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renal cell carcinomas

Thursday 18 September 2003

renal cell carcinoma, RCC, RCCs, kidney cancer, renal cancer; formerly Grawitz tumor ; formerly hypernephroma


- Wikimedia: eosinophilic, solid and cystic renal cell carcinoma

Digital cases

- Case 248 : Bellini type renal cell carcinoma

Classification (WHO 2016)

- clear cell renal cell carcinoma (and eosinophilic variants)
- papillary renal cell carcinomas

- chromophobe renal cell carcinoma
- collecting duct renal carcinoma (collecting duct type renal cell carcinoma )
- multilocular cystic renal cell neoplasm of low malignant potential
- SDH-deficient renal cell carcinoma
- TFE3-associated renal cell carcinoma
- eosinophilic, solid and cystic renal cell carcinoma (escRCC )
- TFEB-associated renal cell carcinoma
- HLRCC-associated RCC
- medullary renal cell carcinoma
- mucinous tubular and spindle cell renal cell carcinoma
- tubulocystic renal cell carcinoma
- ACD-associated RCC
- oncocytoid renal carcinomas in neuroblastoma survivors
- renal cell carcinoma associated with end-stage renal disease
- clear cell papillary carcinoma
- oncocytic papillary renal cell carcinoma
- follicular renal cell carcinoma
- leiomyomatous renal cell carcinoma
- renal cell carcinoma, unclassified

Benign tumors

- papillary adenoma
- oncocytoma

Clear cell, papillary and chromophobe carcinomas account for 85-90% carcinomas seen in routine practice. The remaining 10-15% of carcinomas consist of rare sporadic and hereditary tumors, some of which had been long recognized, but many of which only emerged as distinct entities in the decade leading up to the WHO publication:
- collecting-duct carcinoma is a rare, often lethal form of carcinoma.
- medullary carcinoma associated with sickle cell trait, has emerged as a distinctive tumor showing some overlapping features with upper tract urothelial carcinoma.
- mucinous tubular and spindle-cell carcinoma and tubulocystic carcinoma were earlier considered as patterns of low-grade collecting-duct carcinoma, but are now recognized as separate tumor entities.
- carcinomas associated with somatic translocations of TFE3 and TFEB comprise a significant proportion of pediatric renal carcinomas.
- oncocytoid renal carcinomas in neuroblastoma survivors was recognized as a unique tumor category in the WHO classification.
- renal carcinoma associated with end-stage renal disease is now recognized as having distinct morphological patterns and behavior.
- clear cell papillary carcinoma
- oncocytic papillary renal cell carcinoma
- follicular renal carcinoma
- leiomyomatous renal cell carcinoma.


- sarcomatoid renal cell carcinoma

  • Can occur in all histologic subtypes of renal cell carcinoma


- von Hippel-Lindau disease (renal clear cell carcinoma)

  • VHL gene mutations at 3p26

- MET germline mutations (papillary renal cell carcinoma)

- hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) (MIM.605839)

  • mutations in the gene encoding fumarate hydratase (FH) (MIM.136850), an enzyme of the Krebs cycle

- paraganglioma and early-onset renal cell cacinoma

  • SDHB germline mutations at 1p36-p35 (MIM.185470) (14685938)

- multicentric papillary renal cell carcinoma associated with renal adenomatosis
- hyperparathyroidism-jaw tumor syndrome (papillary renal cell carcinoma)
- Birt-Hogg-Dube syndrome (BHD)



- Dako: Renal Neoplasms: An Update on Immunohistochemical and Histochemical Features. (PDFs)

Clear Cell RCC expresses vimentin, a variety of low molecular cytokeratins, EMA, CD10 and RCC MA. The latter two have some diagnostic utility when a RCC is considered in a metastatic lesion.

Notable cytokeratin exceptions in CC-RCC are CK7 and high molecular weight cytokeratins.

Cytokeratin 7 coupled with AMACR (a-methylacyl-CoA racemase), is useful when solid forms of Pap-RCCs are encountered.

Several antigens, some uncommonly stocked in immunopathology laboratories, such as parvalbumin, S100A1, caveolin-1, C-kit, PAX2 and E-cadherin have discriminatory efficacy in separating CC-RCC from Ch-RCC.

However, the first line strategy for Ch-RCC should be to stain for CI.

For urothelial carcinoma the presence of high molecular weight cytokeratin, CK 7 and p63 permit confirmation of the diagnosis.

Xp11.2 translocation carcinomas

Xp11.2 translocation carcinomas are a group of neoplasms characterized by a variety of break points at Xp11.2 with translocation to one of several other chromosomes forming fusion genes. They occur most frequently in children and young adults.

Although histologically variable, the most common tumor cell phenotype are clear cells with voluminous cytoplasm and papillary architecture.

Intracellular and stromal calcifications provide additional useful clues to the diagnosis. In general the absence of epithelial markers in translocation carcinomas are powerful clues to the diagnosis.

However, a positive reaction for the nuclear transcription factor TFE3 is definitive in the absence of cytogenetic confirmation.

Some cases may also stain for melanocytic markers, but this is more common in TFEB positive t(6:11) translocation carcinomas.

Open references

- Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome. Beleut M, Zimmermann P, Baudis M, Bruni N, B├╝hlmann P, Laule O, Luu VD, Gruissem W, Schraml P, Moch H. BMC Cancer. 2012 Jul 23;12:310. PMID: 22824167 [Free]


- The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Srigley JR, Delahunt B, Eble JN, Egevad L, Epstein JI, Grignon D, Hes O, Moch H, Montironi R, Tickoo SK, Zhou M, Argani P; The ISUP Renal Tumor Panel. Am J Surg Pathol. 2013 Oct;37(10):1469-1489. PMID: 24025519

- Takahashi M, Teh BT, Kanayama HO. Elucidation of the molecular signatures of renal cell carcinoma by gene expression profiling. J Med Invest. 2006 Feb;53(1-2):9-19. PMID: 16537991

- Takahashi M, Sugimura J, Yang X, Vogelzang N, Teh BS, Furge K, Teh BT. Gene expression profiling of renal cell carcinoma and its implications in diagnosis, prognosis, and therapeutics. Adv Cancer Res. 2003;89:157-81. PMID: 14587873


- Uncommon and recently described renal carcinomas. Srigley JR, Delahunt B. Mod Pathol. 2009 Jun;22 Suppl 2:S2-S23. PMID: 19494850 [Free]

- Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med. 2005 Dec 8;353(23):2477-90. PMID: 16339096

- Pavlovich CP, Schmidt LS. Searching for the hereditary causes of renal-cell carcinoma. Nat Rev Cancer. 2004 May;4(5):381-93. PMID: 15122209

- Dal Cin P. Genetics in renal cell carcinoma. Curr Opin Urol. 2003 Nov;13(6):463-6. PMID: 14560139

- Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol. 2003 Dec;170(6 Pt 1):2163-72. PMID: 14634372

- Bodmer D, van den Hurk W, van Groningen JJ, Eleveld MJ, Martens GJ, Weterman MA, van Kessel AG. Understanding familial and non-familial renal cell cancer. Hum Mol Genet. 2002 Oct 1;11(20):2489-98. PMID: 12351585