The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dube Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC were elucidated. Outside of the epithelial category, advances in our understanding of angiomyolipoma, including the epithelioid and epithelial cystic variants, were considered. In addition, the apparent relationship between cystic nephroma and mixed epithelial and stromal tumor was discussed, with the consensus that these tumors form a spectrum of neoplasia. Finally, it was thought that the synovial sarcoma should be removed from the mixed epithelial and mesenchymal category and placed within the sarcoma group. The new classification is to be referred to as the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia.

The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia

A unique renal neoplasm characterized by eosinophilic cytoplasm and solid and cystic growth was recently reported in patients with tuberous sclerosis complex (TSC). We searched multiple institutional archives and consult files in an attempt to identify a sporadic counterpart. We identified 16 morphologically identical cases, all in women, without clinical features of TSC. The median age was 57 years (range, 31 to 75 y). Macroscopically, tumors were tan and had a solid and macrocystic (12) or only solid appearance (4). Average tumor size was 50 mm (median, 38.5 mm; range, 15 to 135 mm). Microscopically, the tumors showed solid areas admixed with variably sized macrocysts and microcysts that were lined by cells with a pronounced hobnail arrangement. The cells had voluminous eosinophilic cytoplasm with prominent granular cytoplasmic stippling and round to oval nuclei with prominent nucleoli. Scattered histiocytes and lymphocytes were invariably present. Thirteen of 16 patients were stage pT1; 2 were pT2, and 1 was pT3a. The cells demonstrated a distinct immunoprofile: nuclear PAX8 expression, predominant CK20-positive/CK7-negative phenotype, patchy AMACR staining, but no CD117 reactivity. Thirteen of 14 patients with follow-up were alive and without disease progression after 2 to 138 months (mean: 53 mo; median: 37.5 mo); 1 patient died of other causes. Although similar to a subset of renal cell carcinomas (RCCs) seen in TSC, we propose that sporadic "eosinophilic, solid, and cystic RCC," which occurs predominantly in female individuals and is characterized by distinct morphologic features, predominant CK20-positive/CK7-negative immunophenotype, and indolent behavior, represents a novel subtype of RCC.

Eosinophilic, Solid, and Cystic Renal Cell Carcinoma: Clinicopathologic Study of 16 Unique, Sporadic Neoplasms Occurring in Women.

Clear cell papillary renal cell carcinoma: differential diagnosis and extended immunohistochemical profile.

Accumulating evidence suggests that renal cell tumors represent a group of histologically and molecularly heterogeneous diseases, even within the same histological subtype. In accordance with the increased understanding of the morphological, immunohistochemical, molecular, and epidemiological characteristics of renal cell tumors, the World Health Organization (WHO) classification of renal cell tumors has been modified. This review provides perspectives on both new and current subtypes of renal cell tumors, as well as on the emerging/provisional renal cell carcinomas in the new 2016 WHO classification, which focuses on features of their molecular pathological epidemiology. The WHO classification will require additional revisions to enable the classification of renal cell tumors as clinically meaningful subtypes and provide a better understanding of the unique characteristics of renal cell tumors.

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Renal Cell Tumors: Understanding Their Molecular Pathological Epidemiology and the 2016 WHO Classification.

Although histologic features enable an accurate diagnosis in most renal carcinomas, overlapping morphologic findings between some renal neoplasms make subclassification difficult. Some renal carcinomas show papillary architecture but are composed extensively of cells with clear cytoplasm, and it is unclear whether they should be classified as clear cell renal cell carcinomas or papillary renal cell carcinomas. We analyzed the immunohistochemical profiles and the cytogenetic patterns of 14 renal carcinomas showing papillary architecture in which there were variable amounts of cells with clear cytoplasm. The patients were 8 women and 6 men (mean age: 54 y). Immunohistochemistry and fluorescence in situ hybridization analysis distinguished 2 different groups. The first consisted of 10 renal cell carcinomas with strong immunoreactivity for α-methyl coenzyme A racemase, of which 9 also expressed cytokeratin 7. All of these neoplasms showed gains of chromosome 7 or 17 and chromosome Y was lost in all the male patients whereas 3p deletion was detected only in one case. In the other 4 renal cell carcinomas, cytokeratin 7 was not detected and α-methylacyl-CoA racemase was positive in only 1. In these neoplasms, no gain of chromosome 7 or 17 and no loss of chromosome Y were observed, whereas 3p deletion was detected in 3 of them. None of the 14 neoplasms showed immunoreactivity for TFE3. The combined use of immunohistochemistry and cytogenetics enabled us to provide a definitive diagnosis for 12 of 14 renal cell carcinomas with papillary architecture and clear cell components: 9 cases were confirmed to be papillary renal cell carcinomas and 3 cases were confirmed to be clear cell renal cell carcinomas. Despite these ancillary techniques, 2 cases remained unclassified. Our study establishes the utility of these procedures in accurately classifying the great majority of renal cell carcinomas with these findings.

Renal cell carcinomas with papillary architecture and clear cell components: The utility of immunohistochemical and cytogenetical analyses in differential diagnosis: Editorial comment

Multilocular cystic renal cell carcinoma (RCC) is an uncommon renal neoplasm composed of thin fibrous septa lining multiple cystic spaces and associated with an excellent prognosis. Clear cells with generally low-grade nuclear features line the cystic spaces and may be present within the fibrous septa, although solid mass-forming areas are by definition absent. Despite the excellent prognosis, molecular-genetic alterations are similar to those of clear cell RCC. Immunohistochemical staining characteristics, however, have not been well elucidated. We studied 24 cases of multilocular cystic RCC, classified according to the 2004 World Health Organization System. Immunohistochemical analysis was performed using an automated immunostainer for CD10, cytokeratin 7 (CK7), α-methylacyl-CoA-racemase, epithelial membrane antigen (EMA), cytokeratin CAM 5.2, carbonic anhydrase IX (CA-IX), estrogen/progesterone receptors, smooth muscle actin, PAX-2, and vimentin. Twenty-four cases of grade 1 to 2 clear cell RCC were stained for comparison. Multilocular cystic RCC and control cases of clear cell RCC showed the following results, respectively: CD10 (63%, 96%), CK7 (92%, 38%), α-methylacyl-CoA-racemase (21%, 67%), vimentin (58%, 33%), estrogen receptor (8%, 8%), CAM 5.2 (100%, 96%), EMA, CA-IX, PAX-2 (all 100%), and progesterone receptor (0%). Smooth muscle actin highlighted myofibroblastic cells within the septa of multilocular cystic RCC and the fine capillary vascular network of clear cell RCC. In summary, multilocular cystic RCC showed expression of common clear cell RCC markers CA-IX, EMA, and PAX-2, supporting the hypothesis that multilocular cystic RCC is a subtype of clear cell RCC. In contrast to clear cell RCC, tumors less frequently expressed CD10 (63% and often focal vs. 96% and diffuse) and more frequently expressed CK7 (92%), often diffusely (63%). Coexpression of CA-IX and CK7 represents a point of overlap with the recently described clear cell papillary RCC, which also may show a prominent cystic architecture. However, the latter lacks mutation of the VHL gene and deletion of chromosome 3p by molecular methodologies.

Shams Halat

Papers

Multilocular cystic renal cell carcinoma: similarities and differences in immunoprofile compared with clear cell renal cell carcinoma.