ALK Expression Without ALK Rearrangement in EWSR1::ATF1-Fused Inflammatory and Nested Testicular Sex Cord Tumor

Inflammatory and nested testicular sex cord tumor (IN-TSCT) is a recently recognized, rare testicular sex cord–stromal neoplasm characterized by a recurrent EWSR1::ATF1 fusion and potentially aggressive clinical behavior. Because of its nested epithelioid morphology accompanied by prominent inflammatory infiltrates, IN-TSCT may be mistaken for seminoma, while frequent diffuse CD30 expression further complicates the differential diagnosis with lymphoma. We report a case of IN-TSCT in a 54-year-old man presenting with intermittent left testicular pain. Scrotal ultrasonography demonstrated a well-defined, heterogeneously hypoechoic intratesticular mass with minimally increased internal vascularity. Radical orchiectomy revealed a 1.5 × 1.4 cm epithelioid neoplasm arranged in nests and cords with a prominent inflammatory infiltrate. The tumor cells expressed the sex cord–stromal markers SF-1 and calretinin and showed diffuse CD30 expression. RNA-based next-generation sequencing identified an EWSR1::ATF1 fusion, establishing the diagnosis of IN-TSCT. Unexpectedly, the tumor also demonstrated strong ALK immunoreactivity with both the ALK1 and D5F3 antibody clones, despite the absence of an ALK fusion by RNA sequencing or an ALK rearrangement by fluorescence in situ hybridization. The combined expression of CD30 and ALK may mimic anaplastic large cell lymphoma and represents an important diagnostic pitfall. The patient remained free of recurrence or metastasis 18 months after orchiectomy. This case expands the recognized immunophenotypic spectrum of IN-TSCT and demonstrates that strong ALK immunoreactivity does not necessarily indicate an underlying ALK fusion or rearrangement. Given the potentially aggressive clinical behavior reported in IN-TSCT, long-term oncologic surveillance is warranted.