CONTEXT.—: Squamous lesions of the esophagus encompass a spectrum of disorders ranging from reactive changes and benign papilloma to squamous dysplasia and squamous cell carcinoma, which may pose diagnostic challenges especially in superficial biopsies. OBJECTIVE.—: To provide a review on the typical features of squamous neoplasia in the esophagus, with an emphasis on the key diagnostic features as well as differential diagnosis from mimicking lesions. DATA SOURCES.—: Data sources include published peer-reviewed literature and personal experiences of the authors. CONCLUSIONS.—: Accurate diagnosis of squamous neoplasia requires adherence to established diagnostic criteria, attention to subtle histologic features, and correlation with clinical and imaging findings. In difficult cases, multiple biopsies may be necessary to reach a definitive diagnosis.

CONTEXT.—: Pathologist interobserver discordance is significant in grading of prostate cancer, limiting reliability. Diagnostic reproducibility may be improved with digital images, but adoption faces workflow, cost, and quality challenges. A novel digital method using an alternative tissue processing approach and novel laser microscopy system potentially addresses these issues. OBJECTIVE.—: To evaluate the capability of this new method for primary diagnostic interpretation in clinical prostate biopsy specimens. DESIGN.—: Forty patients with a high likelihood of prostate cancer based on magnetic resonance imaging consented to investigational core biopsy. A subset of samples was used for direct comparison of physical slide preparation effects and time-tracking determination with multiphoton microscopy. Twenty samples were processed for diagnostic comparison between multilevel digital slides and subsequently produced physical slides. A reference diagnosis based on all data was established using grade groups. Level of diagnostic match and requests for immunohistochemistry were compared between physical and digital diagnoses. Immunohistochemical staining and length measurements were secondary outcomes. RESULTS.—: Interpretations based on direct multiphoton imaging yielded diagnoses that were at least as accurate as standard histology; cancer diagnosis correlation was 89% (51 of 57) by physical slides and 95% (53 of 56) by multiphoton microscopy. Grade-level concordance was 73% (44 of 60) by either method. Immunohistochemistry for routine prostate cancer-associated markers on these alternatively processed tissues was unaffected. Alternatively processed tissues resulted in longer measured core and cancer lengths, suggestive of improved orientation and visualization. CONCLUSIONS.—: Findings support high potential for complete interpretation of prostate core biopsies using solely multiphoton microscopy of intact specimens, with potential diagnostic benefits as well as reduced processing time and reduced processing complexity.

CONTEXT.—: We previously examined pituitary adenomas with immunohistochemical (IHC) stains for steroidogenic factor 1, Pit-1, anterior pituitary hormones, cytokeratin CAM 5.2, and the α-subunit of human chorionic gonadotropin and found that a screening panel comprising stains for steroidogenic factor 1, Pit-1, and adrenocorticotropic hormone successfully classified most cases and reduced the overall number of stains required. OBJECTIVES.—: To examine the potential role of IHC stain for T-box transcription factor (Tpit) in the classification of our series of pituitary adenomas and to update our screening panel as necessary. DESIGN.—: We collected 157 pituitary adenomas from 2 institutions and included these in tissue microarrays. Immunostains for Tpit were scored in a blinded fashion using the Allred system. Adenomas were assigned to a gold standard class based on IHC pattern followed by application of available clinical and serologic information. Test characteristics were calculated. Correlation analyses, cluster analyses, and classification tree analyses were used to see whether IHC staining patterns reliably reflected adenoma class. RESULTS.—: Of the cases collected, 147 (93.6%) had sufficient material for Tpit analysis. IHC stain for Tpit identified 8 null cell adenomas (all nonfunctioning clinically) as silent corticotrophs; Tpit stains showed better sensitivity, specificity, positive predictive value, and negative predictive value than IHC for adrenocorticotropic hormone and cytokeratin CAM 5.2. Correlation analyses continued to show the expected relationships among IHC stains. Cluster analyses showed grouping of adenomas into clinically consistent groups. Classification tree analysis underscored the central role of transcription factor IHC stains, including Tpit, in adenoma classification. CONCLUSIONS.—: Substitution of Tpit stain for the adrenocorticotropic hormone stain improves our prior algorithm by reducing the number of false-negatives and false-positives. As a result, fewer adenomas are classified as null cell adenoma, and more adenomas are classified as silent corticotroph adenoma.

CONTEXT.—: This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. OBJECTIVE.—: To accurately reflect the preexisting diseases and pathologic conditions of decedents with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection through autopsy. DESIGN.—: Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple-choice and open-ended survey responses. RESULTS.—: Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than 1 preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. CONCLUSIONS.—: Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of comorbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.

CONTEXT.—: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged, currently pandemic virus, and the etiologic agent of coronavirus disease 2019 (COVID-19). Clinical testing for antibodies to SARS-CoV-2 has rapidly become widespread, but data regarding the interlaboratory performance of these serologic assays are limited. OBJECTIVE.—: To describe the development and initial results of the College of American Pathologists (CAP) SARS-CoV-2 Serology Survey. DESIGN.—: Members from the CAP Microbiology and Diagnostic Immunology and Flow Cytometry Committees formed a working group to support development of a new proficiency testing survey for anti-SARS-CoV-2 antibody assays. Supplemental questions in the survey assessed the state of SARS-CoV-2 serologic testing among participating laboratories as of July 2020. Results were analyzed for agreement by immunoglobulin (Ig) isotype tested, assay manufacturer, and methodology. RESULTS.—: A total of 4125 qualitative results were received from 1110 laboratories participating in the first survey. Qualitative agreement for assays measuring anti-SARS-CoV-2 total antibodies or IgG was greater than 90% for all 3 samples in the survey. Qualitative agreement for IgM and IgA for the negative sample was greater than 95%, but lacked consensus for the other 2 samples. CONCLUSIONS.—: These initial data suggest overall excellent agreement and comparable performance for most qualitative anti-SARS-CoV-2 IgG and total antibody assays across all participating clinical laboratories, regardless of specific target antigen or assay methodology.

Comment in Arch Pathol Lab Med. 2021 Aug 1;145(8):920-921. Arch Pathol Lab Med. 2021 Aug 1;145(8):921-922.

CONTEXT.—: Immune checkpoint inhibitors (CPIs), including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors and the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, are being increasingly used for treating many advanced malignancies. However, CPI therapy is also associated with gastrointestinal and hepatobiliary adverse effects. OBJECTIVES.—: To review the adverse effects of CPI therapy on the gastrointestinal tract and hepatobiliary system. To describe histopathologic patterns and discuss differential diagnostic considerations in the diagnosis of CPI injuries. DATA SOURCES.—: Published peer-reviewed literature in the English language and personal experience in the diagnosis of CPI injuries. CONCLUSIONS.—: The pathologic manifestations of CPI therapy-induced gastrointestinal and hepatobiliary injury are broad. The patterns of esophageal CPI injury include lymphocytic inflammation and ulcerative esophagitis, while those of gastric injury include chronic active gastritis, lymphocytic gastritis, focal enhancing gastritis, and periglandular inflammation. The duodenal injury may present as duodenitis with villous blunting and granulomas. We also noticed active colitis, microscopic colitis, chronic active colitis, increased apoptosis, ischemic colitis, and nonspecific inflammatory reactive changes in colonic injuries. The reported histologic features of hepatobiliary injuries are panlobular hepatitis, centrilobular necrosis, portal inflammation with bile duct injury, steatosis, nodular regenerative hyperplasia, and secondary sclerosing cholangitis. In summary, we discuss the pathologic features and differential diagnosis of CPI therapy-induced gastrointestinal and hepatobiliary injury. Recognition of CPI injury is important to determine the proper management that often includes cessation of CPI therapy, and administration of steroids or other immunosuppressive agents, based on severity of injury.

CONTEXT.—: Epstein-Barr virus is a ubiquitous oncogenic virus. During the past 5 decades, the virus has been linked to several disease entities, both neoplastic and nonneoplastic. Several Epstein-Barr virus-associated conditions affect the digestive organs, ranging from mild transient inflammatory conditions to more debilitating and even fatal diseases. OBJECTIVE.—: To discuss the clinicopathologic aspects of some newly or recently recognized Epstein-Barr virus-related conditions encountered in the digestive system and their therapeutic implications. DATA SOURCES.—: Published peer-reviewed literature was reviewed. CONCLUSIONS.—: This article highlights the importance of recognizing the discussed lesions because they influence the direct clinical management or serve as a potential predictive marker for therapy.

CONTEXT.—: Cancer staging provides critical information for patients and treating physicians to battle against cancer, predict prognosis, and guide treatment decisions. The American Joint Committee on Cancer (AJCC) staging system uses a tumor, node, metastasis (TNM) scoring algorithm and is the foremost classification system for adult cancers. This system is updated every 6 to 8 years to allow sufficient time for implementation of changes and for relevant examination and discussion of data validating those changes in staging. OBJECTIVE.—: To review the updates in the 8th edition American Joint Committee on Cancer staging system on hepato-pancreato-biliary cancer. DATA SOURCES.—: Literature review. CONCLUSIONS.—: The 8th edition, published in 2016 and implemented on January 1, 2018, has been in use for approximately 3 years. Compared with the 7th edition, some of the changes are quite radical. This review aims to provide a summary of the changes/updates of the 8th edition with focus on hepato-pancreato-biliary cancers, and evaluate its performance through literature review.

CONTEXT.—: Studies on the adoption of voice recognition in health care have mostly focused on turnaround time and error rate, with less attention paid to the impact on the efficiency of the providers. OBJECTIVE.—: To study the impact of voice recognition on the efficiency of grossing biopsy specimens. DESIGN.—: Timestamps corresponding to barcode scanning for biopsy specimen bottles and cassettes were retrieved from the pathology information system database. The time elapsed between scanning a specimen bottle and the corresponding first cassette was the length of time spent on the gross processing of that specimen and is designated as the specimen time. For the first specimen of a case, the specimen time additionally included the time spent on dictating the clinical information. Therefore, the specimen times were divided into the following 2 categories: first-specimen time and subsequent-specimen time. The impact of voice recognition on specimen times was studied using both univariate and multivariate analyses. RESULTS.—: Specimen complexity, prosector variability, length of clinical information text, and the number of biopsies the prosector grossed that day were the major determinants of specimen times. Adopting voice recognition had a negligible impact on specimen times. CONCLUSIONS.—: Adopting voice recognition in the gross room removes the need to hire transcriptionists without negatively impacting the efficiency of the prosectors, resulting in an overall cost saving. Using computer scripting to automatically enter clinical information (received through the electronic order interface) into report templates may potentially increase the grossing efficiency in the future.

CONTEXT.—: The World Health Organization Classification of Tumours: Digestive System Tumors, 5th edition, was published in 2019 and shows several impactful changes as compared with the 4th edition published in 2010. Changes include a revised nomenclature of serrated lesions and revamping the classification of neuroendocrine neoplasms. Appendiceal goblet cell adenocarcinoma is heavily revised, and intrahepatic cholangiocarcinoma is split into 2 subtypes. New subtypes of colorectal carcinoma and hepatocellular carcinoma are described. Precursor lesions are emphasized with their own entries, and both dysplastic and invasive lesions are generally recommended to be graded using a 2-tier system. Hematolymphoid tumors, mesenchymal tumors, and genetic tumor syndromes each have their own sections in the 5th edition. New hematolymphoid lesions include monomorphic epitheliotropic intestinal T-cell lymphoma; duodenal-type follicular lymphoma; intestinal T-cell lymphoma, not otherwise specified; and indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. This paper will provide an in-depth look at the changes in the 5th edition as compared with the 4th edition. OBJECTIVE.—: To provide a comprehensive, in-depth update on the World Health Organization classification of digestive tumors, including changes to nomenclature, updated diagnostic criteria, and newly described entities. DATA SOURCES.—: The 5th edition of the World Health Organization Classification of Tumours: Digestive System Tumours, as well as the 4th edition. CONCLUSIONS.—: The World Health Organization has made many key changes in its newest update on tumors of the digestive system. Pathologists should be aware of these changes and incorporate them into their practice as able or necessary.