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Context.--In prostate cancer, 'tertiary' higher-grade patterns (TPs) have been associated with biochemical recurrence after radical prostatectomy. Objective.--To determine variation regarding definition and application of TPs. Design.--Online survey regarding TPs in a range of grading scenarios circulated to 105 experienced urologic pathologists. Results.--Among 95 respondents, 40 of 95 (42%) defined TPs as 'third most common pattern' and 55 (58%) as 'minor pattern/less than 5% of tumor.' In a tumor with pattern 3 and less than 5% pattern 4, of the 95 respondents, 35 (37%) assigned 3 + 3 = 6 with Tp4, while 56 (59%) assigned 3 + 4 = 7. In a tumor with pattern 4 and less than 5% pattern 5, of the 95 respondents, 51 (54%) assigned 4 + 4 = 8 with TP5, while 43 (45%) assigned 4 + 5 = 9. Six scenarios were presented in which the order of most common patterns was 3, 4, and 5 (Group 1) or 4, 3, and 5 (Group 2) with varying percentages. In both groups, when pattern 5 was less than 5%, we found that 98% and 93% of respondents would assign 3 + 4 = 7 or 4 + 3 = 7 with TP5. In scenarios with 15% or 25% pattern 5, most respondents (70% and 80%, respectively) would include pattern 5 as the secondary grade, that is, 3 + 5 = 8 (Group 1) or 4 + 5 = 9 (Group 2). For 85 of 95 (89%), a TP would not impact Grade Group assignment. Conclusions.--This survey highlights substantial variation in practice patterns regarding definition and application of 'tertiary' grading in radical prostatectomy specimens. High consistency was observed in 3 + 4 = 7/4 + 3 = 7 scenarios with truly minor pattern 5. These findings should inform future studies assessing the standardization and predictive value of 'tertiary' patterns. (Arch Pathol Lab Med. 2020;144:356-360; doi: 10.5858/arpa.2019-0224-OA), It is well known that some prostate cancers comprise more than 2 grades. (1-5) While most of so-called tertiary grading reported in the literature refers to a higher grade--typically pattern [...]

Mitochondrial fission and fusion are linked to synaptic activity in healthy neurons and are implicated in the regulation of apoptotic cell death in many cell types. We developed fluorescence microscopy and computational strategies to directly measure mitochondrial fission and fusion frequencies and their effects on mitochondrial morphology in cultured neurons. We found that the rate of fission exceeds the rate of fusion in healthy neuronal processes, and, therefore, the fission/fusion ratio alone is insufficient to explain mitochondrial morphology at steady state. This imbalance between fission and fusion is compensated by growth of mitochondrial organelles. Bcl-[x.sub.L] increases the rates of both fusion and fission, but more important for explaining the longer organelle morphology induced by Bcl-[x.sub.L] is its ability to increase mitochondrial biomass. Deficits in these Bcl-[x.sub.L]--dependent mechanisms may be critical in neuronal dysfunction during the earliest phases of neurodegeneration, long before commitment to cell death.

Context.--While biopsies are now increasingly being performed for the diagnosis of renal cortical neoplasms, the influence of the rendered pathological diagnoses on the clinical management is only rarely documented. Objectives.--To report our experience with consecutively performed renal biopsies and the potential impact of the diagnosis on subsequent clinical management. Design.--Material from needle biopsies performed consecutively at our institution between 2006 and 2011 was reviewed. The influence of the reported pathology results on the clinical management was determined from patient follow-up medical record review. Results.--In total, 218 percutaneous biopsies for renal masses were performed during this period. Among them, 181 (83%) yielded neoplastic tissue, including 81 clear cell renal cell carcinomas, 29 low-grade oncocytic neoplasms, 7 papillary renal cell carcinomas, 5 clear cell papillary renal cell carcinomas, 5 angiomyolipomas, and 14 urothelial carcinomas. Fourteen additional cases (6%) contained lesional material from clinically known nonneoplastic processes, for a total diagnostic yield of 89%. Twenty-three (11%) were nonrepresentative of lesional tissue. In 10 of these, repeat biopsies or resections established the diagnosis of renal tumors. Biopsy diagnosis was confirmed in 29 of 30 cases (97%) on subsequent nephrectomy. Following the biopsy diagnosis, there were significant differences in the clinical management; overall, 79% of clear cell renal cell carcinomas received therapeutic interventions, and 17% were put on active surveillance. In contrast, 77% of the benign or low-grade lesions were put on active surveillance. Conclusions.--Accurate and specific diagnosis can be rendered on renal core biopsy in most renal tumors, and the biopsy diagnosis can have a definitive role in their clinical management. (Arch Pathol Lab Med. 2014;138:1673-1679; doi: 10.5858/arpa.2013-0574-0A), With increased popularity and the improvements in imaging modalities, up to 70% of renal cortical tumors are now discovered incidentally, most with a median tumor size of less than 4 [...]

* Context.--Cystic lesions of the kidney may be accompanied by a range of neoplasms with distinct prognoses and future risks of developing additional tumors. In addition, some renal tumors, with or without accompanying renal cysts, may show a prominent cystic component. In the adult population, neoplasms occurring in a background of renal cystic diseases and cystic renal neoplasms often pose diagnostic challenges because of their many overlapping features. Objective.--To review the clinicopathologic characteristics of common entities in the spectrum of neoplastic and potential preneoplastic cystic lesions encountered in adults, with an emphasis on renal cystic diseases associated with tumor development and on renal neoplasms with predominantly cystic morphology. Data Sources.--The relevant English-language literature was reviewed, accompanied by the authors' experience at their practicing institution. Conclusions.--The presence of multiple renal cysts, both acquired and syndromic, can be associated with a variety of renal tumors. The morphology of the cysts and associated tumor types can help predict the genetic or acquired basis of the lesions, and particularly in specimens with no accompanying pertinent clinical history, such potential associations should be suggested in surgical pathology reports. (Arch Pathol Lab Med. 2012; 136:400-409; doi: 10.5858/arpa.2011-0485-RA), Various hereditary, acquired, and neoplastic conditions can lead to cyst formation in the kidney. Although the most frequently encountered form of renal cystic lesion is the unilocular, simple renal cortical [...]

* Benign glandular inclusions in axillary lymph nodes are very rare events that have to be distinguished from metastatic carcinoma. We report an exceptional instance in which a patient with invasive ductal carcinoma had benign glandular inclusions in the form of sclerosing adenosis in 2 sentinel lymph nodes. The lymph nodes did not contain metastatic carcinoma. Immunohistochemical studies facilitated the correct diagnosis. (Arch Pathol Lab Med. 2008;132:1439-1441), Because of the need to distinguish them from micrometastases, benign glandular inclusions associated with axillary lymph nodes have attracted increasing interest since the advent of sentinel lymph node mapping. The [...]

* Context.--Distinguishing low-grade and high-grade non-invasive papillary urothelial carcinoma based on morphologic criteria can be challenging and adjunct markers are highly desirable. Survivin, presumably an antiapoptotic protein, was previously proposed as a prognostic marker for urothelial carcinoma. Objective.--To assess interobserver variability by 2004 World Health Organization classification and the value of survivin and Ki-67 as potential markers for grading non-invasive papillary urothelial carcinoma. Design.--Fifty-one bladder biopsies were graded blindly by 5 experienced general surgical pathologists. The protein and messenger RNA expression of survivin and Ki-67 was evaluated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction using paraffin-embedded tissue. The immunohistochemistry result was quantitatively analyzed using a computer-based color deconvolution module. Results.--The diagnostic agreement among 5 pathologists was fair to poor, with 32% of the cases graded differently by at least 2 raters. All cases were divided into 3 groups: consensus low-grade, consensus high-grade, and indeterminate. The percentage of urothelial cells with positive survivin nuclear staining (survivin score) was significantly higher in the high-grade than in the low-grade group (P < .001). Survivin score outperformed Ki-67 in separating the high-grade group from the low-grade group and showed a significantly higher predictive accuracy for high-grade recurrence than the histologic grade. The disagreement of grading for the indeterminate group could be resolved by their survivin scores in most cases. Survivin messenger RNA level correlated well with survivin score by immunohistochemistry but was not a more discriminating marker. Conclusions--Significant interobserver variability exists in grading low-grade versus high-grade papillary urothelial carcinoma. Survivin immunohistochemical staining can be a useful adjunct tool for the grading of challenging cases., Noninvasive papillary urothelial carcinoma is the most common type of bladder cancer encountered in clinical practice. The pathologic grade of these tumors at first diagnosis is usually critical in determining [...]