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Updated: Jan 24, 2026

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TFE-Altered Renal Cell Carcinoma: A Contemporary Review With Practical Insights and Diagnostic Pearls for Surgical

Christopher G Przybycin1, Jane K Nguyen1, Reza Alaghehbandan1,2

  • 1Diagnostics Institute, Department of Pathology, Cleveland Clinic, Cleveland, OH.

Advances in Anatomic Pathology
|January 23, 2026
PubMed

Insights

MiT-family renal cell carcinomas (RCC), including TFE3- and TFEB-altered subtypes, exhibit diverse features. Accurate diagnosis is crucial for patient prognosis and treatment decisions in advanced disease.

Area of Science:

  • Oncology
  • Genetics
  • Pathology

Background:

  • The category of MiT-family renal cell carcinoma (RCC) has expanded beyond the initial recognition of ASPCR1::TFE3 gene fusions.
  • It now encompasses TFE3-rearranged RCC, TFEB-rearranged RCC, and TFEB-amplified RCC, presenting significant variations.

Purpose of the Study:

  • To review the morphologic, immunohistochemical, and molecular findings of TFE-altered RCCs.
  • To provide a practical diagnostic approach for these complex entities.

Main Methods:

  • Literature review summarizing key diagnostic features.
  • Analysis of morphologic, immunohistochemical, and molecular data.
  • Development of a diagnostic strategy.

Main Results:

  • TFE-altered RCC subtypes display considerable variation in appearance and clinical behavior.
  • These tumors can mimic each other and common RCC subtypes, complicating diagnosis.
  • Distinctive immunohistochemical and molecular markers aid in differentiation.

Conclusions:

  • Accurate diagnosis of TFE-altered RCCs is essential for patient care.
  • This diagnosis provides critical prognostic information.
  • Informed treatment decisions for advanced disease rely on precise classification.
Keywords:
TFE3-rearrangedTFEB-amplifiedTFEB-rearrangedkidney cancerrenal cell carcinoma

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