Kidney tumor

• Renal cell carcinoma (RCC) composed of clear cells separated by thick fibromuscular bands and associated with mutation of TCEB1 gene

• Low grade clear cells with voluminous cytoplasm
• Transecting thick fibromuscular septae imparting multilobular appearance
• Biallelic inactivation of TCEB1 gene: mutation with concurrent monosomy 8 or loss of heterozygosity at 8q21
• Lack VHL mutations, hypermethylation or loss of heterozygosity at 3p (Histopathology 2019;74:31, Mod Pathol 2015;28:845, Histopathology 2019;74:60)

• Vast majority are incidental: pT1a
• Rare tumors are pT3a

• No recurrence or metastasis reported to date

Contributed by Maria Tretiakova, M.D., Ph.D.

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Which is true about TCEB1 mutated renal cell carcinoma?


1. Definitive diagnosis is based on documenting either TCEB1 mutation or absence of chromosome 8 (monosomy 8)
2. Morphologically identical to clear cell renal cell carcinoma with prominent fibromuscular stroma
3. Multiple reports indicate relatively high incidence of this tumor type
4. TCEB1 and TFEB genes belong to the same family of transcription factors
5. Typically pursue aggressive course

B. TCEB1 mutated renal cell carcinoma is a distinct genomic entity of RCC with clear cell phenotype, mutations of TCEB1 gene with concurrent loss of heterozygosity at chromosome 8. Histologically these tumors are similar to conventional clear cell renal cell carcinoma but contain thick traversing fibromuscular bands transecting the tumor parenchyma and imparting multinodular appearance. Based on peculiar stromal prominence, these tumors were included into the 2016 World Health Organization Classification as a provisional entity of RCCs with (angio)leiomyomatous stroma. Grossly tumors are unifocal, small, well circumscribed and often encapsulated with tan nodular cut surface. On microscopy, neoplastic cells have voluminous clear cytoplasm, low grade nuclei and could be arranged in several architectural patterns in various combinations: solid alveolar, nested, cystic or tubulopapillary. Immunostaining shows a characteristic pattern: diffuse membranous box-like expression of CAIX, diffuse HIF1α, strong CK7 in the majority but not 100% of tumors cells, patchy and weak CD10, negative HMWCK, GATA3 and TFE3. Virtually all reported cases are incidental low stage indolent tumors with no recurrences or metastases.

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Reference: TCEB1 mutated renal cell carcinoma

Which immunohistochemical results will raise concern of TCEB1 mutated renal cell carcinoma in 45 year old patient with 3 cm encapsulated tumor having prominent stroma and clear cell morphology, shown here?


1. HMWCK-, CD10-, TFE3+, RCC+
2. HMWCK-, CK7-, CAIX+, CD10+
3. HMWCK-, CK7+, CAIX+, CD10-
4. HMWCK+, CK7+, CAIX+, GATA3+

C. The microscopic image shows a clear cell tumor with solid alveolar and microcystic areas with abundant fibromuscular stroma separating tumor into nodules. These features are often seen in conventional clear cell renal cell carcinoma but also raise a suspicion of rare indolent tumor entity of renal cell carcinoma with (angio)leiomyomatous stroma including TCEB1 mutated RCC. From the above panels, only answer B is consistent with TCEB1 mutated RCC; but definitive diagnosis requires molecular studies confirming mutation of TCEB1 gene and loss of heterozygosity at 8q21/monosomy 8.

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Reference: TCEB1 mutated renal cell carcinoma