Kidney tumor

• Histologic variant of chromophobe renal cell carcinoma (ChRCC) with at least 80% of cells with eosinophilic cytoplasm

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• Usually well circumscribed, lobulated and with beige to brown to yellow coloration
  • Eosinophilic variant more likely to have brown coloration compared with classic, which is typically more beige-yellow (Am J Surg Pathol 2008;32:1822)

Contributed by Timothy Isaac Miller, M.D., M.A. and Maria Tretiakova, M.D., Ph.D.

Contributed by Timothy Isaac Miller, M.D., M.A. and Maria Tretiakova, M.D., Ph.D.

• Oncocytoma:
  • Round, hyperchromatic nuclei; smooth nuclear border
  • Cells arranged in a nested or tubular pattern
  • Lacks nuclear pleomorphism, oval nuclei, multiple nucleoli
  • CK7 usually negative
  • Hale colloidal iron focal positive staining confined to luminal borders
  • No copy number alterations or losses of chromosomes 1 and X / Y (Hum Pathol 2020;104:18)
• Hybrid oncocytic / chromophobe tumors (HOCT) (Histol Histopathol 2013;28:1257):
  • Can be sporadic but also often found in association with renal oncocytomatosis or Birt-Hogg-Dubé (BHD) syndrome
  • Sporadic / oncocytomatosis: solid alveolar pattern, scattered cells with perinuclear halos but with no raisinoid nuclei
  • BHD: admixed areas of oncocytoma and ChRCC, scattered chromophobe cells, intracytoplasmic vacuoles
  • No aggressive behavior
  • Usually parvalbumin, antimitochondrial antigen and CK7 positive
  • Sporadic cases do not exhibit mutations in genes that are recurrently mutated in oncocytoma or ChRCC; syndromic cases with folliculin gene mutations (Mod Pathol 2019;32:1698)
• Eosinophilic variant of clear cell renal cell carcinoma:
  • Usually area with traditional clear cell morphology (unless limited biopsy)
  • CK7 and KIT negative, vimentin and CAIX positive
  • Biallelic inactivation of VHL gene

Which of the following is the most likely immunohistochemical profile of the renal neoplasm shown?

1. CK7+, KIT+, vimentin-, CAIX-
2. CK7+, KIT+, vimentin-, CAIX+
3. CK7+, KIT+, vimentin+, CAIX-
4. CK7-, KIT+, vimentin-, CAIX-
5. CK7-, KIT-, vimentin+, CAIX+

A. CK7+, KIT+, vimentin-, CAIX-

The image shown is chromophobe renal cell carcinoma (ChRCC), eosinophilic variant. Histologic clues to the diagnosis of ChRCC are the raisinoid nuclei, perinuclear clearing / halos and well defined cell borders. Furthermore, > 80% of the cells have an eosinophilic cytoplasm, thus making it the eosinophilic variant of ChRCC. The immunoprofile of ChRCC is typically CK7+, KIT+, vimentin- and CAIX-. The other entity to consider is oncocytoma, but in this case the degree of nuclear pleomorphism (with enlarged, wrinkled and oval nuclei) favors ChRCC. Answer D (CK7-, KIT+, vimentin-, CAIX-) would be the immunohistochemical profile most typical of oncocytoma, although vimentin can often be focally positive. Answer E is the immunoprofile most typical of clear cell renal cell carcinoma; while there is an eosinophilic variant of this condition, the perinuclear clearing and raisinoid nuclei are still most characteristic of ChRCC (Pathol Res Pract 2015;211:303).

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Reference: Chromophobe eosinophilic variant

Which of the following is true regarding chromophobe renal cell carcinoma (ChRCC), eosinophilic variant compared with the classic type of ChRCC?

1. No differences in cytogenetics have been found between the eosinophilic variant and classic ChRCC
2. The classic variant is more likely to have a brown coloration grossly
3. The classic variant typically has smaller cells than the eosinophilic variant
4. The eosinophilic variant must have 100% eosinophilic cells
5. The prognosis of the eosinophilic variant is the same as classic ChRCC

E. The prognosis of the eosinophilic variant is the same as classic ChRCC

Studies have shown no difference in prognosis between the eosinophilic variant of ChRCC and classic ChRCC. Answer A is wrong as a recent study showed that the eosinophilic variant frequently has less chromosomal instability compared with classic ChRCC and is often characterized by doubled hypodiploidy (Eur J Surg Oncol 2008;34:687, Cancers (Basel) 2019;11:1492, Am J Surg Pathol 2008;32:1822, Cancers (Basel) 2019;11:1492, Hum Pathol 2020;104:18, Am J Surg Pathol 2008;32:1822). Answer B is wrong as the eosinophilic variant is more likely to be brown in coloration grossly. Answer C is wrong as the eosinophilic variant typically has smaller cells compared with classic ChRCC. Answer D is wrong because, by definition, the eosinophilic variant only needs to have > 80% eosinophilic cells.

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Reference: Chromophobe eosinophilic variant