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.

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

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.

Surgical excision.

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

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.