Surgical pathology of cystic lesions of the mediastinum.M Petkar, P Vaideeswar, JR Deshpande
Histopathology Division, Laboratory Department, Farwania Hospital, Kuwait., Kuwait
BACKGROUND: Mediastinal cysts are uncommonly encountered in a pathologist's experience. AIMS: To study the incidence, location, clinical presentation and histologic subtypes of cysts in the mediastinum. MATERIALS and METHODS: Cystic lesions of the mediastinum, surgically excised over a period of 22 years were studied after retrieval of relevant clinical data and slides. RESULTS: Thirty-nine mediastinal cysts were encountered in the study period. Most of the patients (81.5 %) were symptomatic. Histologically, foregut cysts (19 cases, 50 %) were the most common followed by teratomatous cysts (ten cases, 26.3 %) and thymic cysts (four cases, 10.5 %). Bronchogenic cysts represented 63 % of the fore-gut cysts. Unusual lesions in the form of cystic mediastinal tuberculous lymphadenitis and cystic schwannoma were seen in three patients. CONCLUSIONS: Despite varied location and histology, clinical presentation of mediastinal cysts are similar. Surgical intervention is the preferred line of management.
Keywords: Adult, Child, Child, Preschool, Female, Human, Male, Mediastinal Cyst, pathology,physiopathology,surgery,Middle Age,
Cystic lesions of the mediastinum are rare entities. Considering the numerous structures located within the mediastinum, the cysts are anatomically and histologically diverse. The present study examines the spectrum of mediastinal cysts with emphasis on their clinical and pathological features.
Cystic lesions of the mediastinum, diagnosed radiologically and/or per-operatively and subsequently surgically excised over a period of 22 years (1979-2000) were studied. Solid tumours with cystic foci were excluded from the study. The relevant clinical data and slides were reviewed. The lesions were then classified with respect to their anatomical location and histopathology.
During a span of 22 years, 39 mediastinal cysts were encountered. Histologically, foregut cysts were the most common mediastinal cysts (50 %), followed by benign cystic teratomas (26.3 %) and thymic cysts (10.5 %). On the basis of anatomic location [Table:1], foregut cysts were mostly located in the middle and posterior mediastinum whereas teratomatous and thymic cysts had an almost exclusive anterior mediastinal location.
Among the 19 foregut cysts, 12 were bronchogenic, two gastric, one oesophageal and four undifferentiated cysts. Bronchogenic cysts were seen in seven males and five females; nearly all cases were seen between the third and fourth decades of life. All were diagnosed with help of chest roentgenograms. Computed tomography helped in confirming and clearly defining the lesions in five . The patients presented with varied symptomatology consisting of chest pain, fever, cough, dyspnoea or haemoptysis of varying duration. The cysts ranged in size from as small as 1.5 cm to as large as 10x 7 x 5 cm. Only one cyst was located in the superior mediastinum where a radiological diagnosis of thymic or dermoid cyst was made. The cysts were spherical, unilocular with a glistening smooth capsule, containing mucoid material. Histologically, the cysts were lined by pseudo-stratified, ciliated columnar epithelium with mucous glands and smooth muscle layer. In addition, nodules of hyaline cartilage [Figure - 1] were seen in seven. Foci of calcification were seen in three cases. One cyst also showed foci of pseudo-epitheliomatous hyperplasia of the metaplastic squamous epithelium [Figure - 2] with extensive haemorrhage and fibrosis.
Of the two gastric cysts studied, one was discovered incidentally on chest radiography and computed tomography in a two-year old male child with left axillary lymphadenitis. The second case, an 11-years-old female, had repeated episodes of pyrexia of unknown origin. Both cysts were located in the posterior mediastinum and showed thick wall, partly rugose and partly smooth inner lining and little mucoid material. They were lined by typical gastric epithelium [Figure - 3] with double layered smooth muscle and neural plexus replete with ganglion cells [Figure - 4]. The second case also showed foci of ulceration, reflected by a haemorrhagic area on gross inspection.
An oesophageal cyst was present in a 22-year-old female, who had recurrent fever, cough and chest pain. Per-operatively, it was seen as a large cyst (10 cm) in the middle mediastinum compressing the right bronchus. The lining was ulcerated squamous epithelium with distinct circular and longitudinal smooth muscle layer.
Undifferentiated cysts shared in common the location and clinical features as the bronchogenic cysts, except in one case, which was situated in the anterior mediastinum. They were unilocular and revealed marked destruction of the lining and replacement by granulation tissue with proliferating capillaries, fibroblasts, histiocytes and lymphocytes. Large areas of haemorrhage, smooth muscle bundles and bony plates were seen in one. Identifiable cuboidal lining [Figure - 5] was seen in two cases alone.
There were 10 cases of cystic teratomas. Majority of the patients presented in the third decade of life with dyspnoea, chest pain and fever. There were four males and six females. One cyst was discovered incidentally in a 24-year-old male who had a left supraclavicular swelling. This eventually turned out to be a “dermoid cyst” in direct communication with an anterior mediastinal cystic tumour. Except for a 54-year-old female who had middle mediastinal cyst, all teratomatous cysts were located in the anterior mediastinum. All had the usual characteristics of teratoma with an admixture of derivatives of the three germinal layers. Two also showed an involuted thymic tissue in the wall.
There were three unilocular and one multilocular thymic cyst, affecting two males and females each. The unilocular types were seen in adults; two of them presented with cough and chest pain. The third patient was asymptomatic. They had thick or thin walls with brown fluid or blood. The lining was cuboidal in two. The third cyst, devoid of any epithelium, showed fibrosis, chronic inflammation and cholesterol clefts. Multilocular cyst was seen in a 7-year-old male child with congenital rubella syndrome and congenital isolated pulmonary stenosis. The lining was cuboidal or stratified squamous [Figure - 6] with fibrosis, lymphocytes, foreign body giant cells and cholesterol clefts in the wall. All had thymic tissue at the periphery. None were positive for human immunodeficiency virus (HIV).
Pericardial cyst was seen as an ovoid, calcified structure adherent to the left, posterior atrioventricular groove in a 20-year-old male, operated for aortic regurgitation. It had flattened lining. Partly encapsulated, nodular, spongy mass, lymphangioma were excised in two middle-aged females with dull aching chest pain for over two years. It revealed multiple, proteinaceous fluid- filled spaces lined by endothelial cells. Focal aggregates of lymphocytes were present.
A surprising and unusual histology was seen in two cysts where a presumptive diagnosis of thymic and dermoid cysts was made. However, the thick grey-white wall revealed multiple caseating tuberculous granulomas with few identifiable lymphoid follicles [Figure - 7]. These were cystic tuberculous lymph nodes. A 30-year-old male with chest pain and cough had a small well-encapsulated posterior mediastinal cyst. It contained amber-coloured hazy fluid with a white glistening wall. The latter on microscopy showed the classic Antoni A and Antoni B areas of schwannoma.
Although mediastinal cysts are being discovered with increasing frequency, in any pathologist’s experience, they are relatively uncommon. The rarity of mediastinal cysts can be gauged from the fact that there were only 39 cases in this present study, spanning 22 years. Reports in literature also present a similar picture, where they have been found to represent 18-25 % of mediastinal masses affecting individuals of all ages.,
Mediastinal cysts can be classified on the basis of their anatomical location and histomorphology. Thus, the cysts may be found either in the superior, anterior, middle or posterior mediastinum. Histologically, they may be classified into foregut cysts, cystic teratomas, thymic cysts and a large miscellaneous group. Foregut cysts are further categorised on the basis of their anomalous embryonic origin into bronchogenic, oesophageal, gastric and undifferentiated cysts. Despite this wide repertoire of location and morphology, the symptomatology is nearly identical. Chest pain is a common symptom and is thought to be result of irritation or inflammation of the parietal or mediastinal pleura. Other symptoms like cough, dyspnoea and dysphagia are all considered manifestations of compression or irritation of major airways and oesophagus by the cysts.,,, Severity would depend on the size of the lesion. Thirty-two of our patients were symptomatic and presented with the above complaints. Six in addition had fever. This occurs due to infection and can sometimes lead to fistulisation with the airways. In contrast to other cysts, gastric cysts are frequently associated with dreaded complications like persistent sinuses in the chest wall, osteomyelitis of adjacent bones, acute oesophagitis and pulmonary suppuration or haemorrhage, attributed to peptic digestion. None of our patients had these complications. Cough, that is productive of hair or sebum is virtually pathognomonic of a teratoma.
Foregut cysts were the most common cysts encountered in this study, constituting 50% of cases. This is well within the reported range of 20-50%.,  Bronchogenic cysts are mostly found in the middle or posterior mediastinum at the level of tracheal bifurcation, as seen in most of our cases. Their incidence varies from 40-67%;,, we had an incidence of 63%. These cysts are known to occur in all age groups, but are frequently detected in adults., In the present series, all were adults with no significant sex preponderance. Ochsner strongly advocated that only those cysts lined by ciliated epithelium with either cartilage or glands or both in the wall were qualified to be labelled as bronchogenic. Cartilage was identified in only seven of our cases. Similar findings were seen in other studies., Hence cysts can be designated as bronchogenic on the basis of pseudo-stratified columnar epithelium, smooth muscle bundles and mucous glands as seen in all our cases.
Since they are similar in location to bronchogenic cysts, most authors group oesophageal cysts under an umbrella of broncho-oesophageal cysts.,, However, Sirivella et al are of the opinion that the presence of distinct double layer of smooth muscle within the cyst that does not contain cartilage suggests an oesophageal origin. We had only one such case in a young male.
Gastric cyst is often associated with vertebral anomalies. It has also been documented that patients with gastric cysts are usually symptomatic at an early age since the highly differentiated gastric epithelial lining produces secretion of low pH. We had two gastric cysts. Both were young but their modes of presentation were dissimilar from those described in various reviews. Moreover, radiological investigations did not reveal any vertebral anomaly. Incidence is varied, from as low as 2.1% to as high as 20 %.,, Microscopically both revealed ulcerated gastric mucosa, double layered muscular wall and myenteric plexus.
It has been observed that around 20% of the fore-gut cysts lack specific histologic features to permit classification possibly because of prior haemorrhage or infection,, and are termed undifferentiated or nonspecific cysts. These formed 21% of our cases. Patchy cuboidal lining was seen in only two of them.
Benign cystic teratomas of the mediastinum are rare lesions, accounting for approximately 8% of all tumours of this region. Patients are usually young adults and about 36-62% of patients are found to be asymptomatic.,, While ten patients in this series had a mean age of 30.1 years, the size varied from 5-30 cm. Such large cysts invariably lead to symptoms. Thus it came as no surprise that almost all patients in the series were symptomatic. Grossly, the tumours had a large cystic centre and 50% of the lesions contained a ball of hair; ectodermal derivatives predominated. Interestingly involuted thymic remnants were identified in the wall of two cases, which gives credence that these tumours are derived from thymic anlage.
Thymic cysts are classified as unilocular or multilocular. Unilocular cysts are considered to be congenital, originating from the remnants of thymopharyngeal duct and hence may be located more often in the neck. All thymic cysts in the study were anterior mediastinal in location. One of the three patients with unilocular cysts was asymptomatic. All showed thin walled tense cysts filed with brown fluid. This feature is in accordance with the observations of Graeber et al who stated that these cysts are generally asymptomatic and symptoms develop due to enlargement of the cysts secondary to fluid accumulation.
Suster et al postulated that the aetiology of multilocular thymic cyst to be a reaction to inflammation. This view is reinforced by reports of such cysts in HIV disease. Reports of multiple small cysts, Dubois’ abscesses, found in infants with congenital syphilis probably belong to this category. Thus they show pericystic fibrosis, are filled with turbid or haemorrhagic fluid and along with variable epithelial lining, have fibrosis, inflammation, haemorrhage and cholesterol clefts in their walls., All these features were seen in our case with congenital rubella syndrome. The HIV testing was negative in all the patients.
Among mediastinal cysts, pericardial cysts are also common lesions with frequencies ranging from 18-20%.,,, They are usually asymptomatic discovered on routine radiological examination in the fourth to fifth decades of life, where they appear as well marginated, small or large, spherical or tear drop-shaped cysts that characteristically abuts the heart, chest wall and diaphragm. They are unilocular with clear fluid and flat mesothelial cells set on loose fibrous wall. We had only one case, forming 2.63 % of all cysts.
Fewer than 1% of all lymphangiomas are confined to the mediastinum. They are not apparent until later in life on account of the soft yielding nature. There were two adult females who were symptomatic for over two years with chest pain . Grossly, they had a spongy appearance with typical microscopy.
Surgical intervention is the preferred line of management of all mediastinal cysts, regardless of size and clinical presentation, so as to prevent development of various complications. Potentially the most serious but rare complication is malignant transformation which can occur in bronchogenic cysts,, multilocular thymic cysts and mature cystic teratoma. Besides, excision aids in arriving at a definite histologic diagnosis. This is best exemplified by three unusual, unexpected and surprising mediastinal cystic lesions which comprised two cystic mediastinal tuberculous lymphadenitis and cystic schwannoma. In our country, tuberculosis is rampant. Hence though uncommon, tuberculosis can be considered in the differential diagnosis of mediastinal cysts. Neurogenic tumours are common in the posterior mediastinum; therefore a cystic lesion in that location should suggest a cystic schwannoma.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7]