No abstract

A 16-year-old previously asymptomatic boy presented with complaints of fatigue, weight loss, and back pain for several months. Imaging studies revealed a large superior mediastinal mass, numerous bilateral pulmonary nodules, and multiple lytic bone lesions. A needle biopsy from a sternal lesion showed a poorly differentiated carcinoma, immunoreactive for cytokeratins and EMA and immunonegative for various organ/tissue-specific markers. His past medical history was significant for excision of a parotid gland tumor 5 years earlier. Histologic review of the salivary gland tumor revealed a pleomorphic adenoma containing a microscopic focus of invasive carcinoma (carcinoma ex pleomorphic adenoma). By immunohistochemistry, both the salivary gland tumor and the disseminated carcinoma expressed PLAG1 with a strong nuclear pattern. Fluorescence in situ hybridization (FISH), using dual-color, break-apart probes for PLAG1, showed rearrangement of the gene in both the salivary gland and the disseminated tumors. FISH demonstrated additional cytogenetic aberrations in the carcinoma, including polysomy for chromosome 8 (in both the primary salivary gland and the metastatic tumors) and PLAG1 amplification (in the metastatic tumor). We conclude that in the proper clinicopathologic setting, application of PLAG1 immunohistochemistry and FISH for PLAG1 gene rearrangement may be valuable in establishing the diagnosis of carcinoma ex pleomorphic adenoma as the source of a cancer of unknown primary site.