Skip to main content
Log in

Cytogenetic and immunohistochemical study of 42 pigmented microcystic chromophobe renal cell carcinoma (PMChRCC)

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Pigmented microcystic chromophobe renal cell carcinoma (PMChRCC) is a recently described morphologic variant of ChRCC. We have identified 42 cases in 40 patients in the last 24 years. We have investigated their clinical, morphologic, immunohistochemical, and cytogenetic features. Chromosomal abnormalities of chromosomes 7 and 17 were evaluated by automated dual-color silver-enhanced in situ hybridization on paraffin-embedded tissue. Chromosomal imbalance was defined on the basis of changes in both chromosomal index and signal distribution. The main age was 60.20 years, being 34 males and 6 women. The mean tumor diameter was 4.84 cm, with 39 intrarenal tumors. Grossly, the tumors were solid with a brown dark colored. Microscopically, tumors consisted of pale and eosinophilic cells arranged in microcysts or microalveolar in a cribriform pattern; there were microcalcifications and a dark brown pigment, mostly extracellular. One case showed sarcomatoid transformation. All tumors were positive for epithelial membrane antigen (EMA), Claudin 7, and E-cadherin. Monosomy of 7 and 17 chromosomes was present in 1/36 cases and 2/37 cases, respectively. Polysomy of chromosome 7 and 17 was found in 26/36 cases and in 4/37, respectively. With a median follow-up of 74.05 months, 37 patients were alive without disease and two were alive with disease progression. PMChRCCs expand the morphologic spectrum of the ChRCC with an unusual immunohistochemical profile. Cytogenetically, they showed monosomy to chromosome (CHR) 17 as other ChRCCs and polysomy of CHR 7 infrequent to ChRCCs. We present the probably largest series of PMCRCC, confirming their low aggressive behavior, with exceptional sarcomatoid transformation and distant metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Truong LD, Shen SS (2011) Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med 135(1):92–109

    PubMed  Google Scholar 

  2. Thoenes W, Störkel S, Rumpelt HJ (1985) Human chromophobe cell renal carcinoma. Virchows Arch B Cell Pathol Incl Mol Pathol 48(3):207–217

    Article  PubMed  CAS  Google Scholar 

  3. Thoenes W, Störkel S, Rumpelt HJ, Moll R, Baum HP, Werner S (1988) Chromophobe cell renal carcinoma and its variants—a report on 32 cases. J Pathol 155(4):277–287

    Article  PubMed  CAS  Google Scholar 

  4. Michal M, Hes O, Svec A, Ludvíková M (1998) Pigmented microcystic chromophobe cell carcinoma: a unique variant of renal cell carcinoma. Ann Diagn Pathol 2(3):149–153

    Article  PubMed  CAS  Google Scholar 

  5. Hes O, Vanecek T, Perez-Montiel DM, Alvarado Cabrero I, Hora M, Suster S, Lamovec J, Curik R, Mandys V, Michal M (2005) Chromophobe renal cell carcinoma with microcystic and adenomatous arrangement and pigmentation—a diagnostic pitfall. Morphological, immunohistochemical, ultrastructural and molecular genetic report of 20 cases. Virchows Arch 446(4):383–393

    Article  PubMed  CAS  Google Scholar 

  6. Dundr P, Pesl M, Povýsil C, Tvrdík D, Pavlík I, Soukup V, Dvorácek J (2007) Pigmented microcystic chromophobe renal cell carcinoma. Pathol Res Pract 203(8):593–597

    Article  PubMed  Google Scholar 

  7. Dhingra K, Sneige N, Pandita TK, Johnston DA, Lee JS, Emami K, Hortobagyi GN, Hittelman WN (1994) Quantitative analysis of chromosome in situ hybridization signal in paraffin-embedded tissue sections. Cytometry 16(2):100–112

    Article  PubMed  CAS  Google Scholar 

  8. Sandinha MT, Farquharson MA, Roberts F (2004) Identification of monosomy 3 in choroidal melanoma by chromosome in situ hybridisation. Br J Ophthalmol 88(12):1527–1532

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Russell AJ, Sibbald J, Haak H, Keith WN, McNicol AM (1999) Increasing genome instability in adrenocortical carcinoma progression with involvement of chromosomes 3, 9 and X at the adenoma stage. Br J Cancer 81(4):684–689

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Mantoan Padilha M, Billis A, Allende D, Zhou M, Magi-Galluzzi C (2013) Metanephric adenoma and solid variant of papillary renal cell carcinoma: common and distinctive features. Histopathology 62(6):941–953

    Article  PubMed  Google Scholar 

  11. Ohe C, Kuroda N, Takasu K, Senzaki H, Shikata N, Yamaguchi T, Miyasaka C, Nakano Y, Sakaida N, Uemura Y (2012) Utility of immunohistochemical analysis of KAI1, epithelial-specific antigen, and epithelial-related antigen for distinction of chromophobe renal cell carcinoma, an eosinophilic variant from renal oncocytoma. Med Mol Morphol 45(2):98–104

    Article  PubMed  CAS  Google Scholar 

  12. Molinié V, Balaton A, Rotman S, Mansouri D, De Pinieux I, Homsi T, Guillou L (2006) Alpha-methyl CoA racemase expression in renal cell carcinomas. Hum Pathol 37(6):698–703

    Article  PubMed  CAS  Google Scholar 

  13. Bing Z, Lal P, Lu S, Ziober A, Tomaszewski JE (2013) Role of carbonic anhydrase IX, α-methylacyl coenzyme a racemase, cytokeratin 7,and galectin-3 in the evaluation of renal neoplasms: a tissue microarray immunohistochemical study. Ann Diagn Pathol 17(1):58–62

    Article  PubMed  Google Scholar 

  14. Lin F, Brown RE, Shen T, Yang XJ, Schuerch C (2004) Immunohistochemical detection of P504S in primary and metastatic renal cell carcinomas. Appl Immunohistochem Mol Morphol 12(2):153–159

    Article  PubMed  CAS  Google Scholar 

  15. Lhermitte B, de Leval L (2012) Interpretation of needle biopsies of the kidney for investigation of renal masses. Virchows Arch 461(1):13–26

    Article  PubMed  Google Scholar 

  16. Barocas DA, Mathew S, Del Pizzo JJ, Vaughan ED Jr, Sosa RE, Fine RG, Akhtar M, Scherr DS (2007) Renal cell carcinoma sub-typing by histopathology and fluorescence in situ hybridization on a needle-biopsy specimen. BJU Int 99(2):290–295

    Article  PubMed  Google Scholar 

  17. Brunelli M, Eble JN, Zhang S, Martignoni G, Delahunt B, Cheng L (2005) Eosinophilic and classic chromophobe renal cell carcinomas have similar frequent losses of multiple chromosomes from among chromosomes 1, 2, 6, 10, and 17, and this pattern of genetic abnormality is not present in renal oncocytoma. Mod Pathol 18(2):161–169

    Article  PubMed  CAS  Google Scholar 

  18. Monzon FA, Alvarez K, Gatalica Z, Bridge JA, Nelson M, Kim HJ, Hagenkord JM (2009) Detection of chromosomal aberrations in renal tumors: a comparative study of conventional cytogenetics and virtual karyotyping with single-nucleotide polymorphism microarrays. Arch Pathol Lab Med 133(12):1917–1922

    PubMed  Google Scholar 

  19. Brunelli M, Delahunt B, Gobbo S, Tardanico R, Eccher A, Bersani S, Cossu-Rocca P, Parolini C, Balzarini P, Menestrina F, Cheng L, Eble JN, Martignoni G (2010) Diagnostic usefulness of fluorescent cytogenetics in differentiating chromophobe renal cell carcinoma from renal oncocytoma: a validation study combining metaphase and interphase analyses. Am J Clin Pathol 133(1):116–126

    Article  PubMed  Google Scholar 

  20. Tan MH, Wong CF, Tan HL, Yang XJ, Ditlev J, Matsuda D, Khoo SK, Sugimura J, Fujioka T, Furge KA, Kort E, Giraud S, Ferlicot S, Vielh P, Amsellem-Ouazana D, Debré B, Flam T, Thiounn N, Zerbib M, Benoît G, Droupy S, Molinié V, Vieillefond A, Tan PH, Richard S, Teh BT (2010) Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma. BMC Cancer 10:196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Vieira J, Henrique R, Ribeiro FR, Barros-Silva JD, Peixoto A, Santos C, Pinheiro M, Costa VL, Soares MJ, Oliveira J, Jerónimo C, Teixeira MR (2010) Feasibility of differential diagnosis of kidney tumors by comparative genomic hybridization of fine needle aspiration biopsies. Genes Chromosomes Cancer 49(10):935–947

    Article  PubMed  CAS  Google Scholar 

  22. Sperga M, Martinek P, Vanecek T, Grossmann P, Bauleth K, Perez-Montiel D, Alvarado-Cabrero I, Nevidovska K, Lietuvietis V, Hora M, Michal M, Petersson F, Kuroda N, Suster S, Branzovsky J, Hes O (2013) Chromophobe renal cell carcinoma-chromosomal aberration variability and its relation to Paner grading system: an array CGH and FISH analysis of 37 cases. Virchows Arch 463(4):563–573

    Article  PubMed  CAS  Google Scholar 

  23. Carvalho JC, Wasco MJ, Kunju LP, Thomas DG, Shah RB (2011) Cluster analysis of immunohistochemical profiles delineates CK7, vimentin, S100A1 and C-kit (CD117) as an optimal panel in the differential diagnosis of renal oncocytoma from its mimics. Histopathology 58(2):169–179

    Article  PubMed  Google Scholar 

  24. Petersson F, Gatalica Z, Grossmann P, Perez Montiel MD, Alvarado Cabrero I, Bulimbasic S, Swatek A, Straka L, Tichy T, Hora M, Kuroda N, Legendre B, Michal M, Hes O (2010) Sporadic hybrid oncocytic/chromophobe tumor of the kidney: a clinicopathologic, histomorphologic, immunohistochemical, ultrastructural, and molecular cytogenetic study of 14 cases. Virchows Arch 456(4):355–365

    Article  PubMed  Google Scholar 

  25. Gill AJ, Pachter NS, Chou A, Young B, Clarkson A, Tucker KM, Winship IM, Earls P, Benn DE, Robinson BG, Fleming S, Clifton-Bligh RJ (2011) Renal tumors associated with germline SDHB mutation show distinctive morphology. Am J Surg Pathol 35(10):1578–1585

    Article  PubMed  Google Scholar 

  26. Gill AJ, Hes O, Papathomas T, Šedivcová M, Tan PH, Agaimy A, Andresen PA, Kedziora A, Clarkson A, Toon CW, Sioson L, Watson N, Chou A, Paik J, Clifton-Bligh RJ, Robinson BG, Benn DE, Hills K, Maclean F, Niemeijer ND, Vlatkovic L, Hartmann A, Corssmit EP, van Leenders GJ, Przybycin C, McKenney JK, Magi-Galluzzi C, Yilmaz A, Yu D, Nicoll KD, Yong JL, Sibony M, Yakirevich E, Fleming S, Chow CW, Miettinen M, Michal M, Trpkov K (2014) Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients. Am J Surg Pathol 38(12):1588–1602

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kuroda N, Tanaka A, Yamaguchi T, Kasahara K, Naruse K, Yamada Y, Hatanaka K, Shinohara N, Nagashima Y, Mikami S, Oya M, Hamashima T, Michal M, Hes O (2013) Chromophobe renal cell carcinoma, oncocytic variant: a proposal of a new variant giving a critical diagnostic pitfall in diagnosing renal oncocytic tumors. Med Mol Morphol. 46(1):49–55

    Article  PubMed  Google Scholar 

  28. Peckova K, Martinek P, Ohe C, Kuroda N, Bulimbasic S, Condom Mundo E, Perez Montiel D, Lopez JI, Daum O, Rotterova P, Kokoskova B, Dubova M, Pivovarcikova K, Bauleth K, Grossmann P, Hora M, Kalusova K, Davidson W, Slouka D, Miroslav S, Buzrla P, Hynek M, Michal M, Hes O (2015) Chromophobe renal cell carcinoma with neuroendocrine and neuroendocrine-like features. Morphologic, immunohistochemical, ultrastructural, and array comparative genomic hybridization analysis of 18 cases and review of the literature. Ann Diagn Pathol 19(4):261–268

    Article  PubMed  Google Scholar 

  29. Foix MP, Dunatov A, Martinek P, Mundó EC, Suster S, Sperga M, Lopez JI, Ulamec M, Bulimbasic S, Montiel DP, Alaghehbandan R, Peckova K, Pivovarcikova K, Ondrej D, Rotterova P, Skenderi F, Prochazkova K, Dusek M, Hora M, Michal M, Hes O (2016) Morphological, immunohistochemical, and chromosomal analysis of multicystic chromophobe renal cell carcinoma, an architecturally unusual challenging variant. Virchows Arch 469(6):669–678

    Article  PubMed  CAS  Google Scholar 

  30. Argani P, Yonescu R, Morsberger L, Morris K, Netto GJ, Smith N, Gonzalez N, Illei PB, Ladanyi M, Griffin CA (2012) Molecular confirmation of t(6;11)(p21;q12) renal cell carcinoma in archival paraffin-embedded material using a break-apart TFEB FISH assay expands its clinicopathologic spectrum. Am J Surg Pathol 36(10):1516–1526

    Article  PubMed  PubMed Central  Google Scholar 

  31. Argani P, Aulmann S, Karanjawala Z, Fraser RB, Ladanyi M, Rodriguez MM (2009) Melanotic Xp11 translocation renal cancers: a distinctive neoplasm with overlapping features of PEComa, carcinoma, and melanoma. Am J Surg Pathol 33(4):609–619

    Article  PubMed  Google Scholar 

  32. Argani P, Olgac S, Tickoo SK, Goldfischer M, Moch H, Chan DY, Eble JN, Bonsib SM, Jimeno M, Lloreta J, Billis A, Hicks J, De Marzo AM, Reuter VE, Ladanyi M (2007) Xp11 translocation renal cell carcinoma in adults: expanded clinical, pathologic, and genetic spectrum. Am J Surg Pathol 31(8):1149–1160

    Article  PubMed  Google Scholar 

  33. Argani P, Hicks J, De Marzo AM, Albadine R, Illei PB, Ladanyi M, Reuter VE, Netto GJ (2010) Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. Am J Surg Pathol 34(9):1295–1303

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ribalta T, Lloreta J, Munné A, Serrano S, Cardesa A (2000) Malignant pigmented clear cell epithelioid tumor of the kidney: clear cell (“sugar”) tumor versus malignant melanoma. Hum Pathol 31(4):516–519

    Article  PubMed  CAS  Google Scholar 

  35. Siracusano S, Novara G, Antonelli A, Artibani W, Bertini R, Carini M, Carmignani G, Ciciliato S, Cunico SC, Lampropoulou N, Longo N, Martorana G, Minervini A, Mirone V, Simeone C, Simonato A, Valotto C, Zattoni F, Ficarra V, members of the SATURN Project—LUNA Foundation (2012) Prognostic role of tumour multifocality in renal cell carcinoma. BJU Int 110(11 Pt B):E443–E448

    Article  PubMed  Google Scholar 

  36. Delahunt B, McKenney JK, Lohse CM, Leibovich BC, Thompson RH, Boorjian SA, Cheville JC (2013) A novel grading system for clear cell renal cell carcinoma incorporating tumor necrosis. Am J Surg Pathol 37(3):311–322

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We want to thank Loli Martinez Ruiz, Marian Martinez Galán, Jessica Bassola Casanova, Silvia Hurtado Mas, Maria Jose Trujillo Perez, Yolanda Rodríguez Díez, and Ingrid Strohecker Santos, pathology technicians, for their efforts.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francisco Javier Queipo Gutiérrez.

Ethics declarations

Ethical responsibilities of authors

Virchows Archiv conforms to the ICMJE recommendation for qualification of authorship. The ICMJE recommends that authorship be based on the following four criteria:

  • Substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work

  • Drafting the work or revising it critically for important intellectual content

  • Final approval of the version to be published

  • Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved

All individuals listed as co-authors of the manuscript must qualify for every one of the four criteria listed above. Should an individual’s contributions to the manuscript meet three of the criteria or fewer, then they should not be listed as a co-author on the manuscript; instead, their contributions should be acknowledged in the “Acknowledgements” section of the manuscript.

The manuscript has not been submitted to more than one journal for simultaneous consideration. The manuscript has not been published previously (partly or in full).

Consent to submit has been received explicitly from all co-authors, as well as from the responsible authorities—tacitly or explicitly—at the institute/organization where the work has been carried out, before the work is submitted.

No data have been fabricated or manipulated (including images) to support the conclusions.

Each author has collaborated in the preparation, writing, or correction of the original manuscript. All authors have read and approved the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gutiérrez, F.J.Q., Panizo, Á., Tienza, A. et al. Cytogenetic and immunohistochemical study of 42 pigmented microcystic chromophobe renal cell carcinoma (PMChRCC). Virchows Arch 473, 209–217 (2018). https://doi.org/10.1007/s00428-018-2389-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-018-2389-y

Keywords

Navigation