Monday, November 10, 2014

Oncocytoma: A Benign Kidney Tumor Often Confused for Cancer

Upwards of 15-20% of kidney tumors may be benign lesions. While physicians and surgeons can use patient information, radiographic imaging and biopsy to provide information, the definitive diagnosis of cancer or benign tumor is established only after the tumor has been removed. For instance, smaller tumors, female sex and age are associated with benign tumors - younger women are nearly twice as likely as age-matched men to have benign masses.[1-5] While certain characteristics are indicative of benign tumors (i.e. fat always indicates an angiomyolipoma), many other benign tumors – like oncocytoma – can appear similar to renal cell carcinoma (RCC) on CT scan and biopsy.

This blog will review oncocytoma, one of the most common benign tumors of the kidney.


Epidemiology and Etiology

Renal oncocytoma is one of the most common of benign renal masses, accounting for 3-7% of kidney tumors.[6] Oncocytomas appear as enhancing renal masses and are often indistinguishable from clear-cell RCC on CT scans (see Diagnosis below). Both oncocytomas and clear-cell RCC pick up contrast material and enhance brightly. However, oncocytoma is a distinct entity from RCC with unique cell of origin and cytogenetic abnormalities.[7-8]

Oncocytomas are more common in older patients with small, incidentally discovered renal masses. [4,9] Generally, they are more common in men than women (2:1 ratio), present in the 4th to 6th decade of life and can present bilaterally, multifocally or recur in 6-13% of cases.[10] Patients with the rare, Birt-Hogg-Dubé, genetic syndrome can present with oncocytomatosis – the presence of multiple oncocytomas in both kidneys. [11] Oncocytomas are benign tumors and rare case reports of metastatic oncocytoma represent either malignant degeneration, coexistence of RCC or pseudometastases (not really metastatic disease).[12]


Diagnosis

In general, oncocytoma appear similar to RCC on imaging. However, a number of characteristic radiographic findings are common in oncocytoma:
  • On CT scan, bright, rapidly-enhancing pattern and a central stellate scar [13]
  • On angiography, a spoke wheel pattern of feeding arteries may be present
  • On MRI, a well-defined capsule, central stellate scar, and distinctive pattern on T1 and T2 images may indicate oncocytoma.[14,15]
The similar appearance of clear-cell RCC and oncocytoma on contrast-enhanced CT scan.
The Houndsfield Unit (HU) -based enhancement patterns for clear-cell RCC and oncocytoma are overlapping on CT scan. [13]




Renal biopsy has a limited role in the diagnosis of oncocytoma, particularly because it can be difficult to distinguish from chromophobe RCC (see our blog entry on Renal Cell Carcinoma: Implications of Histology for more information about chromophobe RCC), the eosinophilic-variant of clear-cell RCC (a rare and potentially aggressive form of kidney cancer) and may be co-exist with RCC in 7-32% of cases. However, surgical series indicate that if oncocytoma is present with RCC in the same tumor, the tumor is often low-grade and indolent (benign-behaving).[16]


Histology and Pathology

Oncocytomas appear grossly as tan, homogenous tumors with a distinct border (composed of a well-formed pseudocapsule) and typically have a central stellate scar. Microscopically, cells are derived from distal tubules, are rounded and highly-eosinophlic (pink) due to an abundance of mitochondria (the energy producing portion of the cell). As stated above, it can extremely difficult to distinguish oncocytoma from chromophobe RCC or the eosinophilic-variant of clear-cell RCC under the microscope. Cells are typically arranged in a nested pattern and can demonstrate perinephric extension, pleomorphism (variability in size and shape), prominent nucleoli and atypia, making the distinction between RCC difficult.[17,18] On a percutaneous renal biopsy, where only a portion of tumor is present and cellular architecture is incomplete, distinguishing oncocytoma from RCC can be extremely challenging.


From pathologyatlas.com

To distinguish ococytoma from RCC, a number of features can be examined. Chromosomal abnormalities associated with RCC are not present in oncocytoma, and oncocytoma will commonly present with loss of chromosome 1p, loss of Y- or 14q- and rearrangements of 11q13. [7,8] Hale's colloidal iron stain has traditionally been used to identify oncoctyoma, however can have nonspecific staining patterns leading to difficult interpretation.[19] One of the distinguishing cellular features of oncocytoma is uniform, round mitochondria with lamellar cristae – in chromphobe RCC, mitochondria are variable in size and shape with tubulocystic cristae; and in eosinophilic-variant of clear-cell RCC, mitochondria are pleomorphic and have attenuated cristae.[20] Researchers at Johns Hopkins are taking advantage of differences in mitochondria among oncocytoma and RCC to come up with a better, preoperative diagnostic test to distinguish oncocytoma before a sending a patient to surgery.


Electron micropscopy of oncocytoma with uniform, round mitochondria (left) and chromophobe RCC with the pale area around the nucleus is predominantly occupied by microvesicles and irregular mitochondria (right).[20]

Management

Most often oncocytoma are clinically assumed to be RCC and have the same management strategies available including active surveillance, radical nephrectomy (for large tumors of uncertain etiology) and nephron-sparing surgeries including partial nephrectomy and thermal ablation. Oncocytomas under active surveillance can demonstrate rapid growth and are often the fastest growing tumors in active surveillance studies! Therefore, growth rate is not able to distinguish oncocytoma from RCC during periods of AS.[21,22] When the diagnosis of oncocytoma is known or highly-suspected, nephron-sparing approaches should be employed due to the benign nature of these lesions. At Johns Hopkins, partial nephrectomy is preferred to thermal ablation as a definitive diagnosis can be made from analysis of the tumor rather than biopsy specimens.



This blog is adapted from the Handbook of Urology, Chapter 24: Angiomyolipoma, Oncocytoma and Retroperitoneal Fibrosis, by Phillip M. Pierorazio, MD; Edited by John Kellogg Parsons, John B. Eifler, and Misop Han available from Wiley.


 








  1. Kutikov A, Fossett LK, Ramchandani P, et al.: Incidence of benign pathologic findings at partial nephrectomy for solitary renal mass presumed to be renal cell carcinoma on preoperative imaging. Urology 2006; 68(4): 737-40.
  2. Kouba E, Smith A, McRackan D, Wallen EM, Pruthi RS: Watchful waiting for solid renal masses: insight into the natural history and results of delayed intervention. J Urol 2007; 177(2): 466-70; discussion 470.
  3. Pierorazio PM, Murphy AM, Benson MC, McKiernan JM: Gender discrepancies in the diagnosis of renal cortical tumors. World J Urol 2007; 25(1): 81-5.
  4. Cao Y, Paner GP, Perry KT, Flanigan RC, Campbell SC, Picken MM: Renal neoplasms in younger adults: analysis of 112 tumors from a single institution according to the new 2004 World Health Organization classification and 2002 American Joint Committee on Cancer Staging System. Arch Pathol Lab Med 2005; 129(4): 487-91.
  5. Snyder ME, Bach A, Kattan MW, Raj GV, Reuter VE, Russo P: Incidence of benign lesions for clinically localized renal masses smaller than 7 cm in radiological diameter: influence of sex. J Urol 2006; 176(6 Pt 1): 2391-5; discussion 2395-6.
  6. Morra MN, Das S: Renal oncocytoma: a review of histogenesis, histopathology, diagnosis and treatment. J Urol 1993; 150(2 Pt 1): 295-302.
  7. Lindgren V, Paner GP, Omeroglu A, et al.: Cytogenetic analysis of a series of 13 renal oncocytomas. J Urol 2004; 171(2 Pt 1): 602-4.
  8. Paner GP, Lindgren V, Jacobson K, et al.: High incidence of chromosome 1 abnormalities in a series of 27 renal oncocytomas: cytogenetic and fluorescence in situ hybridization studies. Arch Pathol Lab Med 2007; 131(1): 81-5.
  9. Skolarus TA, Serrano MF, Berger DA, et al.: The distribution of histological subtypes of renal tumors by decade of life using the 2004 WHO classification. J Urol 2008; 179(2): 439-43; discussion 443-4.
  10. Minor LD, Picken MM, Campbell SC: Benign renal tumors. AUA Update 2003; 22: 170-175.
  11. 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.
  12. Oxley JD, Sullivan J, Mitchelmore A, Gillatt DA: Metastatic renal oncocytoma. J Clin Pathol 2007; 60(6): 720-2.
  13. Pierorazio PM1, Hyams ES, Tsai S, Feng Z, Trock BJ, Mullins JK, Johnson PT, Fishman EK, Allaf ME. Multiphasic enhancement patterns of small renal masses (≤4 cm) on preoperative computed tomography: utility for distinguishing subtypes of renal cell carcinoma, angiomyolipoma, and oncocytoma. Urology. 2013 Jun;81(6):1265-71. doi: 10.1016/j.urology.2012.12.049. Epub 2013 Apr 17.
  14. Licht MR: Renal adenoma and oncocytoma. Semin Urol Oncol 1995; 13(4): 262-6.
  15. Harmon WJ, King BF, Lieber MM: Renal oncocytoma: magnetic resonance imaging characteristics. J Urol 1996; 155(3): 863-7.
  16. Ginzburg S, Uzzo R, Al-Saleem T, Dulaimi E, Walton J, Corcoran A, Plimack E, Mehrazin R, Tomaszewski J, Viterbo R, Chen DY, Greenberg R, Smaldone M, Kutikov A. Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy. J Urol. 2014 Feb;191(2):296-300. doi: 10.1016/j.juro.2013.07.059. Epub 2013 Jul 27.
  17. 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.
  18. Perez-Ordonez B, Hamed G, Campbell S, et al.: Renal oncocytoma: a clinicopathologic study of 70 cases. Am J Surg Pathol 1997; 21(8): 871-83.
  19. Leroy X, Moukassa D, Copin MC, Saint F, Mazeman E, Gosselin B: Utility of cytokeratin 7 for distinguishing chromophobe renal cell carcinoma from renal oncocytoma. Eur Urol 2000; 37(4): 484-7.
  20. Tickoo SK, Lee MW, Eble JN, Amin M, Christopherson T, Zarbo RJ, Amin MB. Ultrastructural observations on mitochondria and microvesicles in renal oncocytoma, chromophobe renal cell carcinoma, and eosinophilic variant of conventional (clear cell) renal cell carcinoma. Am J Surg Pathol. 2000 Sep;24(9):1247-56.
  21. Kawaguchi S, Fernandes KA, Finelli A, Robinette M, Fleshner N, Jewett MA: Most renal oncocytomas appear to grow: observations of tumor kinetics with active surveillance. J Urol 2011; 186(4): 1218-22.
  22. Siu W, Hafez KS, Johnston WK, 3rd, Wolf JS, Jr.: Growth rates of renal cell carcinoma and oncocytoma under surveillance are similar. Urol Oncol 2007; 25(2): 115-9.

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