Biphasic Diffuse Malignant Mesothelioma, Pleural
Diffuse malignant mesothelioma (DMM) is an aggressive neoplasm of the pleura, usually in individuals with history of asbestos exposure. MM is the most common primary tumor of the pleura, presenting as diffuse mass that is identifiable clinically. DMM should be distinguished from the more favorable prognosis of localized malignant mesothelioma and well-differentiated papillary malignant mesothelioma.
The 2015 World Health Organization (WHO) Classification of Tumors of the Pleura classified the major histologic types of DMM as epithelioid, sarcomatoid (desmoplastic), and biphasic mesothelioma.
Biphasic DMM is the second most common histologic variant of pleural malignant mesothelioma, accounting for 20–35% of the cases (epithelioid and sarcomatoid accounting for approximately 60% and 20% of cases, respectively).
The average age at the time of diagnosis of biphasic DMM is similar to that of other DMMs which is 69.
As with other DMMs, biphasic DMM is more common in males than females.
Pleural surfaces surrounding the lungs and may extend into the interlobar fissures.
Surgical resection (decortication or pneumonectomy) and/or chemotherapy are the current methods of treatment.
As with other DMMs, the overall prognosis of biphasic DMM is very poor, with the overall survival being 9–17 months. The majority of the patients die of complications of local extension to the lung parenchyma and diaphragm, resulting in respiratory failure.
Biphasic DMM and sarcomatoid DMM have a somewhat poorer prognosis than epithelioid DMM.
As with other DMMs, biphasic DMM typically present as a thick whitish rind, growing along the pleural surface and extending into the interlobar fissures.
Biphasic DMM is characterized by the presence of epithelioid and sarcomatoid components, with each representing at least 10% of the overall histology of the tumor. The epithelioid cells may be arranged in a papillary or tubulopapillary pattern (psammoma bodies may be present). The sarcomatoid portion of the tumor is usually composed of tightly packed spindle cells, with the occasional presence of osseous and cartilaginous differentiation. As with other DMMs, diagnosis of biphasic DMM remains challenging when relying exclusively on the histological evaluation of the tumor, with the utilization of immunohistochemistry play a pivotal role in reaching the diagnosis.
The epithelioid portion of biphasic DMM is usually positive for WT-1, calretinin, cytokeratin 5/6 (CK 5/6), and D2-40 (podoplanin). The sarcomatoid component may lose immunoreactivity for various markers; they remain positive for D2-40, calretinin, AE1/AE3, and CAM5.2, but negative for desmin, h-caldesmon, S-100p, and myoglobin.
As with other DMMs, biphasic DMMs are typically negative for adenocarcinoma markers as TTF-1, CEA (<5% positive), Ber-EP4 (20% positive), and MOC-31 (10% positive).
- Biphasic synovial sarcoma
Biphasic tumor composed of glandular structures admixed with atypical spindle shaped cells. Positive staining for BCL-2 and CD99, may also be positive for cytokeratin, EMA, and calretinin, but consistently negative for WT-1.
The most helpful diagnostic utility is the characteristic chromosomal translocation, t(X;18)(SYT-SSX), demonstrated by FISH or PCR.
- Metastatic carcinosarcoma
Biphasic tumor with carcinoma component admixed with a sarcomatous component that may contain heterologous elements (osteoid and cartilage). Positive for EMA and CD10, while negative for CK5/6, WT-1, and GLUT-1.
- Metastatic melanoma
Spindle cell melanoma can mimic the sarcomatoid component of biphasic diffuse malignant mesothelioma, especially on biopsy. Positive for S100 and WT-1.
References and Further Reading
- Husain, A. N., Colby, T. V., Ordóñez, N. G., Allen, T. C., Attanoos, R. L., Beasley, M. B., Butnor, K. J., Chirieac, L. R., Churg, A. M., Dacic, S., Galateau-Sallé, F., Gibbs, A., Gown, A. M., Krausz, T., Litzky, L. A., Marchevsky, A., Nicholson, A. G., Roggli, V. L., Sharma, A. K., Travis, W. D., Walts, A. E., & Wick, M. R. (2017). Guidelines for pathologic diagnosis of malignant mesothelioma: 2017 update of the consensus statement from the international mesothelioma interest group. Archives of Pathology and Laboratory Medicine. https://doi.org/10.5858/arpa.2017-0124-RA.