A Novel Prognostic Criteria and Targeted Therapy in Sarcomatoid Variant of Chromophobic Renal Cell Carcinoma

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V. V. Ermilov
O. V. Dolzhanski
A. Agarwal
H. A. Mouhammed


Chromophobic renal cell carcinoma (CRCC) is a rare subtype of renal cell carcinoma, accounting for only 5.9% of epithelial kidney tumors. This study reports the findings studied in chromophobic renal cell carcinoma case with sarcomatoid differentiation in a 66-year-old patient admitted in Federal State Budgetary Institution (FSBI). This study concludes that, the criteria of aggressive behavior for chromophobic renal cell carcinoma include the following characteristics: The size of the tumor more than 7.0 cm; presence of necrosis; grade III according to Paner et al. classification; sarcomatoid differentiation (more than 30.0%); positive reaction with common acute lymphocytic leukemia antigen (CD10); nuclear expression of p53 in more than 80.0% of tumor cells; proliferation marker Ki67 in more than 9.0% of tumor cells. In this case, the indication for targeted therapy was sarcomatoid differentiation (in more than 10.0% of the tumor) and a strong reaction with Vascular endothelial growth factor; 5-6 points ((VEGF-A).

Sarcomatoid differentiation, renal cell carcinoma, epithelial kidney tumors, tumor cells.

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Ermilov, V. V., Dolzhanski, O. V., Agarwal, A., & Mouhammed, H. A. (2019). A Novel Prognostic Criteria and Targeted Therapy in Sarcomatoid Variant of Chromophobic Renal Cell Carcinoma. International Research Journal of Oncology, 2(2), 1-13. Retrieved from http://journalirjo.com/index.php/IRJO/article/view/30103
Case Report


Quiroga-Garza G, Khurana H, Shen S, Ayala AG, Ro JY. Sarcomatoid chromophobe is renal cell carcinoma with heterologous sarcomatoid elements. A case report and review of the literature. Arch Pathol Lab Med. 2009;133 (11):1857-1860.

De Peralta-Venturina M, Moch H, Amin M, Tamboli P, Hailemariam S, Mihatsch M, Javidan J, Stricker H, Ro JY, Amin MB. Sarcomatoid differentiation in renal cell carcinoma: A study of 101 cases. Am J Surg Pathol. 2001;25(3):275-284.

Ebru T, Fulya OP, Hakan A, Vuslat YC, Necdet S, Nuray C, Filiz O Analysis of various potential prognostic markets and survival data in clear cell renal cell carcinoma. Int Braz J Urol. 2017;43(3): 440-454.

Osman WM, Youssef NS. Combined use of COX-1 and VEGF immunohisto-chemistry refines the carried out a histopathologic prognosis of renal cell carcinoma. Int J Clin Exp Pathol. 2015; 8(7):8165-8177.

Chowdhury S, Matrana MR, Tsang C, Atkinson B, Choueiri TK, Tannir NM. Systematic therapy for metastatic non-clear cell renal cell carcinoma: Recent progress and future directions. Hematol Oncol Clin North Am. 2011;25(4):853- 869.

Yang Y, Vocke CD, Rickets CJ, Wei D, Padilla-Nash HM, Lang M, Sourbier C, Killian JK, Boyle SL, Worrell R, Meltzer PS, Reed T, Merino MJ, Metwalli AR, Linehan WM. Genomic and metabolic characteriza-tion of chromophobe is a renal cell carcinoma cell line model (UOK276). Genes Chromosomes Cancer. 2017; 56(10):719-729.

Zhang Z, Min J, Yu D, Shi H, Xie D. Renal collision tumour of papillary cell carcinoma and chromophobe cell carcinoma with sarcomatoid transformation: A case report and review of the literature. Can Urol Assoc J. 2014;8(7-8):E536-9.

Kuroda N, Tamura M, Hes O, Michal M, Gatalica Z. Chromophobe renal cell carcinoma with neuroendocrine differentia-tion and sarcomatoid change. Pathol Int. 2011;61:552–4.

Parada DD, Peña KB. Chromophobe renal cell carcinoma with neuroendocrine differentiation. APMIS. 2008;116:859–65.

Roy S, Hooda S, Huang GJ, Pantanowitz L, Parwani AV. A novel case of concurrent renal tumors: Chromophobe renal cell carcinoma and carcinoid tumor of the kidney with brief review of renal neuroendocrine tumors. Int J Surg Pathol. 2012;20:531–5.

Nagashima Y. Chromophobe renal cell carcinoma: Clinical, pathological and molecular biological aspects. Pathol Int. 2000;50:872–8.

Lane BR, Jour G, Zhou M. Renal neuroendocrine tumors. Indian J Urol. 2009;25:155–60.

Urological Surgical Pathology. - 3rd ed./edited by David G. Bostwick, Liang Cheng. Philadelphia: Elsevier; 2014.

Tanaka Y, Koie T, Hatakeyama S, Hashimoto Y, Ohyama C. Chromophobe is renal cell carcinoma with concomitant sarcomatoid transformation and osseous metaplasia: A case report. BMC Urol. 2013;13:72.

Shuch B, Said J, LaRochelle JC, Zhou Y, Li G, Klatte T, Pouliot F, Kabbinavar FF, Belldegrun as, Pantuck AJ. Histologic evaluation of metastases in renal cell carcinoma with sarcomatoid transformation and its implications for systemic therapy. Cancer. 2010;116 (3):616-624.
Available:https://doi: 10.1002 / cncr.24768 19998348

Practical renal pathology: A diagnostic approach/ edited by Donna J. Lager, Neil A. Abrahams. Philadelphia: Elsevier; 2013.

Zhang T, Gong J, Maia MC, Pal SK. Systematic therapy for non-clear cell renal cell carcinoma. Am Soc Clin Oncol Educ Book. 2017;37:337-342.

Shuch B, Bratslavsky G, Linehan WM, Srinivasan R. Sarcomatoid renal cell carcinoma: A comprehensive review of the biology and current treatment strategies. Oncologist. 2012;17(1):46-54.
Available:https://doi:10.1634/ theoncologist .2011-0227

Oda H, Nakatsuru Y, Ishikawa T. Mutations of the p53 gene and p53 protein overexpression are associated with sarcomatoid transformation in renal cell carcinomas. Cancer Res. 1995;55(3):658-662.

Cserni G, Kovács BR, Tarján M, Sápi Z, Domján Z, Szabó Z. Sarcomatoid renal cell carcinoma with foci of chromophobe carcinoma. Pathol Oncol Res. 2002;8(2): 142-144.

Wu J, Joseph SO, Muggia FM. Targeted therapy: Its status and promise in selected solid tumors part I: Areas of major impact. Oncology (Williston Park). 2012;26(10): 936-943.

Kobayashi N, Suzuki K, Murakami H, Kagawa E, Aoki I, Nagashima Y. chromophobe is renal cell carcinoma with sarcomatoid transformation in a dog. J Vet Diagn Invest. 2010;22(6):983-987.

Martignoni G, Pea M, Brunelli M, Chilosi M, Zamó A, Bertaso M, Cossu-Rocca P, Eble JN, Mikuz G, Puppa G, Badoual C, Ficarra V, Novella G, Bonetti F. CD10 is expressed in a subset of chromophobe renal cell carcinomas. Mod Pathol. 2004; 17(12):1455-1463.

Paner GP, Amin MB, Alvarado-Cabrero I, Young AN, Stricker HJ, Moch H, 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;34:1233-1240.

Moskvina LV, Andreeva YU, Malkov PG, Frank GA. New approaches to the classification, gradation and forecast pochernkletocny cancer. Archives of pathology. 2014;2(76):60-70. The link is active on 12.01.2018.

Nefedova NA, Davydov S. Yu. The role of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) in tumor angiogenesis. Modern Problems of Science and Education. 2015;3:51-64.

Varlamov AV, Paltseva EM, Sekacheva MI, Skipenko OG, Fedorov DN. The influence of preoperative drug therapy on the expression of angiogenesis markers in colorectal cancer metastases in the liver. Archives of Pathology. 2017;79(1):36-42.

Iliopoulos O, Eng C. Genetic and clinical aspects of familial renal neoplasms. Semin Oncol. 2000;27(2):138-49.

Rohan SM, Xiao Y, Liang Y, Dudas ME, Al-Ahmadie HA, Fine SW, Gopalan A, Reuter VE, Rosenblum MK, Russo P, Tickoo SK. Clear-cell papillary renal cell carcinoma: Molecular and immunohisto-chemical analysis with emphasis on the von Hippel-Lindau gene and hypoxia-inducible factor pathway-related proteins. Mod Pathol. 2011;24(9):1207-20.
DOI: 10.1038/modpathol.2011.80
[Epub 2011 May 20]

Giménez-Bachs JM, Salinas-Sánchez AS, Sánchez-Sánchez F, Lorenzo-Romero JG, Donate-Moreno MJ, Pastor-Navarro H, García-Olmo DC, Escribano-Martínez J, Virseda-Rodríguez JA. Determination of vhl gene mutations in sporadic renal cell carcinoma. Eur Urol. 2006 Jun; 49(6):1051-7.
[Epub 2005 Dec 20]

Duan DR, Humphrey JS, Chen DY, Weng Y, Sukegawa J, Lee S, Gnarra JR, Linehan WM, Klausner RD. Characterization of the VHL tumor suppressor gene product: localization, complex formation, and the effect of natural inactivating mutations. Proc Natl Acad Sci USA. 1995;92(14): 6459-63.

Turner KJ, Moore JW, Jones A, Taylor CF, Cuthbert-Heavens D, Han C, Leek RD, Gatter KC, Maxwell PH, Ratcliffe PJ, Cranston D, Harris AL. Expression of hypoxia-inducible factors in human renal cancer: Relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res. 2002;62(10):2957-61.

Linehan WM, Rubin JS, Bottaro DP. VHL loss of function and its impact on oncogenic signaling networks in clear cell renal cell carcinoma. Int J Biochem Cell Biol. 2009;41(4):753-6.
DOI: 10.1016/j.biocel.2008.09.024
[Epub 2008 Oct 2]

Kenck C, Wilhelm M, Bugert P, Staehler G, Kovacs G. Mutation of the VHL gene is associated exclusively with the development of non-papillary renal cell carcinomas. J Pathol. 1996;179(2):157-61.

Corless CL, Kibel AS, Iliopoulos O, Kaelin WG Jr. Immunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues. Hum Pathol. 1997;28(4):459-64.

Brannon AR, Reddy A, Seiler M, Arreola A, Moore DT, Pruthi RS, et al. Molecular stratification of clear cell renal cell carcinoma by consensus clustering reveals distinct subtypes and survival patterns. Genes Cancer. 2010;1(2):152–63.

Brannon AR, Haake SM, Hacker KE, Pruthi RS, Wallen EM, Nielsen ME, et al. Meta-analysis of clear cell renal cell carcinoma gene expression defines a variant subgroup and identifies gender influences on tumor biology. European urology. 2012;61(2):258–68.

Song SH, Jeong IG, you D, Hong JH, Hong B, Song C, Jung WY, Cho YM, Ahn H, Kim CS.VEGF/VEGFR2 and PDGF-b / PDGFR-β expression in nonmetastatic renal cell carcinoma: A retrospective study in 1,091 conservative patients. Int J Clin Exp Pathol. 2014;7(11):7681-7689.

Minardi D, Santoni M, Lucarini G, Mazzucchelli R, Burattini l, Conti A, Bianconi M, Scartozzi M, Milanese G, Primio RD, Montironi R, Cascinu S, Muzzonigro G. Tumor VEGF expression correlates with tumor stage and identities prognostically different groups in patients with clear cell renal cell. Urol Oncol. 2015; 33(3):113.e1-7.

Stubbs C, Bardoli AD, Afshar M, Pirrie S, Miscoria M, Wheeley I, Porfiri E. A study of angiogenesis markers in patients with renal cell carcinoma undergoing therapy with sunitinib. Anticancer Res. 2017;37(1): 253-259. Available:https://10.21873/anticanres.Eleven thousand three hundred fifteen

Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473(7347): 298-307.

Michaelson MD, McKay RR, Werner L, Atkins MB, Van Allen EM, Olivier KM, Song J, Signoretti S, McDermott DF, Choueiri TK. Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer. 2015;121(19):3435-3443.

Baumgarten P, Blank AE, Franz K, Hattingen E, Dunst m, Zeiner P, Hoffmann K, Bähr O, Mäder L, Goeppert B, Machein M, Seifert V, Steinbach JP, Plate Kh, Harter PN, Mittelbronn M. Differential expression of vascular endothelial growth factor a, its receptors, VEGFR-1, and3-and co-receptors neuropilin-1 and -2 does not predict bevacizumab response in human astrocytomas. Neuro Oncol. 2016;18(2): 173-183.

Available:https://doi: 10.1093/ neuonc / no Desar IM, Stillebroer AB, Oosterwijk E, Leenders WP, van Herpen CM, van der Graaf WT, Boerman OC, Mulders PF, Oyen WJ. 111In-bevacizumab imaging of renal cell cancer and evaluation of neoadjuvant treatment with the vascular endothelial growth factor receptor inhibitor sorafenib.

Desar IM, Stillebroer AB, Oosterwijk E, Leenders WP, van Herpen CM, van der Graaf WT, Boerman OC, Mulders PF, Oyen WJ. 111In-bevacizumab imaging of renal cell cancer and evaluation of neoadjuvant treatment with the vascular endothelial growth factor receptor inhibitor sorafenib. J Nucl Med. 2010;51(11):1707-1715.