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Background: The vast majority of polyomavirus nephropathy (PVN) is due to BK virus, but rare cases result from JC virus reactivation. To date, only a handful of biopsy-proven JC-PVN cases have been reported. Here, we describe the clinical and pathologic findings in 7 patients with biopsy-proven JC-PVN., Methods: Search of the pathology archives at 2 institutions found 7 cases of JC-PVN. Clinical data were extracted from the electronic medical records, and the biopsies were reviewed., Results: Four cases were diagnosed at 6 y posttransplant or later. The remaining 3 cases presented within approximately 2 y posttransplant, of which 2 showed subclinical JC-PVN on surveillance biopsy. Two early presenting patients were treated for acute rejection just before acquiring JC-PVN. Late presenting patients had higher chronicity, which correlated to worse outcome. All but 1 biopsy showed nonspecific inflammation within areas of interstitial fibrosis without significant inflammation in unscarred cortex. The earliest presenting patient was the exception and showed active inflammation with tubulitis. Viral cytopathic changes were detected in all cases with moderate or high-histologic viral load (pvl), showing preference for the distal tubules and medulla. The 2 cases with low pvl did not demonstrate cytopathic changes but were SV40 positive., Conclusions: JC-PVN can be insidious in presentation, which may cause delayed or missed diagnosis. Unlike BK-PVN, which typically occurs early in the posttransplant period, JC-PVN can occur both early and late following transplant. Overreliance on negative plasma and urine BK viral loads to exclude PVN can be a pitfall., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

At some tertiary breast care centers, where many patients are referred from other institutions, it is routine to repeat testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) in excision specimens if these tests were performed on the preceding biopsy at the referring facility. The goal of this study is to assess the value of this practice. We documented results from ER, PR, and HER2 testing in 541 consecutive invasive breast cancers excised over a 2.5-year period and analyzed the subset (n=153) for which testing was performed on the excision specimen solely due to the fact that testing on the preceding biopsy was performed at an outside institution. The rates and directions of biopsy-to-excision change were as follows: ER [1.3% (2/153), 100% from (+) to (-)]; PR [4% (6/153), 83% from (+) to (-)]; HER2/neu assessed by immunohistochemistry [21% (29/137)]; HER2/neu assessed by fluorescence in situ hybridization [3.3% (2/61); 50% from amplified to nonamplified and 50% vice versa]. There were no ER(-) and PR(-) biopsy cases that became ER and/or PR(+) in the excision. By coordinate analysis for the hormone receptors [ie, ER and/or PR(+) being indicative of "hormone receptor" (HR) positivity], there were no cases that changed from HR(+) in the biopsy to HR(-) in the excision (or vice versa), which suggests that repeat testing for ER and PR in this setting is of limited value. In an analysis that incorporated both immunohistochemistry and in situ fluorescence hybridization results, there were 2 cases with a clinically significant biopsy-to-excision change in HER2/neu status in which that change was detected primarily because the excision was retested. These findings provide baseline data for formulating policies on whether repeat testing should routinely be performed in the described scenario.

An aberrant p53 immunophenotype may be identified in several histotypes of endometrial carcinoma, and is accordingly recognized to lack diagnostic specificity in and of itself. However, based on the high frequency with which p53 aberrations have historically been identified in endometrial serous carcinoma, a mutation-type immunophenotype is considered to be highly sensitive for the histotype. Using an illustrative case study and a review of the literature, we explore a relatively routine diagnostic question: whether the negative predictive value of a wild-type p53 immunophenotype for serous carcinoma is absolute, that is, whether a p53-wild type immunophenotype is absolutely incompatible with a diagnosis of serous carcinoma. The case is an advanced stage endometrial carcinoma that was reproducibly classified by pathologists from 3 institutions as serous carcinoma based on its morphologic features. By immunohistochemistry, the tumor was p53-wild type (DO-7 clone), diffusely positive for p16 (block positivity), and showed retained expression of PTEN, MSH2, MSH6, MLH1, and PMS2. Next generation sequencing showed that there indeed was an underlying mutation in TP53 (D393fs*78, R213*). The tumor was microsatellite stable, had a low mutational burden (4 mutations per MB), and displayed no mutations in the exonuclease domain of DNA polymerase epsilon (POLE) gene. Other genomic alterations included RB1 mutation (R46fs*19), amplifications in MYST3 and CRKL, and ARID1A deletion (splice site 5125-94&#95;5138del108). A review of the recent literature identified 5 studies in which a total of 259 cases of serous carcinoma were whole-exome sequenced. The average TP53 mutational rate in endometrial serous carcinoma was only 75% (range, 60 to 88). A total of 12 (33%) of 36 immunohistochemical studies reported a p53-aberrant rate of <80% in endometrial serous carcinoma. We discuss in detail several potential explanations that may underlie the scenario of serous carcinoma-like morphology combined with p53-wild-type immunophenotype, including analytic limitations, a nonserous histotype displaying morphologic mimicry of serous carcinoma, and true biological phenomena (including the possibility of a TP53-independent pathway of endometrial serous carcinogenesis). Ultimately, our central thematic question is provisionally answered in the negative. At present, the available data would not support a categorical conclusion that a p53 alteration is a necessary and obligate component in the genesis and/or diagnosis of endometrial serous carcinoma. On the basis of their collective experience, the authors proffer some recommendations on the use of p53 immunohistochemistry in the histotyping of endometrial carcinomas.