Search

The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high-grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as currently defined and lends credence to the effort of subclassifying some tumors as truly "high-grade endometrial stromal sarcomas." Our study also shows that, in the context of undifferentiated endometrial sarcomas, recognition of cytomorphologic features on routine hematoxylin and eosin-stained sections may be used to select tumors with specific molecular genetic changes-that is, translocations involving YWHAE. Our conclusions will help further efforts towards proper sub-classification of these tumors which will aid in diagnosis and potentially affect clinical management.

It has been reported that Fuhrman grading is not appropriate for chromophobe renal cell carcinoma (RCC). The objective of this study was to determine whether nucleolar grading and the recently described chromophobe RCC grading system by Paner and colleagues provide prognostic information. Pathologic features of 185 patients with chromophobe RCC treated surgically between 1970 and 2006 were reviewed, including nucleolar grade, chromophobe RCC grade, the 2010 TNM groupings, sarcomatoid differentiation, and coagulative tumor necrosis. Cancer-specific (CS) survival was estimated using the Kaplan-Meier method, and associations with CS survival were evaluated using Cox proportional hazard regression models. Twenty-three patients died from RCC at a mean of 3.0 years after surgery (median 1.3; range 0 to 16) with estimated CS rates (95% confidence interval) of 89% (84 to 94), 86% (81 to 92), and 85% (78 to 91) at 5, 10, and 15 years after surgery. Univariate associations with CS survival included the 2010 TNM stage groupings, sarcomatoid differentiation, coagulative tumor necrosis, chromophobe RCC grade, and nucleolar grade (all P<0.001). These last 4 features remained significantly associated with CS survival after adjusting for the 2010 TNM stage groupings. When the analysis was restricted to the 155 patients with nonsarcomatoid TNM stage groupings I and II chromophobe RCC, only stage grouping (I vs. II) was significantly associated with CS survival (P=0.03). Although the chromophobe RCC grading system described by Paner and colleagues and nucleolar grade are associated with CS survival in chromophobe RCC, they add no additional prognostic information once TNM stage and sarcomatoid differentiation are assessed.