| Abstract|| |
Pericardial mesotheliomas are rare tumors which often present with features of constrictive pericarditis. We present clinical, imaging, histological, and immunohistochemical findings of three cases presenting with chronic constrictive pericarditis. Two of these cases were initially treated as tuberculous pericarditis. Histologically, all the three cases were of an epithelioid type and showed positivity for more than one mesothelial markers. Two patients had a fatal outcome, and one was lost to follow-up.
Keywords: Chronic constrictive pericarditis, imaging, immunohistochemistry, mesothelioma, morphology, pericardium
|How to cite this article:|
Hui M, Harshavardhana K R, Uppin SG. Pericardial mesothelioma presenting as chronic constrictive pericarditis. A series of three cases from a single institution. Indian J Pathol Microbiol 2018;61:573-6
|How to cite this URL:|
Hui M, Harshavardhana K R, Uppin SG. Pericardial mesothelioma presenting as chronic constrictive pericarditis. A series of three cases from a single institution. Indian J Pathol Microbiol [serial online] 2018 [cited 2020 Jun 5];61:573-6. Available from: http://www.ijpmonline.org/text.asp?2018/61/4/573/243004
| Introduction|| |
Mesothelioma is an uncommon and highly lethal neoplasm arising from the cells lining the serosal membranes. The most frequent sites of involvement are pleura (65%–70%) followed by peritoneum (30%–35%). It is the third most common primary pericardial tumor following angiosarcoma and rhabdomyosarcoma. It has an insidious onset and often presents as chronic constrictive pericarditis, cardiac tamponade, and heart failure. Histopathology is the gold standard for diagnosis. Here, we report three cases of pericardial mesotheliomas presenting as chronic constrictive pericarditis.
| Case Report|| |
Of the three patients, the youngest was a 28-year-old male, and the remaining two were middle-aged females of 45 and 46 years, respectively. All of them had a similar clinical presentation with a cough and shortness of breath. One of the patients, in addition, had chest pain and the other had palpitation. The duration of illness ranged from 2 to 18 months. Two of them were initially diagnosed outside with pulmonary tuberculosis and were on treatment with antitubercular drugs. One of the patients at presentation to our hospital had subcutaneous nodule at the site of prior pericardial fluid drainage. In this patient, the cytological examination of drained pericardial fluid had revealed only lymphocytes without any evidence of malignant cells. Subsequently, the same underwent anterior mini-thoracotomy and pericardial biopsy at another hospital. The fluid drained this time was reported to contain malignant cells, and concurrent biopsy was reported as mesothelioma.
Two dimension echocardiography was suggestive of chronic constrictive pericarditis in all the three patients. There was no evidence of pulmonary embolism or blood clot. Contrast-enhanced computed tomography (CT) chest showed thickened pericardium on anterolateral aspect extending onto right atrium in one patient.[Figure 1] The remaining two showed hyperdense mass enhancing on contrast involving right anterolateral aspect of pericardium in one and left side of the pericardium encasing the major pulmonary trunk extending up to ascending aorta posteriorly and inferiorly surrounding left ventricle in the other. The former also had moderate pericardial effusion, bilateral pleural effusions with the collapse of the underlying lung.
|Figure 1: (a) Case 1: Contrast-enhanced computed tomography chest shows enhancing thickening (white arrow) of the pericardium and minimal right pleural effusion (white arrow head). (b) Case 2: Nonenhanced computed tomography chest shows hyperdense mass involving left side of the pericardium (white arrow head) with pericardial effusion (white arrow); (c) Case 2: Gadolinium-enhanced axial T1 weighted images show diffuse heterogeneous enhancement of pericardial mass. (d) Case 3: Contrast-enhanced computed tomography chest shows a well-defined enhancing mass along the anterolateral aspect of the pericardium. There are pericardial effusion and bilateral pleural effusions (white arrowhead) with the collapse of the underlying lung|
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Gross and microscopy
The specimens examined included pericardiectomy specimen in two patients, and CT-guided biopsy in one. The patient presenting with a subcutaneous nodule at the fluid drainage site had also excision biopsy of the same examined. Grossly, the pericardiectomy specimens revealed multiple gray-white to tan colored bits of thickened pericardium showing nodularity measuring 6 cm × 5 cm × 1.5 cm and 6 cm × 4 cm × 2 cm, respectively. These were firm in consistency. The surface was smooth without any granularity or papillary formations. CT-guided biopsy comprised linear cores of tissue measuring 1, 0.6, and 2 cm.
Microscopy was suggestive of epithelioid mesothelioma in all the three cases. Histology showed dense fibrous tissue with areas of hyalinization infiltrated by cords and sheets of polygonal cells. The cells had moderate dense eosinophilic cytoplasm and round-to-oval vesicular nuclei. Some of the nuclei had distinct nucleoli and intranuclear inclusions. In one of the cases, few cells had signet-ring morphology with cytoplasmic vacuole pushing the nuclei to the periphery. [Figure 2] The excised subcutaneous nodule in one of the patients showed metastatic deposits of mesothelioma. A combination of at least a minimum of two mesothelioma markers were done in each case to confirm the diagnosis. Negative expression of TTF1, napsin A, GCDFP-15, and estrogen receptor ruled out a possibility of metastatic carcinoma, especially from the lung and breast. The immunohistochemistry (IHC) results of all the three cases are provided in [Table 1].
|Figure 2: (a) Case 1: Histology section showing dense fibrous tissue infiltrated by cords and sheets of polygonal cells. Few cells with signet-ring morphology also seen (black arrow); (H and E, ×40), (b) Case 2: Biopsy of the nodule show infiltration by cords and nests of polygonal cells (H and E, ×100). On immunohistochemistry, cells are negative for (c) TTF-1, (d) GCDFP-15 and (e) estrogen receptor, but show positivity for (f) calretinin and (g) D2-40. (PolyHRP × 100), (h) Case 3: Histological section show linear cores of tissue comprised sheets of polygonal cells. These cells have a moderate amount of eosinophilic to clear cytoplasm (H and E, ×100)|
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|Table 1: Immunohistochemical study of all the cases of pericardial mesothelioma|
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Two patients succumbed to their illness of which one developed septic shock in the postoperative period. The third patient was lost to follow-up.
| Discussion|| |
Pericardial mesothelioma is a rare tumor accounting for <5% of all mesotheliomas. The incidence is <0.0022% in an autopsy series of 500,000 cases. Antemortem diagnosis can be made in only 10%–20% of cases. In a series of 120 cases published by Nambiar et al., 75% of the diagnosis were made postmortem, indicating the insidious nature of this highly malignant tumor. It can occur in a wide age range and is seen more commonly in the fifth to sixth decade of life. Although pleural and peritoneal mesotheliomas have been linked to exposure to asbestos, its association with pericardial mesotheliomas is not clear. A prior history of irradiation has also been noted. In the present series, none of the cases had any history of childhood or occupational exposure to asbestos or any irradiation.
The clinical features range from nonspecific symptoms including orthopnea, cough, and substernal chest pain to various cardiac manifestations such as constrictive pericarditis, cardiac tamponade, and heart failure. All the cases in our series presented with constrictive pericarditis and the first two cases were initially treated with tuberculosis. Hence, malignant mesotheliomas should be considered in the differential diagnosis in all cases of unexplained constrictive pericarditis. The diagnosis is often delayed as there are no pathognomic signs or symptoms. It can be either localized or can diffusely infiltrate the myocardium. Chest X-ray may reveal pericardial effusion and pericardiocentesis is done to relieve the symptoms. However, the diagnostic yield of pericardial fluid cytology is very low. In the present series, pericardial cytology was done in only in the second patient. In this patient, the pericardial fluid examination was done twice; both in outside hospitals. Initial fluid examination done at presentation was reported to have only lymphocytes and reactive mesothelial cells with no evidence of malignancy. Subsequent examination of the fluid drained at the time of mini-thoracotomy and pericardial biopsy was suggestive of malignant effusion. However, these cytology slides were not submitted for review at our institute. Nilsson and Rasmuson in their review on 17 cases have reported malignant cells in the pericardial fluid in 24% of cases. Definite diagnosis usually requires a multimodal approach that includes imaging studies and tissue sampling for histologic evaluation. The sensitivity of echocardiography and CT scan is low, especially in diffusely infiltrating tumors accounting for 12% and 44%, respectively. The localization and extent of the tumor to determine its resectability can be better delineated on magnetic resonance imaging. The histological features which suggest malignancy are infiltration of deep tissues, atypical cells, and necrosis. IHC also provides a diagnostic clue. The various morphological patterns described in literature include epithelioid, sarcomatoid, and biphasic subtype. Makarawate et al. have reported two cases of pericardial mesothelioma, one of which had epithelioid and the other biphasic morphology. The biphasic variant was reported by Karadzic et al. in a case of pericardial mesothelioma presenting as constrictive pericarditis. Histopathology was suggestive of epithelioid mesotheliomas in all the three cases in our series. None of the cases had any spindle cell component. Both Suman et al. and Kainuma et al. reported pericardial mesothelioma presenting as constrictive pericarditis and histopathology was suggestive of epithelioid subtype in both the cases., Karadzic et al. reported similar presentation of pericardial mesothelioma. However, on histopathology, it showed a biphasic morphology. Hence, neither all cases of pericardial mesotheliomas present with constrictive pericarditis nor do they have specific epithelioid morphology.
A robust panel of markers including two carcinoma markers and two mesothelioma markers are required for a definite diagnosis. The mesothelial markers used were WT1, calretinin, D2-40, and CK5/6 and the carcinoma markers were chosen depending on the differential diagnosis considered. Given epithelioid morphology, the main differential diagnosis in our study was metastatic carcinoma, especially from the lung and breast. In the first case, some of the cells showed signet-ring morphology with cytoplasmic vacuole pushing the nuclei to the periphery. However, these cells were negative for intracellular mucin. CD 34 was done in this case to rule out the possibility of epithelioid hemangioendothelioma which involve pericardium and the neoplastic endothelial cells with intracytoplasmic lumina may mimic signet-ring cells. IHC was diagnostic of epithelioid mesothelioma in this case. The second patient had an unusual presentation with subcutaneous tumor deposits at the site of prior drainage of fluid. The incidence of chest wall deposits via needle biopsy tracks, surgical scars, and drainage tubes after aspiration of large amount of effusions has been estimated to be 15%.
Radical surgery is the treatment of choice for localized disease. The diffusely infiltrative tumors present at a late-stage and are not amenable to surgery. Palliative treatment-like pericardiectomy prevents cardiac tamponade and provides symptomatic relief. The overall prognosis is poor. It responds poorly to radiotherapy with a low median survival. Studies have shown a variable outcome following use of chemotherapeutic agents like pemetrexed in combination with cisplatin.
| Conclusion|| |
Diagnosis is challenging as most of these patients present late in the course of the disease and imaging as well as the cytological diagnosis is often inconclusive. Hence, a high index of suspicion in cases of grossly thickened pericardium with pericardial effusion and recurrent pericarditis is warranted. The importance of histopathology and ancillary studies like IHC has been emphasized in this article in establishing the diagnosis of these rare tumors, especially in the setting of noncontributory imaging and cytological examination.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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Shantveer G Uppin
Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082, Telangana
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]