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Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.

The pericytic (perivascular myoid cell) family of tumors is a distinctive group of mesenchymal neoplasms encountered in superficial sites and only rarely seen in viscera. The pericytic family subtends a spectrum of lesions, namely, glomus tumors and variants; myopericytoma, including myofibroma; and angioleiomyoma. In light of the contemporary classification of pericytic lesions, we identified and reviewed 17 cases of renal pericytic tumors from the files of 6 referral centers. These tumors presented over an age range of 17 to 76 years (mean 46.7, median 53), with essentially equal male-female ratio. History of hypertension (available in 11 patients) was noted in 7 (64%), which persisted even after surgical resection, including in 2 younger patients (17 and 30 years). The tumors (1.7-11.0 cm) included glomus tumors (n=11); glomangiomyoma (n=1); glomus tumor with atypical features (n=1); and angioleiomyoma (n=1), as well as tumors showing features overlapping pericytic tumor subtypes (n=3). The histomorphology observed in these renal examples closely resembled that of their soft tissue counterparts, a subset with symplastic changes and atypical features, and pericytic immunophenotype. Despite large size and deep site, no progression was identified during a median of 7 months follow-up (1-62 months). In context of prior reported experience, our series identifies a wide morphologic spectrum, including lesions presenting composite morphologies. Taken with the experience of others, our series further corroborates that malignant behavior is rare, and that criteria associated with aggression among soft tissue pericytic tumors may not be predictive for those in the kidney., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Adult renal epithelial neoplasms (RENs) comprise several distinct clinicopathologic entities with potential prognostic and therapeutic differences. Individual cases can show overlapping morphologic features, necessitating the use of ancillary methods. The purpose of this study was to determine the diagnostic utility of cytokeratin (CK) subtype expression pattern in a wide range of adult RENs. RENs (including clear cell [conventional] renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, renal oncocytoma, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), urothelial carcinoma, metanephric adenoma (MA), tubulocystic carcinoma (TC) (also known as low-grade collecting duct carcinoma), and mucinous tubular and spindle cell carcinoma) were immunostained for CK subtypes (CK5/CK6, 7, 8, 13, 14, 17, 18, 19, 20), high molecular weight CKs 1, 5, 10, 14 (HMWCK), and vimentin (Vim). The expression pattern of normal kidney was also examined and correlated with RENs. Although there is some overlap, subtypes of RENs show distinctive CK expression profiles that may be useful in several differential diagnostic settings. Clear cell RCCs typically showed a restricted expression pattern of CK8, CK18 and Vim. Papillary RCCs typically expressed CK7, CK8, CK18, CK19, and Vim and could be distinguished from MA (CK7-). Chromophobe RCCs were typically CK7+, CK8+, CK18+, and Vim-, and could be distinguished from oncocytomas (typically CK7-). In oncocytomas, nonspecific staining of unblocked endogenous biotin is a potentially significant diagnostic pitfall. CDC, RMC, and TC demonstrated similar CK expression profiles (with the exception of HMWCK expression limited to CDC), supporting a close relationship between these entities. A panel of CK5/CK6, CK17, and Vim may be helpful in distinguishing CDC (typically CK5/CK6-, CK17-, Vim+) and urothelial carcinoma (typically CK5/CK6+, CK17+, Vim-). In conclusion, CK expression patterns may be helpful in several differential diagnostic situations when dealing with adult RENs.

Purpose: Tumor size has been used as one of the criteria to stratify renal cell carcinoma (RCC) into different pathological stages (pT). The recent 2002 UICC/TNM classification of malignant epithelial renal tumors is modified to substratify pT1 RCC into pT1a (less than 4.0 cm) and pT1b (greater than 4.0 but less than 7.0 cm). In this study we ascertained if this stage modification has prognostic relevance., Materials and Methods: A total of 259 consecutive radical nephrectomy specimens of organ confined RCC from 1970 to 1997 at 1 institution, including 153 of conventional RCC (CRCC), 71 of papillary RCC, 28 of chromophobe RCC, 1 of collecting duct carcinoma and 6 of RCC not otherwise specified, with a mean clinical followup of 7.5 years (median 6.4) were included in the study., Results: There were 115 pT1a (44.4%), 95 pT1b (36.7%) and 49 pT2 tumors (18.9%). Disease recurrences (DR) and disease specific death occurred in 2 (1.7%) and 0 cases (0%) of pT1a, 7 (7.3%) and 5 (5.3%) of pT1b, and 16 (32.6%) and 12 (24.5%) of pT2. DR for pT1b was higher compared with pT1a (all histological subtypes RR 3.68), although this difference was not statistically significant (p = 0.106). If only CRCCs were analyzed, DR in the pT1b group was statistically higher compared with pT1a (RR 8.54, p = 0.047). Disease specific survival in pT1a could not be evaluated because no deaths occurred in this subgroup. DR and disease specific survival were significantly different between pT1b and pT2 tumors for all histological subtypes (RR 5.51, p = 0.001 and 5.49, p = 0.001) and for the CRCC subtype (RR 5.50, p = 0.001 and 5.18, p = 0.005, respectively). Using size as a continuous variable the logarithmic change in tumor size was a significant predictor of DR (RR 8.82, p = 0.001). All statistical analyses were adjusted for age and sex., Conclusions: Substaging RCC into pT1a and pT1b yields prognostically important information, validating the 2002 TNM modification for malignant renal epithelial malignancies. The substratification of pT1 is particularly useful in tumors with CRCC histology.

Just two and a half decades ago adult renal cell neoplasms, i.e., those arising from the renal tubules or collecting duct epithelium, were subdivided into two major subtypes: "clear cell carcinoma" and "granular cell carcinoma." Subsequent detailed morphologic and/or cytogenetic studies have resulted in the recognition of several distinctive subtypes of adult renal epithelial neoplasms, which has led to the promulgation of a refined contemporary histologic classification of these tumors. This study examines the prognostic significance of histologic subtyping in accordance with the new classification in a consecutive series of 405 cases treated at a single institution. Cases were histologically classified into 28 (7%) benign tumors [27 (6.7%) renal oncocytomas, 1 (0.2%) metanephric adenoma] and 377 (93%) malignant tumors [255 (63%) conventional (clear cell) renal cell carcinoma, 75 (18.5%) papillary renal cell carcinoma, 24 (5.9%) chromophobe renal cell carcinoma, and 23 (5.7%) renal cell carcinoma, unclassified]. A total of 25 (6.6%) malignant tumors showed evidence of sarcomatoid change. Kaplan-Meier survival analysis with log-rank test showed histologic type (p = 0.002), Fuhrman's nuclear grade (p = 0.001), TNM stage (p = 0.001), vascular invasion (p = 0.001), and necrosis (p = 0.001) to be significantly associated with disease-specific survival and progression-free survival, based on follow-up of 368 patients (mean 64.5 months, median 56 months). The 5-year disease-specific survival for chromophobe renal cell carcinoma, papillary renal cell carcinoma, conventional (clear cell) renal cell carcinoma, and renal cell carcinoma, unclassified was 100%, 86%, 76%, and 24%, respectively; no patient with a benign tumor diagnosis progressed or died of disease. The 5-year progression-free survival for chromophobe renal cell carcinoma, papillary renal cell carcinoma, conventional (clear cell) renal cell carcinoma, and renal cell carcinoma, unclassified was 94%, 88%, 70%, and 18%, respectively. Malignant tumors with sarcomatoid change had a 35% and 27%, 5-year disease-specific and progression-free survival, respectively. Cox proportional hazards regression analysis showed TNM stage (p = 0.001), nuclear grade (p = 0.01), and necrosis (p = 0.05) to be significant predictors of disease-specific survival. In conclusion, our study shows that the histologic categorization of adult renal epithelial neoplasms performed by routine light microscopic hematoxylin and eosin-based examination in accordance with the contemporary classification scheme has prognostic utility.

Little is known about the association of angiomyolipoma and adult renal-cell neoplasia. We studied the clinicopathologic features of 36 patients with concurrent angiomyolipoma and renal-cell neoplasia from the consultation and surgical pathology files of nine institutions. HMB-45 immunoreactivity was analyzed in both neoplasms. Twenty-five sporadic cases of patients with angiomyolipoma and renal-cell neoplasia and 11 cases of patients with tuberous sclerosis, as defined by Gomez' criteria, had mean ages of 59 and 53 years, respectively, and female-male ratios of 2:1 and 5:1, respectively. The mean size of the angiomyolipomas was 1 cm in the sporadic cases and 3 cm in those patients with tuberous sclerosis (medians: 0.5 and 3 cm, respectively, P =.002). The mean sizes of the renal-cell neoplasms were 5 cm in sporadic cases and 6 cm in patients with tuberous sclerosis (medians: 4 and 5 cm, respectively; P =.88). In both clinical settings, angiomyolipoma was more commonly the incidental tumor. Clear-cell (conventional) renal-cell carcinoma was the most common renal-cell neoplasm in both groups of patients, accounting for approximately two thirds of the tumors. In patients with tuberous sclerosis, 27% of renal-cell neoplasms were oncocytomas, compared with 8% in sporadic cases (P =.15). Papillary neoplasia, chromophobe, and collecting-duct renal-cell carcinoma were found only in sporadic cases. All of the 22 renal-cell neoplasms studied were negative for HMB-45, whereas all 25 angiomyolipomas studied were positive.

Sarcomatoid renal cell carcinoma is not a distinct histologic entity and represents high-grade transformation in different subtypes of renal cell carcinoma. It is not known whether any particular histologic type has a predilection for sarcomatoid change or whether the primary histologic type of renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952 consecutively histologically subtyped renal cell carcinomas, the incidence of sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma, 3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One hundred one renal cell carcinomas with sarcomatoid change were studied, and clinicopathologic parameters were correlated with outcome. The mean age of patients was 60 years (range, 33-80 years), and the male-to-female ratio was 1.6:1. The median tumor size was 9.2 cm (range, 3-25 cm). The primary histologic subtype of the carcinoma component was conventional (clear cell) renal carcinoma in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in three with focal rhabdomyosarcomatous component in two of them. The spindled elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%). The histologic grade of the spindled elements was intermediate to high in 92 cases and low in nine cases. Most cases were TNM stages III and IV (seven stage I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88 patients; 61 (69%) patients died of disease and had a median survival time of 19 months. Distant metastases, most frequently to the lungs, were documented in 51 (66%) of 77 patients who had available clinical information regarding distant metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10 years, respectively, compared with a cohort of renal cell carcinomas without sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%, respectively. Kaplan-Meier survival analysis showed that tumors with high TNM stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and angiolymphatic invasion (p = 0.0282) were associated with decreased survival rates. The primary histologic subtype of the carcinoma component and the type and grade of the sarcomatoid component did not affect survival. In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable in predicting outcome among renal cell carcinomas with sarcomatoid change (p = 0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and tumor size, patients with tumors with sarcomatoid differentiation had a worse prognosis than did patients with tumors without sarcomatoid change (p = 0.0001). In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis. Because tumors with even a small component of sarcomatoid change may have an adverse outcome, this finding, when present, should be noted in the surgical pathology report.

Renal cell carcinomas often show varying degrees of necrosis and cystic change. The prognostic importance of necrosis so extensive that only a few tumor cells can be identified is not clear. We gathered clinicopathologic and follow-up data on a group of eight such cases ("type I"). These patients were compared with two other groups of renal cell carcinomas: those with extensive necrosis (>50%), yet with readily identifiable tumor ("type II"), and cancers with extensive cystic change not resulting from necrosis, usually multiloculated ("type III"). The groups showed similar demographic characteristics, and within each group there was great variation in tumor size. Conventional (clear cell) histology was more common than papillary morphology in all groups. The type II neoplasms tended to be of higher nuclear grade and pathologic stage than the other groups. While one of six type I patients with follow up progressed 131 months after diagnosis, eight of 20 type II patients showed progression. None of the six type III patients with follow up progressed. We conclude that renal cell carcinomas showing extensive necrosis are capable of aggressive behavior, and patients with these lesions cannot be assured of cure following surgery. Pathologists must be aware of this entity and extensively sample any renal lesion showing extensive necrosis. The tumors showing a greater amount of viable neoplastic cells yet at least 50% necrosis had a higher rate of progression than did the type I patients. The lack of progression of any of the type III cases supports the idea that type III multiloculated cystic renal cell carcinomas may carry a distinctly better prognosis than other forms of renal cell carcinoma.

Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29-202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.