• Clear cell renal cell carcinoma:
  The main characteristic of clear cell RCC is the co-expression of cytokeratins (CK 8/18, 19) and vimentin. RCC is ck7 & ck20 negative (as are HCC, germ cell ca., adrenal cort. ca., and prostate)². Dedifferentiation leads to an increasing expression of vimentin and finally disappearance of keratins on the immunohistologic level. The perimembranous positivity changes to a perinuclear (centroplasmic) positivity. The presence of brush border-associated antigens like villin, CD 10 (69% are pos.²) and CD 13 supports the proposed histogenetic development from the proximal tubule. A kidney specific gamma GT antibody, which can be applied on paraffin sections, is helpful in differential diagnosis of metastatic clear cell carcinoma of unknown primary as it proves the renal origin.
• Chromophil (papillary) renal cell carcinoma:
  Chromophil RCC have an immunohistologic profile similar to clear cell RCC. The vimentin expression can be very weak overall but pronounced at the basal cell pole in the highly differentiated basophilic cell types. Lectins like DBA and SBA are found in chromophil RCC but not in clear cell RCC. Mab RCC 38 selectively reacts with chromophil RCC and can serve as a marker for this special kidney tumor type. Almost 100% have CD10 positivity; & only 3% K903 positive [L-06-9888]; and, amongst the papillary, you may find small foci of standard clear cell RCC; often with copious stromal foam cells [L07-7141]. The common antigen characteristics are a strong argument for the close relationship between clear cell and chromophil RCC and their origin from the proximal tubule.
• Renal Oncocytoma (RO):
  As a rule oncocytomas do not express vimentin (rare expression of vimentin²), but in central regressive areas they can show focal vimentin positivity.  They also lack antigens of the proximal tubule (CD10 neg.) and are positive for antigens of the collecting duct, especially those of the intercalated cells like carbonic anhydrase C and H+ ATPase. The band 3 anion carrier protein found in type a intercalated cells can be detected only in oncocytomas, consistent with origin in the collecting duct. While CD 44s can be found on the cell surface, CD 44v6 is totally absent. The ck7 & ck 20 panel can help distinguish oncocytoma (80% ck20 pos.) from chromophobe RCC (50% are ck7 pos. & 20 neg)²...84% ck7 pos.One, two, or all three patterns were identified in individual cases. Noted in some cases was a zonal staining quality, i.e., regions of tumor demonstrated diffuse cytoplasmic staining, with other distinct regions showing the dot-like or the perinuclear pattern, possibly representing a clonal phenomenon. Vimentin-positive cases always showed a diffuse cytoplasmic pattern. Ck20 dot-like positivity for CAM 5.2 has been previously described to occur in 73% of ROs but in 0% of RCCs, and therefore if present distinguishes between these lesions (Bonsib et al. 1991 ); the staining corresponds to single large [nucleus sized] cytoplasmic condensations of intermediate filaments referred to as globular filamentous bodies [we have seen this with ck8, L06-10544].
• Chromophobe renal cell carcinoma:
  Chromophobe RCC are strongly positive for cytokeratin 8/18 (LMW-ker),  often (100% had strong cytoplasmic staining with peripheral-cell accentuation³) for CK 7 (only 8% ck7 pos.²) but weakly positive for CK 19 and 100%⁴ negative for vimentin. Positive for EGFR⁵. They share the positivity for carbonic anhydrase C and some lectins like DBA, SBA, and WGA with oncocytomas but lack band 3 anion carrier positivity. Another distinctive feature is the co-expression of CD 44s and CD44v6 on the cell membrane, which is of differential diagnostic importance.
• Collecting duct carcinoma:
  Collecting duct carcinomas are medullary-centered; may co-express cytokeratins (CK 8/18) and vimentin. They show pronounced cytoplasmic positivity for CK 19 and UEA-1 but lack CK 13, antigens of the proximal tubule and of the intercalated cells. Their columnar epithelial differentiation is reminiscent of the principal cells of the medullary collecting duct. They can have papillaryfeatures². Are K903 positive.
• Urothelial carcinoma:
  These can have granular cytoplasm and papillary features. The immunohistological profile of pelvic/intrarenal urothelial carcinoma differs totally from those mentioned above. They express cytokeratins typical of both columnar epithelium (CK 8/18, 19, 7, and 20) and squamous epithelium (CK 5/14/17, and 13...but ck7 & ck20 negative if true SCC [L07-1853]) and lack vimentin. Thus immunohistology favors histogenesis from urothelial cells within the ducts of Bellini.
• Neuroendocrine tumors of the kidney:
  The neuroendocrine tumors of the kidney lack vimentin and squamous cell-specific cytokeratins. They are positive for columnar epithelial cytokeratins (CK 8/18, and 19), and depending on a prevailing endocrine or neurogenic differentiation, may be positive for chromogranin, synaptophysin, and neurofilaments. These antigens cannot be detected in any other RCC.
• Metanephric adenoma:
  In solid tumor areas, the tumor cells express vimentin only whereas in more differentiated tubular or glomeruloid areas some cytokeratins can be found but not CK 19. Lack of NCAM is of importance for the differential diagnosis of nephroblastoma.
• Angiomyolipoma:
  This tumor may be sporadic or associated with tuberous sclerosis. It is HMB45 positive. [LMC-05-6301] .

• In Summary

  Summing up the data, there is immunohistological diversity among the renal cell neoplasms. The immunohistological differences reflect the different histogenesis of the tumors and point to histogenetic relationships in case of common findings (clear cell RCC and chromophil RCC, oncocytomas and chromophobe RCC).

References:

1. essentially copied from John N. Eble, M.D., Indiana University School of Medicine Indianapolis, IN and Stephan Storkel, M.D., University of Witten/Herdecke, Wuppertal, Germany on the USCAP web site 4/24/01
2. Kim M, Applied Immunohistochemistry & Molecular Morphology 10(4):332-338, Dec. 2002 (Dr. Armstrong's journal)
3. Leroy X, et. al., Utility of Cytokeratin 7 for Distinguishing Chromophobe RCC from Renal Oncocytoma, Eur. Urol. 37(4):484-7, April 2000.
4. Abrahams NA, et. al., "Chromophobe...", Histopathology 45(6):593-602, December 2004.
5. Shah, Sejal, "Expression of EGFR...", Poster #29, ASCP annual meeting in Las Vegas, 10/2006 .

(posted 2002; latest update 15 August 2007)