UROPATHOLOGY

RENAL CELL CARCINOMA VS. RENAL ONCOCYTOMA Report of A Case With Overlap Features and Review of the Literature BETTE LAZZARO, M.D. PAUL GONICK, M.D. SHEILA MORIBER KATZ, M.D. From the Departments of Pathology and Urologic SurgeD; Hahnemann University Hospital, Philadelphia, Pennsylvania

ABSTRACT--Although the salient features of renal oncocytomas and renal cell carcinomas havei been discussed in the recent literature, renal masses with features of both entities will presentl diagnostic difficulty, especially when the cells are diffusely eosinophilic on microscopic examina- I tion. A case of a firm, tan, rounded mass replacing the lower pole of the kidney is discussed. The] final diagnosis of renal cell carcinoma, granular cell type, was made after multiple sections of the tumor were examined, and after electron microscopy was performed. A thorough search by light microscopy should be made for clear cell loci, necrosis, mitotic activity, and vascular or capsula r invasion, features generally accepted as pathognomonic for renal cell carcinoma. Cellular and espe' cially nuclear pleomorphism is typically focal or mild in renal oncocytomas. True oncocytic tumor~ will be packed with mitochondria on electron microscopy; however, granular renal cell carcinomoz will contain mitochondria as well as other cellular organelles, lipid, and glycogen. Electron micros copy should be performed on tumors suspected of being oncocytomas because eosinophilia on he matoxylin and eosin stain, as demonstrated by this case, is' not a predictable measure of mitochon dria content, hnmunoperoxidase staining for vimentin in oncocytomas has recently been shown t~ be negative, and may offer a method of ruling out oncocytoma in vimentin-positive tumors, pendl ing further studies'.

Renal oneocytoma, a benign tumor composed of eosinophilie cells which show abundant mitoehondria on electron microscopy, ("oneoeytes") is a well-documented entity. T M The tumor may be as large as 26 cm in diameter, and the eosinophilic cells may mimic the granular cell type of renal cell carcinoma by light microscopy. Grossly, oncoeytomas are well-circumscribed, firm, and mahogany or tan, frequently with a central scarred area. 1-5 However, the gross appearance of renal cell carcinoma, classically yellow or ()range with areas of necrosis, may overlap with that of oncoeytoma when the lesion is large, firm, tan, and well-circumscribed. Microscopically mi52

totic activity and necrosis are not, seen in onc~ cytomas, and hemorrhage is onl~ focal. Gell.~ lar pleomorphism is typically focal or mild.~7!l W~jep~rt herein a'ease which, on initial iI spee i , ad the gross and microscopic appea I anee of oneoeytoma: that is, a firm. tan. weli circumscribed renal mass composed 0~ eosinophilie cells, which showed no evidence0i lymphatic, vascular, or capsular invasiOI There was question as to whether this repfI sented oneoevtoma or renal cell carcinoma, a~l our purpose'here is to emphasize the imp0~ tanee of cellular features, tumor heterogenei~ [~ adequate sampling, and electron micros conV ~.~; distinguishing the two. J

UROLOGY / JANUARY 1991 / VOLUME XXXVII.. N[;MBI~I

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Nephrectomy .specimen showing 5 x 4 x 4-cm mass.

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Benal arteriogram showing poorly vas":ularized round mass replacing most of lower pole.

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Case Report

The patient was a thlrtv-one-year-old hvper~f~nsive black man on hem;dialysis for end-stage .renal disease seeondary to focal segmental . :iglomerulosclcrosis. There was also a history of :.::drUg abuse (heroine, cocaine) with hepatitis B :and hepatitis A screens indieative of acute or re:Yl : :~eent infection. IIIV antibodies were negative. -i.;): :The patient had eomplained of four to five ! ilm0nths of intermittent acute burning left flank ?Pain. Urinalysis revealed 5-10 red blood cells :pet high-powered field. Arteriogram of the left ::kiitney on admission showed a r o u n d mass in i;;}flie lower pole approximately 5 cm in diame::{{4r,:with a hypovascular or nonvascular appear: i}~ee. The capsular arteries were somewhat i'0'~arged and the interface of the mass with the ' i;~egal parenchyma was sharp, with a "beak" at 7~tliekidney ed ge, .su gg estin g a'c Yst (Fi g. 1). The :,:;.,~,~: :~lra!aression was one of hemorrhagie or infected i:eY~.t, but tumor could not be ruled out. Com.:ilSti~erized tomography (CT) scan showed a left -ite~al mass which appeared to be solid. !~;:::Eeft radieal nephreetomy was performed, a ~ the patient's postoperative course was un-

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eventful, with no evidence of metastatic disease at the time. The patient is without evidence of reeurrenee or metastasis seven months following discharge. Pathology

The nephreetomy specimen eonsistcd of a 90-g kidney with attached perinephric fat and left adrenal gland. Dissection revealed a 5 x 4 x 4-cm firm, light tan, bulging round mass replacing the entire lower pole of the kidney (Fig. 2). The cut surface was smooth and homogeneous, except for an irregular creseent-shaped central zone. The tumor was well-circumscribed and surrounded by a thin rim of compressed cortex covered by intact renal capsule. The renal parenehyma not involved by tumor showed advanced atrophic changes consistent w i t h e n d - s t a g e r e n a l disease. T h e perinephric fat, adrenal gland, renal pelvis, ureter, vessels, and renal hilar lymph nodes showed no gross abnormalities. Mieroscopically, the tumor consisted of uniformly eosinophilic cells forming sheets, nests, and extensive papillary. structures (Fig 3A). There were areas of mild to moderate cellular pleomorphism, with many large vesicular nuclei and prominent nueleoli (Fig. 3B). Mitotic activity was not seen. Virtually all the eells on the initial sections showed bright eosinophilic cytoplasm which

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FmURE 4. Electron micrograph showing areas of abundant mitochondria (black arrou;s); lipid (black arrowheads) is also present. appeared ~ a n u l a r in some areas. No tumor cells were seen invading adjacent parenchyma or capsule, and the perinephrie and hilar structures, including vessels and lymphatics, were mieroscopically free of tumor. Due to the diffusely eosinophilie appearanee of the cells, the lack of microscopic invasion, and the gross appearance, the differential diagnosis was oneocytoma versus renal cell careinoma. Eleetron mieroseopy showed seattered mitochondria, as well as Golgi apparatus, rough endoplasmic reticulum, and oeeasional glycogen and lipid droplets (Fig. 4). Based on the electron microscopic findings, additional hematoxylin and eosin (H&E) sections of the tumor were taken: these showed foei of atypical d e a r cells, with focal areas of tumor necrosis that had not been appreciated initially (Fig. 5). Periodic aeid-Sehiff (PAS) staining with and without diastase revealed no signifieant glyeo-

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Focal clear cell change with necrosis,~,:

gen content, and showed intact basal lamina i{ many areas. Immunoperoxidase staining for li~ sozyme, present in normal proximal convolut~ tubules, was equivocal. I m m u n o p e r o x i d a ~ staining for vimentin showed focal positivity.,~ The final diagnosis was renal cell carcinom~ granular cell type, confirmed by an independ] ent consultant, is Comment Oncocytomas have been reported more fr, quently over the past several years. There some thought that the increased incidence due not only to increased awareness of the et tit); but also to possible unknown environme tal factors. 4-r The increased incidence of re~ cell carcinoma in patients with end-stage r e g l disease, such as ours, has been documented There does not appear to be a relationsh

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between renal failure or injury and development of oncoeytomas. ~ Clinicall); oncocytomas are asyrnptomatic more frequently than renal cell carcinomas, and our patient did have several months of flank pain.~ 5.7.8 Mieroseopic hematuria, which our patient also had, is to be expected more frequently with renal cell carcinomas. ~,a-5,Ts Angiographically, the classic pattern for oncocytomas is a "spokewheel" pattern of vessels with an even background blush, but caution is advised in that renal cell carcinomas may occasionally show this pattern. 2s The arteriogram of our lesion was not strongly suggestive of neoplasm, probably because of poor dye uptake within the tumor, giving a hypovaseular or cystic impression.~7 The salient features distinguishing granular renal cell carcinomas from oncoeytomas have (:been discussed in case reports from the recent :literature. ~-~t Cases with overlap features, how;lever, will present diagnostic difficulty, espe::' ,emll y when they are diffusely eosinophilic on 'microscopic examination. The mass described !.:.here had gross features of both entities: It was :well-circumscribed, firm and tan but had an ir::,':regular crescent-shaped central zone suggesting ~necrosis. In addition, bulging from the cut sur; ~face.as seen in our specimen has been described 'i'as a feature of oncocytomas. '4 In difficult cases ?.isuch as this, we recommend strict attention to ::,cellular features and extensive sampling of the :i':/tumor :~ Microscopically, cellular p l e o m o r p h i s m should be mild or focal in oncocytomas, and !mitotic activity should not be present. Nuclei, ::~:however, may show moderate variation in size, :;and multinucleation is occasionally seen. '~ The ii~tegree of pleomorphism does not approach that ' ::~eenin other oncocytic neoplasms, specifically .~':the Hurthle cell tumor of the thyroid. In our :~case, there were areas of moderate cellular and, ~tnore importantly.; nuclear pleomorphism with -imany large vesicular nuclei and prominent nu•,icleoli. These features are not consistent with :i!;bneocytoma. ~-a-c' In addition, a papillary con::i:~iguration was prominent. Papillary configurai:hOn should be at most focal, and Merino and '~4LiVolsi :_~ ren,~,~,,,,~no papillary formation at all in '!:their series, ta '~ (Ejeekam e t al. 9 report 1 case ii ~vhieh did show a predominantly papillary pat