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Chromophobe Renal Cell Carcinoma

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Rare Kidney Tumors

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Abstract

Chromophobe renal cell carcinoma (ChRCC) makes up approximately 5% of all cases of renal cell carcinoma (RCC) [1]. First described in 1985, this rare subtype of RCC was originally thought to arise from the intercalated cells of the collecting ducts. This disease is challenging to diagnose, and on biopsy, this malignancy can share histologic similarities with benign oncocytomas using conventional evaluation or even be misclassified as the more common clear-cell RCC [2–4]. Therefore, careful histologic attention is needed to appropriately capture these cases. Histologically, two variants of ChRCC are recognized: classic ChRCC and an eosinophilic variant [5]. The classic type is more common and is characterized by large cells with pale “chromophobe” cytoplasm and a perinuclear halo or clearing. On the other hand, the tumor cells in the eosinophilic variant display a dense eosinophilic cytoplasm and perinuclear halos (Fig. 4.1).

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References

  1. Lopez-Beltran A, Carrasco JC, Cheng L, Scarpelli M, Kirkali Z, Montironi R. 2009 Update on the classification of renal epithelial tumors in adults. Int J Urol. 2009;16(5):432–43. https://doi.org/10.1111/j.1442-2042.2009.02302.x.

    Article  PubMed  Google Scholar 

  2. Thoenes W, Storkel S, Rumpelt HJ. Human chromophobe cell renal carcinoma. Virchows Arch B Cell Pathol Incl Mol Pathol. 1985;48(3):207–17.

    Article  CAS  PubMed  Google Scholar 

  3. Störkel S, Steart PV, Drenckhahn D, Thoenes W. The human chromophobe cell renal carcinoma: Its probable relation to intercalated cells of the collecting duct. Virchows Arch B Cell Pathol Incl Mol Pathol. 1988;56(1):237–45. https://doi.org/10.1007/BF02890022.

    Article  Google Scholar 

  4. Delongchamps NB, Galmiche L, Eiss D, et al. Hybrid tumour “oncocytoma-chromophobe renal cell carcinoma” of the kidney: A report of seven sporadic cases. BJU Int. 2009;103(10):1381–4. https://doi.org/10.1111/j.1464-410X.2008.08263.x.

    Article  PubMed  Google Scholar 

  5. Podduturi V, Yourshaw CJ, Zhang H. Eosinophilic variant of chromophobe renal cell carcinoma. Proc (Bayl Univ Med Cent). 2015;28(1):57–8.

    Article  Google Scholar 

  6. Speicher MR, Schoell B, du Manoir S, et al. Specific loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe renal cell carcinomas revealed by comparative genomic hybridization. Am J Pathol. 1994;145(2):356–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Iqbal MA, Akhtar M, Ali MA. Cytogenetic findings in renal cell carcinoma. Hum Pathol. 1996;27(9):949–54.

    Article  CAS  PubMed  Google Scholar 

  8. Davis CF, Ricketts CJ, Wang M, et al. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014;26(3):319–30. https://doi.org/10.1016/j.ccr.2014.07.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Guo J, Tretiakova MS, Troxell ML, et al. Tuberous sclerosis-associated renal cell carcinoma: a clinicopathologic study of 57 separate carcinomas in 18 patients. Am J Surg Pathol. 2014;38(11):1457–67. https://doi.org/10.1097/PAS.0000000000000248.

    Article  PubMed  Google Scholar 

  10. Pavlovich CP, Walther MM, Eyler RA, et al. Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol. 2002;26(12):1542–52. https://doi.org/10.1097/00000478-200212000-00002.

    Article  PubMed  Google Scholar 

  11. Delahunt B, Sika-Paotonu D, Bethwaite PB, et al. Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. Am J Surg Pathol. 2007;31(6):957–60. https://doi.org/10.1097/01.pas.0000249446.28713.53.

    Article  PubMed  Google Scholar 

  12. Steffens S, Janssen M, Roos FC, et al. The Fuhrman grading system has no prognostic value in patients with nonsarcomatoid chromophobe renal cell carcinoma. Hum Pathol. 2014;45(12):2411–6. https://doi.org/10.1016/j.humpath.2014.08.002.

    Article  PubMed  Google Scholar 

  13. Paner GP, Amin MB, Alvarado-Cabrero I, et al. A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade. Am J Surg Pathol. 2010;34(9):1233–40. https://doi.org/10.1097/PAS.0b013e3181e96f2a.

    Article  PubMed  Google Scholar 

  14. Delahunt B, Cheville JC, Martignoni G, et al. The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol. 2013;37(10):1490–504. https://doi.org/10.1097/PAS.0b013e318299f0fb.

    Article  PubMed  Google Scholar 

  15. Prasad SR, Narra VR, Shah R, et al. Segmental disorders of the nephron: histopathological and imaging perspective. Br J Radiol. 2007;80(956):593–602. https://doi.org/10.1259/bjr/20129205.

    Article  CAS  PubMed  Google Scholar 

  16. Chen F, Zhang Y, Senbabaoglu Y, et al. Multilevel genomics-based taxonomy of renal cell carcinoma. Cell Rep. 2016;14(10):2476–89. https://doi.org/10.1016/j.celrep.2016.02.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fahey CC, Rathmell WK. A tale of two cancers: Complete genetic analysis of chromophobe renal cell carcinoma contrasts with clear cell renal cell carcinoma. Mol Cell Oncol. 2015;2(2):e979686. https://doi.org/10.4161/23723556.2014.979686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Birt AR, Hogg GR, Dubé WJ, et al. Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol. 1977;113(12):1674. https://doi.org/10.1001/archderm.1977.01640120042005.

    Article  CAS  PubMed  Google Scholar 

  19. Schmidt LS, Warren MB, Nickerson ML, et al. Birt-Hogg-Dubé syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet. 2001;69(4):876–82. https://doi.org/10.1086/323744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schmidt LS, Linehan WM. Molecular genetics and clinical features of Birt–Hogg–Dubé syndrome. Nat Rev Urol. 2015;12(10):558–69. https://doi.org/10.1038/nrurol.2015.206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rathmell KW, Chen F, Creighton CJ. Genomics of chromophobe renal cell carcinoma: implications from a rare tumor for pan-cancer studies. Oncoscience. 2015;2(2):81–90. https://doi.org/10.18632/oncoscience.130.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lara PN, Jonasch E, editors. Kidney cancer. 2nd ed. New York: Springer International Publishing; 2015. https://doi.org/10.1007/978-3-319-17903-2.

    Book  Google Scholar 

  23. Nickerson ML, Warren MB, Toro JR, et al. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome. Cancer Cell. 2002;2(2):157–64. https://doi.org/10.1016/S1535-6108(02)00104-6.

    Article  CAS  PubMed  Google Scholar 

  24. Nagy A, Zoubakov D, Stupar Z, Kovacs G. Lack of mutation of the folliculin gene in sporadic chromophobe renal cell carcinoma and renal oncocytoma. Int J Cancer. 2004;109(3):472–5. https://doi.org/10.1002/ijc.11694.

    Article  CAS  PubMed  Google Scholar 

  25. Khoo SK, Kahnoski K, Sugimura J, et al. Inactivation of BHD in sporadic renal tumors. Cancer Res. 2003;63(15):4583–7.

    CAS  PubMed  Google Scholar 

  26. Lim DHK, Rehal PK, Nahorski MS, et al. A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene. Hum Mutat. 2010;31(1):E1043–51. https://doi.org/10.1002/humu.21130.

    Article  PubMed  Google Scholar 

  27. Tsun Z-Y, Bar-Peled L, Chantranupong L, et al. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol Cell. 2013;52(4):495–505. https://doi.org/10.1016/j.molcel.2013.09.016.

    Article  CAS  PubMed  Google Scholar 

  28. Hong SB, Oh H, Valera VA, et al. Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-β signaling. Mol Cancer. 2010;9(1):160. https://doi.org/10.1186/1476-4598-9-160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hong SB, Oh H, Valera VA, Baba M, Schmidt LS, Linehan WM. Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization. PLoS One. 2010;5(12):e15793. https://doi.org/10.1371/journal.pone.0015793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Medvetz DA, Khabibullin D, Hariharan V, et al. Folliculin, the product of the Birt-Hogg-Dube tumor suppressor gene, interacts with the adherens junction protein p0071 to regulate cell-cell adhesion. PLoS One. 2012;7(11):e47842. https://doi.org/10.1371/journal.pone.0047842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nahorski MS, Seabra L, Straatman-Iwanowska A, et al. Folliculin interacts with p0071 (plakophilin-4) and deficiency is associated with disordered Rhoa signalling, epithelial polarization and cytokinesis. Hum Mol Genet. 2012;21(24):5268–79. https://doi.org/10.1093/hmg/dds378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol. 2013;49(4):243–54. https://doi.org/10.1016/j.pediatrneurol.2013.08.001.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008;372(9639):657–68. https://doi.org/10.1016/S0140-6736(08)61279-9.

    Article  CAS  PubMed  Google Scholar 

  34. Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A. 2002;99(21):13571–6. https://doi.org/10.1073/pnas.202476899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006;355:1345–56. https://doi.org/10.1056/NEJMra055323.

    Article  CAS  PubMed  Google Scholar 

  36. Washecka R, Hanna M. Malignant renal tumors in tuberous sclerosis. Urology. 1991;37(4):340–3. https://doi.org/10.1016/0090-4295(91)80261-5.

    Article  CAS  PubMed  Google Scholar 

  37. Yang P, Cornejo K, Sadow P, Cheng L, Wang M, Wu C. Renal cell carcinoma in tuberous sclerosis complex. Am J Surg Pathol. 2014;38(7):895–909. https://doi.org/10.1097/PAS.0000000000000237.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bjornsson J, Short MP, Kwiatkowski DJ, Henske EP. Tuberous sclerosis-associated renal cell carcinoma. Clinical, pathological, and genetic features. Am J Pathol. 1996;149(4):1201–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Welter C, Kovacs G, Seitz G, Blin N. Alteration of mitochondrial DNA in human oncocytomas. Genes Chromosomes Cancer. 1989;1(1):79–82.

    Article  CAS  PubMed  Google Scholar 

  40. Kovacs A, Storkel S, Thoenes W, Kovacs G. Mitochondrial and chromosomal DNA alterations in human chromophobe renal cell carcinomas. J Pathol. 1992;167(3):273–7. https://doi.org/10.1002/path.1711670303.

    Article  CAS  PubMed  Google Scholar 

  41. Chomyn A. Mitochondrial genetic control of assembly and function of complex I in mammalian cells. J Bioenerg Biomembr. 2001;33(3):251–7.

    Article  CAS  PubMed  Google Scholar 

  42. Amin MB, Paner GP, Alvarado-Cabrero I, et al. Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases. Am J Surg Pathol. 2008;32(12):1822–34. https://doi.org/10.1097/PAS.0b013e3181831e68.

    Article  PubMed  Google Scholar 

  43. Thoenes W, Störkel S, Rumpelt HJ, Moll R, Baum HP, Werner S. Chromophobe cell renal carcinoma and its variants--a report on 32 cases. J Pathol. 1988;155(4):277–87. https://doi.org/10.1002/path.1711550402.

    Article  CAS  PubMed  Google Scholar 

  44. Crotty TB, Farrow GM, Lieber MM. Chromophobe cell renal carcinoma: Clinicopathological features of 50 cases. J Urol. 1995;154(3):964–7. https://doi.org/10.1016/S0022-5347(01)66944-1.

    Article  CAS  PubMed  Google Scholar 

  45. Volpe A, Novara G, Antonelli A, et al. Chromophobe renal cell carcinoma (RCC): Oncological outcomes and prognostic factors in a large multicentre series. BJU Int. 2012;110(1):76–83. https://doi.org/10.1111/j.1464-410X.2011.10690.x.

    Article  PubMed  Google Scholar 

  46. Motzer RJ, Bacik J, Mariani T, Russo P, Mazumdar M, Reuter V. Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology. J Clin Oncol. 2002;20(9):2376–81. https://doi.org/10.1200/JCO.2002.11.123.

    Article  PubMed  Google Scholar 

  47. Escudier B, Porta C, Schmidinger M, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v58–68. https://doi.org/10.1093/annonc/mdw328.

    Article  CAS  PubMed  Google Scholar 

  48. Tsimafeyeu I, Demidov L, Kharkevich G, et al. Phase II, multicenter, uncontrolled trial of single-agent capecitabine in patients with non-clear cell metastatic renal cell carcinoma. Am J Clin Oncol. 2012;35(3):251–4. https://doi.org/10.1097/COC.0b013e31820dbc17.

    Article  CAS  PubMed  Google Scholar 

  49. Choueiri TK, Plantade A, Elson P, et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol. 2008;26(1):127–31. https://doi.org/10.1200/JCO.2007.13.3223.

    Article  CAS  PubMed  Google Scholar 

  50. Tannir NM, Plimack E, Ng C, et al. A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma. Eur Urol. 2012;62(6):1013–9. https://doi.org/10.1016/j.eururo.2012.06.043.

    Article  CAS  PubMed  Google Scholar 

  51. Dutcher JP, De Souza P, McDermott D, et al. Effect of temsirolimus versus interferon-alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies. Med Oncol. 2009;26(2):202–9. https://doi.org/10.1007/s12032-009-9177-0.

    Article  CAS  PubMed  Google Scholar 

  52. Koh Y, Lim HY, Ahn JH, et al. Phase II trial of everolimus for the treatment of nonclear-cell renal cell carcinoma. Ann Oncol. 2013;24(4):1026–31. https://doi.org/10.1093/annonc/mds582.

    Article  CAS  PubMed  Google Scholar 

  53. Tannir NM, Jonasch E, Albiges L, et al. Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (ESPN): A randomized multicenter phase 2 trial. Eur Urol. 2016;69(5):866–74. https://doi.org/10.1016/j.eururo.2015.10.049.

    Article  CAS  PubMed  Google Scholar 

  54. Armstrong AJ, Halabi S, Eisen T, et al. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): A multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016;17(3):378–88. https://doi.org/10.1016/S1470-2045(15)00515-X.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Choueiri TK, Fay AP, Gray KP, et al. PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol. 2014;25(11):2178–84. https://doi.org/10.1093/annonc/mdu445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Vanderbilt-Ingram Cancer Center, Nashville, TN, USA

    Aaron R. Lim & W. Kimryn Rathmell

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Correspondence to W. Kimryn Rathmell .

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  1. Department of Hematology and Oncology, Strasbourg University Hospital, Hopital Civil, Strasbourg, France

    Gabriel G. Malouf

  2. Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Nizar M. Tannir

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Lim, A.R., Rathmell, W.K. (2019). Chromophobe Renal Cell Carcinoma. In: Malouf, G., Tannir, N. (eds) Rare Kidney Tumors. Springer, Cham. https://doi.org/10.1007/978-3-319-96989-3_4

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