Answer: Metastatic alveolar soft part sarcoma

Histology: The patient had a thigh mass resected previously, which was diagnostic of Alveolar Soft Part Sarcoma. The specimen has a compact nested architecture. It is composed of cells with vesicular chromatin and prominent nucleoli, and voluminous eosinophilic to pale cytoplasm. Mitotic activity is minimal. Where the nests are larger, cells are somewhat discohesive, giving rise to an alveolar pattern. Ultrastructural examination of this patient’s primary soft tissue tumor resected previously demonstrated diagnostic membrane bound rhomboidal crystals, which correspond to the PAS-positive diastase resistant cytoplasmic crystals which can be observed on formalin-fixed paraffin embedded tissue sections.

Discussion: The differential diagnosis of alveolar soft part sarcoma essentially revolves upon tumors composed of polygonal cells, which demonstrate the nested/alveolar pattern. This differential includes renal cell carcinoma, alveolar rhabdomyosarcoma, granular cell tumor, malignant melanoma, and paraganglioma. Renal cell carcinomas will typically be immunoreactive for cytokeratin or EMA. Paragangliomas should label with neuroendocrine markers, and demonstrate S100-positive sustentacular cells at the periphery. Malignant melanomas should label for S100, HMB45, Melan-A, and microphthalmia transcription factor.

Alveolar soft part sarcoma is a rare and poorly understood entity. It comprises 0.5% of soft tissue sarcomas. The classic presentation is that of a painless, slowly growing soft tissue mass in a young adult. Paradoxically, despite its slow growth in its primary site, the lesion often presents with metastases to the lung and brain. Typical locations include the lower legs of adults and the head and neck area of children. Immunohistochemistry is inconsistent in this tumor, in that 50% show focal desmin positivity, and 25% are S100 protein positive. Most cases are non-immunoreactive for all markers. Recently, Ladanyi et al have demonstrated that alveolar soft part sarcoma is characterized by a specific chromosome translocation, a derX t(X;17) (p11.2;q25), which fuses the TFE3 gene on Xp11;2 to a novel gene, ASPL, on 17q25. This chromosome translocation can be detected by reverse transcriptase polymerase chain reaction, and may prove to be the gold standard for the diagnosis of this rare entity.