—  SPECIALTY CONFERENCE  —

Genitourinary Pathology

Case 2 - Renal Oncocytosis

Victor E. Reuter
Memorial Sloan-Kettering Cancer Center
New York, New York


Click on each slide thumbnail image for an enlarged view
Clinical History:
This 47 year-old male with vague abdominal symptoms was found to have a 3.0 cm mass within the left kidney by abdominal CT scan. At the time of nephrectomy, it became clear that the kidney contained multiple lesions ranging in size from 0.1cm to 3.0 cm.

Diagnosis: Renal Oncocytosis



Case 2 - Figure 1 - Oncocytosis: Multiple cortical tumor nodules.
Case 2 - Figure 2 - Oncocytosis: Oncocytic tumor cells infiltrating among renal tubules.


Case 2 - Figure 3 - Oncocytosis: Minute oncocytic nodules. Could any of these structures represent "in situ" disease?
Case 2 - Figure 4 - Oncocytosis: Hybrid tumor. Several oncocytic microcysts are present near a solid nest of tumor cells with nuclear features reminiscent of chromophobe RCC.

Discussion
The slide you have examined contains numerous oncocytic nodules involving the kidney parenchyma. The tumor cells have abundant densely eosinophilic cytoplasm and round nuclei with moderately large nucleoli. Similar cases were originally reported as case reports by Warfel and Eble,1  Isreali et al,2  and Katz et al 3 and called "Oncocytomatosis". Subsequently we reported 14 cases (19 specimens) with innumerable oncocytic nodules in the kidney and highlighted the fact that these lesions invariably showed additional associated findings.4  We suggested the term "renal oncocytosis" for this entire morphologic spectrum. In our series, six cases (43%) had histologically or radiologically proven bilateral involvement. Each specimen had at least one dominant tumor (2.0 to 10.5 cm), in addition to numerous other microscopic to macroscopic oncocytic nodules. Additional features observed were: a) interstitial pattern, with the oncocytic tubules/acini diffusely intermingling with, and 'infiltrating' between, non-neoplastic parenchyma (1 case), b) diffuse oncocytic change in the non-neoplastic tubules, cytologically difficult to separate from the oncocytic nodules (7 cases) and c) benign oncocytic cortical cysts (4 cases). The dominant mass in 13 specimens was a renal oncocytoma and in two, a chromophobe renal cell carcinoma. In four specimens, the largest tumor was considered as 'hybrid' because of the presence of mixed histologic features of both tumor types. Most smaller nodules had the morphologic features of renal oncocytoma, but a few had the appearance of chromophobe renal cell carcinoma or nodules with 'hybrid' features. The association of numerous renal oncocytoma-like nodules with lesions having either mixed or pure chromophobe renal cell carcinoma morphology suggests that renal oncocytoma and chromophobe renal cell carcinoma may be genetically related.5-8 

Interestingly, Weirich et al published a series of families with oncocytomas which were commonly multiple and had similar morphologic features as described by us.9  A group of familial oncocytomas, including their molecular abnormalities, were reported by Junker et al. and compared to a similar number of sporadic tumors. Another recent and very provocative development is the work done by a group of investigators at the National Institutes of Health.10  They have studied patients with the Brit-Hogg-Dube (BHD) syndrome, an autosomal dominant disease characterized by the development of skin lesions (predominantly fibrofolliculomas) on the face, neck and upper trunk. These patients are at increased risk for the development of spontaneous pneumothorax as well as renal neoplasms. These renal tumors have a relatively varied histologic appearance, including multiple oncocytic nodules (Oncocytosis), oncocytomas, chromophobe renal carcinomas and hybrid lesions. Interestingly, 9% of cases were tumors with Conventional (Clear cell) morphology. This fact supports the hypothesis that the BHD gene is important in the development of tumors of all types and may be a clue as to a common genetic pathway for all renal cortical neoplasms. We anxiously await the characterization of this gene or genes.

References

  1. Warfel KA, Eble JW. Renal oncocytomatosis. J Urol 1982;127:1179-80.
  2. Israeli RS, Wise GJ, Bansal S, Gerard PS, Castella A. Bilateral oncocytomatosis in a patient with renal failure. Urology 1995;46:873-5.
  3. Katz DS, Gharagozloo AM, Peebles TR, Oliphant M. Renal oncocytomatosis. Am J Kid Dis 1996;27:579-82.
  4. Tickoo SK, Reuter VE, Amin MB, Srigley JR, Epstein JI, Min K-W, Rubin MA, Ro JY. Renal oncocytosis. A morphologic study of fourteen cases. Am J Surg Pathol 1999;23:1094-1101.
  5. Noguchi S, Nagashima Y, Shuin T, Kubota Y, Kitamura H, Yao M, Hosaka M. Renal oncocytoma containing "chromophobe" cells. Int J Urol 1995;2:279-80.
  6. Dukhuizen T, van den Berg E, Störkel S, de Vries B, van der Veen AY, Wilbrink M, van Kessel AG, de Jong B. Renal oncocytoma with t(5;12;11), der(1)t(1;8) and add19): "true" oncocytoma or chromophobe adenoma? Int J Cancer 1997;73:521-4.
  7. Presti JC, Moch H, Reuter VE, Huynh D, Waldman FM. Chromosome 1 and 14 loss in renal oncocytomas. Proc Am Urol Assoc 1996;155:414A.
  8. Junker K, Weirich G, Moravek P, Podhola M, Ilse B, Hartmann A, Schubert J. Familial and sporadic renal oncocytomas. A comparative molecular-genetic analysis. Eur Urol 2001;40:330-336.
  9. Weirich G, Glenn G, Junker K, Merino M, Störkel S, Lubensky I, Choyke P, Pack S, Amin M, Walther MM, Linehan WM, Zbar B. Familial renal oncocytoma: clinicopathological study of 5 families. J Urol 1998;160:335-40.
  10. Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, Merino MJ. Renal tumors in the Birt-Hogg-Dube syndrome. Am J Surg Pathol 2002;26:1542-1552.