18.19.4 Mediastinal tumours and cysts 4368 Y.C. Ga

18.19.4 Mediastinal tumours and cysts 4368 Y.C. Gary Lee and Helen E. Davies

section 18  Respiratory disorders 4368 Future developments Current treatments for malignant pleural effusion are crude. Compounds such as iodine and silver nitrate have been used in some countries, as alternatives to talc, and have shown effectiveness with acceptable side effect profiles. The development of novel pleurodesis agents that induce fibrosis without pleural inflammation, for example, tumour growth factor-​β (TGFβ), may allow effective pleurodesis without the adverse events associated with talc use. IPC and pleurodesis are approaches with completely different pros and cons; trials are underway to combine both strategies. Instilling talc via IPC inserted has shown benefits in a randomized trial. Placement of IPC in the same setting of thoracoscopic talc poudrage has shown promise. Sclerosant-​ eluded IPC produced effective pleurodesis in animal studies. Direct inhibition of pleural fluid accumulation (via manipulation of vascular permeability mediators) may become possible, and will be preferable over interventional procedures of secondary preven- tion of fluid recurrence. Studies to date have mostly considered malignant effusions as a single disease entity. Work is underway to better phenotype pa- tients with malignant effusions to identify subgroups of patients who will benefit symptomatically from fluid drainage, and to tailor available therapies to patients with different underlying cancers, staging, effusion biology (e.g. rate of recurrence) and comorbidity. Patient-​reported outcome measures are increasingly adopted as key measures of treatment outcome instead of radiological determin- ation of fluid accumulation. Acknowledgements Prof Lee is a National Health & Medical Research Council (NHMRC) Career Development Fellow and receives research project grant funding from the NHMRC, New South Wales Dust Disease Board, Sir Charles Gairdner Research Advisory Committee, Westcare, and the Cancer Council of Western Australia. FURTHER READING Azzopardi M, et al. (2014). Current controversies in the management of malignant pleural effusions. Semin Respir Crit Care Med, 35, 723–​31. Bhatnagar R, et al. (2018). Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion. N Engl J Med, 378, 1313–22. Bott M, et al. (2011). The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet, 43, 668–​72. Boutin C, et  al. (1993). Thoracoscopy in pleural malignant meso- thelioma: a prospective study of 188 consecutive patients. Part 2: prognosis and staging. Cancer, 72, 394–​404. Brims FJ, Lee YC, Creaney J (2013). The continual search for ideal biomarkers for mesothelioma: the hurdles. J Thorac Dis, 5, 364–​6. Clive AO, et al. (2014). Predicting survival in malignant pleural ef- fusion: development and validation of the LENT prognostic score. Thorax, 69, 1098–​104. Davies HE, et al. (2012). Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA, 307, 2383–​9. Davies HE, Musk AW, Lee YC (2008). Prophylactic radiotherapy for pleural puncture sites in mesothelioma: the controversy continues. Curr Opin Pulm Med, 14, 326–​30. Dresler CM, et al. (2005). Phase III intergroup study of talc poudrage vs. talc slurry sclerosis for malignant pleural effusion. Chest, 127, 909–​15. Fysh ET, et al. (2012). Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion. Chest, 142, 394–​400. Fysh ET, et al. (2013). Clinical outcomes of indwelling pleural catheter-​ related pleural infections: an international multicenter study. Chest, 144, 1597–​602. Fysh ET, et al. (2015). Predictors of clinical use of pleurodesis and/​or indwelling pleural catheter therapy for malignant pleural effusion. Chest, 147, 1629–​34. Peto J, et al. (1999). The European mesothelioma epidemic. Br J Cancer, 79, 666–​72. Putnam JBJ, et  al. (2000). Outpatient management of malignant pleural effusion by a chronic indwelling pleural catheter. Ann Thorac Surg, 69, 369–​75. Rintoul RC, et  al. (2014). Efficacy and cost of video-​assisted thoracoscopic partial pleurectomy versus talc pleurodesis in pa- tients with malignant pleural mesothelioma (MesoVATS): an open-​ label, randomised, controlled trial. Lancet, 384, 1118–​27. Robinson BWS, et al. (2003). Mesothelin-​family proteins and diag- nosis of mesothelioma. Lancet, 362, 1612–​16. Robinson LA (2006). Solitary fibrous tumor of the pleura. Cancer Control, 13, 264–​9. Sugarbaker DJ, et al. (1999). Resection margins, extrapleural nodal status, and cell type determine postoperative long-​term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients. J Thorac Cardiovasc Surg, 117, 54–​65. Tapias LF, et al. (2015). Validation of a scoring system to predict recurrence of resected solitary fibrous tumors of the pleura. Chest, 147, 216–​23. Thomas R, et al. (2015). Physiology of breathlessness associated with pleural effusions. Curr Opin Pulm Med, 21, 338–​45. Treasure T, et al. (2011). Extra-​pleural pneumonectomy versus no extra-​ pleural pneumonectomy for patients with malignant pleural meso- thelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol, 12, 763–​72. Vogelzang NJ, et al. (2003). Phase III study of pemetrexed in combin- ation with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol, 21, 2636–​44. Zalcman G, et al. (2016). Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet, 387, 1405–14. 18.19.4  Mediastinal tumours and cysts Y.C. Gary Lee and Helen E. Davies ESSENTIALS Mediastinal masses are most conveniently categorized by their anatomical site in the anterior, middle, or posterior mediastinum.

18.19.4  Mediastinal tumours and cysts 4369 Most present as a radiographic abnormality alone, or in association with symptoms arising from compression of other mediastinal struc- tures. Systemic symptoms such as fever or weight loss are more likely with malignant tumours such as lymphomas or thymomas. Anterior mediastinal masses—​commonly caused by thymic tu- mours (including thymic lymphoma), germ cell tumours, and thy- roid masses. Thymomas are often benign, but they can be locally invasive and associated with para-​neoplastic phenomena such as myasthenia gravis (in 30%). Middle mediastinal masses—​most commonly caused by lymph node enlargement (e.g. secondary to carcinoma, lymphoma, sar- coidosis, tuberculosis, or histoplasmosis), bronchogenic carcinomas and cysts arising from mediastinal structures such as the pericar- dium, bronchi, or oesophagus. Giant follicular lymph node hyper- plasia (Castleman’s disease or angiofollicular lymphoid hyperplasia) is a rare condition; patients may present with symptoms secondary to compression of local structures or with constitutional features; frank malignant transformation may arise. Posterior mediastinal masses—​neurogenic tumours account for most; if benign they tend to be asymptomatic, while pressure effects are frequently seen with malignant tumours. Introduction and anatomy The mediastinum encompasses all the intrathoracic structures with the exclusion of the lungs and pleura. It encompasses the heart, great vessels, trachea, oesophagus, thymus, nerves, thoracic duct, and lymph nodes. The superior boundary is the thoracic inlet represented by a plane at the level of the first rib. The inferior boundary is the diaphragm. The mediastinum has traditionally been subdivided into several compartments: a superior and inferior compartment, with the latter being subdivided into anterior, middle, and posterior divisions. In fact there are no true anatomical boundaries and structures in the superior mediastinum are contiguous with those inferiorly, hence a more logical subdivision is simply into anterior, middle, and pos- terior compartments (Figs 18.19.4.1 and 18.19.4.2). Such a division helps to compartmentalize what is complex anatomy and give some guide to the most likely pathology occurring in any particular area. Detailed knowledge of normal mediastinal anatomy is a prerequisite to the interpretation of both normal and abnormal chest radiographs. It is not within the remit of this chapter to describe the anatomy in de- tail, but major structures can be identified on CT imaging. • Anterior mediastinum: This is bounded anteriorly by the sternum and posteriorly by the pericardium, aorta, and brachiocephalic vessels. It contains the remnant of the thymus gland, branches of the internal mammary artery, veins, and associated lymph nodes. • Middle mediastinum: This contains the heart and pericardium, as- cending aorta, and aortic arch, lower half of the superior vena cava with azygos vein tributary, inferior vena cava, brachiocephalic vessels, pulmonary arteries and veins, bifurcation of the trachea and major bronchi, bronchial lymph nodes, phrenic nerves, and the vagus nerve. • Posterior mediastinum: The area located behind the pericardium and in front of the vertebral bodies. It is bordered laterally by the mediastinal pleura. It contains structures in the paravertebral Fig. 18.19.4.1  Posteroanterior chest radiograph with diagrammatic overlay to illustrate normal mediastinal structures: (1) trachea, (2) right main bronchus, (3) left main bronchus, (4) left main pulmonary artery, (5) right upper lobe pulmonary vein, (6) right interlobular artery, (7) right lower and middle lobe vein, (8) aortic knuckle, (9) superior vena cava, (10) azygos vein. Anterior Middle (b) Posterior (a) Posterior Middle Anterosuperior Fig. 18.19.4.2  A schematic representation of the mediastinal compartments: (a) lateral projection showing division into
anterior (or anterosuperior), middle and posterior compartments; (b) cross-​sectional depiction.

section 18  Respiratory disorders 4370 gutter as well as the descending thoracic aorta, oesophagus, azygos, and hemiazygos veins, thoracic duct, lymph nodes, and autonomic nerves. Lymph nodes are present in all three compartments thereby knowledge of their anatomical relationships, together with sites of drainage, is important when interpreting radiographic medias- tinal enlargement. The most important group of visceral nodes lie in the middle mediastinum and are predominantly subcarinal and paratracheal. Bronchopulmonary and hilar nodes are numerous but not visible radiographically unless pathologically enlarged. Clinical investigation Radiological assessment Most mediastinal cysts and tumours are discovered incidentally following a chest radiograph. Occasionally there may be symp- toms such as cough, chest pain, or breathlessness, or features re- sultant from compression of the numerous surrounding mediastinal structures. CT imaging is the most appropriate subsequent investigation for any patient with a suspected mediastinal mass and frequently facili- tates accurate diagnosis. It allows localization, characterization, and definition of the relationship of the mass to adjacent structures. The presence of calcification, fluid attenuation, heterogeneity, and vascu- larity can also be ascertained. Radio-​labelled 18fluorodeoxyglucose-​positron emission tomog- raphy (18FDG-​PET) combined with CT scanning (PET-​CT) is in- creasingly used in the evaluation of mediastinal masses. It is a useful tool for predicting loco-​regional involvement of lung or thyroid ma- lignancies, and for detection of distant disease. False positives may result from inflammatory processes such as granulomatous disease. MRI is more sensitive in the assessment of spinal tumours and de- tection of neural or vascular invasion than CT and may be favoured in some patients due to the lower adherent radiation dose. Tissue sampling Fine needle aspiration sampling is of limited use in assessment of mediastinal abnormalities and histological confirmation is favoured. Anterior mediastinal lesions can be readily approached percutan- eously, and while aspiration of clear fluid will supplement the radio- logical suspicion of a cyst, cytological examination alone may be insufficient for a pathological diagnosis. Anterior mediastinotomy will allow open biopsy of such lesions. Endobronchial ultrasound-​guided transbronchial needle as- piration (EBUS-​TBNA) is increasingly used in the assessment of middle mediastinal lymph nodes. This technique has superseded conventional ‘blind’ transbronchial needle aspiration, affording image guided aspiration of subcarinal, pretracheal, paratracheal, and hilar nodes. Endoscopic ultrasound-​guided fine needle aspiration (EUS-​FNA) may be used to sample aorto-​pulmonary window (AP or subaortic), subcarinal, para-​oesophageal, and pulmonary ligament nodes. Mediastinoscopy is performed through an incision in the neck and allows inspection of structures surrounding the superior vena cava and trachea as far as the carina. It is particularly useful in obtaining lymph node biopsies prior to possible surgery for lung cancer, especially in areas inaccessible to EBUS-​TBNA. Bronchoscopy alone is of limited value when evaluating medias- tinal masses unless there is a suspicion of a concomitant bronchial neoplasm. Neural tumours arising in the posterior mediastinum usually require surgical resection and there is little to be gained by preceding this with fine needle aspiration. Clinical features It is not surprising that the diversity of anatomical structures in the mediastinum is reflected by an equally diverse range of neo- plastic, developmental, and inflammatory masses (Table 18.19.4.1). Table 18.19.4.1  Mediastinal masses Anterior compartment Thymus Thymoma Carcinoma Hyperplasia Cyst Lymphoma Ectopia Germ cell tumours Benign Malignant Thyroid Lipoma, lipomatosisa Middle compartment Lymphadenopathya Sarcoidosis Infection including tuberculosis Malignancy: metastatic, lymphoma Giant follicular lymph node hyperplasia (Castleman’s disease) Mediastinal cysts Pericardial cysts Bronchogenic cysts Posterior compartment Oesophageal Enteric cysts Oesophageal duplication Neurenteric cysts Leiomyoma Carcinoma Vascular abnormalitiesa Aneurysm Haemangioma Anomalous vessels Neural tumours Neurilemmoma or schwannoma Neurofibroma Malignant schwannoma Ganglioneuroma, ganglioneuroblastoma Neuroblastoma Phaeochromocytoma Ependymoma Bochdalek diaphragmatic hernia a May be present in more than one compartment.

18.19.4  Mediastinal tumours and cysts 4371 Although clinical symptoms and signs may give diagnostic clues, many mediastinal masses, particularly those that are benign, are asymptomatic and usually detected on routine chest radiography. Many studies have documented the relative frequency of different causes of primary mediastinal tumours and cysts, with neurogenic tumours and thymic tumours being the commonest (approximately 20% each), followed by lymphoma, reduplication cysts, germ cell tu- mours, and thyroid masses. Mediastinal masses in children are more likely to be malignant than in adults. Common symptoms are cough and chest pain, which arise as a consequence of distortion of the normal mediastinal anatomy. Non-​ specific constitutional symptoms such as fever or weight loss are more likely to occur with a malignant tumour (e.g. lymphoma or thymoma). Compression of vital structures can also result in specific symp- toms: tracheal or bronchial compression leads to breathlessness with stridor or wheeze; oesophageal narrowing results in dysphagia; su- perior vena caval compression produces the characteristic features of facial and periorbital oedema, chemosis, and distended veins; involvement of the recurrent laryngeal nerve results in hoarseness and a bovine cough (this usually results from a malignant tumour but can develop with a benign lesion such as aneurysm of the aortic arch); involvement of the sympathetic chain (also likely to be due to malignant infiltration) results in the characteristic features of Horner’s syndrome with enophthalmos, miosis, ptosis, and unilat- eral facial anhidrosis; compression of intercostal nerves may pro- duce neuralgia; and intraspinal extension of tumours may lead to long tract signs. Anterior mediastinal masses Thymus The normal thymus is located in the superior portion of the anterior mediastinum. Its main function is the production of T lymphocytes. Radiologically, the normal thymus can only be seen in childhood and regression occurs during adolescence. Enlargement of the thymus is the commonest single cause of an anterior mediastinal mass and may be due to the development of a thymoma, thymic carcinoma, thymic hyperplasia, or a thymic cyst. The thymus can also be the site of involvement by lymphoma, particularly Hodgkin’s disease. Thymomas These arise due to neoplastic epithelial proliferation of the thymus gland and can present at any age, peak incidence being in middle age (Fig. 18.19.4.3). They are often benign with no overt cellular atypia, but can rarely behave in a malignant fashion with invasion of adja- cent structures and the occurrence of distant metastases (invasive thymoma). Histologically, thymomas are classified into subtypes A, AB, B1, B2, and B3 according to the morphological appearance of the neo- plastic epithelial cells and relative epithelial cell: lymphocyte propor- tions. This classification correlates closely with the Masaoka staging system, modified by Koga et al., and predicts tumour behaviour: I: Completely encapsulated IIA: Microscopic transcapsular invasion IIB: Transcapsular infiltration into thymus or, mediastinal soft tissue; not breaching pleura or pericardium III: Macroscopic invasion of neighbouring organ IVA: Pleural or pericardial dissemination IVB: Distant metastases; lymphatic or haematogenous spread Localized symptoms of chest pain and cough are more common with malignant disease. Systemic symptoms may arise; myasthenia gravis affects approximately 30% of patients; other rare associations include red-​cell aplasia, hypogammaglobulinaemia, systemic lupus erythematosus, and polymyositis. Surgical resection is curative in most cases. Minimally invasive operative approaches without sternotomy are favoured whenever possible. Local invasion is less common, but often precludes com- plete removal and recurrence is the rule. In these patients, therapy is palliative, and consists of a combination of surgical debulking, radiotherapy, and chemotherapy. Long-​term follow up is advocated in all cases as delayed recurrence may occur. Thymic carcinoma Thymic carcinoma (or type C thymoma) is an aggressive malignancy of thymic epithelial cells exhibiting cellular atypia no longer specific to the thymus. There is a male preponderance. Patients commonly pre- sent with loco-​regional metastases (e.g. lymph node and pulmonary). Treatment is with surgical resection and adjuvant chemotherapy, but the overall prognosis is poor (5 year survival approximately 30%). Thymic hyperplasia Thymic enlargement may be ‘true’ or ‘follicular’. The former typ- ically arises in childhood, peaking in adolescence; retention of normal histological and architectural features is seen. Follicular thymic hyperplasia is characterized by the presence of lymphoid fol- licles in the thymus regardless of its size. It occurs in approximately two-​thirds of patients with myasthenia gravis. It is also known as lymphoid hyperplasia or autoimmune thymitis. Thymic cysts These are uncommon. They can be unilocular or multilocular and usually contain straw-​coloured fluid. Most patients are asymptom- atic, but since cystic change can occur in some thymomas and in Hodgkin’s disease, thorough cytological examination of the cyst’s contents and its wall is required to exclude malignant disease. Thymic lymphoma This is fairly common, particularly in patients with nodular scler- osing type Hodgkin’s disease. The presence of systemic symptoms and other mediastinal and/​or hilar nodes should alert the clinician to the possibility of lymphoma. Ectopic thymus Ectopic and accessory thymic tissue may occur anywhere along the path of embryonic thymic development as a result of failure of des- cent, sequestration, or involution. It is rare in adults, but may be in- cidentally detected in childhood. Histological examination reveals normal thymic tissue. Germ cell tumours Extragonadal germ cell tumours account for about 15% of all me- diastinal cysts and tumours, and approximately 5–​10% of all germ cell tumours are found in the mediastinum. Their exact aetiology is unknown, but they are thought to derive from abnormal migration

section 18  Respiratory disorders 4372 of primitive germinal cells or developing thymic cells exhibiting germ cell potential. Germ cell tumours may be malignant or benign (80%), the former being more common in childhood. Malignant tumours are more prevalent in men (approximately 9:1), typically in their third to fifth decades; benign tumours exhibit an equal sex differential. Elevation of serum tumour markers such as alpha-​fetoprotein (α-​FP) or β-​human chorionic gonadotrophin (β-​HCG) is present in most cases. Benign germ cell tumours These consist of a disorganized mixture of ectodermal, mesodermal, and endodermal tissues and may include skin, hair, cartilage, bone, epithelium, teeth, and neural tissue. Tumours include mature (be- nign) teratomas, teratodermoids, epidermoid cysts, and dermoid cysts. Mature teratomas account for up to 70% of mediastinal germ cell tumours, and CT appearances give a strong indication of this diagnosis. Surgical excision is the treatment of choice to minimize risk of expansion and exclude malignant change. Malignant germ cell tumours These are classically divided into seminomas and nonseminomatous germ cell tumours. Most nonseminomatous tumours are malig- nant teratomas; teratocarcinomas, choriocarcinomas, embryonal carcinomas, and yolk-​sac carcinomas are less common. Histological analysis often reveals a spectrum of malignant tissue; and mixed germ cell tumours are now recognized. Nonseminomatous germ cell tumours range from well differen- tiated to trophoblastic; in most patients elevated serum levels of β-​ human chorionic gonadotrophin (β-​hCG) and α-​fetoprotein (AFP) are seen, which can be used both diagnostically and to monitor treatment response. Seminomas tend to be nonsecretory. Both types of tumour are highly malignant and invade adjacent mediastinal structures. They are not curable by surgery, although this may be needed for diagnostic purpose and utilized as part of a multimodality treatment approach, particularly for non-​ seminomatous tumours, following adjuvant chemotherapy. Both types are responsive to cisplatin based chemotherapy; response rates are high, although cure rates are lower than for gonadal germ cell tumours. Radiotherapy may be used in the treatment of seminomas. Thyroid masses Retrosternal extension of an enlarged thyroid is one the commoner causes of a mass in the superior mediastinum. Women are more frequently affected. Most are benign multinodular goitres that arise in the neck and extend into the mediastinum through the thoracic inlet. They may contain cystic areas, sometimes with haemorrhage and areas of calcification. Radiographically, they have a sharply de- fined and often lobulated outline. While they rarely cause symp- toms, compression of the trachea at the thoracic inlet can result in respiratory distress and is an indication for surgical resection. Thyroid cancer may also involve the mediastinum, either by direct extension or by metastasizing to intrathoracic nodes. Lipoma, lipomatosis Lipomata are well-​circumscribed mesenchymal tumours originating from adipose tissue. Localized lipomata may arise throughout the mediastinum (more common anteriorly), or diffuse accumulations of unencapsulated adipose tissue (lipomatosis) be seen. Detection is frequently incidental, although symptoms may develop from their mass effect. The diagnosis is made radiologically, with homogeneous fat attenuation masses described. Middle mediastinal masses Lymphadenopathy Enlarged lymph nodes are not confined to the middle mediastinum, although this is the commonest site of intrathoracic lymphadenop- athy. Reactive changes occur in association with many pulmonary infections, but in most cases the nodes are not significantly enlarged and remain undetected on plain chest radiography. Gross lymph- adenopathy is a feature of carcinoma and lymphoma, with sarcoid- osis, tuberculosis, and histoplasmosis being other possibilities. Treatment depends on the underlying cause. Giant follicular lymph node hyperplasia (Castleman’s disease) This is a rare condition of unknown aetiology characterized by nonclonal lymph node hyperplasia. It may be classified by site: localized to a single lymph node (unicentric) or involving multiple nodes (multicentric); or histologically into the more common hya- line vascular type with lymphoid follicles and penetrating capil- laries, or a plasma cell type with sheets of mature plasma cells within interfollicular tissues surrounding germinal centres. Multicentric dis- ease may be associated with human herpes virus-​8 (HHV-​8) positivity. Fig. 18.19.4.3  An incidentally detected anterior mediastinal mass on the chest radiograph (panel (a)) of an asymptomatic 45-​year-​old woman. Computed tomography (b) axial and (c) coronal views were highly suggestive of a thymic tumour and surgical resection confirmed a type B1 thymoma.

18.19.4  Mediastinal tumours and cysts 4373 Unicentric Castleman’s disease is often detected incidentally, but patients with multicentric disease frequently develop systemic symp- toms with fever, anaemia, and weight loss. Hepatosplenomegaly may be evident, and an association with POEMS syndrome is rec- ognized (POEMS is an acronym for features of the syndrome: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin abnormalities). There are no diagnostic radiographic features (Fig. 18.19.4.4) and the diagnosis is usually made after surgical resection or biopsy. Single site Castleman’s disease is generally benign and surgical resection is curative. In patients with multicentric disease, progres- sive hyperplasia with generalized lymphadenopathy may develop as a consequence of malignant transformation. There is no standard treatment: corticosteroids, chemotherapy, and immunomodulation (e.g. anti-​IL-​6 monoclonal antibodies) may be considered. Antiviral agents may be given if HHV-​8 is detected. Mediastinal cysts Cysts within the mediastinum are a relatively common cause of a me- diastinal mass. They can arise in association with the pericardium, bronchi, gut, or thoracic duct. Most patients are asymptomatic. Pericardial cysts These develop embryologically in relationship to the pericar- dium, although direct communication with the pericardial sac is rare. Radiographically they appear as smooth, clearly demarcated densities, which can be mistaken for a pericardial fat pad or a hernia through the foramen of Morgagni. Aspiration reveals clear fluid. Surgical excision is not recommended. Bronchogenic cysts Bronchogenic cysts arise in association with the major airways and are thought to reflect ventral budding of the primitive foregut. They are lined by respiratory epithelium and may contain inspis- sated mucus. Symptoms are uncommon, but local pressure on the trachea or bronchi can result in cough or wheeze. Occasionally the cysts communicate with the trachea and trigger repeated infec- tions. Surgical excision is the treatment of choice, particularly if there are associated symptoms (Fig. 18.19.4.5). Fig. 18.19.4.4  Chest radiograph (a) and CT scan (b) showing a large middle mediastinal mass (arrows) which on histology showed features of Castleman’s disease. Fig. 18.19.4.5  Chest radiograph (a) and CT scan (b) showing a large mass in the mediastinum (arrows) due to a bronchogenic cyst that had been present for 20 years. It was removed when compression of the oesophagus resulted in dysphagia.

section 18  Respiratory disorders 4374 Posterior mediastinal masses Enteric cysts Enteric cysts (oesophageal duplication and neurenteric cysts) are rare. Oesophageal duplication cysts adhere to the oesophagus and arise from abnormal development of the dorsal foregut. They are typically lined by gastric or oesophageal mucosa, and may also be evident in the middle mediastinum. Neurenteric cysts arise from developmental areas where the dorsal foregut and notochord are in close proximity. They are classically lined by enteric and neural tissue and are commonly associated with vertebral anomalies. Both types may coexist with other gastro- intestinal malformations. Surgical resection is recommended and the prognosis good. Oesophageal tumours are commonly symptomatic prior to vis- ible radiographic change (Fig. 18.19.4.6). Vascular abnormalities Vascular anomalies are not limited to the posterior mediastinum (Fig. 18.19.4.7). However, aneurysms of the descending thoracic aorta can result in abnormal shadows in the posterior mediastinum. Contrast enhanced imaging will differentiate from other posterior mediastinal lesions. Neural tumours Tumours, particularly those found in the paravertebral gut- ters, are likely to be neural in origin. Benign tumours tend to be asymptomatic, while malignant tumours cause pressure effects. Occasionally, spinal cord compression results from direct exten- sion into the intravertebral foramen. Tumours arising from peripheral nerve cell sheaths include neurilemmoma (schwannoma) and neurofibroma, and also their malignant counterparts. Tumours of the autonomic chain include ganglioneuroma and neuroblastoma. A neurilemmoma is the commonest neural tumour arising in the mediastinum. These are most common in middle age, and most are asymptomatic. Neurilemmomas can extend into the intravertebral foramen, producing a dumb-​bell appearance, and may erode adjacent bone, hence CT scanning or MRI should be undertaken prior to surgical excision. Neurofibromata are also common. These may be solitary, with clinical and radiological features very similar to those of a neurilemmoma, or more generalized in neurofibromatosis. Surgical resection is recommended, partly because of the small risk of developing malignant neurosarcoma which carries a poor prognosis. Ganglioneuroma arise from the autonomic plexus and are usu- ally perispinal in position. Associated endocrine symptoms in- clude hypertension, flushing, sweating, and diarrhoea. These tumours are often very large before they become clinically ap- parent. Prognosis is good after surgical resection. Ganglioneuroblastoma and neuroblastoma represent the malignant end of the spectrum and predominantly arise in childhood. Neuroblastoma in particular are highly invasive, with metastatic spread and systemic symptoms common at the time of presentation. Surgical resection is preferred, with adjuvant chemotherapy and radiotherapy considered on an individual basis. Ependymomas rarely occur in the mediastinum and are thought to derive from paravertebral ependymal rests. They have a predilection for the posterior mediastinum. Bochdalek posterior diaphragmatic hernia Developmental diaphragmatic defects may result in congenital her- niation of gastrointestinal contents through the posterior part of Fig. 18.19.4.6  Following presentation with worsening dysphagia; a benign oesophageal leiomyoma was confirmed histologically following endoscopic biopsy.

18.19.4  Mediastinal tumours and cysts 4375 the diaphragm. These often present clinically in infancy, although may be incidentally detected in approximately 6% of adults. FURTHER READING Adkins RB, Maples MD, Ainsworth J (1994). Primary malignant me- diastinal tumours. Ann Thorac Surg, 38, 648–​59. Bower RJ, Kiesewetter WB (1977). Mediastinal masses in infants and children. Arch Surg, 112, 1003–​9. Duwe BV, et  al. (2005). Tumors of the mediastinum. Chest, 128, 2893–​909. Hejna M, Haberl I, Raderer M (1999). Non surgical management of malignant thymoma. Cancer, 85, 1871–​84. Jeung M-​Y, et al. (2002). Imaging cystic masses of the mediastinum. RadioGraphics, 22, S79–​S93. Kim D-​J, et al. (2005). Prognostic and clinical relevance of the World Health Organization scheme for the classification of thymic epithe- lial tumors. Chest, 127, 755–​61. Koga K, et al. (1994). A review of 79 thymomas: modification of sta- ging system and reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int, 44, 359–67. Medford AR, et  al. (2010). Endobronchial ultrasound-​guided transbronchial needle aspiration (EBUS-​TBNA):  applications in chest disease. Respirology, 15, 71–​9. Moran CA, et al. (2012). Thymomas II: a clinicopathologic cor- relation of 250 cases with a proposed staging system with emphasis on pathologic assessment. Am J Clin Pathol, 137, 451–​61. Morrissey B, et al. (1993). Percutaneous needle biopsy of the medi- astinum: review of 94 procedures. Thorax, 48, 632–​7. Shields TW, Reynolds M (1988). Neurogenic tumours of the thorax. Surg Clin North Am, 68, 645–​68. Thomas CR Jnr, Wright CD, Loehrer PJ Snr (1999). Thymoma: state of the art. J Clin Oncol, 17, 2280–​9. Weissferdt A, et al. (2018). Thymoma: a clinicopathological correl- ation of 1470 cases. Hum Pathol, 73, 7–15. Fig. 18.19.4.7  Aneurysmal dilatation of the superior vena cava (a and b) resulting in incidentally detected radiographic abnormality (arrows).

SECTION 19 Rheumatological disorders Section editor: Richard A. Watts 19.1 Joints and connective tissue—​structure and function   4379 Thomas Pap, Adelheid Korb-​Pap, Christine Hartmann,
and Jessica Bertrand 19.2 Clinical presentation and diagnosis of rheumatological disorders   4386 Christopher Deighton and Fiona Pearce 19.3 Clinical investigation   4395 Michael Doherty and Peter C. Lanyon 19.4 Back pain and regional disorders   4406 Carlo Ammendolia and Danielle Southerst 19.5 Rheumatoid arthritis   4415 Kenneth F. Baker and John D. Isaacs 19.6 Spondyloarthritis and related conditions   4441 Jürgen Braun and Joachim Sieper 19.7 Infection and arthritis   4457 Graham Raftery and Muddassir Shaikh 19.8 Reactive arthritis   4464 Carmel B. Stober and Hill Gaston 19.9 Osteoarthritis   4470 Andrew J. Barr and Philip G. Conaghan 19.10 Crystal-​related arthropathies   4482 Edward Roddy and Michael Doherty 19.11 Autoimmune rheumatic disorders and vasculitides   4495 19.11.1 Introduction   4495 David A. Isenberg and Ian Giles 19.11.2 Systemic lupus erythematosus and
related disorders   4499 Anisur Rahman and David A. Isenberg 19.11.3 Systemic sclerosis (scleroderma)   4513 Christopher P. Denton and Carol M. Black 19.11.4 Sjögren’s syndrome   4532 Wan-​Fai Ng 19.11.5 Inflammatory myopathies   4537 Ingrid E. Lundberg, Hector Chinoy, and Robert Cooper 19.11.6 Large vessel vasculitis   4546 Raashid Luqmani and Cristina Ponte 19.11.7 ANCA-​associated vasculitis   4556 David Jayne 19.11.8 Polyarteritis nossdosa   4569 Loïc Guillevin 19.11.9 Small vessel vasculitis   4573 Richard A. Watts 19.11.10 Behçet’s syndrome   4579 Sebahattin Yurdakul, Izzet Fresko, and Hasan Yazici 19.11.11 Polymyalgia rheumatica   4584 Bhaskar Dasgupta and Eric L. Matteson 19.11.12 Kawasaki disease   4590 Brian W. McCrindle 19.12 Miscellaneous conditions presenting to
the rheumatologist   4598 Stuart Carter, Lisa Dunkley, and Ade Adebajo