TFE3-rearranged renal cell carcinoma - Expanding the histomorphological spectrum.

Background: Transcription factor E3 (TFE3)-rearranged renal cell carcinoma (RCC) shows heterogeneity involving clinical, morphological, and molecular features, and it has many histopathological differential diagnoses.

Aim: We aimed to study the histomorphology of the TFE3-rearranged RCC to know the morphological pattern, cytomorphology, and morphological clues to diagnose and to know the tumor behavior and prognosis.

Materials and methods: It was a retrospective study; a total of 104 renal cell tumors were diagnosed on nephrectomy from January 2022 to January 2024, out of which a histopathological diagnosis of TFE3-rearranged RCC was rendered in five cases.

Results: The mean age was 40 years (range 30-62 years). The male-to-female ratio was 4:1. The growth patterns were isolated papillary (three cases), a dominant papillary (one case), and a mixed (one case). Abundant and both eosinophilic and clear cytoplasm (all cases), focal oncocyte-like morphology, and eosinophilic cytoplasmic inclusion or hyaline globules-like material were noted. Pseudostratification (three cases), the mid and apical position of the nuclei, and hobnail morphology (four cases) were noted. The papillary core showed psammoma bodies (four cases), foamy macrophages (all cases), hyalinization (four cases), and lymphoid aggregates (two cases). A moderate degree of peritumoral lymphocytic infiltration (three cases) and xanthogranulomatous inflammation (one case) were noted. On immunohistochemistry, all cases showed diffuse and strong positivity for TFE3, variable positivity for alpha methylacyl CoA racemase, and variable and apical accentuation of staining for CD10. CK7 was negative to occasional positive.

Conclusion: Identifying this new molecularly defined tumor's morphology will help exclude the differential diagnosis and understand this tumor's clinical and biological features.