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MiTF/TTF Translocation-Associated Carcinoma

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  • Renal carcinomas with translocations involving MiTF/TFE family, which includes TFE3 (Ch Xp11.2) and TFEB (Ch 6p21).
  • TFE3 fuses mainly with ASPL [t(X;17)] or PRCC [t(X;1]), and each has unique morphological features.
  • Uncommon, but with relatively higher incidence in pediatric patients and young adults.
  • A small subset may develop in young patients with past exposures to chemotherapy for childhood malignancies.
  • Previously, these tumors can easily be lumped with clear cell RCC because of the overlapped "clear cell" features.
  • Histology:
    • ASPL-TFE3 carcinoma – has abundant or "voluminous" clear cell cytoplasm (image A) and psammoma bodies; less often papillary.
    • PRCC-TFE3 carcinoma – clear cell with papillary architecture (image B).

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    • Alpha-TFEB carcinoma - dual population of larger clear cells forming nests and centrally has smaller cells clustered around hyaline nodules (image C).
    • Some tumors may also have eosinophilic cytoplasm.
  • Immunohistochemistry:
    • Most are keratin– or focal+. (Unusual for epithelial tumor to have no keratin and contrasts to most RCCs).
    • Nuclear TFE3+ (image D) or TFEB+. (To confirm diagnosis and distinguish from other tumors, mainly clear cell RCC).
    • Melanoma markers (HMB45+ or MART1+). (Only other tumor in kidney that has this + is angiomyolipoma).
  • TFE3 carcinomas are suggested to be more aggressive, particularly when in adults, but data regarding behavior is still limited.
  • DDX: Clear cell RCC: lacks papillary architecture, voluminous cytoplasm, and second population of small cells, and is TFE3- and TFEB-.