Steve C. Campbell

We reviewed 954 primary nonurothelial epithelial renal neoplasms with primary resection at Memorial Sloan-Kettering Cancer Center between the years 1980 and 1995 and classified 70 cases (7%) as renal oncocytomas. The study population was composed of 39 men and 31 women, and the mean age was 65 years (range 25 to 86 years). Fifty-six patients (80%) were asymptomatic at presentation, six (4%) had flank pain, six (4%) presented with a mass, and two (3%) had hematuria. Sixty-one were treated with total or radical nephrectomy, nine with partial nephrectomy. The right kidney was involved in 35 cases (50%), the left kidney in 32 (46%). Three cases (4%) were bilateral. Sixty-one cases (87%) were unifocal, nine (13%) multifocal. All the tumors were well circumscribed but unencapsulated. Forty-five (64%) were described as brown or red, whereas the remainder were variously described as tan to yellow. Central fibrosis or scar was described in 23 cases (33%), and gross areas of hemorrhage or cystic changes in 14 (20%). The mean size was 5.2 cm and median 5.0 cm (range 1.5 cm to 14 cm). Histologically, the tumors were characterized by a mixture of architectural patterns: compact cellular nests and acini embedded in a hyalinized, hypocellular stroma were present in 62 cases (89%), a solid nested architecture in 47 cases (67%), and a variable tubular component in 50 cases (71%). Small papillae, pseudopapillae, and intratubular epithelial tufts were seen in 19 cases (27%). Cytologically, the neoplasms also showed a mixture of cell types, the most common being the classic oncocyte, which consisted of round or polygonal cells with moderate to abundant granular, eosinophilic cytoplasm, and small round nuclei with evenly dispersed granular chromatin. Small basophilic nucleoli were visible in many of these cells in all cases. Thirty-one cases (44%) had a variable number of oncocytic cells with pyknotic nuclei and 20 (30%) contained clusters of small cells with a high nuclear/cytoplasmic ratio and dense hyperchromatic nuclei (so-called oncoblasts). Foci of tubules with clear cells embedded in a hyalinized stroma were present in six cases (9%). Cellular atypia was evident in 42 cases (60%) and was marked in 21 (30%). Eleven cases (16%) exhibited mitotic activity, albeit low. No case had atypical mitoses or necrosis. Twenty-two cases (31%) had areas of calcification within the hyalinized stroma, 12 (17%) had calcospherites, and three (4%) had osseous and myeloid metaplasia. Vascular invasion was present in three cases (4%), and invasion of perinephric fat in 14 (20%). One patient presented with liver metastasis. Fourteen cases (20%) were pT1, 42 (60%) pT2, and 14 (20%) pT3. After a mean follow-up of 58 months (range 1 to 181), 62 patients (89%) were alive with no evidence of tumor, six (9%) had died of other causes, one was alive with stable metastatic disease in the liver 58 months after diagnosis, and one died with metastatic disease to bone and liver. We conclude that renal oncocytomas have a varied morphologic appearance and their pathologic diagnosis should be based on a constellation of architectural and cytologic features. The overwhelming majority of cases behave in a benign fashion, although in rare instances they can metastasize. The presence of atypical morphologic features do not alter the excellent prognosis associated with oncocytomas and do not predict an aggressive clinical course.

Renal mass sampling (RMS) can be carried out by core biopsy or fine needle aspiration with each presenting potential advantages and limitations. The literature about RMS is confounded by a lack of standardized techniques, ambiguous terminology, imprecise definitions of accuracy, substantial rates of non-informative biopsies, and recurrent diagnostic challenges with respect to eosinophilic neoplasms. Despite these concerns, RMS has an expanding role in the evaluation and treatment of renal masses, in order to stratify biological aggressiveness and guide management that can range from surgery to active surveillance. Non-informative biopsies can be managed with surgical excision or repeat biopsy, with the latter showing encouraging results in recent studies. We propose a new classification in which all biopsies are categorized as non-informative versus informative, with the latter being subclassified as confirmed accurate, presumed accurate or confirmed inaccurate. This terminology will facilitate the comparison of results from various studies and stimulate progress. Incorporation of novel biomarkers and molecular fingerprinting into RMS protocols will likely allow for more rational management of patients with renal masses in the near future.

The scrotum is an uncommon site for the presentation of extramammary Paget disease (EMPD). We describe a case of EMPD that was discovered in a patient who had been previously diagnosed and treated for squamous cell carcinoma in situ of the scrotum 3 years earlier. Pathologic examination of the current scrotectomy specimen revealed an erythematous patch with areas of pale induration. Microscopic examination revealed areas with the characteristic histology of Paget disease adjacent to areas characteristic of Bowen disease. Immunohistochemical findings demonstrated a strong expression of carcinoembryonic antigen, cytokeratin 7, and low-molecular-weight cytokeratins (CAM 5.2) in both of these areas, giving support to the overall diagnosis of EMPD. High-molecular-weight cytokeratins (34betaE12) were uncharacteristically expressed in the cytoplasm of the Paget cells with equal or greater strength than in the surrounding keratinocytes, suggesting some degree of squamous differentiation. Very few publications have reported the coexistence of EMPD with squamous cell carcinoma in situ, occurring mostly in the vulva. To our knowledge, our case is the first report of scrotal EMPD with features of Bowen disease. Our findings support the theory that primary EMPD arises multifocally from multipotential epidermal cells.

Abstract Context. —It has recently been shown by cytogenetics that there is a high incidence of chromosome 1 abnormalities in renal oncocytomas. Objective. —To confirm the cytogenetic results by fluorescence in situ hybridization (FISH) analysis. Design. —Nine additional cytogenetic analyses were added to those reported in our recent study, with a total of 27 tumors studied, which makes it the largest series of renal oncocytomas studied to date by cytogenetics and/or FISH. We used the LSI 1p36/LSI 1q25 Dual Color Probe Set to make the analyses. Results. —In this study, combined cytogenetics and FISH showed loss of chromosome arm 1p1 in 48% of renal oncocytomas. By FISH, deletion of 1p36.3 was observed in 59% of renal oncocytomas, whereas by cytogenetics, abnormality in chromosome 1 was seen in 32% of tumors. However, the incidence of chromosome 1 abnormalities among 9 bilateral tumors was much higher than in single tumors (88% vs 28%, respectively). Loss of only the 1p36.3 site occurred in 2 renal oncocytomas with translocation of chromosome 1, as shown by cytogenetics. Concordance between the 2 techniques, when they were used simultaneously to detect chromosome 1p1 abnormality, was 82%. Conclusions. —This study further confirmed our prior results demonstrating the widespread occurrence of chromosome 1 abnormalities in renal oncocytomas. Although no abnormalities in chromosome 1 in tumors with normal karyotypes were detected by FISH using the current set of probes, a much higher incidence of such abnormalities was found in bilateral tumors, suggesting that genetic alterations related to the development of renal oncocytoma reside in this region.

CONTEXT: It has recently been shown by cytogenetics that there is a high incidence of chromosome 1 abnormalities in renal oncocytomas. OBJECTIVE: To confirm the cytogenetic results by fluorescence in situ hybridization (FISH) analysis. DESIGN: Nine additional cytogenetic analyses were added to those reported in our recent study, with a total of 27 tumors studied, which makes it the largest series of renal oncocytomas studied to date by cytogenetics and/or FISH. We used the LSI 1p36/LSI 1q25 Dual Color Probe Set to make the analyses. RESULTS: In this study, combined cytogenetics and FISH showed loss of chromosome arm 1p1 in 48% of renal oncocytomas. By FISH, deletion of 1p36.3 was observed in 59% of renal oncocytomas, whereas by cytogenetics, abnormality in chromosome 1 was seen in 32% of tumors. However, the incidence of chromosome 1 abnormalities among 9 bilateral tumors was much higher than in single tumors (88% vs 28%, respectively). Loss of only the 1p36.3 site occurred in 2 renal oncocytomas with translocation of chromosome 1, as shown by cytogenetics. Concordance between the 2 techniques, when they were used simultaneously to detect chromosome 1p1 abnormality, was 82%. CONCLUSIONS: This study further confirmed our prior results demonstrating the widespread occurrence of chromosome 1 abnormalities in renal oncocytomas. Although no abnormalities in chromosome 1 in tumors with normal karyotypes were detected by FISH using the current set of probes, a much higher incidence of such abnormalities was found in bilateral tumors, suggesting that genetic alterations related to the development of renal oncocytoma reside in this region.