The ongoing global pandemic of coronavirus disease 2019 has rapidly disrupted traditional modes of operation in healthcare and education. In March 2020, institutions in the United States began to implement a range of policies to discourage direct contact and encourage social distancing. These measures have placed us in an unprecedented position where education can no longer occur at close quarters -most notably, around a multi-headed microscope -but must instead continue at a distance. This guide is intended to be a resource for pathologists and pathologists-in-training who wish to leverage technology to continue collaboration, teaching, and education in this era. The manuscript is focused mainly on anatomic pathology; however, the technologies easily lend themselves to clinical pathology education as well. Our aim is to provide curated lists of various online resources that can be used for virtual learning in pathology, provide tips and tricks, and share our personal experience with these technologies.The lists include video conferencing platforms, pathology websites, free online educational resources, including social media, and whole-slide imaging collections. We are currently living through a unique situation without a precedent or guidebook, and we hope that this guide will enable the community of pathology educators worldwide to embrace the opportunities that 21st century technology provides.
Although there is consensus on the cost-effectiveness of a universal approach of screening all colorectal cancer patients for Lynch syndrome (LS) using mismatch-repair (MMR) protein immunohistochemistry (IHC) and/or microsatellite instability (MSI) testing, the question of universal versus selective screening of endometrial cancer patients remains to be resolved. We have prospectively implemented a selective screening algorithm for newly diagnosed endometrial cancer patients, triggered by patient age 50 years or younger, personal/family cancer pedigree that meets Bethesda guideline criteria, and/or presence of MMR-associated tumor morphology. Four-protein MMR IHC and MSI testing were performed if any of the criteria were met. This algorithm excluded screening of older patients without a cancer pedigree and whose tumors lacked MMR morphology. The aim of this study was to retrospectively determine whether these exclusion criteria missed any tumors with abnormal MMR. Among 273 consecutive patients with newly diagnosed endometrial cancers, 181 (66%) lacked criteria for screening. Retrospective MMR IHC confirmed intact MMR in 177 (97.8%) of these 181 unscreened patients, loss of MSH6 in 1 patient (0.5%), and loss of MSH1/PMS2 due to MLH1 promoter hypermethylation in 3 patients (1.7%). In comparison, 41% of patients fulfilling 1 or more criteria for screening had abnormal MMR IHC/MSI, mostly consisting of loss of MLH1/PMS2. MMR morphology contributed to detection of 92% of the abnormal MMR cases while cancer pedigree contributed to detection of the remainder. All of the abnormalities due to MSH2 and PMS2 were detected by the screening algorithm, but 1 of the 4 MSH6 cases was not. The latter finding is consistent with the literature that MSH6 endometrial cancers exhibit a phenotype different than those of the other MMR genes. We conclude that a genotype-specific approach to screening endometrial cancer for LS could consist of universal testing by MSH6 IHC and selective testing by MLH1, PMS2, and MSH2 IHC on the basis of age, cancer pedigree, and MMR morphology. Cost-effectiveness of this hybrid selective strategy deserves further study, particularly in comparison with a universal strategy. Further work to identify phenotypic features of endometrial cancers with methylated MLH1 that would allow them to be excluded from LS screening would also contribute to cost-effectiveness.
Background: Pancreatic cancer is often locally and distally aggressive, but initial presentation as cecal perforation is uncommon.
The genetic disease ataxia telangiectasia (AT) results from mutations in the ataxia telangiectasia mutated (ATM) gene. AT patients develop a progressive degeneration of cerebellar Purkinje neurons. Surprisingly, while ATM plays a criticial role in the cellular reponse to DNA damage, previous studies have localized ATM to the cytoplasm of rodent and human Purkinje neurons. Here we show that ATM is primarily localized to the nucleus in cerebellar Purkinje neurons in postmortem human brain tissue samples, although some light cytoplasmic ATM staining was also observed. No ATM staining was observed in brain tissue samples from AT patients, verifying the specificity of the antibody. We also found that antibodies against components of the Mre11/Rad50/Nbs1 (MRN) complex showed strong staining in Purkinje cell nuclei. However, while ATM is present in both the nucleoplasm and nucleolus, MRN proteins are excluded from the nucleolus. We also observed very high levels of topoisomerase 1 (TOP1) in the nucleus, and specifically the nucleolus, of human Purkinje neurons. Our results have direct implications for understanding the mechanisms of neurodegeneration in AT and AT-like disorder.
Background Human papillomavirus–related oropharyngeal squamous cell carcinoma (HPV‐OPSCC) presents frequently as metastasis in a neck lymph node that may be cystic or necrotic. Fine‐needle aspiration (FNA) biopsies are often first‐line diagnostic procedures. p16 immunohistochemistry (IHC) is a surrogate marker for high‐risk HPV (hrHPV) infection but can be challenging to interpret. This study evaluated the use of hrHPV in situ hybridization (ISH) in cytology cell blocks of cystic neck lesions. Methods Twenty‐four FNA cases with cell blocks and surgical correlates were evaluated. p16 IHC and hrHPV ISH were assessed on cell blocks (C‐p16 and C‐hrHPV ISH), and hrHPV ISH on surgical samples (S‐hrHPV ISH). All results were classified as negative, positive, or equivocal. Results Two cases were excluded because of insufficient tissue on recut. On the basis of C‐hrHPV ISH cases, 12 were positive, 5 were negative, and 5 were equivocal. All 12 positive C‐hrHPV ISH cases had concordant S‐hrHPV ISH with no false positives. Of the 5 negative C‐hrHPV ISH cases, 4 had concordant S‐hrHPV ISH, and 1 had a discordant S‐hrHPV ISH. Of the 5 equivocal C‐hrHPV ISH cases, S‐hrHPV ISH were both positive and negative. Fourteen cases were equivocal by C‐p16; 9 cases were reliably classified by C‐hrHPV ISH (5 positive, 4 negative; 64%). Conclusions C‐hrHPV ISH can be reliably used, especially when positive. A negative or equivocal interpretation of C‐hrHPV ISH may warrant repeat testing. Compared to C‐p16, C‐hrHPV ISH is more frequently diagnostic and could be helpful for HPV‐OSCC diagnosis and management.
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