PREVALENCE, MORPHOLOGY AND BIOLOGY OF RENAL CELL CARCINOMA IN VON HIPPEL-LINDAU DISEASE COMPARED TO SPORADIC RENAL CELL CARCINOMA

Purpose

Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology.

Materials and Methods

We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease.

Results

The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p <0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm.

Conclusions

Von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.     

Infiltrating lobular carcinoma of the breast: an evaluation of the incidence and consequence of bilateral disease

A histological review of 1003 invasive breast carcinomas identified 103 patients with infiltrating lobular carcinoma, for whom clinical and survival data were collected in each case. Six patients had bilateral carcinoma at diagnosis and 14 developed a contralateral carcinoma during the period of follow-up. The major factor predicting patients at risk of developing a contralateral carcinoma was histological type. Analysis of survival data on the patients with bilateral disease showed poor survival in the group with synchronous bilateral disease, but no difference in survival between patients with metachronous bilateral and unilateral disease. This suggests that the development of a metachronous contralateral carcinoma does not necessarily reduce the probability of survival of patients with infiltrating lobular carcinoma.     

Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an international multicentre experience

OBJECTIVE: To present a multicentre experience and the largest cohort to date of nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because it is rare the single-institutional experience is limited. PATIENTS AND METHODS: We retrospectively studied 10 337 patients from 12 urological centres to identify patients with N0M0 synchronous bilateral RCC; the clinicopathological features and cancer-specific survival were compared to a cohort treated for N0M0 unilateral RCC. RESULTS: In all, 153 patients had synchronous bilateral solid renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell RCC was the major histological subtype (76%), and papillary RCC was the next most frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group performance status (ECOG PS) and T classification, but bilateral RCCs were more frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19% vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC had a similar prognosis (P = 0.63); multifocality did not affect survival (P = 0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman grade, but not laterality, as independent prognostic factors for cancer-specific survival. CONCLUSIONS: Patients with N0M0 synchronous bilateral RCC and N0M0 unilateral RCC have a similar prognosis. The frequency of a familial history for RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in bilateral synchronous than in unilateral RCC. The significant pathological findings in synchronous bilateral RCC are papillary subtype and multifocality.     

Der bilaterale Nierentumor Therapiemanagement und histopathologische Ergebnisse mit Langzeitverlauf bei 66 Patienten

Bilateral renal cell carcinoma is detected at an incidence rate of 1.6-6% of all renal tumors. The management, histopathological results and the long-term follow-up of 66 patients with bilateral renal cell carcinoma (29 synchronous, 37 asynchronous tumors) are presented in this issue. The incidence rate of bilateral renal cell carcinoma (RCC) at our hospital was 3.5%. Nephron-sparing surgery should be used first for the smaller and favourably located tumor when radical nephrectomy of the contralateral tumor is necessary. Thus, the patients can be spared dialysis. The histopathological results showed a significantly higher incidence rate of chromophil RCCs in cases of synchronous bilateral renal tumors (36%). The 5-year survival rate was 82%. Patients with asynchronous renal cell carcinomas were significantly younger than those with synchronous RCCs (median age: 60.2 years). The histopathological results were similar to unilateral renal cell carcinomas. Clear cell carcinoma was detected in 70% of cases. The 5-year survival rate was 61% and lower than that of synchronous tumors (82%). There was no significant difference because of the small number of cases. Current standardised techniques of nephron-sparing surgery achieve good survival rates, therefore making bilateral nephrectomy only necessary in very poor cases. In cases of chromophil renal cell carcinomas, the contralateral kidney should always be carefully examined, because these tumors were significantly more often detected to be bilateral. The risk of also developing a tumor in the contralateral kidney increases with decreasing age at first manifestation (< 55 years, 6%). Especially in those younger than 55 years, partial nephrectomy seems to be recommended for unilateral renal tumors in patients with a normal contralateral kidney (tumor size < 4 cm in diameter).     

Bilateral breast carcinoma: clinical characteristics and its impact on survival

The higher incidence of breast cancer, the improvements in diagnosis and treatment, together with the growing life expectancy have brought about an increase in the number of patients at risk for bilateral breast carcinoma. The aim of this study is to describe the characteristics of patients suffering from bilateral breast carcinoma who underwent surgery at the Breast Pathology Service of the Buenos Aires British Hospital and to analyze impact on survival. Between January 1970 and May 2007, 4,085 cases of breast carcinoma in 3,864 patients were treated at the Breast Diseases Division of the Buenos Aires British Hospital. A retrospective study of 194 patients with bilateral breast carcinoma was carried out: 80 synchronous and 114 metachronous. In order to compare survival, a group of 2,237 patients with unilateral breast carcinoma who had undergone surgery was analyzed. The risk of developing a contralateral breast carcinoma was 0.9% per year, with an accumulated risk at 15 years of 12.75%. The 5-year survival was 85.9% for unilateral carcinomas, 94.6% for metachronous carcinoma, and 63.3% for synchronous carcinoma. The 15-year survival was 65.5% for unilateral carcinomas, 52.3% for metachronous, and 37.2% for synchronous. The incidence of bilateral carcinomas is low. Survival was worse in patients with metachronous carcinoma diagnosed within 5 years of the first malignancy. Survival in patients with metachronous carcinoma diagnosed after 5 years is similar to those with unilateral carcinoma. Synchronous carcinoma was associated to worse survival, being an independent risk factor for mortality.     

High incidence of and risk factors for metachronous bilateral upper tract urothelial carcinoma in Taiwan

AIM: Urothelial carcinoma (UC) can occur multifocally in the whole urothelium. A higher rate of bilateral metachronous upper tract (UT) UC was noted in Taiwan. The incidence and risk factors were largely unknown and hence were explored in the study. METHODS: From January 1977 through June 2003, 462 patients with unilateral UT-UC were studied retrospectively. The cumulative incidence of contralateral recurrence was analysed with the Kaplan-Meier analysis. Potential risk factors for contralateral recurrence including age, smoking, bladder cancer, renal function, diagnostic year etc. were evaluated with the log-rank test. Independent risk factors were identified by using the Cox regression analysis. RESULTS: The median follow-up time was 34 months (6-337). Among the 462 patients, 52 (11.3%) developed metachronous contralateral UC. The 2, 5, and 10-year contralateral disease-free survivals were 93.5%, 84.0%, and 75.7%, respectively. The median time to contralateral recurrence was 31.0 months. With the univariate analysis, only poor renal function (serum creatinine < or > OR =2.0 mg/dL, P < 0.001) and late diagnostic year (before or after 1990, P < 0.001) were risk factors for contralateral recurrence. In the multivariate analysis, poor renal function (hazard ratio: 2.98; 95% confidence interval: 1.67-5.33; P < 0.001) and late diagnostic year (hazard ratio: 4.27; 95% confidence interval: 1.71-10.65; P = 0.002) remained independent risk factors. CONCLUSIONS: The incidence of metachronous UT-UC is high in Taiwan. Patients who had either chronic renal insufficiency or a disease diagnosed after 1990 had a higher risk of contralateral recurrence.     

Von Hippel—Lindau病肾癌的临床特征分析

目的 探讨Von Hippel-Lindau（VHL）病肾癌的临床特点。方法回顾分析28例VHL病肾癌患者的临床资料。就初诊年龄、肿瘤部位、同时或异时癌、肿瘤的组织病理等与散发性肾癌进行比较。结果VHL肾癌初诊年龄44．6岁，双肾癌15例、多灶性肾癌16例、伴双侧多发肾囊肿20例。共切除87个实性肿瘤。术后病理：透明细胞癌86个，Fuhrman分级Ⅰ级73个、Ⅱ级12个、Ⅲ级1个；钙化结节1个。TNM分期ⅠA期、ⅠB期、Ⅱ期、Ⅲ期分别为8例、7例、8例和1例。与散发性肾癌组相比，VHL病肾癌组患者发病年龄早（P〈0．05），双肾多灶性肾癌及伴双侧多发肾囊肿比例高（P〈O．001），高级别肿瘤比例低（P〈O．05）。结论VHL病肾癌不同于散发性肾癌，有其独特的临床病理特征，这对该病诊断治疗具有一定指导价值。     

Clear cell endocrine pancreatic tumor mimicking renal cell carcinoma: a distinctive neoplasm of von Hippel-Lindau disease

The dominantly inherited von Hippel-Lindau disease is characterized by clear cell neoplasms in various organs including the kidney and pancreas. Determination of primary versus metastatic lesion in this setting can be a diagnostic dilemma. The authors present five cases of clear cell endocrine pancreatic tumor (EPT) closely mimicking renal cell carcinomas in five patients with a family history or histologic evidence of von Hippel-Lindau disease. In fact, two of these tumors were confused with metastatic renal cell carcinoma by fine-needle aspiration. All five tumors had a component of clear cells arranged in nests, cords, and tubules with central hemorrhage separated by thin-wall vessels resembling renal cell carcinoma. However, these tumors also exhibited cords and festoons and a gyriform pattern suggestive of an endocrine neoplasm, and expressed chromogranin and synaptophysin. Vascular invasion was identified in four tumors, one of which metastasized. The concurrent primary renal cell carcinomas and the multicentric microcystic adenomas found in three patients did not show reactivity for the neuroendocrine markers. Focal clear cell change was noted in only one of 29 endocrine pancreatic tumors arising in patients without von Hippel-Lindau disease. Eleven metastatic renal cell carcinomas in the pancreas did not show immunoreactivity with the endocrine markers. Clear cell EPTs closely mimicking renal cell carcinoma are distinctive neoplasms of von Hippel-Lindau disease. In contrast to clear cell EPT, metastatic renal cell carcinoma does not express neuroendocrine markers and lacks neurosecretory granules by electron microscopy. Von Hippel-Lindau disease should be strongly suspected in patients with renal cell carcinoma, clear cell EPT, and multifocal microcystic serous adenomas.     

Von Hippel-Lindau disease with multiple malignant renal tumors: the importance of genetic testing

We present an adult man who, while being evaluated for gross hematuria, was found to have polycystic kidneys and multiple bilateral renal cell carcinomas. Further evaluation and the presence of a significant family history of cancer suggested the diagnosis of von Hippel-Lindau disease. Through the aid of genetic testing, this unusual diagnosis was confirmed and led to the identification of other family members with the von Hippel-Lindau gene. Patients with von Hippel-Lindau disease have an increased incidence of malignant carcinomas and the syndrome can mimic the presentation of other cystic diseases of the kidney. Early diagnosis and genetic screening of family members is essential to improve the prognosis and survival of those affected.     

Contralateral metachronous tumor occurrence is more frequently associated with distant metastases or postoperative intrarenal recurrence in renal cell carcinoma patients

Objective: To analyze the prognosis of patients with sporadic bilateral renal cell carcinoma (RCC). Methods: From January 1979 to December 2007, 984 patients with sporadic RCC underwent surgery at our department. Of these, 53 patients (5.7%) presenting with bilateral RCC were included in this retrospective analysis. Results: Thirty‐one of the 53 bilateral RCC patients had synchronous RCC, and 22 had metachronous RCC. Distant metastases by the time of the bilateral tumor occurrence were found in four patients (13%) in the synchronous group and in 10 patients (48%) in the metachronous group. No difference was found between the two groups in terms of overall survival. In contrast, survival after the second surgery in the metachronous group was significantly lower than that after the first surgery (P < 0.001) in the synchronous group (P = 0.02). In addition, the incidence of local recurrence after partial nephrectomy was higher in the metachronous group (26%) compared to the synchronous group (4%, P = 0.04) or the unilateral RCC patients (0.4%, P < 0.01). Conclusions: Metachronous occurrence of RCC in the contralateral kidney is associated with an unfavorable prognosis, suggesting that metachronous contralateral tumors might be metastasis of the original tumors. A stricter follow‐up schedule is advisable for metachronous bilateral RCC patients.     

Management and outcome of bilateral testicular germ cell tumors: A 25‐year single center experience

Objectives: To analyze risk factors, management, histology, and outcome of bilateral testicular germ cell tumors (TGCT) based on a 25‐year single center experience. Methods: Out of 612 patients treated for TGCT between 1982 and 2007, 17 (3%) were found to have bilateral disease. Data of these patients were reviewed and analyzed. Results: Eleven patients (65%) were identified with metachronous and 6 (35%) with synchronous bilateral TGCT. One patient had a cryptorchism in childhood. Patients with metachronous bilateral disease presented at lower stages than those with synchronous bilateral disease (stage I: 82% vs 33%, P = 0.02). In metachronous bilateral TGCT, the interval between the tumors ranged from 4 months to 25 years with a median of 47 months. The risk of developing a TGCT in the contralateral testicle was 26‐fold higher than the a‐priori risk for a healthy individual to develop TGCT. Overall, 74% of the bilateral tumors were seminomas and >50% of the patients had similar histology on both sides. After a median follow up of 121 months for patients with synchronous and 95 months for patients with metachronous bilateral TGCT, all patients were alive with no evidence of disease. Conclusions: Most bilateral TGCT develop metachronously and are seminomas. Although patients with synchronous bilateral disease present at higher stages, both synchronous and metachronous bilateral TGCT carry a similar, excellent prognosis. Patients with unilateral TGCT require careful long‐term monitoring of the remaining testicle due to a 26‐fold increased risk of contralateral disease and a potentially long risk interval of up to 25 years.     

Prognostic significance of synchronous and metachronous bilateral breast cancer

Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast, but the clinical significance of this development is unclear. The purpose of this study was to assess the impact of synchronous bilateral breast cancer or the development of a metachronous contralateral breast primary on the prognosis. In a series of 3210 women age < or = 70 years treated between 1975 and 1995 for primary operable breast cancer, 106 were identified to have bilateral breast cancer. Of these women, 26 were noted to have synchronous bilateral breast primaries (0.8%), and 80 developed a contralateral breast cancer after treatment for an initial primary breast cancer. Using life-tables analysis, there was a significant difference in survival between women with unilateral breast cancer, those with synchronous bilateral breast cancers, and those with metachronous contralateral breast with survivals at 16 years of 53.8%, 42.4%, and 60.1%, respectively (p < 0.0001), from the date of the diagnosis of the first primary tumor. There was no difference in survival seen between the three groups when survival was calculated from the date of diagnosis of the second primary in cases of metachronous contralateral breast cancer (p = 0.31). When contralateral breast cancer was incorporated as a time-dependent covariate in a Cox multivariate model together with the three factors used to determine the Nottingham Prognostic Index (invasive tumor size, grade, and lymph node stage), contralateral breast cancer continued to be a significant prognostic determinant (p = 0.02). The survival of women with synchronous bilateral breast cancer or metachronous breast cancers diagnosed within 2 years of the original primary was worse than those with unilateral disease. However, the time duration to metachronous contralateral breast cancer did not have prognostic significance in a multivariate model compared with the prognostic features of the original primary.     

Metachronous renal tumours after surgical management of oncocytoma

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Oncocytoma is a benign renal tumour that cannot be differentiated from renal cell carcinoma radiographically. Follow‐up after surgery for oncocytoma is highly variable and the natural history of surgically treated renal oncocytoma is poorly defined. We sought to assess the risk of metachronous renal tumours in a cohort of patients treated surgically for renal oncocytoma. We report a large cohort of oncocytoma patients following surgical management. This study defines the risk of metachronous renal tumours after surgical treatment of renal oncocytoma. Our findings suggest that patients with metachronous renal tumours after treatment of renal oncocytoma may have a smaller risk of renal cell carcinoma compared with patients presenting with a primary renal mass. Our findings did not support concern for increased risk of renal cell carcinoma following surgical treatment of primary renal oncocytoma.

OBJECTIVE

? To assess the risk of metachronous renal cell carcinoma (RCC) and benign renal tumours after surgical treatment of primary renal oncocytoma.

PATIENTS AND METHODS

? Patients treated for primary renal oncocytoma between 1970 and 2007 were identified. Tumours were reviewed by a urological pathologist and patients were followed for subsequent renal tumours.

RESULTS

? Of 424 patients with a median follow up of 7.1 year, 17 (4.0%) patients were diagnosed with a metachronous renal tumour at a median of 3.0 years (range 0.3–16 years). Of the 17 metachronous tumours, eight were oncocytoma, four were RCC and five were not resected or biopsied. ? Eleven metachronous tumours occurred after solitary unilateral oncocytoma, five occurred after multifocal unilateral oncocytoma, and one occurred after multifocal bilateral oncocytoma. ? Estimated 10‐year tumour‐free and RCC tumour‐free survival was 94.8% and 98.7%, respectively. Patients with primary multifocal oncocytoma were at higher risk of metachronous tumour (hazard ratio 4.0; P = 0.007). Initial oncocytoma size (hazard ratio 1.1; P = 0.11) was not highly associated with risk of tumour recurrence.

CONCLUSIONS

? To our knowledge, we report the largest cohort of oncocytoma after surgical management. Metachronous renal neoplasm in a patient with previous oncocytoma is more likely to be benign compared with patients who present with a renal tumour for the first time. Multifocal primary oncocytoma is associated with metachronous renal tumours. ? Overall, the risk of metachronous RCC in a patient with an oncocytoma is similar to that of the general population, which does not support the use of routine cross‐sectioning imaging surveillance.     

Pheochromocytoma: inherited associations, bilaterality, and cortex preservation

BACKGROUND: Hereditary pheochromocytoma (HP) is characterized by early onset, bilateral adrenal involvement, low malignancy rate, and genetic linkage with certain familial syndromes. This retrospective review is intended to show the high yield of surveillance, predictable bilaterality, and the challenge of cortex-sparing adrenalectomy. METHODS: From 1964 to 1999, 32 patients with HP were treated at a single institution and followed for a mean of 7 years. There were 15 cases of multiple endocrine neoplasia type 2A (MEN 2A), 12 cases of von Hippel-Lindau (VHL) disease, 3 cases of von Recklinghausen's disease (VRD), and 2 cases of familial pheochromocytoma. Twenty-four of 32 patients underwent bilateral adrenalectomy (9 metachronous). Subtotal resection with orthotopic cortex preservation was performed in 5 patients, and heterotopic autografting was performed in 14 patients. RESULTS: Pheochromocytoma was the first manifestation in 50% of patients with VHL disease and in 27% of patients with MEN 2A. Surveillance uncovered medullary thyroid cancer in 5 of 15 patients with MEN 2A and hemangioblastomas, renal cell carcinoma, and islet cell tumors in 7 of 15 patients with VHL disease and VRD. HP was bilateral in 24 of 32 patients (14/15 in patients with MEN 2A, 7/12 in patients with VHL disease, 2/3 in patients with VRD, and 1/2 in patients with familial pheochromocytoma). In 9 cases of metachronous adrenalectomy, the mean interval was 67 months (range, 9-156 months). Three of 5 patients who underwent orthotopic preservation of the adrenal cortex experienced recurrence compared with 0 of 14 patients with heterotopic autotransplantation of cortical tissue. CONCLUSIONS: Pheochromocytoma frequently heralds coexisting silent VHL disease or MEN-2, mandating surveillance for inherited associations. The long interval of metachronous pheochromocytoma argues against prophylactic removal of the contralateral "normal" adrenal gland. Total adrenalectomy and heterotopic autotransplantation of medulla-free cortex may diminish the need for lifelong steroid substitution and eliminates recurrence.     

Von Hippel-Lindau disease and renal cell carcinoma in a 16-year-old boy.

Von Hippel-Lindau disease is a rare autosomal dominant disorder. Kidney lesions occur in the majority of cases, with renal cell carcinoma noted in 40% and renal cysts in 60%. Renal cell carcinoma in von Hippel-Lindau disease is usually bilateral and occurs at an earlier age than in patients with sporadic renal cell carcinoma. We report on a 16-year-old boy who, to our knowledge, is the youngest patient to present with von Hippel-Lindau disease and renal cell carcinoma. Controversy currently exists regarding the nature of renal cysts in von Hippel-Lindau disease and the optimal therapeutic approach (that is radical versus parenchymal sparing surgery). We review the histology of renal cysts and carcinoma, and discuss the rationale for selecting parenchymal sparing surgery.     

Multifocal renal oncocytoma in a patient with Von Hippel-Lindau mutation

Von Hippel-Lindau disease (VHL) is a rare genetic disease with a lifetime risk of clear cell renal cell carcinoma in approximately 70% of cases. We present a case of a 63-year-old man with bilateral, multifocal renal masses. Genetic testing results were consistent with a VHL deletion. The patient had no other disease manifestations consistent with VHL. The patient underwent staged bilateral nephron-sparing procedures. Pathology of all renal masses revealed oncocytoma. To our knowledge, we describe the first reported case of multiple renal oncocytomas in a male patient with a germline VHL mutation.     

Multiple nephron-sparing procedures in solitary kidney with recurrent, metachronous, nonfamilial renal cell carcinoma

Patients with metachronous bilateral renal cell carcinoma pose a significant challenge given the high mortality of renal cell carcinoma and the poor quality of life should dialysis become necessary. In addition, patients may be subject to morbidity due to potential multiple treatments of the multifocal renal tumors. We present the case of a 71-year-old woman with multifocal, bilateral clear cell carcinoma who maintained a minimal change in serum creatinine after undergoing unilateral radical nephrectomy, subsequent percutaneous radiofrequency ablation, percutaneous cryoablation, laparoscopic cryoablation, and open partial nephrectomy for recurrent renal cell carcinoma in a solitary kidney.     

Diagnosis and management of asymptomatic renal cell carcinomas in von Hippel-Lindau syndrome

Renal cell carcinomas occurred in 6 of 17 subjects with the von Hippel-Lindau syndrome (HLS). In 4 patients, the tumors were discovered by abdominal computed tomography (CT) during a prospective study. Abdominal CT is recommended as a safe and accurate method for screening patients with HLS for renal cell carcinoma. Renal cell carcinoma in HLS tends to be multifocal and bilateral. Because of this, it is recommended that the tumors be treated by surgical enucleation rather than by more extensive surgical procedures which might ultimately lead to the need for dialysis.     

A case of renal oncocytoma with synchronous contralateral renal cell carcinoma

A case of bilateral, synchronous renal cell carcinoma and oncocytoma is reported. The patient was a 70-year-old woman. Computed tomographic scan revealed bilateral low density masses, which had a diameter of approximately 4 cm (right kidney), and 2.5 cm (left kidney). We suspected bilateral renal cell carcinomas, and performed, right nephrectomy and left enucleation of the tumor. Pathological diagnosis was right renal cell carcinoma and left oncocytoma. To our knowledge only 5 previous cases of renal cell carcinoma associated with oncocytoma have been reported in Japan. Two cases were metachronous and three cases were unilateral and synchronous. This is the first reported case of bilateral, synchronous renal cell carcinoma and oncocytoma.     

RENAL ONCOCYTOMA: MULTIFOCALITY, BILATERALISM, METACHRONOUS TUMOR DEVELOPMENT AND COEXISTENT RENAL CELL CARCINOMA

PURPOSE: We analyzed a large series of cases of renal oncocytoma to define the incidence of coexistent renal cell carcinoma, multifocality, bilateralism and metachronous tumor development. MATERIALS AND METHODS: Between 1980 and 1997, 100 men and 38 women with a mean age of 68 years with oncocytoma, were treated surgically at our institution. We analyzed tumor characteristics and reviewed specimens for coexistent renal cell carcinoma. RESULTS: Tumors were discovered incidentally in 58% of the cases. Specimens were obtained from 84 radical and 70 partial nephrectomies. Tumor size ranged from 0.3 to 14.5 cm. (median 3.2). Oncocytoma was unilateral in 131 cases (95%) and bilateral in 7 (5%), while there were multiple oncocytomas in 8 (6%). Mean followup was 41 months (range 0 to 200). The disease specific survival rate was 100% and no patient had metastasis. In 6 patients (4%) metachronous oncocytoma developed during followup. No patient had locally recurrent oncocytoma after partial nephrectomy for a solitary renal oncocytoma. Renal cell carcinoma and oncocytoma were found in 14 patients (10%), including unilateral synchronous disease in 9 and bilateral synchronous disease in 5. CONCLUSIONS: Our data support the benign nature of renal oncocytoma. Multifocality, bilateralism and metachronous tumor develop in approximately 4 to 6% of all cases. Renal cell carcinoma coexisted in 10% of oncocytoma cases.