Oncocytoma

Magnetic resonance imaging for evaluation of renal arterial stenosis was performed on a 62-year-old white man with hypertension and hairy cell leukemia. The scan revealed a well-circumscribed, solid, round renal mass in the lower pole of the right kidney that was 3.5 x 3.4 cm. No evidence of renal stenosis was noted. A radical nephrectomy was performed.

Grossly, the renal mass was 3.5 x 3.5 x 3.0 cm, well circumscribed, solid, tan-brown, soft, and homogeneous. No central scar, necrosis, hemorrhage, or cysts were noted. The tumor appeared to infiltrate but not penetrate the overlying renal capsule. Uninvolved renal parenchyma was unremarkable. Microscopically, the tumor was comprised of intermediate-size round to polygonal cells predominantly in solid sheets with tubules and microcysts at the periphery. The tumor cells had indistinct cell borders, abundant granular and eosinophilic cytoplasm, and round to oval nuclei with a single centrally placed nucleolus. Scattered larger atypical cells with large hyperchromatic nuclei and prominent nucleoli were visible (Figures 1 and 2). The tumor extended into but not through the adjacent renal capsule. Focal vascular invasion was noted and confirmed by endothelial cell immunostains (CD31 and CD34). No necrosis, hemorrhage, or mitotic figures were noted. In immmunohistochemical analyses, the tumor cells were positive for E-cadherin and MAK-6 and negative for vimentin and CK7. Colloidal iron staining was negative. Ultrastructural examination revealed numerous round to oval abnormal mitochondria with some parallel cristae in the tumor cells. No significant rough endoplasmic reticulum, Golgi apparatus, microvesicles, glycogen, or lipid droplets were visible (Figure 3).

What is your diagnosis?

Pathologic Diagnosis: Renal Oncocytoma

Renal oncocytoma is a benign renal epithelial neoplasm. It was first described in 1942 by Zippel and became well accepted only after Klein and Valensi reported 13 additional cases in 1976.1 Oncocytomas are a relative uncommon tumor of the kidney, representing 3.2% to 7% of primary renal neoplasms. Renal oncocytomas affect men twice as often as women, with the patient age ranging from 10 to 94 years (median, 62 years). Signs and symptoms directly related to oncocytomas do not occur in most patients; 66% of patients are asymptomatic. The most common complaints are palpable mass, flank pain, or hematuria. Oncocytomas are usually detected incidentally by imaging studies conducted for unrelated reasons. Radiographically, these neoplasms typically have the appearance of a solid mass with a striking spoke-wheel appearance. However, this morphology is not pathognomonic of oncocytomas; renal cell carcinomas (RCCs) may have the same feature. Therefore, oncocytomas cannot be reliably distinguished from RCCs radiographically.22,3

Grossly, oncocytomas are well circumscribed, nonencapsulated neoplasms that are classically mahogany brown and in larger rumors have a central, stellate, radiating scar. The central scar is not pathognomonic because only 33% of these tumors have scars and some low-grade conventional and chromophobe RCCs may also have central scars. Typical renal oncocytomas range from 3 to 6 cm. Gross hemorrhage is present in up to 20% of cases, but necrosis is rare.3-7

Microscopically, these neoplasms are composed of a uniform population of round to polygonal cells arranging in nested, alveolar, trabecular, tubular, or microcystic patterns. The tumor cells typically have granular eosinophilic cytoplasm, a single round nucleus, evenly dispersed chromatin, and a small centrally placed nucleolus. Mitotic activity is low, but necrosis and atypical mitotic figures are absent. However, invasion of the renal capsule (20%) and vascular spaces (5%) may occur with renal oncocytoma and does not necessarily suggest malignancy or poor prognosis. Hale colloidal iron staining is usually negative but may occasionally be focally positive.3-7 Immunohistochemically, renal oncocytomas are positive for E-cadherin, MAK-6, and band 3 protein and negative for vimentin, N-cadherin, RCC, and CK7. Staining for CD10 is occasionally positive (Table).6,8,9 Ultrastructurally, the cytoplasm is packed with numerous large mitochondria typically with parallel cristae. Occasional microvesicles, typically found in chromophobe RCC rumor cells, may be present. Other organelles, lipid droplets, or glycogen are scant or absent. Microvilli are sparse; completely formed brush borders are usually absent.10 Cytogenetically, these neoplasms have lost chromosomes 1 and Y.7

The main consideration in the differential diagnosis of renal oncocytoma is usually eosinophilic variant of chromophobe RCC (CRCC-E) and conventional (clear cell) RCC with granular cytoplasm (CCRCC-GC). Distinction among these entities is very important because the CRCC-E and CCRCC-GC are malignant neoplasms and the renal oncocytoma is a benign rumor. Most of the time, morphologic features can differentiate the 3 entities. However, when the growth pattern is solid and cell borders are sharper than usual, it is necessary to resort to ancillary studies, such as histochemical, immunohistochemical, ultrastructural, and/or cytogenetic analyses.

Histologically, CRCC-E is characterized by a diffuse, solid growth pattern and rarely exhibits tubules or nests. CRCC-E also had a distinct, thickened cell border (cobblestone or vegetable cell-like appearance), wrinkled raisinoid nuclei and binucleation, coarser chromatin, and perinuclear halos.5,6 CCRCC-GC has a compact alveolar pattern of growth and occasionally exhibits tubulocystic structures with dilated tubules and microcysts. It also contains foci of hemorrhage and necrosis and frequent mitotic features.6 Histochemically, staining with Hale colloidal iron stain typically is diffuse and strongly positive in CRCC-E and weak, focal, and dropletlike in CCRCC-GC.3,7 However, interpretation of this staining pattern is not always straightforward. Additional studies usually are necessary for differentiating among these entities. Increasing numbers of immunohisto-chemical markers are available for diagnosing and differentiating among these 3 renal epithelial neoplasms (Table).6,8,9 Ultrastructurally, both CRCC-E and CCRCC-GC are similar to renal oncocytomas in having abundant mitochondria, which produce a granular and eosinophilic appearance in tissue sections. However, the tumor cells in CRCC-E uniquely also contain variable numbers of cytoplasmic microvesicles 150 to 300 nm in diameter. The cells also have rare short and stubby microvilli. CCRCC-GC tumor cells, however, have long microvilli similar to the brush border of the normal proximal tubules and contain abundant cytoplasmic lipid droplets and glycogen.10 Cytogenetically, CRCC-E tumor cells are commonly hypoploid, with losses of chromosomes 1, Y, 2, 6, 10, 13, and others. CCRCC-GC is characterized by loss of genetic material in chromosome 3p.7

References

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;38:906-914.

2. Defossez SM, Yoder IC, Papanicolau N. Nonspecific magnetic resonance appearance of renal oncocytomas: report of 3 cases and review of the literature. J Urol. 1991;145:552-554.

3. Murphy W, Beckwith J, Farrow G. Kidney neoplasms. In: Tumors of the Kidney, Bladder, and Related Urinary Structures. Washington, DC: Armed Forces Institute of Pathology; 1994:92-117. Atlas of Tumor Pathology, 3rd series, fascicle 11.

4. Amin MB, Crotty TB, Tickoo SK, Farrow CM. Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases. Am J Surg Pathol. 1997;21:1-12.

5. Tickoo SK, Amin MB. Discriminant nuclear features of renal oncocytoma and chromophobe renal cell carcinoma. Am J Clin Pathol. 1998;110:782-787.

6. Plaza JA, Perez-Montiel D, Suster S. Chromophobe cell carcinoma. Check Sample. 2002;30:37-49.

7. Reuter VE, Caudin PB. Adult renal tumors. In: Sternberg SS, ed. Diagnostic Surgical Pathology. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:1785-1805.

8. Qian J, Ramnani DM, Bostwick DC. Immunohistochemistry of kidney tumors. In: Dabbs DJ, ed. Diagnostic Immunohistochemistry. Philadelphia, Pa: Churchill Livingston; 2002:474-485.

9. Bonsib SM, Bromley C, Lager D. Renal oncocytoma: diagnostic utility of cytokeratin-containing globular filamentous bodies. Mod Pathol. 1991;4:16-23.

10. Krishnan B, Truong LD. Renal epithelial neoplasm: the diagnostic implications of electron microscopic study in 55 cases. Hum Pathol. 2002;33:68-79.

Jose A. Plaza, MD; Ping Wen, MD, PhD

Accepted for publication March 10, 2003.

From the Department of Pathology, Ohio State University Medical Center, Columbus.

Corresponding author: Ping Wen, MD, PhD, Department of Pathology, Ohio State University Medical Center, E-410 Doan Hall, 410 West 10th Ave, Columbus, OH 42310-1228 (e-mail: wen-2@medctr.osu.edu).

Reprints not available from the author.

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