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INTRODUCTION AND OBJECTIVE:The oncologic safety of active surveillance in renal oncocytoma is well reported. However concern remains at the hypothetical possibility of renal functional deterioratio...

INTRODUCTION AND OBJECTIVE:The available data on long term outcomes of surgically treated renal oncocytoma (RO) are scant and largely outdated. Herein we describe our institutional outcomes of surg...

INTRODUCTION AND OBJECTIVES:Among the >65,000 new kidney cancer cases in the U.S., about 10% of these patients turn out to have benign renal cell oncocytomas (Onco). They face a 30% risk of complic...

Concern regarding coexisting malignant pathology in benign renal tumors deters renal biopsy and questions its validity. We examined the rates of coexisting malignant and high grade pathology in resected benign solid solitary renal tumors.Using our prospectively maintained database we identified 1,829 patients with a solitary solid renal tumor who underwent surgical resection between 1994 and 2012. Lesions containing elements of renal oncocytoma, angiomyolipoma or another benign pathology formed the basis for this analysis. Patients with an oncocytic malignancy without classic oncocytoma and those with known hereditary syndromes were excluded from study.We identified 147 patients with pathologically proven elements of renal oncocytoma (96), angiomyolipoma (44) or another solid benign pathology (7). Median tumor size was 3.0 cm (IQR 2.2-4.5). As quantified by the R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score, tumor anatomical complexity was low in 28% of cases, moderate in 56% and high in 16%. Only 4 patients (2.7%) were documented as having hybrid malignant pathology, all involving chromophobe renal cell carcinoma in the setting of renal oncocytoma. At a median followup of 44 months (IQR 33-55) no patient with a hybrid tumor experienced regional or metastatic progression.In our cohort of patients with a solitary, sporadic, solid benign renal mass fewer than 3% of tumors showed coexisting hybrid malignancy. Importantly, no patient harbored coexisting high grade pathology. These data suggest that uncertainty regarding hybrid malignant pathology coexisting with benign pathological components should not deter renal biopsy, especially in the elderly and comorbid populations.

SUMMARY Oncocytomas are predominantly benign neoplasms possessing pathogenic mitochondrial mutations and accumulation of respiration-defective mitochondria, characteristics of unknown significance. Using exome and transcriptome sequencing, we identified two main subtypes of renal oncocytoma. Type 1 is diploid with CCND1 rearrangements, whereas type 2 is aneuploid with recurrent loss of chromosome 1, X or Y, and/or 14 and 21, which may proceed to more aggressive eosinophilic chromophobe renal cell carcinoma (ChRCC). Oncocytomas activate 5′ adenosine monophosphate-activated protein kinase (AMPK) and Tp53 (p53) and display disruption of Golgi and autophagy/lysosome trafficking, events attributed to defective mitochondrial function. This suggests that the genetic defects in mitochondria activate a metabolic checkpoint, producing autophagy impairment and mitochondrial accumulation that limit tumor progression, revealing a novel tumor-suppressive mechanism for mitochondrial inhibition with metformin. Alleviation of this metabolic checkpoint in type 2 by p53 mutations may allow progression to eosinophilic ChRCC, indicating that they represent higher risk., Graphical abstract

Purpose: We characterize the genetic abnormalities associated with pathological subtypes of renal tumors, which may help diagnosis or prognostication.Materials and Methods: A comprehensive literature review of genetic abnormalities associated with different renal tumor subtypes was performed.Results: Studies of sporadic and hereditary forms suggest that abnormalities in the von Hippel-Lindau and met genes are the earliest changes in conventional (clear cell) and papillary basophilic renal cancers, respectively. Renal oncocytoma and chromophobe carcinoma have common genetic abnormalities, suggesting a relationship. A similar finding has been observed between papillary adenoma and papillary basophilic renal cancer.Conclusions: These findings suggest that molecular diagnostic testing will help determine histopathological diagnosis, identify tumor types with similar genetic abnormalities suggesting a common origin and indicate potential prognostic markers for future study.

of the PC away from normal renal parenchyma) is classically used for familial Renal Cell Carcinoma (RCC) but has not been widely adopted for sporadic RCC. We investigate whether tumor histology predicts the presence, thickness, and extension of tumor through the PC, potentially identifying tumors best suited for a TE nephron-sparing approach. METHODS: Twenty-five consecutive total or partial nephrectomies for pT1 clear cell, papillary, chromophobe, and oncocytoma were included (N 100 total tumors). Specimens were reviewed for numerous pathological features including stage, grade, lympho-vascular invasion, as well as characteristics of PC such as capsular presence/ absence, mean thickness, continuity, and tumor capsule invasion (TCI). PC parameters (thinnest, thickest and mean) were calculated from multiple measurements using an ocular micrometer, rounded to the nearest tenth of a millimeter. RESULTS: Tumor sizes in each group were similar. PC was complete in: papillary (n 21, 84%), clear cell (n 19, 76%), chromophobe (n 7, 28%), and oncocytoma (n 1, 4%); present but incomplete in oncocytoma (n 14, 56%), chromophobe (n 11, 44%), clear cell (n 6, 24%), and papillary (n 2, 8%); and absent in oncocytoma (n 10, 40%), chromophobe (n 7, 28%), papillary(n 2, 8%), and clear cell (0%). TCI was seen in 30% of papillary and only 8% of clear cell (p-value 0.006) PC. When present, mean thickness of the PC was significantly thicker for clear cell (0.8mm) when compared to the other tumors (papillary and chromophobe 0.6mm and oncocytoma 0.3mm). Multivariate logistic regression demonstrated only tumor type to be significantly associated with TCI (p-value 0.046, OR 10.3 (95%CI)). CONCLUSIONS: In pT1 renal tumors, PC appears predictable based on tumor histology. The PC is likely to be absent or incomplete in renal oncocytoma and chromophobe. Papillary RCC demonstrates the highest % of TCI which could predict higher surgical margin rates during TE surgery. Clear cell RCC possesses the thickest, most complete tumor capsule with minimal TCI and may be best suited for TE partial nephrectomy.

Purpose: Cytogenetic studies of a small number of renal oncocytomas have indicated that loss of chromosomes 1 and Y may be involved in the pathogenesis of this tumor. To evaluate these observations further we selected paraffin embedded renal oncocytoma specimens from 20 male and 10 female patients for fluorescence in situ hybridization analysis.Materials and Methods: Isolated nuclei were prepared from paraffin embedded specimens, and fluorescence in situ hybridization was performed with enumeration probes for chromosomes 1, 12, × and Y.Results: Tumors from 10 male (50 percent) and 4 female (40 percent) patients demonstrated chromosomal alterations. Loss of chromosome Y was observed in specimens from all 10 male patients, and loss of chromosome 1 or gain of chromosome 12 was noted in 5 and 2 of these specimens, respectively. Of the 4 female patients with chromosomal abnormalities 2 had loss of chromosome 1, 1 had gain of chromosome 1 and 1 had gain of chromosome 12.Conclusions: Our results confirm ...

Purpose: Morphometric distinction of renal oncocytoma and renal cell carcinoma was attempted.Materials and Methods: Nuclear morphometric measurements were done from sections of 16 histologically diagnosed renal oncocytomas and renal cell carcinoma controls (grade 1 or 2, stage T1 to 2N0M0).Results: Oncocytomas could be distinguished from carcinomas on the basis of nuclear morphometry in more than 80 percent of the cases. Especially, the shape descriptors (form factors) were significantly different between oncocytomas and carcinomas.Conclusions: Morphometrically determined nuclear shape descriptors can be used to support diagnostic decisions in problematic cases.

We treated 31 patients with renal oncocytoma. Renal cell carcinoma was found existing separately within the same or contralateral kidney in 10 patients (32%). Followup of 29 patients revealed 24 alive with no evidence of disease and 1 alive with recurrent oncocytoma, while 1 with coexistent tumors died of progressive renal cell carcinoma and 3 tumor-free patients died of unrelated diseases. Quantitative deoxyribonucleic acid analysis was performed on cell suspensions of fresh tumor by flow cytometry or by image cytometry on touch preparations from frozen tissue in 16 patients with renal oncocytoma. Ploidy analysis revealed all oncocytomas to be diploid. Frozen tissue immunohistology was performed using murine monoclonal antibody against human HLA-A, B and C (class I) antigens with the avidin-biotin peroxidase technique in 11 patients with renal oncocytoma. Ten oncocytomas did not express these self-recognition antigens and 1 was only weakly positive for antigen expression. In contrast, renal cell carcinomas strongly expressed HLA class I antigens. The high incidence of coexistence of renal oncocytoma and renal cell carcinoma has important clinical implications. Loss of HLA class I antigen expression by renal oncocytomas may provide an additional method for differentiating this lesion from renal cell carcinoma.

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.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.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.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.

Renal oncocytomas were tested for loss of alleles at loci on the short arm of chromosome 3, a genetic change characteristic of human renal cell carcinoma. Five renal oncocytomas did not show loss of alleles at loci on 3p supporting the view that renal oncocytoma is a distinct form of renal neoplasia.

We report a case of renal oncocytoma and confirm a tumor type specific translocation between chromosomes 9 and 11, that is t(9;11)(p23;q13q23). Each of the 45 cytogenetically analyzed metaphases of tumor cells showed a translocation of the long arm of chromosome 11 at q13 to chromosome 9 at 9p23 and to chromosome 20 at 20q13 that resulted in the following karyotype: 6,XX,der(11)ins(9;11)(p23;q13q23)ins(20;11)(q13;q23q25),del(22q13). Since genes encoding mitochondrial enzymes are clustered around the translocation site of chromosomes 11 and 20, they may have a role in the tumorigenesis of renal oncocytoma. In addition, if the development of oncocytomas shows different cytogenetic pathways the cytogenetic aberration of t(9;11)(p23; q12q13) can be of diagnostic help in differentiating a subset of oncocytoma from renal cell carcinoma.

Renal oncocytoma accounts for approximately 3 to 4% of all solid renocortical tumors. An unusual case of renal oncocytoma arising from the wall of a simple renal cyst is reported and the literature is reviewed.

We report a case of simultaneous contralateral oncocytoma and renal cell carcinoma. The diagnosis and prognosis of renal oncocytoma are discussed, and the management of bilateral renal tumors is reviewed.

Flow cytometry was performed on 51 typical specimens of renal oncocytoma. Nuclei were extracted from paraffin-embedded archival material and isolated nuclei were stained with propidium iodide. Of the 51 available tissue blocks 86 per cent were evaluable and 50 per cent of these samples showed a deoxyribonucleic acid (DNA) histogram that was approximately the same as normal renal parenchyma. Of the oncocytoma samples 39 per cent showed a marked increase (more than 10 per cent of the nuclei) in the tetraploid DNA peak, while 11 per cent showed a distinct DNA aneuploid peak. Among 21 evaluable grade 2 oncocytic renal tumors 33 per cent showed a normal DNA histogram, 43 per cent showed a marked increase in the DNA tetraploid peak and 24 per cent showed a DNA aneuploid peak. The common presence of polyploid nuclei containing double quantities of chromosomal DNA may correlate with the long-standing pathological observation that oncocytic tumors often contain a distinct population of large nuclei. Indeed, 86 per cent concurrence was seen between the detection of an abnormal DNA content by flow cytometry and the histopathological presence of large abnormal nuclei in these specimens. Since renal oncocytomas (grade 1 oncocytic tumors) rarely, if ever, metastasize and are relatively noninvasive locally, their markedly abnormal flow cytometry patterns are of considerable interest. Moreover, DNA polyploidy has not been identified previously in renal tumors. The biological significance and mechanism of DNA polyploidy, and the relationship of DNA polyploidy and DNA aneuploidy to the pathogenesis of oncocytic renal tumors require further laboratory investigation. The clinical use of flow cytometry to classify and to predict the behavior of renal tumors will be complicated, since renal oncocytomas commonly have polyploid and aneuploid DNA histograms.

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.

From 1968 to 1983, 254 patients underwent an operation for presumed renal cell carcinoma. In this retrospective review the pathological diagnosis was renal oncocytoma in 11 patients (4 per cent). Renal oncocytomas were present bilaterally in 2 patients, including 1 with a coexisting renal cell carcinoma. In 2 other patients the oncocytomas were multicentric. The angiographic, computerized tomographic and sonographic findings in these patients typified renal cell carcinoma. Surgical treatment comprised radical or partial nephrectomy for unilateral and bilateral lesions, respectively. Because of the benign nature, multicentricity, possible bilaterality and absence of pathognomonic radiographic features, renal oncocytomas should be considered in the differential diagnosis of solid renal masses.

A patient with bilateral renal oncocytoma is presented, and the clinical, radiological and pathological characteristics of this uncommon, clinically benign renal tumor are discussed briefly. Chromosomal analysis studies revealed the following clonal abnormalities: trisomy of chromosome 7, and monosomy of chromosomes 3 and 14, and the X chromosome. A possible clonal abnormality of chromosome 10 and 3 nonclonal anomalies also were identified. The same anomalies were present in both tumors. These karyotypic anomalies are compatible with malignant transformation of the cells of these tumors and, since benign tumors rarely are associated with demonstrable cytogenetic changes, they suggest that oncocytoma, although clinically benign, may have malignant potential.

To our knowledge, we report the first case of bilateral renal oncocytoma. Among more than 100 such cases reported recently no bilateral tumors could be found.

We report a case of bilateral renal oncocytoma, which was diagnosed by biopsy of the left kidney tumor. The patient refused surgical treatment. After a 6-year followup she is well, which proves the benign behavior of this neoplasm. The clinical, morphologic and angiographic characteristics of the tumor are discussed.

A case of multifocal oncocytoma of the kidney is reported. A review of the literature revealed only 2 other cases with multifocal tumors. The occurrence of these multicentric tumors should discourage the attempt of performing partial renal resection as recently advocated by some authors.

Two cases of renal oncocytoma are characterized by histologic electron microscopic, and immunohistochemical evaluation. In one case there was a coexistent renal cell carcinoma. The immunophenotype of the oncocytes provide evidence for an origin from the distal nephron. The results indicate that immunohistochemical methods can be helpful in discriminating renal oncocytoma from (granular type) renal cell carcinoma.