The Pathology and Molecular Genetics of Sarcomatoid Renal Cell Carcinoma: A Mini-Review
Main Article Content
Keywords
carcinosarcoma, pathology reporting, sarcomatoid renal cell carcinoma, TP53, VHL
Abstract
Sarcomatoid renal cell carcinoma is a highly aggressive tumor. It is not a distinct histologic entity as it can be found in any subtypes of renal cell carcinoma. Recent molecular and genetic evidence suggest that sarcomatoid component is transformed from a common progenitor of the associated renal cell carcinoma, and the TP53 gene plays a pivotal role in this process. The presence of sarcomatoid carcinoma indicates poor prognosis, which also correlates with the amount of the sarcomatoid component. Therefore, the presence and quantity of sarcomatoid component should be reflected in pathology reports. However, pathology reporting seems to vary among laboratories prompting the need for a unified reporting system. We propose a pathology reporting system similar to that of transformed follicular lymphoma that is consistent with the molecular pathogenesis to ensure uniform reporting.
References
1. Griffiths IH, Thackray AC. Parenchymal carcinoma of the kidney. Br J Urol. 1949 Jun;21(2):128–51. http://dx.doi.org/10.1111/j.1464-410X.1949.tb10761.x
2. 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. http://dx.doi.org/10.1634/theoncologist.2011-0227
3. Farrow GM, Harrison EG Jr., Utz DC. Sarcomas and sarcomatoid and mixed malignant tumors of the kidney in adults. Cancer. 1968 Sep;22(3):556–63. http://dx.doi.org/10.1002/1097-0142(196809)22:3<556::AID-CNCR2820220310>3.0.CO;2-N
4. Shuch B, Amin A, Armstrong AJ, Eble JN, Ficarra V, Lopez-Beltran A, et al. Understanding pathologic variants of renal cell carcinoma: Distilling therapeutic opportunities from biologic complexity. Eur Urol. 2015 Jan;67(1):85–97. http://dx.doi.org/10.1016/j.eururo.2014.04.029
5. de Peralta-Venturina M, Moch H, Amin M, Tamboli P, Hailemariam S, Mihatsch M, et al. Sarcomatoid differentiation in renal cell carcinoma: A study of 101 cases. Am J Surg Pathol. 2001 Mar;25(3):275–84. http://dx.doi.org/10.1097/00000478-200103000-00001
6. Cheville JC, Lohse CM, Zincke H, Weaver AL, Leibovich BC, Frank I, et al. Sarcomatoid renal cell carcinoma: An examination of underlying histologic subtype and an analysis of associations with patient outcome. Am J Surg Pathol. 2004 Apr;28(4):435–41. http://dx.doi.org/10.1097/00000478-200404000-00002
7. Shuch B, Said J, La Rochelle JC, Zhou Y, Li G, Klatte T, et al. Cytoreductive nephrectomy for kidney cancer with sarcomatoid histology – Is up-front resection indicated and, if not, is it avoidable? J Urol. 2009 Nov;182(5):2164–71. http://dx.doi.org/10.1016/j.juro.2009.07.049
8. Kyriakopoulos CE, Chittoria N, Choueiri TK, Kroeger N, Lee JL, Srinivas S, et al. Outcome of patients with metastatic sarcomatoid renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. Clin Genitourin Cancer. 2015 Apr;13(2):e79–85. http://dx.doi.org/10.1016/j.clgc.2014.08.011
9. Mian BM, Bhadkamkar N, Slaton JW, Pisters PW, Daliani D, Swanson DA, et al. Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. J Urol. 2002 Jan;167(1):65–70. http://dx.doi.org/10.1016/S0022-5347(05)65384-0
10. Merrill MM, Wood CG, Tannir NM, Slack RS, Babaian KN, Jonasch E, et al. Clinically nonmetastatic renal cell carcinoma with sarcomatoid dedifferentiation: Natural history and outcomes after surgical resection with curative intent. Urol Oncol. 2015 Apr;33(4):166 e21–9. http://dx.doi.org/10.1016/j.urolonc.2014.11.021
11. Cangiano T, Liao J, Naitoh J, Dorey F, Figlin R, Belldegrun A. Sarcomatoid renal cell carcinoma: Biologic behavior, prognosis, and response to combined surgical resection and immunotherapy. J Clin Oncol. 1999 Feb;17(2):523–8. http://dx.doi.org/10.1200/JCO.1999.17.2.523
12. Brookman-May S, May M, Shariat SF, Zigeuner R, Chromecki T, Cindolo L, et al. Prognostic effect of sarcomatoid dedifferentiation in patients with surgically treated renal cell carcinoma: A matched-pair analysis. Clin Genitourin Cancer. 2013 Dec;11(4):465–70. http://dx.doi.org/10.1016/j.clgc.2013.04.026
13. Bostwick DG, Cheng L. Urologic surgical pathology. Philadelphia, PA, USA: Elsevier Health Sciences; 2008.
14. DeLong W, Grignon DJ, Eberwein P, Shum DT, Wyatt JK. Sarcomatoid renal cell carcinoma. An immunohistochemical study of 18 cases. Arch Pathol Lab Med. 1993 Jun;117(6):636–40.
15. Kuroda N, Toi M, Hiroi M, Enzan H. Review of sarcomatoid renal cell carcinoma with focus on clinical and pathobiological aspects. Histol Histopathol. 2003 Apr;18(2):551–5.
16. Krishnan B, Truong LD. Renal epithelial neoplasms: The diagnostic implications of electron microscopic study in 55 cases. Hum Pathol. 2002 Jan;33(1):68–79. http://dx.doi.org/10.1053/hupa.2002.30210
17. Morikawa Y, Tohya K, Kusuyama Y, Masui M, Wakasugi C. Sarcomatoid renal cell carcinoma. An immunohistochemical and ultrastructural study. Int Urol Nephrol. 1993;25(1):51–8. http://dx.doi.org/10.1007/BF02552254
18. Jones TD, Eble JN, Wang M, Maclennan GT, Jain S, Cheng L. Clonal divergence and genetic heterogeneity in clear cell renal cell carcinomas with sarcomatoid transformation. Cancer. 2005 Sep;104(6):1195–203. http://dx.doi.org/10.1002/cncr.21288
19. Conant JL, Peng Z, Evans MF, Naud S, Cooper K. Sarcomatoid renal cell carcinoma is an example of epithelial – Mesenchymal transition. J Clin Pathol. 2011 Dec;64(12):1088–92. http://dx.doi.org/10.1136/jclinpath-2011-200216
20. Piva F, Giulietti M, Santoni M, Occhipinti G, Scarpelli M, Lopez-Beltran A, et al. Epithelial to mesenchymal transition in renal cell carcinoma: Implications for cancer therapy. Mol Diagn Ther. 2016 Apr;20(2):111–17. http://dx.doi.org/10.1007/s40291-016-0192-5
21. Jiang F, Moch H, Richter J, Egenter C, Gasser T, Bubendorf L, et al. Comparative genomic hybridization reveals frequent chromosome 13q and 4q losses in renal carcinomas with sarcomatoid transformation. J Pathol. 1998 Aug;185(4):382–8. http://dx.doi.org/10.1002/(SICI)1096-9896(199808)185:4<382::AID-PATH124>3.0.CO;2-4
22. Brunelli M, Gobbo S, Cossu-Rocca P, Cheng L, Hes O, Delahunt B, et al. Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma. Mod Pathol. 2007 Mar;20(3):303–9. http://dx.doi.org/10.1038/modpathol.3800739
23. Ito T, Pei J, Dulaimi E, Menges C, Abbosh PH, Smaldone MC, et al. Genomic copy number alterations in renal cell carcinoma with sarcomatoid features. J Urol. 2016 Apr;195(4 Pt 1):852–8. http://dx.doi.org/10.1016/j.juro.2015.10.180
24. Tretiakova MS, Sahoo S, Takahashi M, Turkyilmaz M, Vogelzang NJ, Lin F, et al. Expression of alpha-methylacyl-CoA racemase in papillary renal cell carcinoma. Am J Surg Pathol. 2004 Jan;28(1):69–76. http://dx.doi.org/10.1097/00000478-200401000-00007
25. Presti JC Jr., Rao PH, Chen Q, Reuter VE, Li FP, Fair WR, et al. Histopathological, cytogenetic, and molecular characterization of renal cortical tumors. Cancer Res. 1991 Mar;51(5):1544–52.
26. Tickoo SK, Alden D, Olgac S, Fine SW, Russo P, Kondagunta GV, et al. Immunohistochemical expression of hypoxia inducible factor-1alpha and its downstream molecules in sarcomatoid renal cell carcinoma. J Urol. 2007 Apr;177(4):1258–63. http://dx.doi.org/10.1016/j.juro.2006.11.100
27. 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 Feb;55(3):658–62.
28. Malouf GG, Ali SM, Wang K, Balasubramanian S, Ross JS, Miller VA, et al. Genomic characterization of renal cell carcinoma with sarcomatoid dedifferentiation pinpoints recurrent genomic alterations. Eur Urol. 2016 Aug;70(2):348–57. http://dx.doi.org/10.1016/j.eururo.2016.01.051
29. Zhang BY, Thompson RH, Lohse CM, Leibovich BC, Boorjian SA, Cheville JC, et al. A novel prognostic model for patients with sarcomatoid renal cell carcinoma. BJU Int. 2015 Mar;115(3):405–11. http://dx.doi.org/10.1111/bju.12781
30. Ro JY, Ayala AG, Sella A, Samuels ML, Swanson DA. Sarcomatoid renal cell carcinoma: Clinicopathologic. A study of 42 cases. Cancer. 1987 Feb;59(3):516–26. http://dx.doi.org/10.1002/1097-0142(19870201)59:3<516::AID-CNCR2820590327>3.0.CO;2-W
31. Macke RA, Hussain MB, Imray TJ, Wilson RB, Cohen SM. Osteogenic and sarcomatoid differentiation of a renal cell carcinoma. Cancer. 1985 Nov;56(10):2452–7. http://dx.doi.org/10.1002/1097-0142(19851115)56:10<2452::AID-CNCR2820561021>3.0.CO;2-C
32. Amin MB, Tamboli P, Javidan J, Stricker H, de-Peralta Venturina M, Deshpande A, et al. Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: An experience of 405 cases. Am J Surg Pathol. 2002 Mar;26(3):281–91. http://dx.doi.org/10.1097/00000478-200203000-00001
33. Shuch B, Pantuck AJ, Pouliot F, Finley DS, Said JW, Belldegrun AS, et al. Quality of pathological reporting for renal cell cancer: Implications for systemic therapy, prognostication and surveillance. BJU Int. 2011 Aug;108(3):343–8. http://dx.doi.org/10.1111/j.1464-410X.2010.09871.x
34. Swerdlow SH, International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues. Geneva, Switzerland: International Agency for Research on Cancer; 2008.
35. Kridel R, Chan FC, Mottok A, Boyle M, Farinha P, Tan K, et al. Histological transformation and progression in follicular lymphoma: A clonal evolution study. PLoS Med. 2016 Dec;13(12):e1002197. http://dx.doi.org/10.1371/journal.pmed.1002197
2. 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. http://dx.doi.org/10.1634/theoncologist.2011-0227
3. Farrow GM, Harrison EG Jr., Utz DC. Sarcomas and sarcomatoid and mixed malignant tumors of the kidney in adults. Cancer. 1968 Sep;22(3):556–63. http://dx.doi.org/10.1002/1097-0142(196809)22:3<556::AID-CNCR2820220310>3.0.CO;2-N
4. Shuch B, Amin A, Armstrong AJ, Eble JN, Ficarra V, Lopez-Beltran A, et al. Understanding pathologic variants of renal cell carcinoma: Distilling therapeutic opportunities from biologic complexity. Eur Urol. 2015 Jan;67(1):85–97. http://dx.doi.org/10.1016/j.eururo.2014.04.029
5. de Peralta-Venturina M, Moch H, Amin M, Tamboli P, Hailemariam S, Mihatsch M, et al. Sarcomatoid differentiation in renal cell carcinoma: A study of 101 cases. Am J Surg Pathol. 2001 Mar;25(3):275–84. http://dx.doi.org/10.1097/00000478-200103000-00001
6. Cheville JC, Lohse CM, Zincke H, Weaver AL, Leibovich BC, Frank I, et al. Sarcomatoid renal cell carcinoma: An examination of underlying histologic subtype and an analysis of associations with patient outcome. Am J Surg Pathol. 2004 Apr;28(4):435–41. http://dx.doi.org/10.1097/00000478-200404000-00002
7. Shuch B, Said J, La Rochelle JC, Zhou Y, Li G, Klatte T, et al. Cytoreductive nephrectomy for kidney cancer with sarcomatoid histology – Is up-front resection indicated and, if not, is it avoidable? J Urol. 2009 Nov;182(5):2164–71. http://dx.doi.org/10.1016/j.juro.2009.07.049
8. Kyriakopoulos CE, Chittoria N, Choueiri TK, Kroeger N, Lee JL, Srinivas S, et al. Outcome of patients with metastatic sarcomatoid renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. Clin Genitourin Cancer. 2015 Apr;13(2):e79–85. http://dx.doi.org/10.1016/j.clgc.2014.08.011
9. Mian BM, Bhadkamkar N, Slaton JW, Pisters PW, Daliani D, Swanson DA, et al. Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma. J Urol. 2002 Jan;167(1):65–70. http://dx.doi.org/10.1016/S0022-5347(05)65384-0
10. Merrill MM, Wood CG, Tannir NM, Slack RS, Babaian KN, Jonasch E, et al. Clinically nonmetastatic renal cell carcinoma with sarcomatoid dedifferentiation: Natural history and outcomes after surgical resection with curative intent. Urol Oncol. 2015 Apr;33(4):166 e21–9. http://dx.doi.org/10.1016/j.urolonc.2014.11.021
11. Cangiano T, Liao J, Naitoh J, Dorey F, Figlin R, Belldegrun A. Sarcomatoid renal cell carcinoma: Biologic behavior, prognosis, and response to combined surgical resection and immunotherapy. J Clin Oncol. 1999 Feb;17(2):523–8. http://dx.doi.org/10.1200/JCO.1999.17.2.523
12. Brookman-May S, May M, Shariat SF, Zigeuner R, Chromecki T, Cindolo L, et al. Prognostic effect of sarcomatoid dedifferentiation in patients with surgically treated renal cell carcinoma: A matched-pair analysis. Clin Genitourin Cancer. 2013 Dec;11(4):465–70. http://dx.doi.org/10.1016/j.clgc.2013.04.026
13. Bostwick DG, Cheng L. Urologic surgical pathology. Philadelphia, PA, USA: Elsevier Health Sciences; 2008.
14. DeLong W, Grignon DJ, Eberwein P, Shum DT, Wyatt JK. Sarcomatoid renal cell carcinoma. An immunohistochemical study of 18 cases. Arch Pathol Lab Med. 1993 Jun;117(6):636–40.
15. Kuroda N, Toi M, Hiroi M, Enzan H. Review of sarcomatoid renal cell carcinoma with focus on clinical and pathobiological aspects. Histol Histopathol. 2003 Apr;18(2):551–5.
16. Krishnan B, Truong LD. Renal epithelial neoplasms: The diagnostic implications of electron microscopic study in 55 cases. Hum Pathol. 2002 Jan;33(1):68–79. http://dx.doi.org/10.1053/hupa.2002.30210
17. Morikawa Y, Tohya K, Kusuyama Y, Masui M, Wakasugi C. Sarcomatoid renal cell carcinoma. An immunohistochemical and ultrastructural study. Int Urol Nephrol. 1993;25(1):51–8. http://dx.doi.org/10.1007/BF02552254
18. Jones TD, Eble JN, Wang M, Maclennan GT, Jain S, Cheng L. Clonal divergence and genetic heterogeneity in clear cell renal cell carcinomas with sarcomatoid transformation. Cancer. 2005 Sep;104(6):1195–203. http://dx.doi.org/10.1002/cncr.21288
19. Conant JL, Peng Z, Evans MF, Naud S, Cooper K. Sarcomatoid renal cell carcinoma is an example of epithelial – Mesenchymal transition. J Clin Pathol. 2011 Dec;64(12):1088–92. http://dx.doi.org/10.1136/jclinpath-2011-200216
20. Piva F, Giulietti M, Santoni M, Occhipinti G, Scarpelli M, Lopez-Beltran A, et al. Epithelial to mesenchymal transition in renal cell carcinoma: Implications for cancer therapy. Mol Diagn Ther. 2016 Apr;20(2):111–17. http://dx.doi.org/10.1007/s40291-016-0192-5
21. Jiang F, Moch H, Richter J, Egenter C, Gasser T, Bubendorf L, et al. Comparative genomic hybridization reveals frequent chromosome 13q and 4q losses in renal carcinomas with sarcomatoid transformation. J Pathol. 1998 Aug;185(4):382–8. http://dx.doi.org/10.1002/(SICI)1096-9896(199808)185:4<382::AID-PATH124>3.0.CO;2-4
22. Brunelli M, Gobbo S, Cossu-Rocca P, Cheng L, Hes O, Delahunt B, et al. Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma. Mod Pathol. 2007 Mar;20(3):303–9. http://dx.doi.org/10.1038/modpathol.3800739
23. Ito T, Pei J, Dulaimi E, Menges C, Abbosh PH, Smaldone MC, et al. Genomic copy number alterations in renal cell carcinoma with sarcomatoid features. J Urol. 2016 Apr;195(4 Pt 1):852–8. http://dx.doi.org/10.1016/j.juro.2015.10.180
24. Tretiakova MS, Sahoo S, Takahashi M, Turkyilmaz M, Vogelzang NJ, Lin F, et al. Expression of alpha-methylacyl-CoA racemase in papillary renal cell carcinoma. Am J Surg Pathol. 2004 Jan;28(1):69–76. http://dx.doi.org/10.1097/00000478-200401000-00007
25. Presti JC Jr., Rao PH, Chen Q, Reuter VE, Li FP, Fair WR, et al. Histopathological, cytogenetic, and molecular characterization of renal cortical tumors. Cancer Res. 1991 Mar;51(5):1544–52.
26. Tickoo SK, Alden D, Olgac S, Fine SW, Russo P, Kondagunta GV, et al. Immunohistochemical expression of hypoxia inducible factor-1alpha and its downstream molecules in sarcomatoid renal cell carcinoma. J Urol. 2007 Apr;177(4):1258–63. http://dx.doi.org/10.1016/j.juro.2006.11.100
27. 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 Feb;55(3):658–62.
28. Malouf GG, Ali SM, Wang K, Balasubramanian S, Ross JS, Miller VA, et al. Genomic characterization of renal cell carcinoma with sarcomatoid dedifferentiation pinpoints recurrent genomic alterations. Eur Urol. 2016 Aug;70(2):348–57. http://dx.doi.org/10.1016/j.eururo.2016.01.051
29. Zhang BY, Thompson RH, Lohse CM, Leibovich BC, Boorjian SA, Cheville JC, et al. A novel prognostic model for patients with sarcomatoid renal cell carcinoma. BJU Int. 2015 Mar;115(3):405–11. http://dx.doi.org/10.1111/bju.12781
30. Ro JY, Ayala AG, Sella A, Samuels ML, Swanson DA. Sarcomatoid renal cell carcinoma: Clinicopathologic. A study of 42 cases. Cancer. 1987 Feb;59(3):516–26. http://dx.doi.org/10.1002/1097-0142(19870201)59:3<516::AID-CNCR2820590327>3.0.CO;2-W
31. Macke RA, Hussain MB, Imray TJ, Wilson RB, Cohen SM. Osteogenic and sarcomatoid differentiation of a renal cell carcinoma. Cancer. 1985 Nov;56(10):2452–7. http://dx.doi.org/10.1002/1097-0142(19851115)56:10<2452::AID-CNCR2820561021>3.0.CO;2-C
32. Amin MB, Tamboli P, Javidan J, Stricker H, de-Peralta Venturina M, Deshpande A, et al. Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: An experience of 405 cases. Am J Surg Pathol. 2002 Mar;26(3):281–91. http://dx.doi.org/10.1097/00000478-200203000-00001
33. Shuch B, Pantuck AJ, Pouliot F, Finley DS, Said JW, Belldegrun AS, et al. Quality of pathological reporting for renal cell cancer: Implications for systemic therapy, prognostication and surveillance. BJU Int. 2011 Aug;108(3):343–8. http://dx.doi.org/10.1111/j.1464-410X.2010.09871.x
34. Swerdlow SH, International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues. Geneva, Switzerland: International Agency for Research on Cancer; 2008.
35. Kridel R, Chan FC, Mottok A, Boyle M, Farinha P, Tan K, et al. Histological transformation and progression in follicular lymphoma: A clonal evolution study. PLoS Med. 2016 Dec;13(12):e1002197. http://dx.doi.org/10.1371/journal.pmed.1002197
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May 22, 2017
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The Pathology and Molecular Genetics of Sarcomatoid Renal Cell Carcinoma: A Mini-Review. (2017). Journal of Kidney Cancer and VHL, 4(2), 19-23. https://doi.org/10.15586/jkcvhl.2017.70
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Kidney Cancer: Review Articles
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