MiT family translocation renal cell carcinoma

Xp11 Translocation RCC

t(6;11) renal cell carcinoma

Epidemiology and Etiology:

• Cytotoxic chemotherapy treatment during childhood
• 15% of translocation carcinomas

Common sites:

Gross features:

Histologic features:

• Mixed alveolar and papillary growth
• Voluminous tumour cells with clear or eosinophilic cytoplasm
• Psammomatous calcifications often abundant in the stroma
• Substantial morphologic overlap with other subtypes of RCC
• Multilocular cystic RCC-like features
• Pleomorphic giant cells
• Tubular growth reminiscent of CDC
• Well-developed fascicles of spindled neoplastic cells with bland nuclei and focal myxoid stroma
• t(6;11) RCC
• distinctive biphasic morphology
• larger and smaller epithelioid cells
• smaller epithelioid cells often clustered around basement membrane material
• cases without the small cell component, dominated by sclerosis, clear cells, or papillary architecture have been reported.

Immunophenotype:

Marker:	Sensitivity:	Specificity:
LMWK (Negative or focally positive)	typically
CK7 (Negative or focally positive)	typically
EMA (negative)
Vimentin (negative)
CD10	consistently
RCC	consistently
PAX2	Most
PAX8	Most
TFE3 (strong, nuclear)	very sensitive (Xp11) but not 100% false negatives occur	Very specific, but excessive antigen retrieval can lead to false positive results – non-neoplastic internal control is very useful
Cathepsin K	60% Almost all t(6;11)	Not expressed in other common RCC subtypes
HMB45	Some Consistently in t(6;11)
Melan-A	Some Consistently in t(6;11)
TFEB	Sensititive for t(6;11) But finicky IHC	Specific for t(6;11) but finicky IHC

Molecular features:

• MiTF/TFE renal translocation carcinomas (1/3 to 50% of pediatric RCC, 1-4% in adults, but even so, many more cases of translocation carcinoma are in adults than in kids due to increased incidence of RCC in adults)
• Xp11.2 translocation renal cell carcinoma
• E3 (TFE3, Xp11.2) gene fusions with 6 other genes

o TFE3 is a member of the MiTF/TFE family of transcription factors

o PRCC/TFE3 fusion is most common

· Papillary renal cell carcinoma gene (PRCC at 1q21)

o ASPSCR1/TFE3 fusion is also common

· Alveolar soft part sarcoma chromosome region, candidate 1 (ASPSCR1 at 17q25) (ASPL)

o NonO (p54^nrb)

o PSF

o CLTC

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

o t(X;10)(p11.2;q23)

• t(6;11)(p21;q12) translocation
• Alpha-TFEB gene fusion
• fusion between alpha gene and transcription factor EB (TFEB) gene
• TFEB is a member of the MiTF/TFE family of transcription factors, similar to TFE3
• Same clinical, morphologic, and immunohistochemical features as Xp11 translocation carcinomas
• Upregulation of Met

Other features:

References:

• Zhou AG, Owens CL, Cosar EF, Jiang Z. Clinical implications of current developments in genitourinary pathology. Arch Pathol Lab Med 2013;137:887-893.
• Srigley JR et al. (The ISUP Renal Tumor Panel) The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J Surg Pathol 2013;37:1469-1489.