Kidney tumor
Adult renal cell carcinoma
MiT family translocation renal cell carcinomas (adults)

Author: Nicole K. Andeen, M.D. (see Authors page)
Editor: Maria Tretiakova, M.D.

Revised: 6 September 2016, last major update September 2016

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: MiT family translocation renal cell carcinoma adults
Cite this page: MiT family translocation renal cell carcinomas (adults). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneytumormalignantASPLTFE3.html. Accessed December 7th, 2016.
Definition / General
  • Harbor gene fusions involving members of the MiT family of transcription factors, including TFE3 and TFEB
  • Histologically diverse, often have papillary, alveolar and nested growth pattern with clear and eosinophilic cells and psammoma bodies
  • More common in children/young adults
Essential Features
  • Papillary with clear and eosinophilic cells, but wide morphologic spectrum
  • Diagnosis often relies on IHC or FISH for translocation (Am J Clin Pathol 2012;137:761)
Terminology
  • Renal cell carcinomas/RCCs associated with Xp11 translocations have gene fusions involving TFE3, which has multiple gene partners; RCCs with t(6:11) translocations have MALAT1-TFEB gene fusions
  • MiT refers to microphthalmia-associated transcription factors
Epidemiology
Sites
  • Kidney
Pathophysiology
  • Overexpression of TFE3 or TFEB activates multiple downstream targets, including those normally activated by MiT family transcriptions factors; thus often expresses the cysteine protease cathepsin K, may express melanocytic markers, and is less likely to express epithelial markers like cytokeratins
Clinical Features
  • In adults, strong female predominance (22 of 28 cases in one series), usually age 35 or less, usually high stage at diagnosis (Am J Surg Pathol 2007;31:1149)
Prognostic Factors
Case Reports
Treatment
Gross Description
  • Tan yellow, frequently hemorrhagic and necrotic; not distinct from other RCCs
Gross Images

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Multiple partially cystic and hemorrhagic tumor nodules with fibrous septa

Micro Description
  • TFE3 rearranged carcinomas usually have papillary and solid alveolar growth pattern, composed of clear to eosinophilic discohesive pseudostratified cells with voluminous cytoplasm and high grade nuclei
  • TFE3 rearranged carcinomas also frequently have psammoma bodies and may contain melanin pigment, similar to a pigmented perivascular epithelioid tumor (PEC)oma (Semin Diagn Pathol 2015;32:103)
  • t(6:11) rearranged carcinomas are characteristically biphasic, with small cells clustered around basement membrane material (reminiscent of Call-Exner bodies in adult granulosa cell tumor), and larger epithelioid cells (Semin Diagn Pathol 2015;32:103)
Micro Images

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TFE3 rearranged carcinoma with papillary and alveolar growth pattern, composed of clear to eosinophilic discohesive pseudostratified cells with voluminous cytoplasm, high grade nuclei, and psammoma bodies. There is strong diffuse nuclear positivity for TFE3 by immunohistochemistry

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TFEB rearranged carcinoma with biphasic appearance: larger epithelioid cells and small cells clustered around basement membrane material

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Translocation carcinoma (adults)



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Xp11 translocation carcinoma

12 year old boy

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Renal tumors with clear
cells and papillary
architecture

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Other epithelioid tumors in the differential
diagnosis of translocation associated
renal cell carcinoma

Positive Stains
Negative Stains
Electron Microscopy Description
  • Features of clear cell carcinoma, including cell junctions, numerous mitochondria, microvilli, basement membrane, abundant glycogen
Molecular / Cytogenetics Description
  • Fluorescence in situ hybridization (FISH) with a TFE3 orTFEB breakapart probe is highly sensitive and specific; it is diagnostic when indeterminate by morphology and immunohistochemistry
  • TFE3 (on Xp11) has been reported with multiple gene partners, including the two most common, ASPL (17q25) and PRCC (1q21), and less commonly NONO (Xq12), PSF/SFPQ (1p34), CLTC (17q23) (WHO 2016, Am J Surg Pathol 2007;31:1149, Expert Rev Anticancer Ther 2010;10:843)
  • t(6;11)(p21;q12): translocation between TFEB and MALAT1 genes result in overexpression of TFEB
  • t(X;17)(p11.2;q25), with balanced translocation of TFE3 gene at Xp11.2 and ASPL gene at 17q25, is present in renal neoplasms, whereas in alveolar soft part sarcoma, this translocation is unbalanced, der(17)t(X;17)(p11.2;q25) (Am J Pathol 2001;159:179)
  • Melanotic Xp11 renal cell carcinoma and PSF/SFPQ-TFE3 perivascular epithelioid cell tumors may share the same genetic abnormality and may be in the same clinico-pathologic spectrum (Am J Surg Pathol 2015;39:1181)
Differential Diagnosis
  • Clear cell renal cell carcinoma: older patients, no true papillae (although pseudopapillary areas due to poor cell cohesion can be seen in high grade clear cell RCC); frequently keratin/EMA+, vimentin+, TFE3-, diffuse CAIX+, 3p deletion present
  • Papillary renal cell carcinoma: predominantly papillary, no nested alveolar patterns, no extensive areas of clear cells; CK7+, TFE3-, trisomy 7 and 17
  • Chromophobe renal cell carcinoma: diffuse CD117 staining favors chromophobe
  • Clear cell papillary renal cell carcinoma: typically a homogeneous low grade population of clear cells without eosinophilic cells, no calcifications, often branched ductular structures, secretory cells with nuclei aligned above basement membrane (resembling secretory endometrium); CK7+, CAIX+, CD10-, AMACR-
  • Clear cell sarcoma of kidney: usually children, cells have indistinct cell borders, TFE3-