Metastatic Large Cell Calcifying Sertoli Cell Tumor: A Case Report, Diagnostic Pitfalls, and Literature Review

Large cell calcifying Sertoli cell tumor (LCCSCT) is a rare testicular neoplasm, with only a small subset of clinically malignant tumors. We report a diagnostically challenging, clinically and histologically malignant LCCSCT in a 37-year-old man with a misleading initial presentation. The patient initially presented with testicular pain and swelling following trauma and was clinically diagnosed with epididymitis and hydrocele. Despite antibiotic therapy, symptoms progressed to include weight loss, night sweats, fever, diffuse pain, and lymphadenopathy. Computed tomography performed 2 months later demonstrated diffuse lymphadenopathy and enhancement of the right testicular tunica. Fine-needle aspiration and core biopsy of a left supraclavicular lymph node revealed a malignant neoplasm with S100 and SOX10 expression, raising concern for a neural crest-derived tumor. Next-generation sequencing identified a PRKAR1A mutation, further confounding the diagnosis. Extensive imaging failed to identify a primary tumor, and the patient showed no response to chemotherapy. Due to progressive disease and persistent testicular pain, a right orchiectomy was performed, revealing a hydrocele, thickened tunica, and an intratesticular mass. Histologic evaluation demonstrated malignant LCCSCT with cytologic atypia, necrosis, invasive growth, and metastatic disease. A focused literature review identified 22 previously reported clinically malignant LCCSCTs, highlighting variable clinical presentations, frequent S100 positivity, and overlapping immunohistochemical and molecular features that represent important diagnostic pitfalls. This case report emphasizes the need to consider metastatic LCCSCT in the differential diagnosis of metastatic S100/SOX10-positive tumors with PRKAR1A mutations, particularly when a testicular lesion is present or suspected.