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Mixed epithelial and stromal tumor (MEST) is a distinctive adult biphasic neoplasm of the kidney characterized by the presence of solid and cystic areas composed of spindled stroma and epithelium lining tubules and cystic spaces respectively. Most MESTs are benign although sarcomatous transformation has rarely been reported. It has not been clearly established whether the epithelial component represents entrapped tubules or constitutes a true neoplastic component. We report an unusual case of a biphasic tumor of the kidney with a benign stroma and a focal component of papillary carcinoma arising in one of the cysts and discuss its pathogenesis. [ABSTRACT FROM PUBLISHER]

Summary: Claudin-7 and claudin-8 code for tight junction proteins expressed in distal nephron epithelium. In a recent oligonucleotide microarray study, we identified claudin-7 and claudin-8 as candidate markers to distinguish chromophobe renal cell carcinoma from other renal tumors, including oncocytoma. Distinction of these lesions can be difficult by light microscopy but is clinically important because chromophobe renal cell carcinoma has malignant biological potential, whereas renal oncocytoma is benign. Claudin-7 and claudin-8 expression was studied by immunohistochemistry in 11 chromophobe renal cell carcinomas and 17 oncocytomas using formalin-fixed paraffin-embedded tissue sections of tumor with adjacent nonneoplastic kidney. Steam antigen retrieval was performed before immunohistochemistry. Specificity was verified by negative control reactions without primary antibody and appropriate membranous staining patterns in positive control tissues (colon carcinoma and adjacent nonneoplastic kidney). Claudin-7 protein was expressed in a membranous pattern in 10 of 11 chromophobe renal cell carcinomas and 4 of 17 oncocytomas (P < .01). Claudin-8 was expressed in multiple patterns: In oncocytoma, 11 of 17 cases showed cytoplasmic, 4 of 17 membranous, and 2 of 17 negative reactions. In chromophobe renal cell carcinoma, 0 of 11 cases showed cytoplasmic, 3 of 11 membranous, and 8 of 11 negative reactions (P < .01). The immunohistochemical pattern of membranous claudin-7 and negative claudin-8 was seen in 7 of 11 chromophobe renal cell carcinomas and 1 of 17 oncocytomas (63% sensitivity, 84% specificity, 88% positive predictive value for chromophobe renal cell carcinoma). Negative claudin-7 and cytoplasmic claudin-8 were observed in 10 of 17 oncocytomas and 0 of 11 chromophobe renal cell carcinomas (59% sensitivity, 100% specificity and positive predictive value for oncocytoma). The distal nephron proteins claudin-7 and claudin-8 have potential use as immunohistochemical biomarkers in the differential diagnosis of chromophobe renal cell carcinoma and oncocytoma. Expression of claudin-7 and claudin-8 may reflect the relationship of chromophobe renal cell carcinoma and oncocytoma to intercalated cells of the cortical collecting duct. It may be necessary to identify additional biomarkers to include with claudin-7 and claudin-8 in a larger immunohistochemical panel to improve diagnostic sensitivity and specificity. [Copyright &y& Elsevier]

The article focuses on the relationship between a positive resection margin in partial nephrectomy (PN) and local recurrence in patients with renal cell carcinoma (RCC). Topics discussed include radical nephrectomy as a mainstay treatment for malignant renal masses and PN as a gold standard for T1 renal masses and description of most RCCs which have a well-developed pseudocapsule. Also mentioned is the role of tumor growth patterns in the recurrence of RCC.

Purpose: Sarcomatoid dedifferentiation in renal cell carcinoma (RCC) represents an aggressive histology where degree of sarcomatoid histology (SH) may impact prognosis for cM0 and cM1 patients. We aimed to evaluate the association of percentage of SH with survival.Materials and Methods: Patients ≥18 years old diagnosed with RCC with any degree of SH after nephrectomy were included (2005-2020) from a single-center. Associations of degree of SH and cM stage with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier curves and Cox proportional hazards regression.Results: One hundred twenty-eight patients were included with 80 (62.5%) cM0 and 48 (37.5%) cM1. cM1 patients were more likely to be male with higher clinical T stage (P = 0.001) than cM0, but a similar proportion had ≥20% SH (47.9% vs. 42.5%, P = 0.55). With median 19.4 months follow-up, SH was associated with worse OS per 10% increase (hazard ratio [HR] 1.12 [95% confidence interval {CI} 1.03-1.23], P = 0.009) and a ≥20% cutoff (HR 2.87 [95% CI 1.27-6.47], P = 0.01). Patients with cM0 disease and <20% SH had better 2-year OS (81.4%) compared to cM0 and ≥20% SH (44.8%) or cM1 patients who received nephrectomy (54.8%). Tumor size was also an independent predictor. Sites of distant metastasis and lines of therapy were similar for metachronous and synchronous patients. SH stratified 2-year RFS (cM0: 70.2% for <20% SH vs. 32.1% for ≥20% SH).Conclusions: SH in RCC is independently associated with OS and RFS. Patients who are cM0 with any SH may be candidates for adjuvant immunotherapy while those with ≥20% SH likely carry micrometastatic disease and should receive closer surveillance. [ABSTRACT FROM AUTHOR]

Context.- Despite decades of research, the role of lymphadenectomy in the management of renal cell carcinoma (RCC) is still not clearly defined. Before the implementation of targeted therapies, lymph node metastases were considered to be a portent of markedly decreased survival, regardless of the tumor stage. However, the role of lymphadenectomy and the relative benefit of retroperitoneal lymph node dissection in the context of modern adjunctive therapies have not been conclusively addressed in the clinical literature. The current pathologic literature does not offer clear recommendations with regard to the minimum number of lymph nodes that should be examined in order to accurately stage the pN in renal cell carcinoma. Although gross examination of the hilar fat to assess the nodal status is performed routinely, it has not yet been determined whether this approach is adequate. Objective.- To evaluate the status of lymph nodes and their rate of identification in the pathologic examination of nephrectomy specimens in adult renal malignancies. Design.- We reviewed the operative and pathology reports of 871 patients with renal malignancies treated by nephrectomy. All tumors were classified according to the seventh edition of the Tumor-Nodes-Metastasis classification. Patients were divided into 3 groups: Nx, no lymph nodes recovered; N0, negative; and N1, with positive lymph nodes. Grossly visible lymph nodes were submitted separately; as per grossing protocol, hilar fatty tissue was submitted for microscopic examination. We evaluated the factors that affected the number of lymph nodes identified and the variables that allowed the prediction of nodal involvement. Results.- Lymph nodes were recovered in 333 of 871 patients (38%): hilar in 125 patients, nonhilar in 137 patients, and hilar and nonhilar in 71 patients. Patients with positive lymph nodes (n = 87) were younger, had larger primary tumors, and had lymph nodes of average size, as well as a higher pT stage, nuclear grade, and rate of metastases. Metastases were seen only in grossly identified lymph nodes (65% hilar, 16% nonhilar); all microscopic nodes were negative. Even with the microscopic examination of fat, hilar lymph nodes were recovered in only 22.5% of patients. A nonhilar route of node metastasis was suspected in 40 patients. Conclusions.- Only grossly identifiable lymph nodes, both hilar and nonhilar, were positive for metastases. Although microscopic examination of the hilar fat increased the number of lymph nodes recovered, the identification rate of these nodes was low (22.5%), and such microscopic nodes were invariably negative. Hence, microscopic examination of the hilar fat may be unnecessary. [ABSTRACT FROM AUTHOR]

Context.—The differential diagnosis of eosinophilic renal tumors can be difficult by light microscopy. In particular, chromophobe renal cell carcinoma (RCC) is difficult to distinguish from oncocytoma. This differential diagnosis is important because chromophobe RCC is malignant, whereas oncocytoma is benign. Furthermore, chromophobe RCC has distinct malignant potential and prognosis compared with eosinophilic variants of other RCC subtypes. Immunohistochemistry is useful for distinguishing chromophobe RCC from other subtypes of renal carcinoma, but no expression marker reliably separates chromophobe RCC from oncocytoma. Objective.—In a previous gene expression microarray analysis of renal tumor subtypes, we found the distal nephron markers claudin-7 and claudin-8 to be overexpressed in chromophobe RCC versus oncocytoma and other tumor subtypes. We have confirmed similar findings in independent microarray data and validated differential claudin-7 protein expression by immunohistochemistry. Design.—Immunohistochemical analysis of claudin-7 in 36 chromophobe RCCs, 43 oncocytomas, 42 clear cell RCCs, and 29 papillary RCCs. Results.—Membranous claudin-7 expression was detected in 67% chromophobe RCCs, compared with 0% clear cell RCCs, 28% papillary RCCs, and 26% oncocytomas (P < .001). Conclusions.—Based on microarray and immunohistochemical data, we propose claudin-7 to be a candidate expression marker for distinguishing chromophobe RCC from other renal tumor subtypes, including the morphologically similar oncocytoma. The clinical utility of claudin-7 should be validated in independent studies of renal tumors, possibly in combination with additional targets in a multiplex immunohistochemical panel. [ABSTRACT FROM AUTHOR]

Context.—Adult renal neoplasms have a predilection for older patients and are clinically and morphologically distinct from renal neoplasms found in pediatric age groups. Relatively rare tumors occur in younger adults (18–45 years of age). Whether these renal tumors are morphologically and clinically distinct from those of older adults has been the subject of controversy. Recent modification of the World Health Organization histologic classification and the American Joint Committee on Cancer staging system of adult renal tumors further highlighted the need for case analysis in this age group. Objective.—To analyze renal tumors in younger adults based on a large surgical series from a single institution. Design.—Of 780 renal mass nephrectomy (partial, total, or radical) specimens that were available for evaluation and had been obtained between 1986 and 2004 at Loyola University Medical Center, 112 specimens were from patients between 18 and 45 years of age. The tumors were reevaluated according to the 2004 World Health Organization classification and the 2002 American Joint Committee on Cancer staging system. Results.—The likelihood of clear cell renal cell carcinoma was significantly reduced from 65% in older adults to 53% in younger adults (18–45 years, P = .04). The reduction trend was more significant when comparing an even younger age group. The majority (64%) of clear cell renal cell carcinoma in younger adults was low stage, T1a. Seventeen percent of these tumors had multilocular cystic features involving more than 50% of the tumor volume (55%–85%). The number of oncocytomas was also significantly lower in younger adults than in older adults (2% vs 11%, P < .001), and this presumably age-related benign neoplasm was not identified in patients younger than 40 years in this study. In contrast, the miscellaneous tumor category showed a remarkable increase, from 4% in older adults to 26% in younger adults (P < .001). The youngest patient group (18–35 years) had a higher incidence of miscellaneous tumors, 37%. Younger female adults tended to have more benign miscellaneous neoplasms than did their male counterparts (64% vs 36%, P < .001). Clear cell and chromophobe renal cell carcinoma occurred more frequently in younger male adults than in female adults (2:1 and 8:1, respectively). Conclusions.–Renal neoplasms are more heterogeneous in younger adults and have a different distribution pattern compared with that in older adults. Malignant and benign renal neoplasms tend to have a contrasting sex distribution in younger adults. [ABSTRACT FROM AUTHOR]

Although most renal epithelial tumors are derived from the proximal nephron, approximately 10% are believed to originate in the distal nephron. This latter group encompasses oncocytoma, chromophobe renal cell carcinoma, and several rare types, including collecting duct carcinoma and renal medullary carcinoma. Despite progress in the classification of renal tumors, a small subset of renal carcinomas remains unclassified (ie, renal cell carcinoma, not otherwise specified). We describe a metastatic tumor consisting of cells with overlapping distal nephron morphologies, including foci of oncocytoma, chromophobe renal cell carcinoma, and collecting duct carcinoma, as well as sarcomatoid dediflerentiation. Special stains were inconclusive, and ultrastructural study demonstrated abundant mitochondria and no microvesicles. The karyotype was hypodiploid with 41 chromosomes and abnormalities reported in all 3 phenotypes present. Rearrangements of 1 p and of 11q13 previously seen in divergent subsets of oncocytomas were concomitantly present in the current tumor. Thus, this malignancy has features consistent with distal nephron derivation and demonstrates the convergence of the varied tumor morphologies arising within this site. Furthermore, this case exemplifies the value of cytogenetic analysis in the characterization of renal cell carcinoma, not otherwise specified. In view of recent advances in treatment approach, especially for collecting duct carcinoma, further categorization of this nondescript and heterogeneous group of renal cell carcinomas, not otherwise specified, at least by its derivation in relationship to the renal nephron (distal vs proximal), may be of value in the choice of treatment modality. [ABSTRACT FROM AUTHOR]

Introduction: Oncocytic neoplasms are renal tumors similar to oncocytoma, but their morphologic variations preclude definitive diagnosis. This somewhat confusing diagnosis can create treatment and surveillance challenges for the treating urologist. We hypothesize that these subtle morphologic variations do not drastically affect the malignant potential of these tumors, and we sought to demonstrate this by comparing clinical outcomes of oncocytic neoplasms to those of classic oncocytoma and chromophobe.Methods: We gathered demographic and outcomes data for patients with variant oncocytic tumors. Oncologic surveillance was conducted per institutional protocol in accordance with NCCN guidelines. Descriptive statistics were used to compare incidence of metastasis and death against those for patients with oncocytoma and chromophobe. Three hundred and fifty-one patients were analyzed: 164 patients with oncocytoma, 28 with oncocytic neoplasms, and 159 with chromophobe tumors.Results: Median follow-up time for the entire cohort was 32.4 months, (interquartile range 9.2-70.0). Seventeen total patients (17/351, 4.9%) died during the course of the study. In patients with oncocytoma or oncocytic neoplasm, none were known to metastasize or die of their disease. Only chromophobe tumors >6 cm in size in our series demonstrated metastatic progression and approximately half of these metastasized tumors demonstrated sarcomatoid changes.Conclusion: Variant oncocytic neoplasms appear to have a natural course similar to classic oncocytoma. These tumors appear to have no metastatic potential, and oncologic surveillance may not be indicated after surgery. [ABSTRACT FROM AUTHOR]