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Review
. 2019 Aug 3;11(8):1110.
doi: 10.3390/cancers11081110.

MiT Family Translocation Renal Cell Carcinoma: from the Early Descriptions to the Current Knowledge

Anna Caliò  1 , Diego Segala  2 , Enrico Munari  3 , Matteo Brunelli  1 , Guido Martignoni  4   5
Affiliations
Review

MiT Family Translocation Renal Cell Carcinoma: from the Early Descriptions to the Current Knowledge

Anna Caliò et al. Cancers (Basel). .

Abstract

The new category of MiT family translocation renal cell carcinoma has been included into the World Health Organization (WHO) classification in 2016. The MiT family translocation renal cell carcinoma comprises Xp11 translocation renal cell carcinoma harboring TFE3 gene fusions and t(6;11) renal cell carcinoma harboring TFEB gene fusion. At the beginning, they were recognized in childhood; nevertheless, it has been demonstrated that these neoplasms can occur in adults as well. In the nineties, among Xp11 renal cell carcinoma, ASPL, PRCC, and SFPQ (PSF) were the first genes recognized as partners in TFE3 rearrangement. Recently, many other genes have been identified, and a wide spectrum of morphologies has been described. For this reason, the diagnosis may be challenging based on the histology, and the differential diagnosis includes the most common renal cell neoplasms and pure epithelioid PEComa/epithelioid angiomyolipoma of the kidney. During the last decades, many efforts have been made to identify immunohistochemical markers to reach the right diagnosis. To date, staining for PAX8, cathepsin K, and melanogenesis markers are the most useful identifiers. However, the diagnosis requires the demonstration of the chromosomal rearrangement, and fluorescent in situ hybridization (FISH) is considered the gold standard. The outcome of Xp11 translocation renal cell carcinoma is highly variable, with some patients surviving decades with indolent disease and others dying rapidly of progressive disease. Despite most instances of t(6;11) renal cell carcinoma having an indolent clinical course, a few published cases demonstrate aggressive behavior. Recently, renal cell carcinomas with TFEB amplification have been described in connection with t(6;11) renal cell carcinoma. Those tumors appear to be associated with a more aggressive clinical course. For the aggressive cases of MiT family translocation carcinoma, the optimal therapy remains to be determined; however, new target therapies seem to be promising, and the search for predictive markers is mandatory.

Keywords: 11) translocation renal cell carcinoma; FISH; MiT family translocation renal cell carcinoma; TFE3; TFEB; TFEB-amplified renal cell carcinoma; Xp11 translocation renal cell carcinoma; t(6.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A chart showing the incidence (number of patients with tumors divided by the number of patients in the age group) of Xp11 translocation renal cell carcinomas (A) and t(6;11) renal cell carcinoma (C) at different ages. A chart showing the clinical behavior of Xp11 translocation renal cell carcinomas (B) and t(6;11) renal cell carcinoma (D) at different ages.
Figure 2
Figure 2
Different morphologies of Xp11 translocation renal cell carcinomas: resembling a clear cell renal cell carcinoma (Magnification: 200×) (A), showing a papillary (Magnification: 25×) (C) or cystic (Magnification: 100×) (E) pattern. An example of strong and diffuse expression of cathepsin K (Magnification: 200×) (B), the nuclear positivity of PAX8 (Magnification: 25×) (D), and the demonstration of TFE3 gene rearrangement by FISH (Magnification: 1000×) (F).
Figure 3
Figure 3
The most common morphology of t(6;11) renal cell carcinoma with larger epithelioid cells and smaller cells clustered around eosinophilic spheres formed by basement membrane material (A, Magnification: 25×; B, Magnification: 200×). Almost all cases are positive for cathepsin K (Magnification: 200×) (C) and HMB45 (Magnification: 200×) (D).
Figure 4
Figure 4
A high-grade renal cell carcinoma (A, Magnification: 50×; B, Magnification: 200×) expressing Melan-A (Magnification: 400×) (C) and showing TFEB gene amplification by FISH (Magnification: 1000×) (D).
See this image and copyright information in PMC

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