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Bilateral Renal Oncocytoma: Report of 2 Cases and Review of Literature
0022-534 7/85/1333-0458$02.00/0 Vol. 133, March
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1985 by The Williams & Wilkins Co.
BILATERAL RENAL ONCOCYTOMA: REPORT OF 2 CASES AND REVIEW OF LITERATURE RONALD W. RASPA, MANUEL FERNANDES AND JOSEPH N. WARD From the Department of Urology, St. Luke's-Roosevelt Hospital Center, New York, New York
ABSTRACT
We report 2 cases of synchronous bilateral renal oncocytoma treated by radical nephrectomy on 1 side and by partial nephrectomy on the other side. Long-term followup serves to confirm the noninvasive nature of this disease. We recommend conservative management based upon radiological and gross pathological "findings. Renal oncocytoma is a rare tumor arising from the proximal renal tubules. 1 The well differentiated lesion has never been associated with metastasis or death. Survival following radical nephrectomy has been the rule, although no long-term survival data are available following partial nephrectomy. We report a favorable outcome in 2 patients with bilateral renal oncocytoma treated by unilateral partial and contralateral radical nephrectomy. CASE REPORTS
Case 1. A 53-year-old Hispanic woman was referred to the urology service for evaluation of urinary tract infections. An excretory urogram (IVP) showed a mass in the lower pole of the left kidney and a partially calcified mass in the middle of the right kidney. There was no history of hematuria, flank pain or weight loss. Physical examination was unremarkable. Blood pressure was 140/90 mm. Hg. A complete blood count showed a hemoglobin of 13.8 gm. per cent with no leukocytosis. Urinalysis was unremarkable, urine culture yielded no growth and urine cytology was negative. A flush aortogram and bilateral selective renal arteriogram revealed a highly vascular, well circumscribed left lower pole mass (fig. 1, A), and a smaller less well circumscribed mass in the middle and lateral portions of the right kidney (fig. 1, B). Both masses were thought to represent renal cell carcinoma. A chest x-ray and bone survey were unremarkable. The patient was explored through a transabdominal chevron incision. The frozen section biopsy from each kidney lesion demonstrated "hypernephroid carcinoma". The vascular pedicle was controlled and the inferior segmental artery was ligated. The capsule was incised sharply along the border of the devascularized segment and the parenchyma was divided bluntly. There was no evidence of perihilar lymphadenopathy and no nodes were sampled. Right nephrectomy was deferred because the left renal blood supply seemed to have been impaired temporarily. A 4 x 6 x 8 cm. tumor was noted in the specimen. Microscopic examination revealed renal cell carcinoma. An IVP later showed good function in the left kidney. Right radical nephrectomy was performed 4 weeks later through a transabdominal incision. The specimen contained a 5 cm. round mass described as "hypernephroma". No tumor was noted in the perihilar lymph nodes. The patient was discharged from the hospital on December 25, 1971. An IVP showed good function and no masses. She had a reaction to the intravenous contrast medium and has since been followed with periodic renal sonograms. Presently, blood urea nitrogen (BUN) is 16 mg./dl. and creatinine is 1.0 mg./dl. Recent re-evaluation of the tumor histology resulted in a diagnosis of grade II bilateral renal oncocytoma (fig. 2). Accepted for publication October 29, 1984.
FIG. 1. Case 1. A, selective left renal arteriogram shows rich neovascularity in well circumscribed mass. B, selective right renal arteriogram reveals less prominent vascularity in mass in mid right kidney.
Case 2. A 66-year-old white man was hospitalized on May 20, 1976 for evaluation of intermittent gross painless hematuria 10 days in duration. The patient gave a history of frequency times 10, nocturia times 3, hesistancy and progressive narrowing of the urinary stream during the last 10 years. The physical examination was unremarkable except for a smooth, firm, mildly enlarged prostate. Blood pressure was 140/90 mm. Hg. Serum chemistry profile, complete blood count and acid phosphatase were normal. Urinalysis showed many red blood cells and urine culture yielded no growth. Urine cytology showed inflammatory changes with atypical degenerated transitional cells. An IVP with tomograms revealed spaceoccupying lesions of the upper two-thirds of the right kidney and of the upper pole of the left kidney. Elevation of the base of the bladder, bladder wall thickening and a large bladder diverticulum also were noted. Renal sonograms showed a solid tumor in the right upper pole and a less dense, well circumscribed mass in the left upper pole. An aortogram revealed bilateral accessory lower pole renal arteries. Selective catheterization of the main renal arteries showed an orange-sized tumor on the right side and a somewhat smaller mass on the left side. Both masses demonstrated arteriovenous shunting and abnormal vascularity thought to be consistent with hypernephroma. An apparent demarcation of the left tumor was noted. An inferior venacavogram was normal. Bone survey and scan were negative for metastases. Left upper pole partial nephrectomy was performed using the 11th rib extrapleural incision. Frozen section showed adenocarcinoma and the tumor was enucleated easily. Biopsy of the remaining renal tissue was negative for malignancy. Although
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BILATERAL REl"JAL ONCOCYT01ViA
459
FIG. 2. Case 1. A, grade II right renal oncocytoma with well differentiated uniformity, and eosinophilic cells with occasional nuclear irregularity and variation. B, left renal oncocytoma demonstrates similar histology. H & E, reduced from X280.
there was no apparent lymphadenopathy a small node was removed, which was free of tumor. Definitive histological study showed the tumor to be renal oncocytoma. Right partial nephrectomy was performed 3 weeks later but rapid enlargement of the lower pole owing to inadequate venous return necessitated total nephrectomy. No lymph nodes were available for examination. The pathological diagnosis was grade I oncocytoma. A recent IVP showed no evidence of tumor recurrence or obstruction. BUN was 35 mg./dl. and creatinine was 2.9 mg./ dl. DISCUSSION
Choi and associates reviewed recently 50 cases of renal oncocytoma described in the literature. 2 A report of 62 tumors (grade I) not included in this review 3 and several additional cases 4 - 16 bring the total to at least 151. To date, 15 multifocal renal oncocytomas have been reported, 2·4- 15 8 of which were bilateral. 2 , 9 - 15 Only 2 patients have been managed by partial nephrectomy 9 ' 17 and long-term followup has not been reported. In our cases involvement of both kidneys necessitated renalsparing surgical procedures. No evidence of disease was noted 8 and 12 years postoperatively. Long-term survival following partial nephrectomy for adenocarcinoma of the kidneys has been reported. Kolln and associates described the first patient with bilateral renal cell carcinoma treated bilateral partial nephrectomy, 18 The patient was free of tumor at 27 months. Of the 32 patients who underwent partial nephrectomy for renal cell carcinoma in a solitary kidney before 1968, 14 had survived less than 1 year, 11 more than 1 year, 5 more than 5 and 2 more than 10 to 1968 reveals years, 19 A review of the literature that 62 patients with localized renal or in a kidney have undergone surgical treatment that resulted in ""'""r""''" tumor removal and preservation of renal function. Of 77 per cent were to be alive without evidence of tumor recurrence, with an average of 45.7 months. 20 In another report 84 per cent of 51 patients were alive 1 to 160 months following conservative surgery for synchronous bilateral renal adenocarcinoma. 21 The local recurrence rate was 10 per cent. Prolonged survival following conservative surgery for renal adenocarcinoma may be owing in part to misdiagnosis. Several renal oncocytomas have been discovered only after re-evaluation of a specimen previously diagnosed as carcinoma. 1- 3 • 22 Indeed, our case 1 was reported previously as bilateral renal adenocarcinoma.23 Renal oncocytoma has been considered invariably a benign tumor or one of limited invasive potential. In 1 patient such a tumor was thought to represent a cyst and was present for 8 years before nephrectomy, with a subsequent 9-year survival free of tumor. 24 Four patients with bilateral tumor, who were treated by biopsy and observation only, were well with no evidence of metastatic disease for 1 to 6 years. 10- 12 ·15 No deaths
have been attributed to this lesion, and partial nephrectomy has been advocated. 3 • 15 ·22 ·24,25 Two recent reports further demonstrate that partial nephrectomy for selected cases of adenocarcinoma may achieve 5-year survival rates comparable to those obtained following radical nephrectomy. 26 ' 27 These favorable results and the technical advances that now allow parenchymal-sparing operations to be done safely are allowing an extension of the traditional indications for this approach to encompass patients with unilateral malignancy and benign disorders of the opposite kidney, which subsequently may lead to functional impairment. 27 ·28 In view of the benign natural history of every reported grade I renal oncocytoma, we strongly recommend partial nephrectomy or enucleation for all such lesions, whether or not the patient has contralateral renal disease. Since a mixed field of well differentiated oncocytic cells and adenocarcinoma has never been reported, the danger of local recurrence or spread following conservative surgery should be minimal once a representative biopsy has been taken. In cases of bilateral oncocytomas grade, when reported, has been identical. However, each lesion should be biopsied, since 1 case of renal oncocytoma has been associated with a contralateral adenocarcinoma. 3 A careful search for multiple lesions must be made since 10 per cent will be multicentric and about half of these will be bilateral. The presence of more than 1 tumor should not dissuade a conservative surgical approach. The tumor is invariably well circumcised and may be encapsulated partially or entirely. 1 Simple enucleation with biopsy of the tumor margin as described for adenocarcinoma28·29 may be accomplished easily, We suggest that polar lesions be treated partial nephrectomy and that multicentric or mid renal lesions be enucleated. In the risk the lesion may be observed after biopsy. A high index of suspicion and familiarity with the clinical and radiological characteristics of this disease are necessary prerequisites for conservative surgical management. Most cases are discovered as incidental findings on an IVP performed for an unrelated -",,h,Am Signs or symptoms resulting from the disease were noted in 18 per cent of the cases reviewed by Choi and associates,2 and 3 patients presented with abdominal masses, 1 ' 2 2 had gross, painless hematuria, 22 · 30 2 complained of abdominal or flank pain, 30·31 1 had gross hematuria and flank pain, 30 and 1 had microscopic hematuria. 1 Hypertension was noted in 8 patients (16 per cent) and was never associated with another sign or symptom. In another recent review 4 of 11 patients (36 per cent) were hypertensive and 2 (18 per cent) had symptoms (flank pain). 9 Microscopic hematuria was noted in half of the cases, In the largest recent review of this disease 41 per cent of the patients were symptomatic, with flank pain being the most common complaint (73 per cent). 3 However, this series included data from patients with "Grade II oncocytoma", which has been shown to have a different natural history (21 per cent showed malignant behavior). Lieber and associates suggest that the unqualified term renal oncocytoma be reserved for the well differentiated tumor. 3
460
RASPA, FERNANDES AND WARD
Fm. 3. Case 2. A, grade I right renal oncocytoma with well differentiated lobular proliferation of large polyhedral eosinophilic cells with prominent nucleoli. H & E, reduced from Xl60. B, left renal oncocytoma demonstrates similar histology. H & E, reduced from X280.
Laboratory tests, IVP, sonography and computerized axial tomography are not diagnostic. Although not pathonomonic the arteriogram may give suggestive evidence as to the nature of the lesion. Angiographic findings may include a spoke-wheel pattern with the peripheral vessels radiating towards the center of the lesion, a homogeneous nephrogram or a sharp, smooth rim. 32 Tumor vessels may appear to be of normal caliber. 32 The mass may be hypovascular25 or hypervascular with apparent tumor neovascularity and staining. 24 Renal cell carcinoma may have any of the classical angiographic findings ascribed to oncocytoma but none of the 155 renal cell carcinomas evaluated angiographically by Ambos and associates showed a spokewheel pattern and a homogeneous blush. 32 The characteristic appearance of this tumor should help to diagnose the disease intraoperath'.ely. The lesion is tan and well circumscribed. 1 It usually1 but not invariably30 is devoid of hemorrhage. A frozen section will show eosinophilic epithelial cells arranged in tubular and alveolar patterns with no mitoses. Nuclear pleomorphism rarely is seen (fig. 3). 2 COMMENTS
Our experience with oncocytoma of the kidney and a knowledge of the universally noninvasive nature of this tumor as described in the literature encourage us to offer conservative surgical therapy to patients with this disease. Sos and associates advocated excisional biopsy with frozen section for patients with subcapsular masses that demonstrate angiographic criteria suggestive of renal oncocytoma. 25 They state that there is no evidence that excisional biopsy of a low grade superficial cortical malignancy before radical nephrectomy adversely affects the prognosis. 25 To our knowledge, no cases of adenocarcinomas have yet been reported to show a spoke-wheel pattern and a homogeneous nephrographic blush. When these features are noted on the arteriogram, sonograms of both kidneys should be obtained to rule out multifocal lesions. The tumor then should be biopsied and if the frozen section confirms the preoperative diagnosis of grade I renal oncocytoma, partial nephrectomy or enucleation should be performed. The number of reported cases of renal oncocytomas increased 8-fold during the last 8 years. As familiarity with this entity increases so should the diagnosis. The incidence of renal oncocytomas varies from 2 to 7 per cent of all renal cell tumors. 13· 22 Assuming an incidence of 5 per cent, one would expect that more than 500 renal oncocytomas could be diagnosed in the coming year. A conservative approach in these patients would allow for substantial renal preservation. Drs. Harold P. Gaetz and Bozidar Lazarevic assisted in the evaluation of the histopathological specimens. REFERENCES
1. Klein, M. J. and Valensi, Q. J.: Proximal tubular adenomas of the kidney with so-called oncocytic features. A clinicopathologic study of 13 cases of a rarely reported neoplasm. Cancer, 38: 906, 1976.
2. Choi, H., Almagro, U. A., McManus, J. T., Norback, D. and Jacobs, S. C.: Renal oncocytoma. A clinicopathologic study. Cancer, 51: 1887, 1983. 3. Lieber, M. M., Tomera, K. M. and Farrow, G. M.: Renal oncocytoma. J. Urol., 125: 481, 1981. 4. van der Walt, J. D., Reid, H. A., Risdon, R. A. and Shaw, J. H.: Renal oncocytoma. A review of the literature and report of an unusual multicentric case. Virch. Arch., 398: 291, 1983. 5. Barnes, C. A. and Beckman, E. N.: Renal oncocytoma and its congeners. Amer. J. Clin. Path., 79: 312, 1983. 6. Chen, K. T. K.: Multifocal renal oncocytoma. J. Urol., 130: 546, 1983. 7. Berger, G., Clermont, A., Pinet, F. and Loire, R.: Pluricentric oncocytoma of the kidney (microangiographic study). Arch. Anat. Path., 21: 287, 1973. 8. Woodard, B. H., Tannenbaum, S. I. and Mossier, J. A.: Multicentric renal oncocytoma. J. Urol., 126: 247, 1981. 9. Fairchild, T. N., Dail, D. H. and Brannen, G. E.: Renal oncocytoma-bilateral, multifocal. Urology, 22: 355, 1983. 10. Shah, I., Parekh, N., Nayak, P. K. and Taher, S.: Renal oncocytoma associated with diffuse lymphoma. Urology, 22: 314, 1983. 11. Hunt, H. A., Tudball, C. F., Sutherland, R. C. and Westmore, D. D.: Bilateral renal oncocytomas: a case report. J. Urol., 129: 1220, 1983. 12. Hara, M., Yoshida, K., Tomita, M., Akimoto, M., Kawai, H. and Fukuda, Y.: A case of bilateral renal oncocytoma. J. Urol., 128: 576, 1982. 13. Mitchell, K. M. and Shilkin, K. B.: Renal oncocytoma. Pathology, 14: 75, 1982. 14. Warfel, K. A. and Eble, J. N.: Renal oncocytomatosis. J. Urol., 127: 1179, 1982. 15. Moura, A. C. F. and Nascimento, A.G.: Renal oncocytoma: report of a case with unusual presentation. J. Urol., 127: 311, 1982. 16. Kay, S. and Armstrong, K. S.: Oncocytic tubular adenoma of the kidney-report of three cases with 28-year follow-up on one. In: Progress in Surgical Pathology. Edited by C. M. Fenoglio and M. Wolff. New York: Masson Publishing USA, Inc., vol. II, chapt. 11, p. 259, 1980. 17. Pearse, H. D. and Houghton, D. C.: Renal oncocytoma. Urology, 13: 74, 1979. 18. Kolln, C. P., Boldus, R. A., Brandon, D. N. K. and Flocks, R. H.: Bilateral partial nephrectomy for bilateral renal cell carcinoma: a case report. J. Urol., 105: 45, 1971. 19. Grabstald, H. and Aviles, E.: Renal cell cancer in the solitary or sole-functioning kidney. Cancer, 22: 973, 1968. 20. Schiff, M., Jr., Bagley, D. H. and Lytton, B.: Treatment of solitary and bilateral renal carcinomas. J. Urol., 121: 581, 1979. 21. Jacobs, S. C., Berg, S. I. and Lawson, R. K.: Synchronous bilateral renal cell carcinoma: total surgical excision. Cancer, 46: 2341, 1980. 22. Yu, G. S. M., Rendler, S., Herskowitz, A. and Molnar, J. J.: Renal oncocytoma. Report of five cases and review of the literature. Cancer, 45: 1010, 1980. 23. Hyman, R. A., Voges, V. and Finby, N.: Bilateral hypernephroma. Amer. J. Roentgen., 117: 104, 1973. 24. Tessler, A. N., Kurusu, S., Klein, M. J. and Valensi, Q. J.: Proximal tubular adenoma of kidney. Urology, 10: 203, 1977. 25. Sos, T. A., Gray, G. F., Jr. and Baltaxe, H. A.: The angiographic appearance of benign renal oxyphilic adenoma. Amer. J. Roentgen., 127: 717, 1976. 26. Topley, M., Novick, A. C. and Montie, J. E.: Long-term results
461
27.
28. 29. 30.
31. 32.
nephn~ctorny for localized :renal adenocarci131: 1050, 1984. Marshall, F. F. and V\Ta!sh, P. C.: In situ management of renal tumors: renal cell carcinoma and transitional cell carcinoma. J. Urol., 131: 1045, 1984. Novick, A. C.: Editorial comments. In situ management of renal tumors: renal cell carcinoma and transitional cell carcinoma. J. Urol., 131: 1049, 1984. Graham, S. D., Jr. and Glenn, J. F.: Enucleative surgery for renal malignancy. J. Urol., 122: 546, 1979. Ejeckam, G., Tolnai, G., Sarkar, K. and McCaughey, W. T. E.: Renal oncocytoma: study of eight cases. Urology, 14: 186, 1979. Harrison, R. H., Baird, J. M. and Kowierschke, S. W.: Renal oncocytoma: ten-year follow-up. Urology, 17: 596, 1981. Ambos, M.A., Bosniak, M.A., Valensi, Q. J., Madayag, M.A. and Lefleur, R. S.: Angiographic patterns in renal oncocytomas. Radiology, 129: 615, 1978. EDITORIAL COMMENT
This is another report testifying to the benign nature of the renal oncocytoma. The authors demonstrate the role of conservative management when the preoperative diagnosis is strongly suspected on the basis of criteria that seldom exist. They rightly affirm that radical
is otherwise the 1:c.anagen1ent of choice except ir:.. the patient a solitary kidney OT bilateral renal tumoro Ho\lvever, the histology in these cases becornes unimportant, since partial nephrectomy on at least 1 side is still the treatment of choice for bilateral renal tumors. It also is noteworthy that the initial histological diagnosis in both cases (the frozen section in case 2) indicated renal cell carcinoma rather than oncocytoma. This emphasizes the dangers of frozen sections, and some renal cell carcinomas will contain areas that have the typical oncocytoma pattern. Except in the case of bilateral renal tumors or tumor in the solitary kidney in the absence of the typical angiographic pattern, the management of renal tumors remains radical nephrectomy. J.B.deK.
REPLY BY AUTHORS Preoperative or intraoperative diagnosis is a necessary prerequisite for conservative treatment of renal oncocytoma. Although the arteriogram occasionally may be suggestive there are no diagnostic radiological findings. We hope that the forthcoming retrospective review of grade I tumors in the large series by Lieber and associates (reference 3 in article) may offer additional radiographic signs. As this entity becomes better known the pathologist may be able to render a timely accurate diagnosis.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1985 by The Williams & Wilkins Co.
BILATERAL RENAL ONCOCYTOMA: REPORT OF 2 CASES AND REVIEW OF LITERATURE RONALD W. RASPA, MANUEL FERNANDES AND JOSEPH N. WARD From the Department of Urology, St. Luke's-Roosevelt Hospital Center, New York, New York
ABSTRACT
We report 2 cases of synchronous bilateral renal oncocytoma treated by radical nephrectomy on 1 side and by partial nephrectomy on the other side. Long-term followup serves to confirm the noninvasive nature of this disease. We recommend conservative management based upon radiological and gross pathological "findings. Renal oncocytoma is a rare tumor arising from the proximal renal tubules. 1 The well differentiated lesion has never been associated with metastasis or death. Survival following radical nephrectomy has been the rule, although no long-term survival data are available following partial nephrectomy. We report a favorable outcome in 2 patients with bilateral renal oncocytoma treated by unilateral partial and contralateral radical nephrectomy. CASE REPORTS
Case 1. A 53-year-old Hispanic woman was referred to the urology service for evaluation of urinary tract infections. An excretory urogram (IVP) showed a mass in the lower pole of the left kidney and a partially calcified mass in the middle of the right kidney. There was no history of hematuria, flank pain or weight loss. Physical examination was unremarkable. Blood pressure was 140/90 mm. Hg. A complete blood count showed a hemoglobin of 13.8 gm. per cent with no leukocytosis. Urinalysis was unremarkable, urine culture yielded no growth and urine cytology was negative. A flush aortogram and bilateral selective renal arteriogram revealed a highly vascular, well circumscribed left lower pole mass (fig. 1, A), and a smaller less well circumscribed mass in the middle and lateral portions of the right kidney (fig. 1, B). Both masses were thought to represent renal cell carcinoma. A chest x-ray and bone survey were unremarkable. The patient was explored through a transabdominal chevron incision. The frozen section biopsy from each kidney lesion demonstrated "hypernephroid carcinoma". The vascular pedicle was controlled and the inferior segmental artery was ligated. The capsule was incised sharply along the border of the devascularized segment and the parenchyma was divided bluntly. There was no evidence of perihilar lymphadenopathy and no nodes were sampled. Right nephrectomy was deferred because the left renal blood supply seemed to have been impaired temporarily. A 4 x 6 x 8 cm. tumor was noted in the specimen. Microscopic examination revealed renal cell carcinoma. An IVP later showed good function in the left kidney. Right radical nephrectomy was performed 4 weeks later through a transabdominal incision. The specimen contained a 5 cm. round mass described as "hypernephroma". No tumor was noted in the perihilar lymph nodes. The patient was discharged from the hospital on December 25, 1971. An IVP showed good function and no masses. She had a reaction to the intravenous contrast medium and has since been followed with periodic renal sonograms. Presently, blood urea nitrogen (BUN) is 16 mg./dl. and creatinine is 1.0 mg./dl. Recent re-evaluation of the tumor histology resulted in a diagnosis of grade II bilateral renal oncocytoma (fig. 2). Accepted for publication October 29, 1984.
FIG. 1. Case 1. A, selective left renal arteriogram shows rich neovascularity in well circumscribed mass. B, selective right renal arteriogram reveals less prominent vascularity in mass in mid right kidney.
Case 2. A 66-year-old white man was hospitalized on May 20, 1976 for evaluation of intermittent gross painless hematuria 10 days in duration. The patient gave a history of frequency times 10, nocturia times 3, hesistancy and progressive narrowing of the urinary stream during the last 10 years. The physical examination was unremarkable except for a smooth, firm, mildly enlarged prostate. Blood pressure was 140/90 mm. Hg. Serum chemistry profile, complete blood count and acid phosphatase were normal. Urinalysis showed many red blood cells and urine culture yielded no growth. Urine cytology showed inflammatory changes with atypical degenerated transitional cells. An IVP with tomograms revealed spaceoccupying lesions of the upper two-thirds of the right kidney and of the upper pole of the left kidney. Elevation of the base of the bladder, bladder wall thickening and a large bladder diverticulum also were noted. Renal sonograms showed a solid tumor in the right upper pole and a less dense, well circumscribed mass in the left upper pole. An aortogram revealed bilateral accessory lower pole renal arteries. Selective catheterization of the main renal arteries showed an orange-sized tumor on the right side and a somewhat smaller mass on the left side. Both masses demonstrated arteriovenous shunting and abnormal vascularity thought to be consistent with hypernephroma. An apparent demarcation of the left tumor was noted. An inferior venacavogram was normal. Bone survey and scan were negative for metastases. Left upper pole partial nephrectomy was performed using the 11th rib extrapleural incision. Frozen section showed adenocarcinoma and the tumor was enucleated easily. Biopsy of the remaining renal tissue was negative for malignancy. Although
458
BILATERAL REl"JAL ONCOCYT01ViA
459
FIG. 2. Case 1. A, grade II right renal oncocytoma with well differentiated uniformity, and eosinophilic cells with occasional nuclear irregularity and variation. B, left renal oncocytoma demonstrates similar histology. H & E, reduced from X280.
there was no apparent lymphadenopathy a small node was removed, which was free of tumor. Definitive histological study showed the tumor to be renal oncocytoma. Right partial nephrectomy was performed 3 weeks later but rapid enlargement of the lower pole owing to inadequate venous return necessitated total nephrectomy. No lymph nodes were available for examination. The pathological diagnosis was grade I oncocytoma. A recent IVP showed no evidence of tumor recurrence or obstruction. BUN was 35 mg./dl. and creatinine was 2.9 mg./ dl. DISCUSSION
Choi and associates reviewed recently 50 cases of renal oncocytoma described in the literature. 2 A report of 62 tumors (grade I) not included in this review 3 and several additional cases 4 - 16 bring the total to at least 151. To date, 15 multifocal renal oncocytomas have been reported, 2·4- 15 8 of which were bilateral. 2 , 9 - 15 Only 2 patients have been managed by partial nephrectomy 9 ' 17 and long-term followup has not been reported. In our cases involvement of both kidneys necessitated renalsparing surgical procedures. No evidence of disease was noted 8 and 12 years postoperatively. Long-term survival following partial nephrectomy for adenocarcinoma of the kidneys has been reported. Kolln and associates described the first patient with bilateral renal cell carcinoma treated bilateral partial nephrectomy, 18 The patient was free of tumor at 27 months. Of the 32 patients who underwent partial nephrectomy for renal cell carcinoma in a solitary kidney before 1968, 14 had survived less than 1 year, 11 more than 1 year, 5 more than 5 and 2 more than 10 to 1968 reveals years, 19 A review of the literature that 62 patients with localized renal or in a kidney have undergone surgical treatment that resulted in ""'""r""''" tumor removal and preservation of renal function. Of 77 per cent were to be alive without evidence of tumor recurrence, with an average of 45.7 months. 20 In another report 84 per cent of 51 patients were alive 1 to 160 months following conservative surgery for synchronous bilateral renal adenocarcinoma. 21 The local recurrence rate was 10 per cent. Prolonged survival following conservative surgery for renal adenocarcinoma may be owing in part to misdiagnosis. Several renal oncocytomas have been discovered only after re-evaluation of a specimen previously diagnosed as carcinoma. 1- 3 • 22 Indeed, our case 1 was reported previously as bilateral renal adenocarcinoma.23 Renal oncocytoma has been considered invariably a benign tumor or one of limited invasive potential. In 1 patient such a tumor was thought to represent a cyst and was present for 8 years before nephrectomy, with a subsequent 9-year survival free of tumor. 24 Four patients with bilateral tumor, who were treated by biopsy and observation only, were well with no evidence of metastatic disease for 1 to 6 years. 10- 12 ·15 No deaths
have been attributed to this lesion, and partial nephrectomy has been advocated. 3 • 15 ·22 ·24,25 Two recent reports further demonstrate that partial nephrectomy for selected cases of adenocarcinoma may achieve 5-year survival rates comparable to those obtained following radical nephrectomy. 26 ' 27 These favorable results and the technical advances that now allow parenchymal-sparing operations to be done safely are allowing an extension of the traditional indications for this approach to encompass patients with unilateral malignancy and benign disorders of the opposite kidney, which subsequently may lead to functional impairment. 27 ·28 In view of the benign natural history of every reported grade I renal oncocytoma, we strongly recommend partial nephrectomy or enucleation for all such lesions, whether or not the patient has contralateral renal disease. Since a mixed field of well differentiated oncocytic cells and adenocarcinoma has never been reported, the danger of local recurrence or spread following conservative surgery should be minimal once a representative biopsy has been taken. In cases of bilateral oncocytomas grade, when reported, has been identical. However, each lesion should be biopsied, since 1 case of renal oncocytoma has been associated with a contralateral adenocarcinoma. 3 A careful search for multiple lesions must be made since 10 per cent will be multicentric and about half of these will be bilateral. The presence of more than 1 tumor should not dissuade a conservative surgical approach. The tumor is invariably well circumcised and may be encapsulated partially or entirely. 1 Simple enucleation with biopsy of the tumor margin as described for adenocarcinoma28·29 may be accomplished easily, We suggest that polar lesions be treated partial nephrectomy and that multicentric or mid renal lesions be enucleated. In the risk the lesion may be observed after biopsy. A high index of suspicion and familiarity with the clinical and radiological characteristics of this disease are necessary prerequisites for conservative surgical management. Most cases are discovered as incidental findings on an IVP performed for an unrelated -",,h,Am Signs or symptoms resulting from the disease were noted in 18 per cent of the cases reviewed by Choi and associates,2 and 3 patients presented with abdominal masses, 1 ' 2 2 had gross, painless hematuria, 22 · 30 2 complained of abdominal or flank pain, 30·31 1 had gross hematuria and flank pain, 30 and 1 had microscopic hematuria. 1 Hypertension was noted in 8 patients (16 per cent) and was never associated with another sign or symptom. In another recent review 4 of 11 patients (36 per cent) were hypertensive and 2 (18 per cent) had symptoms (flank pain). 9 Microscopic hematuria was noted in half of the cases, In the largest recent review of this disease 41 per cent of the patients were symptomatic, with flank pain being the most common complaint (73 per cent). 3 However, this series included data from patients with "Grade II oncocytoma", which has been shown to have a different natural history (21 per cent showed malignant behavior). Lieber and associates suggest that the unqualified term renal oncocytoma be reserved for the well differentiated tumor. 3
460
RASPA, FERNANDES AND WARD
Fm. 3. Case 2. A, grade I right renal oncocytoma with well differentiated lobular proliferation of large polyhedral eosinophilic cells with prominent nucleoli. H & E, reduced from Xl60. B, left renal oncocytoma demonstrates similar histology. H & E, reduced from X280.
Laboratory tests, IVP, sonography and computerized axial tomography are not diagnostic. Although not pathonomonic the arteriogram may give suggestive evidence as to the nature of the lesion. Angiographic findings may include a spoke-wheel pattern with the peripheral vessels radiating towards the center of the lesion, a homogeneous nephrogram or a sharp, smooth rim. 32 Tumor vessels may appear to be of normal caliber. 32 The mass may be hypovascular25 or hypervascular with apparent tumor neovascularity and staining. 24 Renal cell carcinoma may have any of the classical angiographic findings ascribed to oncocytoma but none of the 155 renal cell carcinomas evaluated angiographically by Ambos and associates showed a spokewheel pattern and a homogeneous blush. 32 The characteristic appearance of this tumor should help to diagnose the disease intraoperath'.ely. The lesion is tan and well circumscribed. 1 It usually1 but not invariably30 is devoid of hemorrhage. A frozen section will show eosinophilic epithelial cells arranged in tubular and alveolar patterns with no mitoses. Nuclear pleomorphism rarely is seen (fig. 3). 2 COMMENTS
Our experience with oncocytoma of the kidney and a knowledge of the universally noninvasive nature of this tumor as described in the literature encourage us to offer conservative surgical therapy to patients with this disease. Sos and associates advocated excisional biopsy with frozen section for patients with subcapsular masses that demonstrate angiographic criteria suggestive of renal oncocytoma. 25 They state that there is no evidence that excisional biopsy of a low grade superficial cortical malignancy before radical nephrectomy adversely affects the prognosis. 25 To our knowledge, no cases of adenocarcinomas have yet been reported to show a spoke-wheel pattern and a homogeneous nephrographic blush. When these features are noted on the arteriogram, sonograms of both kidneys should be obtained to rule out multifocal lesions. The tumor then should be biopsied and if the frozen section confirms the preoperative diagnosis of grade I renal oncocytoma, partial nephrectomy or enucleation should be performed. The number of reported cases of renal oncocytomas increased 8-fold during the last 8 years. As familiarity with this entity increases so should the diagnosis. The incidence of renal oncocytomas varies from 2 to 7 per cent of all renal cell tumors. 13· 22 Assuming an incidence of 5 per cent, one would expect that more than 500 renal oncocytomas could be diagnosed in the coming year. A conservative approach in these patients would allow for substantial renal preservation. Drs. Harold P. Gaetz and Bozidar Lazarevic assisted in the evaluation of the histopathological specimens. REFERENCES
1. Klein, M. J. and Valensi, Q. J.: Proximal tubular adenomas of the kidney with so-called oncocytic features. A clinicopathologic study of 13 cases of a rarely reported neoplasm. Cancer, 38: 906, 1976.
2. Choi, H., Almagro, U. A., McManus, J. T., Norback, D. and Jacobs, S. C.: Renal oncocytoma. A clinicopathologic study. Cancer, 51: 1887, 1983. 3. Lieber, M. M., Tomera, K. M. and Farrow, G. M.: Renal oncocytoma. J. Urol., 125: 481, 1981. 4. van der Walt, J. D., Reid, H. A., Risdon, R. A. and Shaw, J. H.: Renal oncocytoma. A review of the literature and report of an unusual multicentric case. Virch. Arch., 398: 291, 1983. 5. Barnes, C. A. and Beckman, E. N.: Renal oncocytoma and its congeners. Amer. J. Clin. Path., 79: 312, 1983. 6. Chen, K. T. K.: Multifocal renal oncocytoma. J. Urol., 130: 546, 1983. 7. Berger, G., Clermont, A., Pinet, F. and Loire, R.: Pluricentric oncocytoma of the kidney (microangiographic study). Arch. Anat. Path., 21: 287, 1973. 8. Woodard, B. H., Tannenbaum, S. I. and Mossier, J. A.: Multicentric renal oncocytoma. J. Urol., 126: 247, 1981. 9. Fairchild, T. N., Dail, D. H. and Brannen, G. E.: Renal oncocytoma-bilateral, multifocal. Urology, 22: 355, 1983. 10. Shah, I., Parekh, N., Nayak, P. K. and Taher, S.: Renal oncocytoma associated with diffuse lymphoma. Urology, 22: 314, 1983. 11. Hunt, H. A., Tudball, C. F., Sutherland, R. C. and Westmore, D. D.: Bilateral renal oncocytomas: a case report. J. Urol., 129: 1220, 1983. 12. Hara, M., Yoshida, K., Tomita, M., Akimoto, M., Kawai, H. and Fukuda, Y.: A case of bilateral renal oncocytoma. J. Urol., 128: 576, 1982. 13. Mitchell, K. M. and Shilkin, K. B.: Renal oncocytoma. Pathology, 14: 75, 1982. 14. Warfel, K. A. and Eble, J. N.: Renal oncocytomatosis. J. Urol., 127: 1179, 1982. 15. Moura, A. C. F. and Nascimento, A.G.: Renal oncocytoma: report of a case with unusual presentation. J. Urol., 127: 311, 1982. 16. Kay, S. and Armstrong, K. S.: Oncocytic tubular adenoma of the kidney-report of three cases with 28-year follow-up on one. In: Progress in Surgical Pathology. Edited by C. M. Fenoglio and M. Wolff. New York: Masson Publishing USA, Inc., vol. II, chapt. 11, p. 259, 1980. 17. Pearse, H. D. and Houghton, D. C.: Renal oncocytoma. Urology, 13: 74, 1979. 18. Kolln, C. P., Boldus, R. A., Brandon, D. N. K. and Flocks, R. H.: Bilateral partial nephrectomy for bilateral renal cell carcinoma: a case report. J. Urol., 105: 45, 1971. 19. Grabstald, H. and Aviles, E.: Renal cell cancer in the solitary or sole-functioning kidney. Cancer, 22: 973, 1968. 20. Schiff, M., Jr., Bagley, D. H. and Lytton, B.: Treatment of solitary and bilateral renal carcinomas. J. Urol., 121: 581, 1979. 21. Jacobs, S. C., Berg, S. I. and Lawson, R. K.: Synchronous bilateral renal cell carcinoma: total surgical excision. Cancer, 46: 2341, 1980. 22. Yu, G. S. M., Rendler, S., Herskowitz, A. and Molnar, J. J.: Renal oncocytoma. Report of five cases and review of the literature. Cancer, 45: 1010, 1980. 23. Hyman, R. A., Voges, V. and Finby, N.: Bilateral hypernephroma. Amer. J. Roentgen., 117: 104, 1973. 24. Tessler, A. N., Kurusu, S., Klein, M. J. and Valensi, Q. J.: Proximal tubular adenoma of kidney. Urology, 10: 203, 1977. 25. Sos, T. A., Gray, G. F., Jr. and Baltaxe, H. A.: The angiographic appearance of benign renal oxyphilic adenoma. Amer. J. Roentgen., 127: 717, 1976. 26. Topley, M., Novick, A. C. and Montie, J. E.: Long-term results
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nephn~ctorny for localized :renal adenocarci131: 1050, 1984. Marshall, F. F. and V\Ta!sh, P. C.: In situ management of renal tumors: renal cell carcinoma and transitional cell carcinoma. J. Urol., 131: 1045, 1984. Novick, A. C.: Editorial comments. In situ management of renal tumors: renal cell carcinoma and transitional cell carcinoma. J. Urol., 131: 1049, 1984. Graham, S. D., Jr. and Glenn, J. F.: Enucleative surgery for renal malignancy. J. Urol., 122: 546, 1979. Ejeckam, G., Tolnai, G., Sarkar, K. and McCaughey, W. T. E.: Renal oncocytoma: study of eight cases. Urology, 14: 186, 1979. Harrison, R. H., Baird, J. M. and Kowierschke, S. W.: Renal oncocytoma: ten-year follow-up. Urology, 17: 596, 1981. Ambos, M.A., Bosniak, M.A., Valensi, Q. J., Madayag, M.A. and Lefleur, R. S.: Angiographic patterns in renal oncocytomas. Radiology, 129: 615, 1978. EDITORIAL COMMENT
This is another report testifying to the benign nature of the renal oncocytoma. The authors demonstrate the role of conservative management when the preoperative diagnosis is strongly suspected on the basis of criteria that seldom exist. They rightly affirm that radical
is otherwise the 1:c.anagen1ent of choice except ir:.. the patient a solitary kidney OT bilateral renal tumoro Ho\lvever, the histology in these cases becornes unimportant, since partial nephrectomy on at least 1 side is still the treatment of choice for bilateral renal tumors. It also is noteworthy that the initial histological diagnosis in both cases (the frozen section in case 2) indicated renal cell carcinoma rather than oncocytoma. This emphasizes the dangers of frozen sections, and some renal cell carcinomas will contain areas that have the typical oncocytoma pattern. Except in the case of bilateral renal tumors or tumor in the solitary kidney in the absence of the typical angiographic pattern, the management of renal tumors remains radical nephrectomy. J.B.deK.
REPLY BY AUTHORS Preoperative or intraoperative diagnosis is a necessary prerequisite for conservative treatment of renal oncocytoma. Although the arteriogram occasionally may be suggestive there are no diagnostic radiological findings. We hope that the forthcoming retrospective review of grade I tumors in the large series by Lieber and associates (reference 3 in article) may offer additional radiographic signs. As this entity becomes better known the pathologist may be able to render a timely accurate diagnosis.