Kidney tumor

• Solid tumor composed of granular pale cells with prominent cell borders, finely reticular cytoplasm, perinuclear halos and wrinkled hyperchromatic nuclei
• First described in 1985 (J Pathol 1988;155:277)
• Cell of origin: intercalated cells of distal convoluted tubules

• Usually large, well circumscribed, hypovascular mass with relatively homogeneous contrast enhancement; may show central scar

Contributed by AFIP and @katcollmd on Twitter


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Contributed by Maria Tretiakova, M.D., Ph.D., Daniel Anderson, M.D., M.B.A. and @katcollmd on Twitter

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• Most commonly used:
  • Hale colloidal iron: stains acid mucopolysaccharides in microvesicles, diffuse and strong, reticular (J Pathol 1988;155:277, Am J Surg Pathol 1998;22:419)
  • CK7: diffuse and strong (compared with oncocytoma with scattered single cells) (Am J Clin Pathol 2007;127:225)
  • CD117 / KIT: membranous (Hum Pathol 2005;36:262)
• Other positive stains:
  • E-cadherin, claudin7 (distal nephron marker) (Arch Pathol Lab Med 2007;131:1541, Hum Pathol 2009;40:206)
  • Kidney specific cadherin (Am J Clin Pathol 2006;126:79, Mod Pathol 2005;18:933)
  • EMA / MUC1 (diffuse cytoplasmic) (Mod Pathol 2004;17:180)
  • Low molecular weight keratin (CK8 / CK18), RCC, CD10 (Mod Pathol 2004;17:1455)
  • Parvalbumin (calcium binding protein) (Mod Pathol 2001;14:760)
  • Cytochrome c oxidase positive versus negative in oncocytoma (Appl Immunohistochem Mol Morphol 2015;23:54)
  • DOG1 (Pathol Res Pract 2015;211:303)
  • PR (90% cells) (Arch Pathol Lab Med 2019;143:1455)
  • PDL1 22C3 expressed in a minority of cases (Med Oncol 2016;33:120)

	Hale	KIT	CK7	S100A1	VIM	CAIX	AMACR	SDH	TFE3
Chromophobe RCC	+++	+++	+++	-	-	-	-	+++	-
Clear cell RCC	-	-	-	-	+++	+++	-	+++	-
Oncocytoma	-	+++	rare	+++	-	-	-	+++	-
Papillary RCC	-	-	+++	-	+++	-	+++	+++	-
Translocation RCC	-	-	-	-	-	-	++	+++	+++
SDH deficient RCC	-	-	-	-	-	-	-	-	-

References: Pathol Res Pract 2015;211:303, Ann Diagn Pathol 2020;44:151448, Am J Surg Pathol 2014;38:e6, Arch Pathol Lab Med 2019;143:1455, Transl Androl Urol 2019;8:S123, Hum Pathol 2020 Jul 13 [Epub ahead of print]

AFIP images

• Multiple losses of whole chromosomes, most often 1, 2, 6, 10, 13, 17, 21 or Y (versus no loss in oncocytoma) (Hum Pathol 1998;29:1181, Mod Pathol 2005;18:161)
• FISH and SNP arrays may be more helpful than karyotyping (Am J Clin Pathol 2010;133:116)
• DNA rearrangement breakpoints within the TERT promoter region
• TP53 and PTEN mutated in 10 - 30% cases (TCGA cohort) (Cancer Cell 2014;26:319)
• NRAS, mTOR and TSC1 / TSC2 in ~5% cases (JCI Insight 2017;2:e92688)
• Mitochondrial (mt) mutations DNA most commonly affect MT-ND5 (Cancer Cell 2014;26:319)
• Increased expression of genes encoding enzymes in the Krebs cycle (expression is suppressed in clear cell RCC) (Cancer Cell 2014;26:319)
• Sarcomatoid tumors have different genetic abnormalities (Mod Pathol 2007;20:303)
• MiRNA expression patterns may be associated with progression, recurrence free survival and overall survival (Sci Rep 2015;5:10328)

Which of the following is true about chromophobe (ChRCC)?

1. Binucleation is pathognomonic
2. Cellulose deposition explains plant-like prominent membranes
3. Cytoplasmic clearing is due to high concentration of lipids
4. Multinucleation is an unfavorable prognostic feature
5. Perinuclear halos are due to accumulation of cytoplasmic microvesicles

E. Perinuclear halos are due to accumulation of cytoplasmic microvesicles. The presence of cytoplasmic microvesicles is a unique and consistent ultrastructural feature of ChRCC. Microvesicles are often concentrated in perinuclear location, corresponding to perinuclear halos on light microscopy. These vesicles lack affinity for H&E stain, resulting in cells with clear, reticular or flocculent cytoplasmic appearance on light microscopy (chromophobe). The origin is uncertain but likely related to defective mitochondria (Am J Surg Pathol 2000;24:1247).

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Reference: Chromophobe

What is the best statement describing chromophobe renal cell carcinoma (ChRCC)?

1. Can be reliably distinguished from clear cell RCC by CK7, CKIT (CD117), CAIX and vimentin
2. Classic autosomal dominant genetic correlation is Birt-Hogg-Dubé syndrome, which is associated with a mutation of the HOGG gene on chromosome 3p
3. Fuhrman / WHO grading is useful prognostic indicator
4. Sarcomatoid dedifferentiation is very common
5. To establish the diagnosis, a documentation of monosomies involving chromosomes 1, 2, 6, 10, 13, 17, 21 or Y is needed

A. Chromophobe shows multiple losses of whole chromosomes, most often 1, 2, 6, 10, 13, 17, 21 or Y but documentation of monosomies is not required for diagnosis. Sarcomatoid change is a significant poor prognostic indicator in chromophobe renal cell carcinoma but observed in ~5% of cases. Birt-Hogg-Dubé is caused by an autosomal dominant mutation of the Folliculin gene (FLCN) at 17p11.2 leading to premature truncation and loss of function of the folliculin protein. Von Hippel-Lindau syndrome, also autosomal dominant, is caused by a mutation of the VHL tumor suppressor gene (3p25-26). Depending on the subtype, VHL is associated with clear cell renal cell carcinoma, CNS and retinal hemangioblastomas, visceral cysts in the kidney, pancreas and epididymis, endolymphatic sac tumors, pancreatic neuroendocrine tumors, paragangliomas and pheochromocytomas (Front Horm Res 2013;41:30). Unlike clear cell renal cell carcinoma, Fuhrman / ISUP grade has no prognostic value. ChRCC by immunostaining CAIX and vimentin are negative and CK7 and CKIT (CD117) positive. Clear cell RCC shows opposite expression with CAIX and vimentin positive and CK7/CKIT negative.

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Reference: Chromophobe