Answer: Metastatic Leydig cell tumor

Histology: The tumor consists of sheets of cells with abundant eosinophilic cytoplasm. Nuclei appear relatively bland without prominent nucleoli or increased mitotic activity.

Discussion: All of the tumors in the differential diagnosis are “pink cell tumors” with abundant eosinophilic cytoplasm. The first three lesions typically would have much greater degree of cytological atypia and more frequent mitotic activity. Melanoma and hepatocellular carcinoma also typically have a nesting appearance. In this case, the additional clinical history of a prior resection of a testicular tumor (type unknown) is very helpful. About 10% of Leydig cell tumors are malignant. They are usually larger than 5 cm. Usually they have a diffuse sheet-like architecture but may be nodular, trabecular, cord-like, pseudoglandular, small vacuolar with lipid, and microcystic. Cells are polygonal with abundant granular eosinophilic cytoplasm. Lipochrome pigment and Reinke crystals present in 15% and 30% of cases, respectively. Nuclei may be round or more irregular with conspicuous nucleoli and typically have nuclear hyperchromasia, although not seen in this case. They may have associated necrosis or lymphovascular invasion. Often tumors show increased mitotic activity (>3 per 10 HPF). Most malignant Leydig cell tumors have at least 4 of the following characteristics: >5 cm; nuclear hyperchromasia and pleomorphism, increased mitoses, vascular invasion, widespread invasion into surrounding the testis, and necrosis. Although these criteria are used in the primary tumor to determine malignancy, it is of interest that in this case the metastases lacks these malignant features. Once lymph node metastases occur more patients die of disease despite additional radiotherapy and/or chemotherapy.