Oral metastasis of pleural sarcomatoid mesothelioma, a rare aggressive variant of mesothelioma and a diagnostic challenge

Abstract

<h3>Introduction</h3> Malignant mesothelioma is a rare neoplasm that most commonly develops after exposure to asbestos and arises from the serosal cells of the pleura or rarely peritoneum. Various histological subtypes have been recog- nized: epithelioid, sarcomatoid, biphasic-epithelioid, and biphasic-sarcomatoid, with the sarcomatoid variant being a less common, but more aggressive variant. Numerous genetic alterations have been identified in the development and progression of malignant mesothelioma, most notably mutations in tumor suppressor genes, <i>neurofibromatosis type 2 (NF2), BRCA1-associated protein-1 (BAP1),</i>and <i>cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF)</i>. Mesothelioma metastasis to the oral cavity is infrequent, with only nineteen cases reported in the literature. Soft tissue involvement of the oral cavity has been reported in the tongue, followed by the mandibu- lar gingiva, and alveolar mucosa. Prognosis for malignant mesothelioma is poor as it is typically unresponsive to conventional chemotherapeutic agents. New targeted therapies are currently in ongoing clinical trials. <h3>Case Findings</h3> An 81-year-old male, undergoing treatment for malignant pleural mesothelioma and with a history of asbestos exposure, presented for evaluation of a raised, necrotic mass on the left posterior mandibular buccal and lingual gingiva. Panoramic radiograph revealed extensive bone loss. The histopathology was that of a sarco- matoid neoplasm. Immunohistochemistry demonstrated positive staining for WT1, cyclin D1, and P53, supporting the diagnosis of metastatic malignant mesothelioma, sarcomatoid variant. Other stains that help to define mesothe- lioma such as CK5/6, calretinin, and D2-40 were negative. Despite equivocal immunostaining results, the diagnosis was further supported by comprehensive genomic analysis with identification of mutated <i>NF2</i>and <i>BAP1</i>tumor sup- pressor genes. <h3>Conclusion</h3> The diagnosis of malignant pleural mesothelioma relies on morphology supplemented with immuno- histochemistry. The diagnosis is challenging, especially so for the sarcomatoid variant, with immunohistochemical staining profiles often being inconsistent. The current case demonstrates the utility of comprehensive genomic analysis in firmly establishing the diagnosis.