Modern Pathologic Diagnosis of Renal Oncocytoma

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Sara E. Wobker
Sean R. Williamson


chromophobe renal cell carcinoma, kidney, oncocytic neoplasm, oncocytoma, renal mass, renal mass biopsy, succinate dehydrogenase-deficient renal cell carcinoma


Oncocytoma is a well-defined benign renal tumor, with classic gross and histologic features, including a tan or mahogany-colored mass with central scar, microscopic nested architecture, bland cytology, and round, regular nuclei with prominent central nucleoli. As a result of variations in this classic appearance, difficulty in standardizing diagnostic criteria, and entities that mimic oncocytoma, such as eosinophilic variant chromophobe renal cell carcinoma and succinate dehydrogenase-deficient renal cell carcinoma, pathologic diagnosis remains a challenge. This review addresses the current state of pathologic diagnosis of oncocytoma, with emphasis on modern diagnostic markers, areas of controversy, and emerging techniques for less invasive diagnosis, including renal mass biopsy and advanced imaging.

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1. Klein MJ, Valensi QJ. Proximal tubular adenomas of kidney with so-called oncocytic features. A clinicopathologic study of 13 cases of a rarely reported neoplasm. Cancer. 1976;38(2):906–14.;2-W
2. Hes O, Moch H, Reuter V. Oncocytoma. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO classification of tumours of the urinary system and male genital organs. 8. 4th ed. Lyon: International Agency for Research on Cancer; 2016. p. 43–4.
3. Ng KL, Morais C, Bernard A, Saunders N, Samaratunga H, Gobe G, et al. A systematic review and meta-analysis of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma. J Clin Pathol. 2016;69(8):661–71.
4. Ng KL, Rajandram R, Morais C, Yap NY, Samaratunga H, Gobe GC, et al. Differentiation of oncocytoma from chromophobe renal cell carcinoma (RCC): Can novel molecular biomarkers help solve an old problem? J Clin Pathol. 2014;67(2):97–104.
5. Williamson SR, Gadde R, Trpkov K, Hirsch MS, Srigley JR, Reuter VE, et al. Diagnostic criteria for oncocytic renal neoplasms: A survey of urologic pathologists. Hum Pathol. 2017;63:149–56.
6. Amin MB, Crotty TB, Tickoo SK, Farrow GM. Renal oncocytoma: A reappraisal of morphologic features with clinicopathologic findings in 80 cases. Am J Surg Pathol. 1997;21(1):1–12.
7. Perez-Ordonez B, Hamed G, Campbell S, Erlandson RA, Russo P, Gaudin PB, et al. Renal oncocytoma: A clinicopathologic study of 70 cases. Am J Surg Pathol. 1997;21(8):871–83.
8. Trpkov K, Yilmaz A, Uzer D, Dishongh KM, Quick CM, Bismar TA, et al. Renal oncocytoma revisited: A clinicopathological study of 109 cases with emphasis on problematic diagnostic features. Histopathology. 2010;57(6):893–906.
9. Petersson F, Sima R, Grossmann P, Michal M, Kuroda N, Hora M, et al. Renal small cell oncocytoma with pseudorosettes A histomorphologic, immunohistochemical, and molecular genetic study of 10 cases. Hum Pathol. 2011;42(11):1751–60.
10. Tan PH, Cheng L, Rioux-Leclercq N, Merino MJ, Netto G, Reuter VE, et al. Renal tumors: Diagnostic and prognostic biomarkers. Am J Surg Pathol. 2013;37(10):1518–31.
11. Reuter VE, Argani P, Zhou M, Delahunt B, Members of the IIiDUPG. Best practices recommendations in the application of immunohistochemistry in the kidney tumors: Report from the International Society of Urologic Pathology consensus conference. Am J Surg Pathol. 2014;38(8):e35–49.
12. Kryvenko ON, Jorda M, Argani P, Epstein JI. Diagnostic approach to eosinophilic renal neoplasms. Arch Pathol Lab Med. 2014;138(11):1531–41.
13. Mazal PR, Exner M, Haitel A, Krieger S, Thomson RB, Aronson PS, et al. Expression of kidney-specific cadherin distinguishes chromophobe renal cell carcinoma from renal oncocytoma. Hum Pathol. 2005;36(1):22–8.
14. Carvalho JC, Wasco MJ, Kunju LP, Thomas DG, Shah RB. 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. 2011;58(2):169–79.
15. Rocca PC, Brunelli M, Gobbo S, Eccher A, Bragantini E, Mina MM, et al. Diagnostic utility of S100A1 expression in renal cell neoplasms: An immunohistochemical and quantitative RT-PCR study. Mod Pathol. 2007;20(7):722–8.
16. Tickoo SK, Amin MB, Zarbo RJ. Colloidal iron staining in renal epithelial neoplasms, including chromophobe renal cell carcinoma: Emphasis on technique and patterns of staining. Am J Surg Pathol. 1998;22(4):419–24.
17. Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG. Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis. Arch Pathol Lab Med. 2007;131(8):1290–7.
18. Hes O, Michal M, Kuroda N, Martignoni G, Brunelli M, Lu Y, et al. Vimentin reactivity in renal oncocytoma: Immunohistochemical study of 234 cases. Arch Pathol Lab Med. 2007;131(12):1782–8.
19. Williamson SR. Renal oncocytoma with perinephric fat invasion. Int J Surg Pathol. 2016;24(7):625–6.
20. Jacob JM, Williamson SR, Gondim DD, Leese JA, Terry C, Grignon DJ, et al. Characteristics of the peritumoral pseudocapsule vary predictably with histologic subtype of T1 renal neoplasms. Urology. 2015;86(5):956–61.
21. Hes O, Michal M, Sima R, Vanecek T, Brunelli M, Martignoni G, et al. Renal oncocytoma with and without intravascular extension into the branches of renal vein have the same morphological, immunohistochemical, and genetic features. Virchows Arch. 2008;452(2):193–200.
22. Wobker SE, Przybycin CG, Sircar K, Epstein JI. Renal oncocytoma with vascular invasion: A series of 22 cases. Hum Pathol. 2016;58:1–6.
23. Xie WL, Lian JY, Li B, Tian XY, Li Z. Mixed epithelial and stromal tumor of kidney with renal vein extension: An unusual case report and review of literature. Histol Histopathol. 2017;32(4):361–9.
24. Fernandez-Pello S, Gonzalez Rodriguez I, Villamil LR, Perez-Carral JR, Menendez CL, Caveda P, et al. Laparoscopic management of right renal angiomyolipoma with involvement of the inferior vena cava: Case report and review of the literature. Scand J Urol. 2013;47(4):340–4.
25. Eble JN. Angiomyolipoma of kidney. Semin Diagn Pathol. 1998;15(1):21–40.
26. Ip PP, Tse KY, Tam KF. Uterine smooth muscle tumors other than the ordinary leiomyomas and leiomyosarcomas: A review of selected variants with emphasis on recent advances and unusual morphology that may cause concern for malignancy. Adv Anat Pathol. 2010;17(2):91–112.
27. Sukov WR, Ketterling RP, Lager DJ, Carlson AW, Sinnwell JP, Chow GK, et al. CCND1 rearrangements and cyclin D1 overexpression in renal oncocytomas: Frequency, clinicopathologic features, and utility in differentiation from chromophobe renal cell carcinoma. Hum Pathol. 2009;40(9):1296–303.
28. Joshi S, Tolkunov D, Aviv H, Hakimi AA, Yao M, Hsieh JJ, et al. The genomic landscape of renal oncocytoma identifies a metabolic barrier to tumorigenesis. Cell Rep. 2015;13(9):1895–908.
29. Paner G, Amin MB, Moch H, Störkel S. Chromophobe renal cell carcinoma. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO classification of tumours of the urinary system and male genital organs. 8. 4th ed. Lyon: International Agency for Research on Cancer; 2016. p. 27–8.
30. Davis CF, Ricketts CJ, Wang M, Yang L, Cherniack AD, Shen H, et al. The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer Cell. 2014;26(3):319–30.
31. Sperga M, Martinek P, Vanecek T, Grossmann P, Bauleth K, Perez-Montiel D, et al. 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. 2013;463(4):563–73.
32. Brunelli M, Eble JN, Zhang S, Martignoni G, Delahunt B, Cheng L. 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. 2005;18(2):161–9.
33. Al-Saleem T, Cairns P, Dulaimi EA, Feder M, Testa JR, Uzzo RG. The genetics of renal oncocytosis: A possible model for neoplastic progression. Cancer Genet Cytogenet. 2004;152(1):23–8.
34. Gobbo S, Eble JN, Delahunt B, Grignon DJ, Samaratunga H, Martignoni G, et al. Renal cell neoplasms of oncocytosis have distinct morphologic, immunohistochemical, and cytogenetic profiles. Am J Surg Pathol. 2010;34(5):620–6.
35. Tickoo SK, Reuter VE, Amin MB, Srigley JR, Epstein JI, Min KW, et al. Renal oncocytosis: A morphologic study of fourteen cases. Am J Surg Pathol. 1999;23(9):1094–101.
36. Srigley JR, Delahunt B, Eble JN, Egevad L, Epstein JI, Grignon D, et al. The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J Surg Pathol. 2013;37(10):1469–89.
37. Petersson F, Gatalica Z, Grossmann P, Perez Montiel MD, Alvarado Cabrero I, Bulimbasic S, et al. Sporadic hybrid oncocytic/chromophobe tumor of the kidney: A clinicopathologic, histomorphologic, immunohistochemical, ultrastructural, and molecular cytogenetic study of 14 cases. Virchows Arch. 2010;456(4):355–65.
38. Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. Solid renal tumors: An analysis of pathological features related to tumor size. J Urol. 2003;170(6 Pt 1):2217–20.
39. Lane BR, Babineau D, Kattan MW, Novick AC, Gill IS, Zhou M, et al. A preoperative prognostic nomogram for solid enhancing renal tumors 7 cm or less amenable to partial nephrectomy. J Urol. 2007;178(2):429–34.
40. Leveridge MJ, Finelli A, Kachura JR, Evans A, Chung H, Shiff DA, et al. Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous biopsy, and the role of repeat biopsy. Eur Urol. 2011;60(3):578–84.
41. Patel HD, Druskin SC, Rowe SP, Pierorazio PM, Gorin MA, Allaf ME. Surgical histopathology for suspected oncocytoma on renal mass biopsy: A systematic review and meta-analysis. BJU Int. 2017;119(5):661–6.
42. Richard PO, Jewett MA, Bhatt JR, Evans AJ, Timilsina N, Finelli A. Active surveillance for renal neoplasms with oncocytic features is safe. J Urol. 2016;195(3):581–6.
43. Amin MB, Paner GP, Alvarado-Cabrero I, Young AN, Stricker HJ, Lyles RH, 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.
44. Gill AJ, Amin MB, Smith S, Trpkov K. Succinate dehydrogenase-deficient renal carcinoma. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO classification of tumours of the urinary system and male genital organs. 8. 4th ed. Lyon: International Agency for Research on Cancer; 2016. p. 35–6.
45. Gill AJ, Hes O, Papathomas T, Sedivcova M, Tan PH, Agaimy A, et al. Succinate dehydrogenase (SDH)-deficient renal carcinoma: A morphologically distinct entity: A clinicopathologic series of 36 tumors from 27 patients. Am J Surg Pathol. 2014;38(12):1588–602.
46. Gill AJ, Pachter NS, Chou A, Young B, Clarkson A, Tucker KM, et al. Renal tumors associated with germline SDHB mutation show distinctive morphology. Am J Surg Pathol. 2011;35(10):1578–85.
47. Williamson SR, Eble JN, Amin MB, Gupta NS, Smith SC, Sholl LM, et al. Succinate dehydrogenase-deficient renal cell carcinoma: Detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma. Mod Pathol. 2015;28(1):80–94.
48. Housley SL, Lindsay RS, Young B, McConachie M, Mechan D, Baty D, et al. Renal carcinoma with giant mitochondria associated with germ-line mutation and somatic loss of the succinate dehydrogenase B gene. Histopathology. 2010;56(3):405–8.
49. Jiang Q, Zhang Y, Zhou YH, Hou YY, Wang JY, Li JL, et al. A novel germline mutation in SDHA identified in a rare case of gastrointestinal stromal tumor complicated with renal cell carcinoma. Int J Clin Exp Pathol. 2015;8(10):12188–97.
50. Yakirevich E, Ali SM, Mega A, McMahon C, Brodsky AS, Ross JS, et al. A novel SDHA-deficient renal cell carcinoma revealed by comprehensive genomic profiling. Am J Surg Pathol. 2015;39(6):858–63.
51. Barletta JA, Hornick JL. Succinate dehydrogenase-deficient tumors: Diagnostic advances and clinical implications. Adv Anat Pathol. 2012;19(4):193–203.
52. Delahunt B, Eble JN. Papillary renal cell carcinoma: A clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol. 1997;10(6):537–44.
53. Folpe AL, Kwiatkowski DJ. Perivascular epithelioid cell neoplasms: Pathology and pathogenesis. Hum Pathol. 2010;41(1):1–15.
54. Hornick JL, Fletcher CD. PEComa: What do we know so far? Histopathology. 2006;48(1):75–82.
55. Martignoni G, Pea M, Reghellin D, Zamboni G, Bonetti F. PEComas: The past, the present and the future. Virchows Arch. 2008;452(2):119–32.
56. Brimo F, Robinson B, Guo C, Zhou M, Latour M, Epstein JI. Renal epithelioid angiomyolipoma with atypia: A series of 40 cases with emphasis on clinicopathologic prognostic indicators of malignancy. Am J Surg Pathol. 2010;34(5):715–22.
57. Eble JN, Amin MB, Young RH. Epithelioid angiomyolipoma of the kidney: A report of five cases with a prominent and diagnostically confusing epithelioid smooth muscle component. Am J Surg Pathol. 1997;21(10):1123–30.
58. He W, Cheville JC, Sadow PM, Gopalan A, Fine SW, Al-Ahmadie HA, et al. Epithelioid angiomyolipoma of the kidney: Pathological features and clinical outcome in a series of consecutively resected tumors. Mod Pathol. 2013;26(10):1355–64.
59. Nese N, Martignoni G, Fletcher CD, Gupta R, Pan CC, Kim H, et al. Pure epithelioid PEComas (so-called epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: Detailed assessment of morphology and risk stratification. Am J Surg Pathol. 2011;35(2):161–76.
60. Martignoni G, Pea M, Bonetti F, Brunelli M, Eble JN. Oncocytoma-like angiomyolipoma. A clinicopathologic and immunohistochemical study of 2 cases. Arch Pathol Lab Med. 2002;126(5):610–12.
61. Martignoni G, Bonetti F, Chilosi M, Brunelli M, Segala D, Amin MB, et al. Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney. Mod Pathol. 2012;25(1):100–11.
62. Skenderi F, Ulamec M, Vranic S, Bilalovic N, Peckova K, Rotterova P, et al. Cystic renal oncocytoma and tubulocystic renal cell carcinoma: Morphologic and immunohistochemical comparative study. Appl Immunohistochem Mol Morphol. 2016;24(2):112–19.
63. Davidson AJ, Hayes WS, Hartman DS, McCarthy WF, Davis CJ, Jr. Renal oncocytoma and carcinoma: Failure of differentiation with CT. Radiology. 1993;186(3):693–6.
64. Sasaguri K, Takahashi N, Gomez-Cardona D, Leng S, Schmit GD, Carter RE, et al. Small (<4 cm) renal mass: Differentiation of oncocytoma from renal cell carcinoma on biphasic contrast-enhanced CT. AJR Am J Roentgenol. 2015;205(5):999–1007.
65. Millet I, Doyon FC, Hoa D, Thuret R, Merigeaud S, Serre I, et al. Characterization of small solid renal lesions: Can benign and malignant tumors be differentiated with CT? AJR Am J Roentgenol. 2011;197(4):887–96.
66. Choudhary S, Rajesh A, Mayer NJ, Mulcahy KA, Haroon A. Renal oncocytoma: CT features cannot reliably distinguish oncocytoma from other renal neoplasms. Clin Radiol. 2009;64(5):517–22.
67. Johnson DC, Vukina J, Smith AB, Meyer AM, Wheeler SB, Kuo TM, et al. Preoperatively misclassified, surgically removed benign renal masses: A systematic review of surgical series and United States population level burden estimate. J Urol. 2015;193(1):30–5.
68. Rowe SP, Gorin MA, Gordetsky J, Ball MW, Pierorazio PM, Higuchi T, et al. Initial experience using 99mTc-MIBI SPECT/CT for the differentiation of oncocytoma from renal cell carcinoma. Clin Nucl Med. 2015;40(4):309–13.
69. Gorin MA, Rowe SP, Baras AS, Solnes LB, Ball MW, Pierorazio PM, et al. Prospective evaluation of (99m)Tc-sestamibi SPECT/CT for the diagnosis of renal oncocytomas and hybrid oncocytic/chromophobe tumors. Eur Urol. 2016;69(3):413–16.