Kidney: Renal cell carcinomas with MiT family translocation

2016-08-01   Pedram Argani 

1.Department of Pathology, The Johns Hopkins Hospital, Baltimore MD (PA) pargani@jhmi.edu

Abstract

Review on Renal cell carcinomas with MiT family translocations, with data on clinics, and the genes involved.

Clinics and Pathology

Epidemiology

Xp11 translocation RCC are the most common RCC in children, and comprises approximately 1% of adult RCC. There are only approximately 50 reported cases of t(6;11) RCC, median age is 31 years. Both RCC have been associated with prior exposure to cytotoxic chemotherapy.

Clinics

These form masses in the kidney. Xp11 translocation RCC are frequently calcified on imaging.

Pathology

Xp11 translocation RCC most commonly feature papillary architecture and epithelioid clear cells, with abundant psammoma bodies. Xp11 translocation RCCs can also present with unusual morphology mimicking other types of RCCs. Xp11 translocation RCCs can show solid or nested growth with clear to granular eosinophilic cytoplasm mimicking clear cell RCC, multilocular cystic RCC-like features, anaplastic/pleomorphic giant cells, tubular growth reminiscent of collecting duct carcinoma, well-developed fascicles of spindled neoplastic cells with bland nuclei in focal myxoid stroma mimicking mucinous tubular and spindle cell carcinoma, sarcomatoid change, oncocytic areas mimicking oncocytoma, oncocytic spindled areas resembling epithelioid angiomyolipoma, trabecular patterns mimicking carcinoid tumor, and colonization of renal pelvic urothelium mimicking urothelial carcinoma.
The t(6;11) RCC typically demonstrates a distinctive biphasic morphology, comprising larger epithelioid cells and small cells clustered around basement membrane material. The larger epithelioid cells may have clear to eosinophilic cytoplasm, and their nested architecture is similar to that of clear cell RCC. The smaller cells clustered around basement membrane material resemble the Call-Exner bodies of adult granulosa cell tumor. These neoplasms typically do not show prominent cytologic atypia or mitotic activity. While these lesions appear well delineated grossly, microscopically they characteristically entrap single native renal tubules at their periphery. Over time and with greater experience a broad range of morphologic appearances have been found in the t(6;11) RCC. Some of the illustrated morphologic appearances in genetically-confirmed cases include extensive hyalinization (both nodular mass-forming hyalinization and diffuse pericellular hyalinization), papillary architecture mimicking papillary RCC, clear cell morphology with an absence of smaller cells mimicking clear cell RCC, oncocytoma like morphology, oncocytic papillary morphology, cystic dilatation of entrapped renal tubules leading to a grossly cystic appearance, tubulocystic carcinoma-like morphology, and higher grade nested architecture which raises the broad differential diagnosis of high grade unclassified RCC.

Treatment

Surgical excision.

Cytogenetics

Cytogenetics morphological

Table 1. TFE3 or TFEB Gene Fusions

Neoplasm

Fusion

Age Range (years)

Translocation

ASPS

ASPSCR1/TFE3

1-71

der(17)(X;17)(p11.2q25)

RCC

ASPSCR1/TFE3

1-75

t(X;17)(p11.2;q25)

RCC

PRCC/TFE3

2-69

t(X;1)(p11.2;q21)

RCC

SFPQ/TFE3

3-68

t(X;1)(p11.2;p34)

RCC

NONO/TFE3

29-51

inv(X)(p11.2q12)

RCC

CLTC/TFE3

14

t(X;17)(p11.2;q23)

RCC

PARP14/TFE3

32

t(X;3)(p11.2;q23)

RCC

DVL2/TFE3

73

t(X;17)(p11;p13)

RCC

LUC7L3/TFE3

 

t(X;17)(p11;q21)

RCC

RBM10/TFE3

32

inv(X)(p11.2p11.23)

RCC

KHSRP/TFE3

 

t(X;19)(p11.2;p13)

Xp11 PEComa

SFPQ/TFE3, NONO/TFE3 and others

9-55

t(X;1)(p11.2;p34), inv(X)(p11.2q12) and others

Melanotic Xp11 Translocation Cancer

SFPQ/TFE3 and likely others

11-55

t(X;1)(p11.2;q34) and likely others

Subset of Epithelioid Hemangioendothelioma

YAP1/TFE3

14-50

t(X;11)(p11.2;q13)

RCC

MALAT1(Alpha)-TFEB

3-68

t(6;11)(p21;q12)

RCC

CLTC/TFEB

 

t(6;17)(p21;q23)

RCC

KHDRBS2/TFEB

 

inv(6)(p21q11)

RCC

COL21/TFEB

 

inv(6)(p21p12)

RCC

TFEB/CADM2

 

t(3;6)(p12;p21)


ASPS= Alveolar soft part sarcoma
RCC= Renal cell carcinoma
PEComa= Perivascular epithelioid cell tumor

Result of the chromosomal anomaly

Description

The t(6;11)(p21;q12) translocation fuses the gene for transcription factor EB ( TFEB) with MALAT1 (Alpha), an untranslated gene of unknown function, resulting in overexpression of native TFEB. Along these lines, the t(6;11) RCCs (also known as Alpha-TFEB RCCs) demonstrate specific nuclear labeling for TFEB protein by immunohistochemistry, whereas TFEB protein is not detected by immunohistochemistry in other neoplasms and normal tissues.

Bibliography

Pubmed IDLast YearTitleAuthors
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165750032006Translocation carcinomas of the kidney after chemotherapy in childhood.Argani P et al
228926012012Molecular confirmation of t(6;11)(p21;q12) renal cell carcinoma in archival paraffin-embedded material using a break-apart TFEB FISH assay expands its clinicopathologic spectrum.Argani P et al
246186162014t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases.Smith NE et al
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Citation

Pedram Argani

Kidney: Renal cell carcinomas with MiT family translocation

Atlas Genet Cytogenet Oncol Haematol. 2016-08-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/5118/kidney-renal-cell-carcinomas-with-mit-family-translocation