290 Rhabdomyosarcomatous Differentiation in a Testicular Germ Cell Tumor Determined by FISH Detection of 12p11.21 Duplication

Abstract

Testicular germ cell tumors (GCTs) with sarcomatous differentiation are rare. They may have histological features identical to paratesticular sarcomas and hence specific molecular diagnostic markers can be useful to establish a definitive diagnosis. A 34-year-old man presents with painless scrotal swelling of 4 months’ duration with midline back pain. On examination, he had a painless firm mass in the scrotum, and CT showed a large testicular mass, an L5 compression fracture, and a right lung lower lobe nodule. Serologic evaluation revealed elevated LDH (1.54x normal), and normal AFP and HCG. Right radical orchiectomy was performed. The specimen weighed 1,348 g, and the testis was entirely replaced by a fleshy focally hemorrhagic and necrotic mass measuring 14.9 x 13.5 x 12.9 cm. Histologically, the tumor cells were ovoid to spindled with hyperchromatic nuclei and areas of rhabdomyoblastic differentiation exhibiting cross striations. Architecturally, the tumor formed fascicles without any other identifiable growth pattern typical of a mixed germ cell tumor. Immunoperoxidase stains for desmin, Myo-D1, myogenin, and MSA were positive, consistent with a diagnosis of rhabdomyosarcoma, embryonal type. However, the differential diagnosis included both primary rhabdomyosarcoma such as that arising within the paratesticular soft tissue and secondary rhabdomyosarcomatous differentiation of a testicular GCT. Given that sarcomas deriving from GCT often retain signature chromosomal anomalies such as isochromosome 12p, FISH studies were performed. FISH did not detect isochromosome 12p but demonstrated ~99% of tumor cells had duplication of the 12p11.21 region, which is a less common, but reported, abnormality in GCT. The differential diagnosis of intrascrotal sarcoma includes both primary paratesticular sarcomas as well as secondary sarcomatous transformation of testicular GCT. Extensive histological sampling and cytogenetic analysis for signature chromosomal anomalies in testicular germ cell tumors may be helpful in establishing a diagnosis when a non-sarcomatous element is not demonstrated.