Objective: TFE3-rearranged renal cell carcinoma (RCC) is a rare subtype of MiT family translocation-associated tumors, usually arising in the kidney of young patients. Extrarenal presentations are exceptionally uncommon and represent a major diagnostic challenge. To our knowledge, only two cases of extrarenal TFE3-rearranged RCC have been reported in the literature to date. We report an unusual case arising in the scalp with cranial bone destruction.

Case Report: A 24-year-old man presented with a rapidly enlarging occipital soft tissue mass evolving over five months. Imaging revealed a scalp tumor with lytic destruction of the cranial vault. Histologically, the tumor showed papillary and pseudopapillary architecture composed of cells with clear to eosinophilic cytoplasm and marked nuclear atypia. Immunohistochemistry demonstrated strong positivity for cytokeratins, CD10, PAX8 and TFE3, while CK7, CK20, EMA and GFAP were negative. A metastatic TFE3-rearranged RCC was initially suspected. However, extensive staging including 18F-FDG PET/CT revealed no renal primary tumor or other lesions. Based on the morphological, immunophenotypic and radiological findings, the diagnosis of extrarenal TFE3-rearranged RCC was retained.

Conclusion: This case highlights the diagnostic complexity of extrarenal TFE3-rearranged RCC and expands the anatomical spectrum of this entity to the scalp with bone destruction. Accurate diagnosis relies on the integration of morphology, immunohistochemistry and imaging findings.