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Diagnosis

Diagnosis

Malignant mesothelioma, biphasic type. 

Discussion

Malignant mesothelioma (MM) presents in middle-aged patients (avg. 50 years old) and is often attributed to a prior history of asbestos exposure; however, many times a clear etiology cannot be established. Patients with MM usually present with chest pain, cough, dyspnea, weight loss, and fatigue. Imaging reveals pleural effusions, thickening of the pleura, and/or pleural plaques. Patients with MM can be treated surgically, via extrapleural pneumonectomy or radical pleurectomy, and with chemotherapy. Since most patients present with advanced disease, which is unresectable, they receive chemotherapy with platinum-based combination agents. These tumors have a very poor overall survival and most patients die within 2 years of diagnosis.

MM arises in the mesothelial cells lining the pleural, peritoneal, and pericardial cavities, but most often arises in the pleural cavities. On histology, malignant mesothelioma has three patterns: epithelioid, sarcomatoid, or biphasic. The majority of these tumors present with a mixture of these three types; however, epithelioid often predominates. This epithelioid pattern contains round, monotonous cells, with minimal to no mitotic activity.Variants include clear cell, deciduoid, adenomatoid, glandular, mucohyaline, and lymphohistiocytic. MM, sarcomatoid type, is characterized by fascicles of spindle cells, which may be arranged in a herringbone or storiform pattern. This variant often includes more severe features such as necrosis, cellular atypia, and increased mitotic activity. Biphasic tumors incorporate features of epithelioid and sarcomatoid patterns. MM with sarcomatoid and biphasic patterns have a worse overall prognosis than tumors with an epithelioid pattern. The invasion of pleural adipocytes, the sheets of tumor cells, and infiltrative growth pattern, allow for a definitive diagnosis of malignancy. The differential diagnoses include metastatic adenocarcinoma, distant metastasis, sarcoma, and synovial sarcoma.

Even with these well characterized patterns, distinguishing MM from metastatic carcinoma of the lung or another distant primary site may be difficult. Diagnosis relies heavily upon IHC interpretation to narrow the list of differentials. When diagnosing MM, at least two negative adenocarcinoma markers and two positive mesothelial markers are recommended. Positive markers frequently used to identify MM include D2-40, WT-1, calretinin, and pancytokeratin. To rule out the differential of adenocarcinoma, CEA, CD15, MOC31, and BerEP4 may be used. Lastly, it is also important to order additional IHC to rule out other potential pulmonary and extra-pulmonary primary tumors.

References

1. Ai J, Stevenson, JP. Current Issues in Malignant Pleural Mesothelioma Evaluation. The Oncologist. 2014; 19,975-984.

2. Davidson, Ben. Prognostic factors in malignant pleural mesothelioma. Human Pathology. 2015; 46, 789-804.

3. Fletcher, Christopher. Diagnostic Histopathology of Tumors: 4th Edition. London: Churchill Livingstone, 2013. Print.

4. Mossman B, Shukla A, Heintz N, Verschraegen C, Thomas A, Hassan R. New Insights into Understanding the Mechanisms, Pathogenesis, and Management of Malignant Mesotheliomas. The American Journal of Pathology. 2013; 182, 1065-1077.

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