and interactions. Skin cells contain receptors for and re spond to peptides, steroid sex hormones, thyroid hormones and neurotransmitters and they both produce (cholecalcif erol) and metabolise (androgens) hormones and precursors to activa te, potentiate and inactivate their functions. /uni25CF Sensory organ with multiple receptors for pain, pressure and movement. FUNCTION OF THE SKIN
Skin and subcutaneous tissue have several important functions: /uni25CF Barrier to the environment enveloping the body and pro tecting against trauma, radiation and pathogens. Secreted sebum and sweat mix to form a microscopic acidic film across the epidermis – ‘the acid mantle’ – which is protec tive against microorg anisms and toxic substances. /uni25CF Regulates temperature and water homeostasis. /uni25CF Organ of  excretion for urea, sodium chloride, potassium and water, as well as sulphur-containing metabolites from drugs (e.g. dimethyl sulphoxide) or food (garlic, cumin). /uni25CF The skin has significant endocrine and metabolic functions and interactions. Skin cells contain receptors for and re spond to peptides, steroid sex hormones, thyroid hormones and neurotransmitters and they both produce (cholecalcif erol) and metabolise (androgens) hormones and precursors to activa te, potentiate and inactivate their functions. /uni25CF Sensory organ with multiple receptors for pain, pressure and movement. FUNCTION OF THE SKIN
Skin and subcutaneous tissue have several important functions: /uni25CF Barrier to the environment enveloping the body and pro tecting against trauma, radiation and pathogens. Secreted sebum and sweat mix to form a microscopic acidic film across the epidermis – ‘the acid mantle’ – which is protec tive against microorg anisms and toxic substances. /uni25CF Regulates temperature and water homeostasis. /uni25CF Organ of  excretion for urea, sodium chloride, potassium and water, as well as sulphur-containing metabolites from drugs (e.g. dimethyl sulphoxide) or food (garlic, cumin). /uni25CF The skin has significant endocrine and metabolic functions and interactions. Skin cells contain receptors for and re spond to peptides, steroid sex hormones, thyroid hormones and neurotransmitters and they both produce (cholecalcif erol) and metabolise (androgens) hormones and precursors to activa te, potentiate and inactivate their functions. /uni25CF Sensory organ with multiple receptors for pain, pressure and movement.

FUNCTIONAL ANATOMY AND PHYSIOLOGY OF SKIN
FUNCTIONAL ANATOMY AND PHYSIOLOGY OF SKIN
Skin can be divided into two layers: the outer epidermis and the inner dermis. Deep to the dermis lies subcutaneous fat and any remnants of  the panniculus carnosus. FUNCTIONAL ANATOMY AND PHYSIOLOGY OF SKIN
Skin can be divided into two layers: the outer epidermis and the inner dermis. Deep to the dermis lies subcutaneous fat and any remnants of  the panniculus carnosus. FUNCTIONAL ANATOMY AND PHYSIOLOGY OF SKIN
Skin can be divided into two layers: the outer epidermis and the inner dermis. Deep to the dermis lies subcutaneous fat and any remnants of  the panniculus carnosus.

FURTHER READING
FURTHER READING
Calonje JE, Brenn T , Lazar A, Billings S. McKee’s pathology of the skin , 5th edn. Amsterdam: Elsevier, 2019. Soyer HP , Argenziano G, Ho ff mann-Wellenhof R, Zalaudek I. Dermos - copy: the essentials , 3rd edn. Philadelphia, PA: Mosby Wolfe, 2020. FURTHER READING
Calonje JE, Brenn T , Lazar A, Billings S. McKee’s pathology of the skin , 5th edn. Amsterdam: Elsevier, 2019. Soyer HP , Argenziano G, Ho ff mann-Wellenhof R, Zalaudek I. Dermos - copy: the essentials , 3rd edn. Philadelphia, PA: Mosby Wolfe, 2020. FURTHER READING
Calonje JE, Brenn T , Lazar A, Billings S. McKee’s pathology of the skin , 5th edn. Amsterdam: Elsevier, 2019. Soyer HP , Argenziano G, Ho ff mann-Wellenhof R, Zalaudek I. Dermos - copy: the essentials , 3rd edn. Philadelphia, PA: Mosby Wolfe, 2020.

Giant congenital pigmented naevus or giant hairy n
Giant congenital pigmented naevus or giant hairy naevus
This hamartoma of naevo-melanocytes causes confusion because its definition and management are contentious. It has a similar histology to compound naevi, but with naevus cells distributed variably throughout all skin layers and into the subdermal fat and muscle and with a tendency to dermatomal distribution ( Figure 45.28 ). Giant congenital pigmented naevi (GCPNs) are precursors of  melanoma but the magnitude of this risk is unclear, largely because of  the lack of  well-conducted studies and variable classification of  the naevus. A 3–5% lifetime risk of  melanoma is quoted. One in three childhood malignant melanomas arise in patients with GCPN, but the risk decreases with age: 15% of  malignant melanomas present at birth, 62% present by puberty and 99% by 45 years of  age. A multidisciplinary management approach is advocated, with initial investigations examining for neurocutaneous mela - nosis as there may be leptomeningeal involvement. Remov al of ed for both aesthetic and oncological GCPN should be consider reasons. Giant congenital pigmented naevus or giant hairy naevus
This hamartoma of naevo-melanocytes causes confusion because its definition and management are contentious. It has a similar histology to compound naevi, but with naevus cells distributed variably throughout all skin layers and into the subdermal fat and muscle and with a tendency to dermatomal distribution ( Figure 45.28 ). Giant congenital pigmented naevi (GCPNs) are precursors of  melanoma but the magnitude of this risk is unclear, largely because of  the lack of  well-conducted studies and variable classification of  the naevus. A 3–5% lifetime risk of  melanoma is quoted. One in three childhood malignant melanomas arise in patients with GCPN, but the risk decreases with age: 15% of  malignant melanomas present at birth, 62% present by puberty and 99% by 45 years of  age. A multidisciplinary management approach is advocated, with initial investigations examining for neurocutaneous mela - nosis as there may be leptomeningeal involvement. Remov al of ed for both aesthetic and oncological GCPN should be consider reasons.

Giant congenital pigmented naevus or giant hairy naevus
Giant congenital pigmented naevus or giant hairy naevus
This hamartoma of naevo-melanocytes causes confusion because its definition and management are contentious. It has a similar histology to compound naevi, but with naevus cells distributed variably throughout all skin layers and into the subdermal fat and muscle and with a tendency to dermatomal distribution ( Figure 45.28 ). Giant congenital pigmented naevi (GCPNs) are precursors of  melanoma but the magnitude of this risk is unclear, largely because of  the lack of  well-conducted studies and variable classification of  the naevus. A 3–5% lifetime risk of  melanoma is quoted. One in three childhood malignant melanomas arise in patients with GCPN, but the risk decreases with age: 15% of  malignant melanomas present at birth, 62% present by puberty and 99% by 45 years of  age. A multidisciplinary management approach is advocated, with initial investigations examining for neurocutaneous mela - nosis as there may be leptomeningeal involvement. Remov al of ed for both aesthetic and oncological GCPN should be consider reasons.

Hair follicles Trichoepithelioma
Hair follicles Trichoepithelioma
These are small skin-coloured nodules found most often in the nasolabial folds. Trichoepithelioma is clinically and histologi - cally similar to a BCC. Hair follicles Trichoepithelioma
These are small skin-coloured nodules found most often in the nasolabial folds. Trichoepithelioma is clinically and histologi - cally similar to a BCC. Hair follicles Trichoepithelioma
These are small skin-coloured nodules found most often in the nasolabial folds. Trichoepithelioma is clinically and histologi - cally similar to a BCC.

Infections
Infections
Skin and soft-tissue infections can be localised or spreading, necrotising or non-necrotising. Localised or spreading non-necrotising infections usually respond to broad-spectrum antibiotics. Localised necrotising infections need surgical debridement as well as antibiotic therapy . Spreading necrotis ing soft-tissue infection constitutes a life-threatening surgical emergency , requiring immediate resuscitation, intravenous antibiotic therapy and urgent surgical intervention with radical debridement. Impetigo Impetigo is a superficial infection of  skin with staphylococci, streptococci or both ( Figure 45.6 ). It is highly infectious and is characterised by blisters that rupture and coalesce to form a honey-coloured crust; it usually a ff ects children. Treatment is directed at washing the a ff ected areas and applying topical antistaphylococcal treatments; broad-spectrum oral antibiotics are required if  streptococcal infection is also implicated. Erysipelas Erysipelas is a sharply demarcated streptococcal infection of the superficial lymphatics, usually associated with broken skin on the face ( Figure 45.7 ). The area a ff ected is erythematous and oedematous. The patient may be febrile and have a leuko cytosis. Prompt administration of  broad-spectrum antibiotics after swabbing the area for culture and sensitivity is usually all that is necessary . Cellulitis/lymphangitis This is a bacterial infection of  the skin and subcutaneous tissue that is more generalised than erysipelas. It is usually associated with broken skin or pre-existing ulceration. It is characterised by an expanding area of  erythematous, oedematous tissue that is painful, in association with fever, malaise and leukocytosis. Erythema tracking along lymphatics may be visible (lymphangitis) ( Figure 45.8 ). The commonest causative Thomas Hodgkin , 1798–1866, curator of  the museum and demonstrator of  morbid anatomy , Guy’s Hospital, London, UK. - - - Streptococcus pyogenes and S. aureus . Blood and organisms are skin cultures for sensitivity should be taken before prompt administration of  broad-spectrum intravenous antibiotics and elevation of  the a ff ected extremity .
(b)
Figure 45.5
Pyoderma gangrenosum affecting the legs
(a)
and the
breasts
(b)
(courtesy of St John’s Institute for Dermatology, London,
UK).
Figure 45.6
Impetigo. Note the honey-coloured crust (courtesy of St
John’s Institute for Dermatology, London, UK).
Figure 45.7
Erysipelas (courtesy of St John’s Institute for Dermatol
ogy, London, UK).
Infections
Skin and soft-tissue infections can be localised or spreading, necrotising or non-necrotising. Localised or spreading non-necrotising infections usually respond to broad-spectrum antibiotics. Localised necrotising infections need surgical debridement as well as antibiotic therapy . Spreading necrotis ing soft-tissue infection constitutes a life-threatening surgical emergency , requiring immediate resuscitation, intravenous antibiotic therapy and urgent surgical intervention with radical debridement. Impetigo Impetigo is a superficial infection of  skin with staphylococci, streptococci or both ( Figure 45.6 ). It is highly infectious and is characterised by blisters that rupture and coalesce to form a honey-coloured crust; it usually a ff ects children. Treatment is directed at washing the a ff ected areas and applying topical antistaphylococcal treatments; broad-spectrum oral antibiotics are required if  streptococcal infection is also implicated. Erysipelas Erysipelas is a sharply demarcated streptococcal infection of the superficial lymphatics, usually associated with broken skin on the face ( Figure 45.7 ). The area a ff ected is erythematous and oedematous. The patient may be febrile and have a leuko cytosis. Prompt administration of  broad-spectrum antibiotics after swabbing the area for culture and sensitivity is usually all that is necessary . Cellulitis/lymphangitis This is a bacterial infection of  the skin and subcutaneous tissue that is more generalised than erysipelas. It is usually associated with broken skin or pre-existing ulceration. It is characterised by an expanding area of  erythematous, oedematous tissue that is painful, in association with fever, malaise and leukocytosis. Erythema tracking along lymphatics may be visible (lymphangitis) ( Figure 45.8 ). The commonest causative Thomas Hodgkin , 1798–1866, curator of  the museum and demonstrator of  morbid anatomy , Guy’s Hospital, London, UK. - - - Streptococcus pyogenes and S. aureus . Blood and organisms are skin cultures for sensitivity should be taken before prompt administration of  broad-spectrum intravenous antibiotics and elevation of  the a ff ected extremity .
(b)
Figure 45.5
Pyoderma gangrenosum affecting the legs
(a)
and the
breasts
(b)
(courtesy of St John’s Institute for Dermatology, London,
UK).
Figure 45.6
Impetigo. Note the honey-coloured crust (courtesy of St
John’s Institute for Dermatology, London, UK).
Figure 45.7
Erysipelas (courtesy of St John’s Institute for Dermatol
ogy, London, UK).
Infections
Skin and soft-tissue infections can be localised or spreading, necrotising or non-necrotising. Localised or spreading non-necrotising infections usually respond to broad-spectrum antibiotics. Localised necrotising infections need surgical debridement as well as antibiotic therapy . Spreading necrotis ing soft-tissue infection constitutes a life-threatening surgical emergency , requiring immediate resuscitation, intravenous antibiotic therapy and urgent surgical intervention with radical debridement. Impetigo Impetigo is a superficial infection of  skin with staphylococci, streptococci or both ( Figure 45.6 ). It is highly infectious and is characterised by blisters that rupture and coalesce to form a honey-coloured crust; it usually a ff ects children. Treatment is directed at washing the a ff ected areas and applying topical antistaphylococcal treatments; broad-spectrum oral antibiotics are required if  streptococcal infection is also implicated. Erysipelas Erysipelas is a sharply demarcated streptococcal infection of the superficial lymphatics, usually associated with broken skin on the face ( Figure 45.7 ). The area a ff ected is erythematous and oedematous. The patient may be febrile and have a leuko cytosis. Prompt administration of  broad-spectrum antibiotics after swabbing the area for culture and sensitivity is usually all that is necessary . Cellulitis/lymphangitis This is a bacterial infection of  the skin and subcutaneous tissue that is more generalised than erysipelas. It is usually associated with broken skin or pre-existing ulceration. It is characterised by an expanding area of  erythematous, oedematous tissue that is painful, in association with fever, malaise and leukocytosis. Erythema tracking along lymphatics may be visible (lymphangitis) ( Figure 45.8 ). The commonest causative Thomas Hodgkin , 1798–1866, curator of  the museum and demonstrator of  morbid anatomy , Guy’s Hospital, London, UK. - - - Streptococcus pyogenes and S. aureus . Blood and organisms are skin cultures for sensitivity should be taken before prompt administration of  broad-spectrum intravenous antibiotics and elevation of  the a ff ected extremity .
(b)
Figure 45.5
Pyoderma gangrenosum affecting the legs
(a)
and the
breasts
(b)
(courtesy of St John’s Institute for Dermatology, London,
UK).
Figure 45.6
Impetigo. Note the honey-coloured crust (courtesy of St
John’s Institute for Dermatology, London, UK).
Figure 45.7
Erysipelas (courtesy of St John’s Institute for Dermatol
ogy, London, UK).

Introduction
Introduction
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Learning objectives
Learning objectives
To understand: The structure and functional properties of skin • The classi /f_i cation of vascular skin lesions • The cutaneous manifestations of generalised disease as • related to surgery Learning objectives
To understand: The structure and functional properties of skin • The classi /f_i cation of vascular skin lesions • The cutaneous manifestations of generalised disease as • related to surgery Learning objectives
To understand: The structure and functional properties of skin • The classi /f_i cation of vascular skin lesions • The cutaneous manifestations of generalised disease as • related to surgery

Necrotising fasciitis
Necrotising fasciitis
Meleney’s synergistic gangrene and Fournier’s gangrene are variants of  a similar disease process. Necrotising fasciitis results from synergistic polymicrobial infection, most commonly a group A β -haemolytic Streptococcus in combination with Staphylococcus , Escherichia coli , Pseudomonas Proteus , Bacteroides or Clostridium ; 80% of  patients have a his tory of  previous trauma/infection and over 60% of  cases commence in the lower extremities. Predisposing conditions include diabetes mellitus, smoking, penetrating trauma, pressure sores, immunosuppression, intravenous drug ab perineal infection (perianal abscess, Bartholin’s cysts) and skin damage/infection (abrasions, bites, boils). Summary box 45.1 Necrotising fasciitis /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Classical clinical signs include oedema stretching beyond visible skin erythema; a woody-hard texture to the subcutane ous tissues; an inability to distinguish fascial planes and muscle Frank Meleney , 1889–1963, American surgeon in the First World War, then became a Professor at Columbia Medical School in New Y ork, NY , USA. Jean Fournier , 1832–1914, French dermatologist, also described tertiary syphilis. Caspar Bartholin (Secundus) , 1655–1709, Professor of  Medicine, Anatomy and Physics, Copenhagen, Denmark, described these glands in 1677. groups on palpation; disproportionate pain in relation to the a ff ected area, with associated skin vesicles and soft-tissue crep - itus ( Figure 45.9 ). Lymphangitis tends to be absent. Early on, patients may be febrile and tachycardic, with a very rapid pro - ve gression to septic shock. Radiographs, which should not ha delayed urgent treatment, may demonstrate air in the tissues. , Management should commence with urgent fluid resus - - citation, monitoring of  haemodynamic status and adminis - tration of high-dose intravenous broad-spectrum antibiotics. This is a surgical emergency and the diseased area should be leeding tis - debrided as soon as possible until viable, healthy , b use, sue is reached. Early surgical review and further debridement is advisable, together with the use of  vacuum-assisted dress - ings. Early skin grafting in selected cases may minimise protein yperbaric oxygen therapy and fluid losses. Where available, h after debridement may be helpful. Mortality of  between 30% and 50% can be expected, even with prompt opera tive inter - vention.
Surgical emergency
Polymicrobial synergistic infection
80% have a history of previous trauma or infection
Rapid progression to septic shock
Urgent resuscitation, antibiotics and surgical debridement
Mortality 30–50%
Figure 45.8
Cellulitis affecting the left leg (courtesy of St John’s
Institute for Dermatology, London, UK).
Necrotising fasciitis
Meleney’s synergistic gangrene and Fournier’s gangrene are variants of  a similar disease process. Necrotising fasciitis results from synergistic polymicrobial infection, most commonly a group A β -haemolytic Streptococcus in combination with Staphylococcus , Escherichia coli , Pseudomonas Proteus , Bacteroides or Clostridium ; 80% of  patients have a his tory of  previous trauma/infection and over 60% of  cases commence in the lower extremities. Predisposing conditions include diabetes mellitus, smoking, penetrating trauma, pressure sores, immunosuppression, intravenous drug ab perineal infection (perianal abscess, Bartholin’s cysts) and skin damage/infection (abrasions, bites, boils). Summary box 45.1 Necrotising fasciitis /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Classical clinical signs include oedema stretching beyond visible skin erythema; a woody-hard texture to the subcutane ous tissues; an inability to distinguish fascial planes and muscle Frank Meleney , 1889–1963, American surgeon in the First World War, then became a Professor at Columbia Medical School in New Y ork, NY , USA. Jean Fournier , 1832–1914, French dermatologist, also described tertiary syphilis. Caspar Bartholin (Secundus) , 1655–1709, Professor of  Medicine, Anatomy and Physics, Copenhagen, Denmark, described these glands in 1677. groups on palpation; disproportionate pain in relation to the a ff ected area, with associated skin vesicles and soft-tissue crep - itus ( Figure 45.9 ). Lymphangitis tends to be absent. Early on, patients may be febrile and tachycardic, with a very rapid pro - ve gression to septic shock. Radiographs, which should not ha delayed urgent treatment, may demonstrate air in the tissues. , Management should commence with urgent fluid resus - - citation, monitoring of  haemodynamic status and adminis - tration of high-dose intravenous broad-spectrum antibiotics. This is a surgical emergency and the diseased area should be leeding tis - debrided as soon as possible until viable, healthy , b use, sue is reached. Early surgical review and further debridement is advisable, together with the use of  vacuum-assisted dress - ings. Early skin grafting in selected cases may minimise protein yperbaric oxygen therapy and fluid losses. Where available, h after debridement may be helpful. Mortality of  between 30% and 50% can be expected, even with prompt opera tive inter - vention.
Surgical emergency
Polymicrobial synergistic infection
80% have a history of previous trauma or infection
Rapid progression to septic shock
Urgent resuscitation, antibiotics and surgical debridement
Mortality 30–50%
Figure 45.8
Cellulitis affecting the left leg (courtesy of St John’s
Institute for Dermatology, London, UK).
Necrotising fasciitis
Meleney’s synergistic gangrene and Fournier’s gangrene are variants of  a similar disease process. Necrotising fasciitis results from synergistic polymicrobial infection, most commonly a group A β -haemolytic Streptococcus in combination with Staphylococcus , Escherichia coli , Pseudomonas Proteus , Bacteroides or Clostridium ; 80% of  patients have a his tory of  previous trauma/infection and over 60% of  cases commence in the lower extremities. Predisposing conditions include diabetes mellitus, smoking, penetrating trauma, pressure sores, immunosuppression, intravenous drug ab perineal infection (perianal abscess, Bartholin’s cysts) and skin damage/infection (abrasions, bites, boils). Summary box 45.1 Necrotising fasciitis /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Classical clinical signs include oedema stretching beyond visible skin erythema; a woody-hard texture to the subcutane ous tissues; an inability to distinguish fascial planes and muscle Frank Meleney , 1889–1963, American surgeon in the First World War, then became a Professor at Columbia Medical School in New Y ork, NY , USA. Jean Fournier , 1832–1914, French dermatologist, also described tertiary syphilis. Caspar Bartholin (Secundus) , 1655–1709, Professor of  Medicine, Anatomy and Physics, Copenhagen, Denmark, described these glands in 1677. groups on palpation; disproportionate pain in relation to the a ff ected area, with associated skin vesicles and soft-tissue crep - itus ( Figure 45.9 ). Lymphangitis tends to be absent. Early on, patients may be febrile and tachycardic, with a very rapid pro - ve gression to septic shock. Radiographs, which should not ha delayed urgent treatment, may demonstrate air in the tissues. , Management should commence with urgent fluid resus - - citation, monitoring of  haemodynamic status and adminis - tration of high-dose intravenous broad-spectrum antibiotics. This is a surgical emergency and the diseased area should be leeding tis - debrided as soon as possible until viable, healthy , b use, sue is reached. Early surgical review and further debridement is advisable, together with the use of  vacuum-assisted dress - ings. Early skin grafting in selected cases may minimise protein yperbaric oxygen therapy and fluid losses. Where available, h after debridement may be helpful. Mortality of  between 30% and 50% can be expected, even with prompt opera tive inter - vention.
Surgical emergency
Polymicrobial synergistic infection
80% have a history of previous trauma or infection
Rapid progression to septic shock
Urgent resuscitation, antibiotics and surgical debridement
Mortality 30–50%
Figure 45.8
Cellulitis affecting the left leg (courtesy of St John’s
Institute for Dermatology, London, UK).

PATHOPHYSIOLOGY OF THE SKIN AND SUBCUTANEOUS TISSU
PATHOPHYSIOLOGY OF THE SKIN AND SUBCUTANEOUS TISSUES Radiation damage
UVR and ionising radiation (IR) damage cellular DNA via the tumour suppressor gene p53 , inhibiting cellular repair and apoptotic mechanisms. There is also evidence that e ff erent immune responses are impaired after skin exposure to UVR, facilitating neoplasia. Friedrich Theodor Schwann , 1810–1882, Professor of  Anatomy , successively at Louvain (1839–1848) and Liege, Belgium (1849–1880). Original research before the age of  27 laid the foundation of  the physiology of  nerve and muscle. The first to deal with problems related to living matter on a purely physical and chemical basis and to recognise the cell as the unit of  living matter. Discovered pepsin and the role of  living organisms in fermentation. Friedrich Von Recklinghausen , 1833–1910, German Professor of  Pathology , also described haemochromatosis. - - Ultraviolet radiation UVR is divisible into A, B and C according to wavelength. UVR, inducing oxidative damage, is the principal cause of skin cancer in all skin types as well as sunburn and skin ageing. UV A and UVB are the principal natural causes of  ultraviolet - (UV)-induced damage (UVC is absorbed by the atmosphere, but can be emitted by artificial sources). UV A has a longer wavelength than and less energy per photon than UVB, but - penetrates more deeply . The e ff ects of UVR are attenuated by melanin and there is an inverse relationship between melanin content and skin susceptibility to UV-induced neoplasia. Some protection is a ff orded by the stratum corneum, which reflects and refracts UVR, and by clothing, protective creams, cloud cover, particulate air pollution and buildings. - Ionising radiation The e ff ects of  IR are dose, wavelength and time dependent. - The skin, with its rapid cellular turnover, shows signs soon after exposure. High-frequency rays cause electron coupling at the molecular level, damaging proteins, polysaccharides and lipids. Infrared radiation Infrared radiation generates heat; cumulative exposure can cause thermal burns.
Figure 45.3
Neuro
/f_i
bromatosis (courtesy of St John’s Institute for
Dermatology, London, UK).
PATHOPHYSIOLOGY OF THE SKIN AND SUBCUTANEOUS TISSUES Radiation damage
UVR and ionising radiation (IR) damage cellular DNA via the tumour suppressor gene p53 , inhibiting cellular repair and apoptotic mechanisms. There is also evidence that e ff erent immune responses are impaired after skin exposure to UVR, facilitating neoplasia. Friedrich Theodor Schwann , 1810–1882, Professor of  Anatomy , successively at Louvain (1839–1848) and Liege, Belgium (1849–1880). Original research before the age of  27 laid the foundation of  the physiology of  nerve and muscle. The first to deal with problems related to living matter on a purely physical and chemical basis and to recognise the cell as the unit of  living matter. Discovered pepsin and the role of  living organisms in fermentation. Friedrich Von Recklinghausen , 1833–1910, German Professor of  Pathology , also described haemochromatosis. - - Ultraviolet radiation UVR is divisible into A, B and C according to wavelength. UVR, inducing oxidative damage, is the principal cause of skin cancer in all skin types as well as sunburn and skin ageing. UV A and UVB are the principal natural causes of  ultraviolet - (UV)-induced damage (UVC is absorbed by the atmosphere, but can be emitted by artificial sources). UV A has a longer wavelength than and less energy per photon than UVB, but - penetrates more deeply . The e ff ects of UVR are attenuated by melanin and there is an inverse relationship between melanin content and skin susceptibility to UV-induced neoplasia. Some protection is a ff orded by the stratum corneum, which reflects and refracts UVR, and by clothing, protective creams, cloud cover, particulate air pollution and buildings. - Ionising radiation The e ff ects of  IR are dose, wavelength and time dependent. - The skin, with its rapid cellular turnover, shows signs soon after exposure. High-frequency rays cause electron coupling at the molecular level, damaging proteins, polysaccharides and lipids. Infrared radiation Infrared radiation generates heat; cumulative exposure can cause thermal burns.
Figure 45.3
Neuro
/f_i
bromatosis (courtesy of St John’s Institute for
Dermatology, London, UK).

PATHOPHYSIOLOGY OF THE SKIN AND SUBCUTANEOUS TISSUES Radiation damage
PATHOPHYSIOLOGY OF THE SKIN AND SUBCUTANEOUS TISSUES Radiation damage
UVR and ionising radiation (IR) damage cellular DNA via the tumour suppressor gene p53 , inhibiting cellular repair and apoptotic mechanisms. There is also evidence that e ff erent immune responses are impaired after skin exposure to UVR, facilitating neoplasia. Friedrich Theodor Schwann , 1810–1882, Professor of  Anatomy , successively at Louvain (1839–1848) and Liege, Belgium (1849–1880). Original research before the age of  27 laid the foundation of  the physiology of  nerve and muscle. The first to deal with problems related to living matter on a purely physical and chemical basis and to recognise the cell as the unit of  living matter. Discovered pepsin and the role of  living organisms in fermentation. Friedrich Von Recklinghausen , 1833–1910, German Professor of  Pathology , also described haemochromatosis. - - Ultraviolet radiation UVR is divisible into A, B and C according to wavelength. UVR, inducing oxidative damage, is the principal cause of skin cancer in all skin types as well as sunburn and skin ageing. UV A and UVB are the principal natural causes of  ultraviolet - (UV)-induced damage (UVC is absorbed by the atmosphere, but can be emitted by artificial sources). UV A has a longer wavelength than and less energy per photon than UVB, but - penetrates more deeply . The e ff ects of UVR are attenuated by melanin and there is an inverse relationship between melanin content and skin susceptibility to UV-induced neoplasia. Some protection is a ff orded by the stratum corneum, which reflects and refracts UVR, and by clothing, protective creams, cloud cover, particulate air pollution and buildings. - Ionising radiation The e ff ects of  IR are dose, wavelength and time dependent. - The skin, with its rapid cellular turnover, shows signs soon after exposure. High-frequency rays cause electron coupling at the molecular level, damaging proteins, polysaccharides and lipids. Infrared radiation Infrared radiation generates heat; cumulative exposure can cause thermal burns.
Figure 45.3
Neuro
/f_i
bromatosis (courtesy of St John’s Institute for
Dermatology, London, UK).

Pilomatrixoma (calcifying epithelioma of Malherbe)
Pilomatrixoma (calcifying epithelioma of Malherbe)
These are benign hair matrix cell tumours that often calcify; 40% are found in the under-10 age group. Josef  Jadassohn , 1863–1936, dermatologist, Breslau, Germany (now Wroc ł aw , Poland). Desire M Bourneville , 1840–1909, physician, Le Bicêtre, Paris, France. Trichilemmoma (naevus sebaceous of Jadassohn) Trichilemmoma is a congenital hamartoma with the appear - ance of  a linear verrucous naevus; 10% lifetime risk of  forming a BCC ( Figure 45.24 ). Adenoma sebaceum (tuberous sclerosis, Bourneville disease) These are facial papules (angiofibromata) that are red-brown depending on skin colour and usually appear on the naso - labial folds, cheek and chin. They usually appear in children before 10 years of  age and increase in size and number until adolescence. Cosmetic removal by argon or pulsed-dye lasers Figure 45.25 ). or scalpel is indicated ( Rhinophyma Rhinophyma is the end-stage sequela of nasal acne rosacea ( Figure 45.26 ). It is nasal sebaceous gland hypertrophy and hyperplasia and tends to a ff ect elderly men (male-to-female ration 12:1). Occult BCCs exist in 3%. Treatment by derm - abrasion or laser resurfacing produces good results.
Figure 45.21
Blue naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.22
Naevus of Ota (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.23
Naevus of Ito (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.24
Naevus sebaceous of Jadassohn (courtesy of St John’s
Institute for Dermatology, London, UK).
Pilomatrixoma (calcifying epithelioma of Malherbe)
These are benign hair matrix cell tumours that often calcify; 40% are found in the under-10 age group. Josef  Jadassohn , 1863–1936, dermatologist, Breslau, Germany (now Wroc ł aw , Poland). Desire M Bourneville , 1840–1909, physician, Le Bicêtre, Paris, France. Trichilemmoma (naevus sebaceous of Jadassohn) Trichilemmoma is a congenital hamartoma with the appear - ance of  a linear verrucous naevus; 10% lifetime risk of  forming a BCC ( Figure 45.24 ). Adenoma sebaceum (tuberous sclerosis, Bourneville disease) These are facial papules (angiofibromata) that are red-brown depending on skin colour and usually appear on the naso - labial folds, cheek and chin. They usually appear in children before 10 years of  age and increase in size and number until adolescence. Cosmetic removal by argon or pulsed-dye lasers Figure 45.25 ). or scalpel is indicated ( Rhinophyma Rhinophyma is the end-stage sequela of nasal acne rosacea ( Figure 45.26 ). It is nasal sebaceous gland hypertrophy and hyperplasia and tends to a ff ect elderly men (male-to-female ration 12:1). Occult BCCs exist in 3%. Treatment by derm - abrasion or laser resurfacing produces good results.
Figure 45.21
Blue naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.22
Naevus of Ota (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.23
Naevus of Ito (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.24
Naevus sebaceous of Jadassohn (courtesy of St John’s
Institute for Dermatology, London, UK).
Pilomatrixoma (calcifying epithelioma of Malherbe)
These are benign hair matrix cell tumours that often calcify; 40% are found in the under-10 age group. Josef  Jadassohn , 1863–1936, dermatologist, Breslau, Germany (now Wroc ł aw , Poland). Desire M Bourneville , 1840–1909, physician, Le Bicêtre, Paris, France. Trichilemmoma (naevus sebaceous of Jadassohn) Trichilemmoma is a congenital hamartoma with the appear - ance of  a linear verrucous naevus; 10% lifetime risk of  forming a BCC ( Figure 45.24 ). Adenoma sebaceum (tuberous sclerosis, Bourneville disease) These are facial papules (angiofibromata) that are red-brown depending on skin colour and usually appear on the naso - labial folds, cheek and chin. They usually appear in children before 10 years of  age and increase in size and number until adolescence. Cosmetic removal by argon or pulsed-dye lasers Figure 45.25 ). or scalpel is indicated ( Rhinophyma Rhinophyma is the end-stage sequela of nasal acne rosacea ( Figure 45.26 ). It is nasal sebaceous gland hypertrophy and hyperplasia and tends to a ff ect elderly men (male-to-female ration 12:1). Occult BCCs exist in 3%. Treatment by derm - abrasion or laser resurfacing produces good results.
Figure 45.21
Blue naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.22
Naevus of Ota (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.23
Naevus of Ito (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.24
Naevus sebaceous of Jadassohn (courtesy of St John’s
Institute for Dermatology, London, UK).

Premalignant lesions Extramammary Paget’s disease (intraepidermal adenocarcinoma)
Premalignant lesions Extramammary Paget’s disease (intraepidermal adenocarcinoma)
This occurs in cutaneous sites that are rich in apocrine glands such as the axillae and the genital and perianal regions. Approximately 25% are associated with an underlying Sir James Paget , 1814–1899, surgeon, St Bartholomew’s Hospital, London, UK. or invasive adenocarcinoma. Early skin changes are subtle and may present as an eczematous lesion or intertrigo. Surgi - cal excision forms the basis of  treatment, with up to 20% demonstrating invasive disease after pathology assessment ( Figure 45.27 ).
Figure 45.27
Extramammary Paget’s disease involving the perineum
(courtesy of St John’s Institute for Dermatology, London, UK).

Premalignant lesions Extramammary Paget’s disease
Premalignant lesions Extramammary Paget’s disease (intraepidermal adenocarcinoma)
This occurs in cutaneous sites that are rich in apocrine glands such as the axillae and the genital and perianal regions. Approximately 25% are associated with an underlying Sir James Paget , 1814–1899, surgeon, St Bartholomew’s Hospital, London, UK. or invasive adenocarcinoma. Early skin changes are subtle and may present as an eczematous lesion or intertrigo. Surgi - cal excision forms the basis of  treatment, with up to 20% demonstrating invasive disease after pathology assessment ( Figure 45.27 ).
Figure 45.27
Extramammary Paget’s disease involving the perineum
(courtesy of St John’s Institute for Dermatology, London, UK).

Premalignant lesions Extramammary Paget’s disease
Premalignant lesions Extramammary Paget’s disease (intraepidermal adenocarcinoma)
This occurs in cutaneous sites that are rich in apocrine glands such as the axillae and the genital and perianal regions. Approximately 25% are associated with an underlying Sir James Paget , 1814–1899, surgeon, St Bartholomew’s Hospital, London, UK. or invasive adenocarcinoma. Early skin changes are subtle and may present as an eczematous lesion or intertrigo. Surgi - cal excision forms the basis of  treatment, with up to 20% demonstrating invasive disease after pathology assessment ( Figure 45.27 ).
Figure 45.27
Extramammary Paget’s disease involving the perineum
(courtesy of St John’s Institute for Dermatology, London, UK).

Purpura fulminans
Purpura fulminans
This is a relatively rare condition in which intravascular throm - bosis produces rapid skin necrosis and haemorrhagic infarc - tion, which progresses rapidly to septic shock and disseminated intravascular coagulation. Usually seen in children, it can occur in adults and may be subdivided into three types based on the aetiological mechanism: ‘acute infectious’, ‘neonatal’ and ‘idiopathic’ purpura fulminans. - Acute infectious is the commonest form. It is associated om multiorgan with a mortality rate of  40–50%, usually fr failure, and is secondary to either an acute bacterial ( Neisseria meningitidis ) or viral infection (varicella). It is most common in children under 7 years, following an upper respiratory tract infection or in asplenia. Endotoxins produce an imbalance in procoagulant and anticoagulant endothelial activity , produc ing protein C deficiency; this gives the clinical picture of  an initial petechial rash developing into confluent ecchymoses and haemorrhagic bullae, which necrose to form well-demarcated lesions that f orm hard eschars. Extensive tissue loss is common, which often culminates in limb amputation ( Figure 45.10
Figure 45.9
Necrotising fasciitis affecting the left orbit and facial skin
(courtesy of St John’s Institute for Dermatology, London, UK).
Purpura fulminans
This is a relatively rare condition in which intravascular throm - bosis produces rapid skin necrosis and haemorrhagic infarc - tion, which progresses rapidly to septic shock and disseminated intravascular coagulation. Usually seen in children, it can occur in adults and may be subdivided into three types based on the aetiological mechanism: ‘acute infectious’, ‘neonatal’ and ‘idiopathic’ purpura fulminans. - Acute infectious is the commonest form. It is associated om multiorgan with a mortality rate of  40–50%, usually fr failure, and is secondary to either an acute bacterial ( Neisseria meningitidis ) or viral infection (varicella). It is most common in children under 7 years, following an upper respiratory tract infection or in asplenia. Endotoxins produce an imbalance in procoagulant and anticoagulant endothelial activity , produc ing protein C deficiency; this gives the clinical picture of  an initial petechial rash developing into confluent ecchymoses and haemorrhagic bullae, which necrose to form well-demarcated lesions that f orm hard eschars. Extensive tissue loss is common, which often culminates in limb amputation ( Figure 45.10
Figure 45.9
Necrotising fasciitis affecting the left orbit and facial skin
(courtesy of St John’s Institute for Dermatology, London, UK).
Purpura fulminans
This is a relatively rare condition in which intravascular throm - bosis produces rapid skin necrosis and haemorrhagic infarc - tion, which progresses rapidly to septic shock and disseminated intravascular coagulation. Usually seen in children, it can occur in adults and may be subdivided into three types based on the aetiological mechanism: ‘acute infectious’, ‘neonatal’ and ‘idiopathic’ purpura fulminans. - Acute infectious is the commonest form. It is associated om multiorgan with a mortality rate of  40–50%, usually fr failure, and is secondary to either an acute bacterial ( Neisseria meningitidis ) or viral infection (varicella). It is most common in children under 7 years, following an upper respiratory tract infection or in asplenia. Endotoxins produce an imbalance in procoagulant and anticoagulant endothelial activity , produc ing protein C deficiency; this gives the clinical picture of  an initial petechial rash developing into confluent ecchymoses and haemorrhagic bullae, which necrose to form well-demarcated lesions that f orm hard eschars. Extensive tissue loss is common, which often culminates in limb amputation ( Figure 45.10
Figure 45.9
Necrotising fasciitis affecting the left orbit and facial skin
(courtesy of St John’s Institute for Dermatology, London, UK).

SKIN TUMOURS Benign lesions
SKIN TUMOURS Benign lesions
Basal cell papilloma (seborrhoeic keratosis, senile keratosis, verruca senilis) Their appearance varies from macular to soft, excrescent, warty lesions – often pigmented and hyperkeratotic – but may be flesh-coloured or pink. They are formed from the basal layer of  epidermal cells and contain melanocytes. Papillary wart (verruca vulgaris) This is a benign skin tumour arising from infection with the human papillomavirus (HPV), which is also responsible for plantar warts and condylomata acuminata. Freckle (ephelis) A freckle is an area of  skin that contains a normal number of  melanocytes, producing an abnormally large number of melanin granules. Lentigo These are small, circumscribed pigmented macules that stem from sun damage and some systemic syndromes. Solar lentigos are commoner in fairer skins. Moles/naevi Melanocytes migrate from the neural crest to the basal epider mis during embryogenesis. When melanocytes aggregate in the dermis or at the dermoepidermal junction, they are called naevus cells. Sophie Spitz , 1910–1956, American dermatopathologist at the Memorial Sloan Kettering Cancer Center, published the first case series of  ‘juvenile melanoma’ in 1948. Junctional naevus A junctional naevus is a dermoepidermal proliferation of naevus cells, visible as deeply pigmented macules or papules that occur commonly in childhood or adolescence, usually progressing to form compound or intradermal naevi with advancing age. Benign mucosal lesions tend to be junctional naevi ( Figure 45.13 ). Compound naevus This is a maculopapular, pigmented lesion that becomes most prominent during adolescence ( Figure 45.14 ). It represents a junctional proliferation of naevus cells, with nests and columns in the dermis. Intradermal naevus Intradermal naevi are faintly pigmented papules in adults that show no junctional proliferation; however, they do show a cluster of  dermal melanocytes ( Figure 45.15 ). Spitz naevus These are reddish brown (occasionally deeply pigmented) nodules, previously termed ‘juvenile melanoma’ ( Figure 45.16 ). They most commonly occur on the face and legs, growing rapidly initially then remaining static or regressing. The di ff er - ential diagnosis is melanoma and excision biopsy is warranted if  there is doubt as to the diagnosis. Spindle cell naevus Spindle cell naevi are dense black lesions that contain spindle cells and atypical melanocytes at the dermoepidermal junction. They are commonly seen on the thighs and a ff ect women more frequently . They may have malignant potential. Halo naevus The halo of  depigmentation around any benign naevus - represents an antibody response to melanocytes. Depigmen - tation may also be a feature of  a malignant melanoma. Halo naevi are associated with vitiligo ( Figure 45.17 ).
Figure 45.13
Junctional naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Café-au-lait spots These are co ff ee-coloured macules of  variable size (from a few millimetres to 10 /uni00A0 cm) ( Figure 45.18 ). Multiple lesions are associated with NF-1 and McCune–Albright syndromes. They are more common in dark-skinned people. Naevus spilus (speckled lentiginous naevus) These are similar in appearance to café-au-lait spots but with hyperpigmented speckles throughout ( Figure 45.19 ). They are benign lesions that are associated with various cutaneous diseases, but whose speckled appearance can be confused with malignant change. The mainstay of  management is observation and serial photography as malignant transformation is rare. Donovan James McCune , 1902–1976, American pediatrician. Fuller Albright , 1900–1969, physician, Massachusetts General Hospital, Boston, MA, USA. Masao Ota , 1885–1945, Japanese dermatologist. Minoru Ito , 1892–1986, Professor of  Dermatology , Tohoku University , Sendai, Honshu, Japan. Mongolian spot A Mongolian spot is a congenital blue-grey macule found on the sacral skin ( Figure 45.20 ). Pigmentation initially deepens and then regresses completely by age 7 years. Blue naevus This is a benign skin lesion that is four times more common in children, typically a ff ecting the extremities and face ( Figure 45.21 ). Naevi of Ota and Ito A naevus of  Ota is a dermal melanocytic hamartoma visible as a blue or grey macule in the trigeminal V1 and V2 dermatomes. It is four times more common in women and most frequently seen in Asian and African people ( Figure 45.22 ). A naevus of  Ito is characterised by dermal melanocytosis in the shoulder region and can occur simultaneously in patients with naevus of  Ota ( Figure 45.23 ).
Figure 45.14
Compound naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.15
Intradermal naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.16
Spitz naevus (courtesy of St John’s Institute for Derma
tology, London, UK).
Figure 45.17
Halo naevus (courtesy of St John’s Institute for Derma
tology, London, UK).
Albert Hippolyte Malherbe , 1845–1945, Professor of  Histology , Anatomy and Surgery , Nantes, France.
(b)
Figure 45.18
Café-au-lait spots. Note the two topographical variants:
in
(a)
the spot has a smooth ‘coast of California’ border, whereas the
upper spot in
(b)
has an irregular ‘coast of Maine’ border. Multiple
smooth-bordered lesions are commonly associated with syndromes
(courtesy of St John’s Institute for Dermatology, London, UK).
Figure 45.19
Naevus spilus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.20
Mongolian spot (courtesy of St John’s Institute for
Dermatology, London, UK).
SKIN TUMOURS Benign lesions
Basal cell papilloma (seborrhoeic keratosis, senile keratosis, verruca senilis) Their appearance varies from macular to soft, excrescent, warty lesions – often pigmented and hyperkeratotic – but may be flesh-coloured or pink. They are formed from the basal layer of  epidermal cells and contain melanocytes. Papillary wart (verruca vulgaris) This is a benign skin tumour arising from infection with the human papillomavirus (HPV), which is also responsible for plantar warts and condylomata acuminata. Freckle (ephelis) A freckle is an area of  skin that contains a normal number of  melanocytes, producing an abnormally large number of melanin granules. Lentigo These are small, circumscribed pigmented macules that stem from sun damage and some systemic syndromes. Solar lentigos are commoner in fairer skins. Moles/naevi Melanocytes migrate from the neural crest to the basal epider mis during embryogenesis. When melanocytes aggregate in the dermis or at the dermoepidermal junction, they are called naevus cells. Sophie Spitz , 1910–1956, American dermatopathologist at the Memorial Sloan Kettering Cancer Center, published the first case series of  ‘juvenile melanoma’ in 1948. Junctional naevus A junctional naevus is a dermoepidermal proliferation of naevus cells, visible as deeply pigmented macules or papules that occur commonly in childhood or adolescence, usually progressing to form compound or intradermal naevi with advancing age. Benign mucosal lesions tend to be junctional naevi ( Figure 45.13 ). Compound naevus This is a maculopapular, pigmented lesion that becomes most prominent during adolescence ( Figure 45.14 ). It represents a junctional proliferation of naevus cells, with nests and columns in the dermis. Intradermal naevus Intradermal naevi are faintly pigmented papules in adults that show no junctional proliferation; however, they do show a cluster of  dermal melanocytes ( Figure 45.15 ). Spitz naevus These are reddish brown (occasionally deeply pigmented) nodules, previously termed ‘juvenile melanoma’ ( Figure 45.16 ). They most commonly occur on the face and legs, growing rapidly initially then remaining static or regressing. The di ff er - ential diagnosis is melanoma and excision biopsy is warranted if  there is doubt as to the diagnosis. Spindle cell naevus Spindle cell naevi are dense black lesions that contain spindle cells and atypical melanocytes at the dermoepidermal junction. They are commonly seen on the thighs and a ff ect women more frequently . They may have malignant potential. Halo naevus The halo of  depigmentation around any benign naevus - represents an antibody response to melanocytes. Depigmen - tation may also be a feature of  a malignant melanoma. Halo naevi are associated with vitiligo ( Figure 45.17 ).
Figure 45.13
Junctional naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Café-au-lait spots These are co ff ee-coloured macules of  variable size (from a few millimetres to 10 /uni00A0 cm) ( Figure 45.18 ). Multiple lesions are associated with NF-1 and McCune–Albright syndromes. They are more common in dark-skinned people. Naevus spilus (speckled lentiginous naevus) These are similar in appearance to café-au-lait spots but with hyperpigmented speckles throughout ( Figure 45.19 ). They are benign lesions that are associated with various cutaneous diseases, but whose speckled appearance can be confused with malignant change. The mainstay of  management is observation and serial photography as malignant transformation is rare. Donovan James McCune , 1902–1976, American pediatrician. Fuller Albright , 1900–1969, physician, Massachusetts General Hospital, Boston, MA, USA. Masao Ota , 1885–1945, Japanese dermatologist. Minoru Ito , 1892–1986, Professor of  Dermatology , Tohoku University , Sendai, Honshu, Japan. Mongolian spot A Mongolian spot is a congenital blue-grey macule found on the sacral skin ( Figure 45.20 ). Pigmentation initially deepens and then regresses completely by age 7 years. Blue naevus This is a benign skin lesion that is four times more common in children, typically a ff ecting the extremities and face ( Figure 45.21 ). Naevi of Ota and Ito A naevus of  Ota is a dermal melanocytic hamartoma visible as a blue or grey macule in the trigeminal V1 and V2 dermatomes. It is four times more common in women and most frequently seen in Asian and African people ( Figure 45.22 ). A naevus of  Ito is characterised by dermal melanocytosis in the shoulder region and can occur simultaneously in patients with naevus of  Ota ( Figure 45.23 ).
Figure 45.14
Compound naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.15
Intradermal naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.16
Spitz naevus (courtesy of St John’s Institute for Derma
tology, London, UK).
Figure 45.17
Halo naevus (courtesy of St John’s Institute for Derma
tology, London, UK).
Albert Hippolyte Malherbe , 1845–1945, Professor of  Histology , Anatomy and Surgery , Nantes, France.
(b)
Figure 45.18
Café-au-lait spots. Note the two topographical variants:
in
(a)
the spot has a smooth ‘coast of California’ border, whereas the
upper spot in
(b)
has an irregular ‘coast of Maine’ border. Multiple
smooth-bordered lesions are commonly associated with syndromes
(courtesy of St John’s Institute for Dermatology, London, UK).
Figure 45.19
Naevus spilus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.20
Mongolian spot (courtesy of St John’s Institute for
Dermatology, London, UK).
SKIN TUMOURS Benign lesions
Basal cell papilloma (seborrhoeic keratosis, senile keratosis, verruca senilis) Their appearance varies from macular to soft, excrescent, warty lesions – often pigmented and hyperkeratotic – but may be flesh-coloured or pink. They are formed from the basal layer of  epidermal cells and contain melanocytes. Papillary wart (verruca vulgaris) This is a benign skin tumour arising from infection with the human papillomavirus (HPV), which is also responsible for plantar warts and condylomata acuminata. Freckle (ephelis) A freckle is an area of  skin that contains a normal number of  melanocytes, producing an abnormally large number of melanin granules. Lentigo These are small, circumscribed pigmented macules that stem from sun damage and some systemic syndromes. Solar lentigos are commoner in fairer skins. Moles/naevi Melanocytes migrate from the neural crest to the basal epider mis during embryogenesis. When melanocytes aggregate in the dermis or at the dermoepidermal junction, they are called naevus cells. Sophie Spitz , 1910–1956, American dermatopathologist at the Memorial Sloan Kettering Cancer Center, published the first case series of  ‘juvenile melanoma’ in 1948. Junctional naevus A junctional naevus is a dermoepidermal proliferation of naevus cells, visible as deeply pigmented macules or papules that occur commonly in childhood or adolescence, usually progressing to form compound or intradermal naevi with advancing age. Benign mucosal lesions tend to be junctional naevi ( Figure 45.13 ). Compound naevus This is a maculopapular, pigmented lesion that becomes most prominent during adolescence ( Figure 45.14 ). It represents a junctional proliferation of naevus cells, with nests and columns in the dermis. Intradermal naevus Intradermal naevi are faintly pigmented papules in adults that show no junctional proliferation; however, they do show a cluster of  dermal melanocytes ( Figure 45.15 ). Spitz naevus These are reddish brown (occasionally deeply pigmented) nodules, previously termed ‘juvenile melanoma’ ( Figure 45.16 ). They most commonly occur on the face and legs, growing rapidly initially then remaining static or regressing. The di ff er - ential diagnosis is melanoma and excision biopsy is warranted if  there is doubt as to the diagnosis. Spindle cell naevus Spindle cell naevi are dense black lesions that contain spindle cells and atypical melanocytes at the dermoepidermal junction. They are commonly seen on the thighs and a ff ect women more frequently . They may have malignant potential. Halo naevus The halo of  depigmentation around any benign naevus - represents an antibody response to melanocytes. Depigmen - tation may also be a feature of  a malignant melanoma. Halo naevi are associated with vitiligo ( Figure 45.17 ).
Figure 45.13
Junctional naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Café-au-lait spots These are co ff ee-coloured macules of  variable size (from a few millimetres to 10 /uni00A0 cm) ( Figure 45.18 ). Multiple lesions are associated with NF-1 and McCune–Albright syndromes. They are more common in dark-skinned people. Naevus spilus (speckled lentiginous naevus) These are similar in appearance to café-au-lait spots but with hyperpigmented speckles throughout ( Figure 45.19 ). They are benign lesions that are associated with various cutaneous diseases, but whose speckled appearance can be confused with malignant change. The mainstay of  management is observation and serial photography as malignant transformation is rare. Donovan James McCune , 1902–1976, American pediatrician. Fuller Albright , 1900–1969, physician, Massachusetts General Hospital, Boston, MA, USA. Masao Ota , 1885–1945, Japanese dermatologist. Minoru Ito , 1892–1986, Professor of  Dermatology , Tohoku University , Sendai, Honshu, Japan. Mongolian spot A Mongolian spot is a congenital blue-grey macule found on the sacral skin ( Figure 45.20 ). Pigmentation initially deepens and then regresses completely by age 7 years. Blue naevus This is a benign skin lesion that is four times more common in children, typically a ff ecting the extremities and face ( Figure 45.21 ). Naevi of Ota and Ito A naevus of  Ota is a dermal melanocytic hamartoma visible as a blue or grey macule in the trigeminal V1 and V2 dermatomes. It is four times more common in women and most frequently seen in Asian and African people ( Figure 45.22 ). A naevus of  Ito is characterised by dermal melanocytosis in the shoulder region and can occur simultaneously in patients with naevus of  Ota ( Figure 45.23 ).
Figure 45.14
Compound naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.15
Intradermal naevus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.16
Spitz naevus (courtesy of St John’s Institute for Derma
tology, London, UK).
Figure 45.17
Halo naevus (courtesy of St John’s Institute for Derma
tology, London, UK).
Albert Hippolyte Malherbe , 1845–1945, Professor of  Histology , Anatomy and Surgery , Nantes, France.
(b)
Figure 45.18
Café-au-lait spots. Note the two topographical variants:
in
(a)
the spot has a smooth ‘coast of California’ border, whereas the
upper spot in
(b)
has an irregular ‘coast of Maine’ border. Multiple
smooth-bordered lesions are commonly associated with syndromes
(courtesy of St John’s Institute for Dermatology, London, UK).
Figure 45.19
Naevus spilus (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.20
Mongolian spot (courtesy of St John’s Institute for
Dermatology, London, UK).

Skin adnexa
Skin adnexa
Adnexal structures such as hair follicles, sebaceous glands and sweat glands span both the epidermal and dermal layers and - contain some keratinocytes in their ducts. In injuries where epidermis is lost, re-epithelialisation occurs from these struc - tures as well as from the wound margins. Hair follicles are tubular invaginations of  the epidermis, from which grow hair shafts (dead keratinised tissue). Strips of smooth muscle (arrector pili) are inserted into the wall of  the hair follicle and elevate it in response to stress and cold. Sebaceous glands are hair follicle appendages situated between the follicle and arrector pili muscle such that muscle contraction compresses the gland and sebum is released (holo crine secretion) along the elevated hair. Simple eccrine and apocrine sw eat glands open into pores in hair follicles. Eccrine glands are distributed throughout the entire body surface, exce pt the lips. They secrete sweat in response to emotion or during thermoregulation. Apocrine glands are found in the axillae and groins and become active at puberty . Their secretion, characteristically malodorous after bacterial degradation, is in response to emotion and hormone secretion.
Hair
Sweat pore
Epidermis
Pilus
muscle
Sebaceous
gland
Dermis
Hair follicle
Subcutis
Figure 45.1
Three-dimensional diagram of the structural layers of the skin and its adnexal structures. (Reproduced from Simonsen T, Aarbakke
J, Kay I
et al. Illustrated pharmacology for nurses
. London: Hodder Arnold, 2006 with kind permission of the illustrator, Roy Lysaa.)
Skin adnexa
Adnexal structures such as hair follicles, sebaceous glands and sweat glands span both the epidermal and dermal layers and - contain some keratinocytes in their ducts. In injuries where epidermis is lost, re-epithelialisation occurs from these struc - tures as well as from the wound margins. Hair follicles are tubular invaginations of  the epidermis, from which grow hair shafts (dead keratinised tissue). Strips of smooth muscle (arrector pili) are inserted into the wall of  the hair follicle and elevate it in response to stress and cold. Sebaceous glands are hair follicle appendages situated between the follicle and arrector pili muscle such that muscle contraction compresses the gland and sebum is released (holo crine secretion) along the elevated hair. Simple eccrine and apocrine sw eat glands open into pores in hair follicles. Eccrine glands are distributed throughout the entire body surface, exce pt the lips. They secrete sweat in response to emotion or during thermoregulation. Apocrine glands are found in the axillae and groins and become active at puberty . Their secretion, characteristically malodorous after bacterial degradation, is in response to emotion and hormone secretion.
Hair
Sweat pore
Epidermis
Pilus
muscle
Sebaceous
gland
Dermis
Hair follicle
Subcutis
Figure 45.1
Three-dimensional diagram of the structural layers of the skin and its adnexal structures. (Reproduced from Simonsen T, Aarbakke
J, Kay I
et al. Illustrated pharmacology for nurses
. London: Hodder Arnold, 2006 with kind permission of the illustrator, Roy Lysaa.)
Skin adnexa
Adnexal structures such as hair follicles, sebaceous glands and sweat glands span both the epidermal and dermal layers and - contain some keratinocytes in their ducts. In injuries where epidermis is lost, re-epithelialisation occurs from these struc - tures as well as from the wound margins. Hair follicles are tubular invaginations of  the epidermis, from which grow hair shafts (dead keratinised tissue). Strips of smooth muscle (arrector pili) are inserted into the wall of  the hair follicle and elevate it in response to stress and cold. Sebaceous glands are hair follicle appendages situated between the follicle and arrector pili muscle such that muscle contraction compresses the gland and sebum is released (holo crine secretion) along the elevated hair. Simple eccrine and apocrine sw eat glands open into pores in hair follicles. Eccrine glands are distributed throughout the entire body surface, exce pt the lips. They secrete sweat in response to emotion or during thermoregulation. Apocrine glands are found in the axillae and groins and become active at puberty . Their secretion, characteristically malodorous after bacterial degradation, is in response to emotion and hormone secretion.
Hair
Sweat pore
Epidermis
Pilus
muscle
Sebaceous
gland
Dermis
Hair follicle
Subcutis
Figure 45.1
Three-dimensional diagram of the structural layers of the skin and its adnexal structures. (Reproduced from Simonsen T, Aarbakke
J, Kay I
et al. Illustrated pharmacology for nurses
. London: Hodder Arnold, 2006 with kind permission of the illustrator, Roy Lysaa.)

Skin and soft-tissue cysts
Skin and soft-tissue cysts
Milia Small, hard, keratin retention cysts ( Figure 45.11 ) seen both in babies and, after chronic sun exposure, in the elderly as part of  Favre–Racouchot syndrome (solar comedones, pseudocysts and leathery , furrowed sun-damaged skin – heightened by smoking). Epidermal cysts These cysts are lined with true stratified squamous epithelium, derived from hair follicle infundibuli or traumatic inclusion. Commonly known as sebaceous cysts, they can occur anywhere. They are fixed to the skin and usually have a central punctum ( Figure 45.12 ). Albert Ludwig Siegmund Neisser , 1855–1916, Director of  the Dermatological Institute, Breslau, Germany (now Wroc ł aw , Poland). Maurice Favre , 1876–1954, French dermatologist. Jean Racouchot , 1908–1994, French dermatologist. Heinrich Meibom (Meibomius) , 1638–1700, Professor of  Medicine, History and Poetry , Helmstadt, Germany , described these glands in 1666. - ). Treatment depends on the clinical state of  the cyst. When inflamed or infected, they should be incised and drained ini - tially; they should be removed later once the inflammation and induration has subsided. It is important to excise the cyst in its entirety as failure to do so usually results in recurrence. Meibomian cysts are epidermal cysts found on the free elid. Trichilemmal (pilar/pilosebaceous) cysts edge of  the ey are derived from the epidermis of  the external root sheath of ollicle; 90% are found in the scalp and 70% are mul - the hair f tiple. They are usually distinguished from epidermal cysts by pathologists, rather than clinically .
Figure 45.10
Acute infectious purpura fulminans caused by menin
gococcal septicaemia. Note the sharply demarcated necrotic areas
distal to the affected end or perforating arteries with surrounding nor
mal skin (courtesy of St John’s Institute for Dermatology, London, UK).
Figure 45.11
Milia (courtesy of St John’s Institute for Dermatology,
London, UK).
Figure 45.12
Multiple scrotal epidermal cysts (courtesy of St John’s
Institute for Dermatology, London, UK).
Skin and soft-tissue cysts
Milia Small, hard, keratin retention cysts ( Figure 45.11 ) seen both in babies and, after chronic sun exposure, in the elderly as part of  Favre–Racouchot syndrome (solar comedones, pseudocysts and leathery , furrowed sun-damaged skin – heightened by smoking). Epidermal cysts These cysts are lined with true stratified squamous epithelium, derived from hair follicle infundibuli or traumatic inclusion. Commonly known as sebaceous cysts, they can occur anywhere. They are fixed to the skin and usually have a central punctum ( Figure 45.12 ). Albert Ludwig Siegmund Neisser , 1855–1916, Director of  the Dermatological Institute, Breslau, Germany (now Wroc ł aw , Poland). Maurice Favre , 1876–1954, French dermatologist. Jean Racouchot , 1908–1994, French dermatologist. Heinrich Meibom (Meibomius) , 1638–1700, Professor of  Medicine, History and Poetry , Helmstadt, Germany , described these glands in 1666. - ). Treatment depends on the clinical state of  the cyst. When inflamed or infected, they should be incised and drained ini - tially; they should be removed later once the inflammation and induration has subsided. It is important to excise the cyst in its entirety as failure to do so usually results in recurrence. Meibomian cysts are epidermal cysts found on the free elid. Trichilemmal (pilar/pilosebaceous) cysts edge of  the ey are derived from the epidermis of  the external root sheath of ollicle; 90% are found in the scalp and 70% are mul - the hair f tiple. They are usually distinguished from epidermal cysts by pathologists, rather than clinically .
Figure 45.10
Acute infectious purpura fulminans caused by menin
gococcal septicaemia. Note the sharply demarcated necrotic areas
distal to the affected end or perforating arteries with surrounding nor
mal skin (courtesy of St John’s Institute for Dermatology, London, UK).
Figure 45.11
Milia (courtesy of St John’s Institute for Dermatology,
London, UK).
Figure 45.12
Multiple scrotal epidermal cysts (courtesy of St John’s
Institute for Dermatology, London, UK).
Skin and soft-tissue cysts
Milia Small, hard, keratin retention cysts ( Figure 45.11 ) seen both in babies and, after chronic sun exposure, in the elderly as part of  Favre–Racouchot syndrome (solar comedones, pseudocysts and leathery , furrowed sun-damaged skin – heightened by smoking). Epidermal cysts These cysts are lined with true stratified squamous epithelium, derived from hair follicle infundibuli or traumatic inclusion. Commonly known as sebaceous cysts, they can occur anywhere. They are fixed to the skin and usually have a central punctum ( Figure 45.12 ). Albert Ludwig Siegmund Neisser , 1855–1916, Director of  the Dermatological Institute, Breslau, Germany (now Wroc ł aw , Poland). Maurice Favre , 1876–1954, French dermatologist. Jean Racouchot , 1908–1994, French dermatologist. Heinrich Meibom (Meibomius) , 1638–1700, Professor of  Medicine, History and Poetry , Helmstadt, Germany , described these glands in 1666. - ). Treatment depends on the clinical state of  the cyst. When inflamed or infected, they should be incised and drained ini - tially; they should be removed later once the inflammation and induration has subsided. It is important to excise the cyst in its entirety as failure to do so usually results in recurrence. Meibomian cysts are epidermal cysts found on the free elid. Trichilemmal (pilar/pilosebaceous) cysts edge of  the ey are derived from the epidermis of  the external root sheath of ollicle; 90% are found in the scalp and 70% are mul - the hair f tiple. They are usually distinguished from epidermal cysts by pathologists, rather than clinically .
Figure 45.10
Acute infectious purpura fulminans caused by menin
gococcal septicaemia. Note the sharply demarcated necrotic areas
distal to the affected end or perforating arteries with surrounding nor
mal skin (courtesy of St John’s Institute for Dermatology, London, UK).
Figure 45.11
Milia (courtesy of St John’s Institute for Dermatology,
London, UK).
Figure 45.12
Multiple scrotal epidermal cysts (courtesy of St John’s
Institute for Dermatology, London, UK).

Skin dimensions
Skin dimensions
The skin is a large organ. In an adult it may have an area of 2 1–2 /uni00A0 m and weigh 15–20 /uni00A0 kg. Skin thickness varies with age, location and sun damage, but in any given region it is thinner in children than in adults. The dermis is between 15 and 40 times thicker than the epidermis, but starts to thin during the fourth decade. The epidermis is thickest on the palms, soles, back and buttocks and thinnest on eyelids (0.5–1 /uni00A0 mm on the sole of the foot; 0.05–0.09 /uni00A0 mm on the eyelid). Skin dimensions
The skin is a large organ. In an adult it may have an area of 2 1–2 /uni00A0 m and weigh 15–20 /uni00A0 kg. Skin thickness varies with age, location and sun damage, but in any given region it is thinner in children than in adults. The dermis is between 15 and 40 times thicker than the epidermis, but starts to thin during the fourth decade. The epidermis is thickest on the palms, soles, back and buttocks and thinnest on eyelids (0.5–1 /uni00A0 mm on the sole of the foot; 0.05–0.09 /uni00A0 mm on the eyelid). Skin dimensions
The skin is a large organ. In an adult it may have an area of 2 1–2 /uni00A0 m and weigh 15–20 /uni00A0 kg. Skin thickness varies with age, location and sun damage, but in any given region it is thinner in children than in adults. The dermis is between 15 and 40 times thicker than the epidermis, but starts to thin during the fourth decade. The epidermis is thickest on the palms, soles, back and buttocks and thinnest on eyelids (0.5–1 /uni00A0 mm on the sole of the foot; 0.05–0.09 /uni00A0 mm on the eyelid).

Sweat glands
Sweat glands
Cystadenoma (hydrocystadenomas, hidradenomas) These are 1- to 3-cm translucent blue cystic nodules.
Figure 45.25
Adenoma sebaceum (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.26
Rhinophyma (courtesy of St John’s Institute for
Dermatology, London, UK).
Sweat glands
Cystadenoma (hydrocystadenomas, hidradenomas) These are 1- to 3-cm translucent blue cystic nodules.
Figure 45.25
Adenoma sebaceum (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.26
Rhinophyma (courtesy of St John’s Institute for
Dermatology, London, UK).
Sweat glands
Cystadenoma (hydrocystadenomas, hidradenomas) These are 1- to 3-cm translucent blue cystic nodules.
Figure 45.25
Adenoma sebaceum (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.26
Rhinophyma (courtesy of St John’s Institute for
Dermatology, London, UK).

VASCULAR LESIONS Congenital  haemangiomata and vas
VASCULAR LESIONS Congenital: haemangiomata and vascular malformations
These can be subclassified biologically into vascular tumours or vascular malformations based on their endothelial charac - teristics, or radiologically into haemangiomata, vascular and lymphatic malformations based on their vascular dynamics. Haemangiomata These are benign endothelial tumours that a ff ect three girls for every boy . Thirty per cent have a herald patch at birth, which then grows rapidly in the first year of  life and slowly involutes over several years, with 70% having resolved by 7 /uni00A0 years of age. Large haemangiomata can trap platelets, leading to thrombocytopenia (Kasabach–Merritt syndrome). Vascular malformations Vascular malformations a ff ect boys and girls equally and are associated with numerous syndromes. They are invariably present at birth but may be missed if  deep to the skin. Vascular malformations subsequently grow in proportion to the child’s growth (rather than in response to sepsis or hormonal stimula tion). Stasis can lead to a localised, consumptive coagulopathy in large venous malformations. Low-flow malformations may cause skeletal hypoplasia, while high-flow malforma tions can cause hypertrophy .
Figure 45.41
Merkel cell tumour (courtesy of St John’s Institute for
Dermatology, London, UK).
VASCULAR LESIONS Congenital: haemangiomata and vascular malformations
These can be subclassified biologically into vascular tumours or vascular malformations based on their endothelial charac - teristics, or radiologically into haemangiomata, vascular and lymphatic malformations based on their vascular dynamics. Haemangiomata These are benign endothelial tumours that a ff ect three girls for every boy . Thirty per cent have a herald patch at birth, which then grows rapidly in the first year of  life and slowly involutes over several years, with 70% having resolved by 7 /uni00A0 years of age. Large haemangiomata can trap platelets, leading to thrombocytopenia (Kasabach–Merritt syndrome). Vascular malformations Vascular malformations a ff ect boys and girls equally and are associated with numerous syndromes. They are invariably present at birth but may be missed if  deep to the skin. Vascular malformations subsequently grow in proportion to the child’s growth (rather than in response to sepsis or hormonal stimula tion). Stasis can lead to a localised, consumptive coagulopathy in large venous malformations. Low-flow malformations may cause skeletal hypoplasia, while high-flow malforma tions can cause hypertrophy .
Figure 45.41
Merkel cell tumour (courtesy of St John’s Institute for
Dermatology, London, UK).

VASCULAR LESIONS Congenital  haemangiomata and vascular malformations
VASCULAR LESIONS Congenital: haemangiomata and vascular malformations
These can be subclassified biologically into vascular tumours or vascular malformations based on their endothelial charac - teristics, or radiologically into haemangiomata, vascular and lymphatic malformations based on their vascular dynamics. Haemangiomata These are benign endothelial tumours that a ff ect three girls for every boy . Thirty per cent have a herald patch at birth, which then grows rapidly in the first year of  life and slowly involutes over several years, with 70% having resolved by 7 /uni00A0 years of age. Large haemangiomata can trap platelets, leading to thrombocytopenia (Kasabach–Merritt syndrome). Vascular malformations Vascular malformations a ff ect boys and girls equally and are associated with numerous syndromes. They are invariably present at birth but may be missed if  deep to the skin. Vascular malformations subsequently grow in proportion to the child’s growth (rather than in response to sepsis or hormonal stimula tion). Stasis can lead to a localised, consumptive coagulopathy in large venous malformations. Low-flow malformations may cause skeletal hypoplasia, while high-flow malforma tions can cause hypertrophy .
Figure 45.41
Merkel cell tumour (courtesy of St John’s Institute for
Dermatology, London, UK).

WEBSITE ADDRESSES
WEBSITE ADDRESSES
American Joint Committee on Cancer for TNM classifications of tumours and up-to-date staging: https://cancerstaging.org/. Dermnet New Zealand – a reliable online educational resource run by a community of  dermatologists and other health specialists: https://www .dermnetnz.org/. International Dermoscopy Society – free to join, this society is run by dermatologists to promote clinical r esearch and education in dermoscopy: https://dermoscopy-ids.org/.
(d)
Epi
WEBSITE ADDRESSES
American Joint Committee on Cancer for TNM classifications of tumours and up-to-date staging: https://cancerstaging.org/. Dermnet New Zealand – a reliable online educational resource run by a community of  dermatologists and other health specialists: https://www .dermnetnz.org/. International Dermoscopy Society – free to join, this society is run by dermatologists to promote clinical r esearch and education in dermoscopy: https://dermoscopy-ids.org/.
(d)
Epi
WEBSITE ADDRESSES
American Joint Committee on Cancer for TNM classifications of tumours and up-to-date staging: https://cancerstaging.org/. Dermnet New Zealand – a reliable online educational resource run by a community of  dermatologists and other health specialists: https://www .dermnetnz.org/. International Dermoscopy Society – free to join, this society is run by dermatologists to promote clinical r esearch and education in dermoscopy: https://dermoscopy-ids.org/.
(d)
Epi

WOUNDS Congenital
WOUNDS Congenital
Cutis aplasia congenita This is a rare condition characterised by the congenital absence of  epidermis, dermis and, in some cases, subcutaneous tissues, with underlying bony defects in 20%. Treatment depends on the severity of  the presentation, but usually involves plastic surgery . Parry–Romberg disease (linear morphoea) A rare variant of  scleroderma a ff ecting up to 3:100 /uni00A0 000 children. It is linked to certain HLA subtypes and to a family history of  autoimmune disease. It is three times more common in females and often develops after an external physical trigger, such as friction or trauma. Moritz Kaposi , 1837–1902, Austrian dermatologist, described xeroderma pigmentosum in 1874. He also described a rare cutaneous sarcoma in Ashkenazi Jews, now more often an AIDS-defining condition. Caleb Hillier Parry , 1755–1822, physician, The General Hospital, Bath, UK. Moritz Heinrich Romberg , 1795–1873, neurologist, Director of  the University Hospital, Berlin, Germany . Parry–Romberg disease is a progressive, hemifacial atro - phy of skin, soft tissue and bone. The disease commonly starts in the late twenties but can present in childhood, when the resulting deformity is worse because it is magnified by di ff eren - tial growth elsew here. The condition is self-limiting, usually by 5–10 years after onset. Once stable, plastic surgery techniques can be employed alone or in combination to reconstruct an aesthetic contour. Coup de sabre is a variant that a ff ects the cranium and scalp and resembles a ‘blow from a sabre’. Spina bifida Failure of  closure of  the caudal neuropore during the fourth week in utero results in incomplete development of  some or all of  the structural elements posterior to the spinal cord. This can occur anywhere, but is commonest in lumbar vertebrae and presents as gross variants: spina bifida occulta, in which there is a bony defect without neural protrusion, and spina bifida cystica, in which there is herniation of  the meninges (meningocele), spinal cord (myelocele) or, most commonly ,
Figure 45.49
Angiosarcoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.50
Kaposi’s sarcoma (courtesy of St John’s Institute for
Dermatology, London, UK).
multidisciplinary approach and is directed towards protecting the spinal cord and preventing cerebrospinal fluid contamina tion, secondary hydrocephalus and meningitis. WOUNDS Congenital
Cutis aplasia congenita This is a rare condition characterised by the congenital absence of  epidermis, dermis and, in some cases, subcutaneous tissues, with underlying bony defects in 20%. Treatment depends on the severity of  the presentation, but usually involves plastic surgery . Parry–Romberg disease (linear morphoea) A rare variant of  scleroderma a ff ecting up to 3:100 /uni00A0 000 children. It is linked to certain HLA subtypes and to a family history of  autoimmune disease. It is three times more common in females and often develops after an external physical trigger, such as friction or trauma. Moritz Kaposi , 1837–1902, Austrian dermatologist, described xeroderma pigmentosum in 1874. He also described a rare cutaneous sarcoma in Ashkenazi Jews, now more often an AIDS-defining condition. Caleb Hillier Parry , 1755–1822, physician, The General Hospital, Bath, UK. Moritz Heinrich Romberg , 1795–1873, neurologist, Director of  the University Hospital, Berlin, Germany . Parry–Romberg disease is a progressive, hemifacial atro - phy of skin, soft tissue and bone. The disease commonly starts in the late twenties but can present in childhood, when the resulting deformity is worse because it is magnified by di ff eren - tial growth elsew here. The condition is self-limiting, usually by 5–10 years after onset. Once stable, plastic surgery techniques can be employed alone or in combination to reconstruct an aesthetic contour. Coup de sabre is a variant that a ff ects the cranium and scalp and resembles a ‘blow from a sabre’. Spina bifida Failure of  closure of  the caudal neuropore during the fourth week in utero results in incomplete development of  some or all of  the structural elements posterior to the spinal cord. This can occur anywhere, but is commonest in lumbar vertebrae and presents as gross variants: spina bifida occulta, in which there is a bony defect without neural protrusion, and spina bifida cystica, in which there is herniation of  the meninges (meningocele), spinal cord (myelocele) or, most commonly ,
Figure 45.49
Angiosarcoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.50
Kaposi’s sarcoma (courtesy of St John’s Institute for
Dermatology, London, UK).
multidisciplinary approach and is directed towards protecting the spinal cord and preventing cerebrospinal fluid contamina tion, secondary hydrocephalus and meningitis. WOUNDS Congenital
Cutis aplasia congenita This is a rare condition characterised by the congenital absence of  epidermis, dermis and, in some cases, subcutaneous tissues, with underlying bony defects in 20%. Treatment depends on the severity of  the presentation, but usually involves plastic surgery . Parry–Romberg disease (linear morphoea) A rare variant of  scleroderma a ff ecting up to 3:100 /uni00A0 000 children. It is linked to certain HLA subtypes and to a family history of  autoimmune disease. It is three times more common in females and often develops after an external physical trigger, such as friction or trauma. Moritz Kaposi , 1837–1902, Austrian dermatologist, described xeroderma pigmentosum in 1874. He also described a rare cutaneous sarcoma in Ashkenazi Jews, now more often an AIDS-defining condition. Caleb Hillier Parry , 1755–1822, physician, The General Hospital, Bath, UK. Moritz Heinrich Romberg , 1795–1873, neurologist, Director of  the University Hospital, Berlin, Germany . Parry–Romberg disease is a progressive, hemifacial atro - phy of skin, soft tissue and bone. The disease commonly starts in the late twenties but can present in childhood, when the resulting deformity is worse because it is magnified by di ff eren - tial growth elsew here. The condition is self-limiting, usually by 5–10 years after onset. Once stable, plastic surgery techniques can be employed alone or in combination to reconstruct an aesthetic contour. Coup de sabre is a variant that a ff ects the cranium and scalp and resembles a ‘blow from a sabre’. Spina bifida Failure of  closure of  the caudal neuropore during the fourth week in utero results in incomplete development of  some or all of  the structural elements posterior to the spinal cord. This can occur anywhere, but is commonest in lumbar vertebrae and presents as gross variants: spina bifida occulta, in which there is a bony defect without neural protrusion, and spina bifida cystica, in which there is herniation of  the meninges (meningocele), spinal cord (myelocele) or, most commonly ,
Figure 45.49
Angiosarcoma (courtesy of St John’s Institute for
Dermatology, London, UK).
Figure 45.50
Kaposi’s sarcoma (courtesy of St John’s Institute for
Dermatology, London, UK).
multidisciplinary approach and is directed towards protecting the spinal cord and preventing cerebrospinal fluid contamina tion, secondary hydrocephalus and meningitis.