The American Journal of Surgical Pathology最新文献

{"title":"NKX6-1 Is a Less Sensitive But Specific Biomarker of Chromophobe Renal Cell Carcinoma","authors":"B. Xie, K. Tong, Jiao Yang, Taoli Wang, L. Cheng, S. Zeng, Zhongliang Hu","doi":"10.1097/PAS.0000000000001872","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001872","url":null,"abstract":"NKX6-1 is a transcription factor that plays a key role in the development, differentiation, and identity maintenance of beta cells of pancreatic islets. Although NKX6-1 expression has also been discovered in pancreatic well-differentiated neuroendocrine tumors (WDNETs) and duodenal WDNETs, its expression in chromophobe renal cell carcinoma (chRCC) is unexplored. Analysis of mRNA expression and immunohistochemistry of NKX6-1 was performed using the kidney cancer cohort from The Cancer Genome Atlas (TCGA) and paraffin-embedded whole-tissue slides from our 196 collected cases, including 48 chRCCs (43 classic and 5 eosinophilic subtypes), 24 renal oncocytomas (ROs), 46 clear cell renal cell carcinomas, 41 papillary renal cell carcinomas, 14 renal urothelial carcinomas, 7 low-grade oncocytic renal tumors (LOTs), 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. NKX6-1 expression was almost exclusively upregulated in chRCC at both the mRNA and protein levels compared with other renal tumors. NKX6-1 was immunohistochemically positive in 39 of 48 (81.3%) chRCCs, but negative in 46 clear cell renal cell carcinomas, 24 ROs, 7 low-grade oncocytic renal tumors, 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. Diffuse, moderate, and focal NKX6-1 staining were seen in 21, 4, and 14 of the 39 chRCCs, respectively. In contrast, NKX6-1 was focally positive in only 1 of 41 (2.4%) papillary renal cell carcinomas and 2 of 14 (14.3%) renal urothelial carcinomas. Therefore, the sensitivity and specificity of NKX6-1 staining were 81.3% and 98% for chRCC, respectively. In conclusion, NKX6-1 may be a novel potential marker for differentiating chRCC from other renal neoplasms, especially from RO.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125800569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcome-based Validation of Confluent/Expansile Versus Infiltrative Pattern Assessment and Growth-based Grading in Ovarian Mucinous Carcinoma","authors":"A. Momeni-Boroujeni, H. Song, L. Irshaid, S. Strickland, C. Parra‐Herran, A. Busca","doi":"10.1097/PAS.0000000000001895","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001895","url":null,"abstract":"The growth pattern (confluent/expansile versus infiltrative) in primary ovarian mucinous carcinoma (OMC) is prognostically important, and the International Collaboration on Cancer Reporting (ICCR) currently recommends recording the percentage of infiltrative growth in this tumor type. Histologic grading of OMC is controversial with no single approach widely accepted or currently recognized by the World Health Organization Classification of Tumours. Since ovarian carcinoma grade is often considered in clinical decision-making, previous literature has recommended incorporating clinically relevant tumor parameters such as growth pattern into the OMC grade. We herein validate this approach, termed Growth-Based Grade (GBG), in an independent, well-annotated cohort from 2 institutions. OMCs with available histologic material underwent review and grading by Silverberg, International Federation of Obstetrics and Gynecology (FIGO), and GBG schema. GBG categorizes OMCs as low-grade (GBG-LG, confluent/expansile growth, or ≤10% infiltrative invasion) or high-grade (GBG-HG, infiltrative growth in >10% of tumor). The cohort consisted of 74 OMCs, 53 designated as GBG-LG, and 21 as GBG-HG. Using Silverberg grading, the cohort had 42 (57%) grade 1, 28 (38%) grade 2, and 4 (5%) grade 3 OMCs. Using FIGO grading, 50 (68%) OMCs were grade 1, 23 (31%) grade 2, and 1 (1%) grade 3. Follow-up data was available in 68 patients, of which 15 (22%) had cancer recurrence. GBG-HG tumors were far more likely to recur compared with GBG-LG tumors (57% vs. 6%; χ2 P<0.0001). Silverberg and FIGO grading systems also correlated with progression-free survival in univariate analysis, but multivariate analysis showed only GBG to be significant (hazard ratio: 10.9; Cox proportional regression P=0.0004). Seven patients (10%) died of disease, all of whom had GBG-HG (log-rank P<0.0001). Multivariate analysis showed that the percentage of infiltrative growth was the only factor predictive of disease-specific survival (hazard ratio: 25.5, Cox P=0.02). Adding nuclear atypia to GBG categories did not improve prognostication. Our study validates the prognostic value of the GBG system for both disease-free survival and disease-specific survival in OMC, which outperformed Silverberg and FIGO grades in multivariate analysis. Thus, GBG should be the preferred method for tumor grading.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128008552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational Landscape of TdT+ Large B-cell Lymphomas Supports Their Distinction From B-lymphoblastic Neoplasms: A Multiparameter Study of a Rare and Aggressive Entity.","authors":"Shweta Bhavsar,&nbsp;Yen-Chun Liu,&nbsp;Sarah E Gibson,&nbsp;Erika M Moore,&nbsp;Steven H Swerdlow","doi":"10.1097/PAS.0000000000001750","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001750","url":null,"abstract":"<p><p>In the current World Health Organization classification, terminal deoxynucleotidyl transferase (TdT) expression in a high grade/large cell B-cell lymphoma (LBCL) indicates a B-lymphoblastic lymphoma/leukemia (B-LBL), although TdT expression in what appear to be mature LBCL or following mature B-cell neoplasms is reported. The frequency of TdT+ LBCL, how to best categorize these cases, and their clinicopathologic features, molecular landscape, and relationship to classic B-LBL remain to be better defined. TdT expression was therefore assessed in 258 LBCL and the results correlated with the cytologic, phenotypic, and cytogenetic findings. Targeted mutational analysis, review of prior biopsies, and assessment of clinical associations was performed in the 6 cases with >10% TdT+ cells. All 6 TdT+ LBCL were blastoid-appearing, CD34-, MYC+, BCL2+, and had MYC rearrangements (R) (5/6 with BCL2 and/or BCL6-R). 5/6 had a prior TdT- LBCL and/or follicular lymphoma and all had an aggressive course. Fifteen nonsynonymous variants in 11 genes were seen in the 4/5 tested cases with mutations. TdT+ and TdT- areas in 1 case showed identical mutations. The mutational profiles were more like those reported in germinal center B-cell type-diffuse LBCL rather than B-LBL. Evolution from preceding TdT- lymphomas was nondivergent in 1/3 tested cases and partially divergent in 2. The clinicopathologic and cytogenetic features of these 6 cases were similar to those found in a meta-analysis that included additional cases of TdT+ LBCL or B-LBL following follicular lymphoma. Thus, TdT+, CD34- large B-cell neoplasms with MYC rearrangements and often a \"double hit\" are rare, frequently a transformational event and aggressive but are distinct from classic B-LBL.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"71-82"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39310656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Frontiers of Serrated Polyps.","authors":"Phoenix D Bell,&nbsp;Joseph C Anderson,&nbsp;Amitabh Srivastava","doi":"10.1097/PAS.0000000000001806","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001806","url":null,"abstract":"<p><p>The serrated pathway of carcinogenesis has been the subject of intense investigation over the past 2 decades, but many gaps in our understanding still need to be resolved. Serrated polyp precursors include hyperplastic polyps, sessile serrated polyps, and traditional serrated adenomas. These are considered discrete entities, but there is emerging molecular data to suggest that they may be more closely related to each other than currently believed. The recent US Multi-Society Task Force surveillance guidelines for patients with serrated polyps are admittedly based on low quality evidence. In this brief review, we discuss the limitations in endoscopic detection and pathologic interpretation of serrated polyps and the implications of these diagnostic difficulties on risk prediction and postpolypectomy surveillance recommendations.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"e64-e70"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39435265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathology of Gastrointestinal Immune-related Adverse Events: A Practical Review for the Practicing Pathologist.","authors":"M Lisa Zhang,&nbsp;Vikram Deshpande","doi":"10.1097/PAS.0000000000001730","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001730","url":null,"abstract":"Immune checkpoint inhibitors target checkpoint proteins with the goal of reinvigorating the host immune system and thus restoring antitumor response. With the dramatic increase in the use of checkpoint inhibitors for cancer treatment, surgical pathologists have assumed a major role in predicting the therapeutic efficacy (score based on programmed cell death ligand 1 immunohistochemistry and mismatch repair protein loss) as well as diagnosing the complications associated with these medications. Immune-related adverse events (irAEs) manifest as histologic changes seen in both the upper and lower gastrointestinal tract, and when viewed in isolation, may be morphologically indistinguishable from a wide range of diseases including infections, celiac disease, and inflammatory bowel disease, among others. Evaluation of biopsies from both the upper and lower gastrointestinal tract can aid in the distinction of gastrointestinal irAEs from their mimics. In the liver, the histologic changes of hepatic irAEs overlap with de novo diseases associated with hepatitic and cholangitic patterns of injury. The diagnosis of irAEs requires communication and collaboration from the pathologist, oncologist, and gastroenterologist. This review provides a background framework and illustrates the histologic features and differential diagnosis of gastrointestinal and hepatic irAEs.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"e15-e26"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39002499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histologic Features of Tacrolimus-induced Colonic Injury.","authors":"Erika Hissong,&nbsp;Maria Mostyka,&nbsp;Rhonda K Yantiss","doi":"10.1097/PAS.0000000000001761","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001761","url":null,"abstract":"<p><p>Tacrolimus is a common immunosuppressant used in solid organ transplant recipients. Although most patients develop diarrheal symptoms, data regarding patterns of injury in patients taking tacrolimus are limited. We performed this study to characterize tacrolimus-related features of colonic injury. We retrospectively identified colonic samples from 20 patients receiving tacrolimus monotherapy. Records were reviewed for symptoms, endoscopic findings, other medications, and infections. None of the patients had gastrointestinal infections or used other drugs known to cause colonic injury; none had received mycophenolate within 6 months of presentation. Cases were evaluated for the nature and distribution of inflammation and crypt abnormalities, including distortion, destruction, and apoptosis. Eighteen (90%) patients were solid organ transplant recipients. Seventeen (85%) had gastrointestinal symptoms, particularly diarrhea (75%). More than 50% had endoscopic colitis and 15% had ulcers and/or erosions. Most (90%) cases showed regenerative epithelial changes; apoptotic crypt cells were present in 55% and numerous in 10% of cases. Neutrophilic cryptitis was present in 60% of cases; 35% showed crypt destruction. Plasma cell-rich lamina propria inflammation and crypt distortion were observed in 40% and 25% of cases, respectively. There was no correlation between therapy duration and features of chronic injury. We conclude that tacrolimus can cause symptomatic colitis. Histologic abnormalities are often mild, featuring regenerative crypts and scattered apoptotic debris. However, 40% of symptomatic patients have chronic colitis, most likely reflecting drug-induced immune dysregulation. Pathologists should be aware of these associations because colitis often resolves with decreasing drug dosage rather than treatment directed toward inflammatory bowel disease.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"118-123"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39240216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphocytic Esophagitis: Current Understanding and Controversy.","authors":"Meredith E Pittman","doi":"10.1097/PAS.0000000000001667","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001667","url":null,"abstract":"<p><p>This review summarizes our current understanding of lymphocytic esophagitis (LE), a novel form of chronic esophagitis that incorporates distinctive histologic, clinical, and endoscopic features. First described as a histologic entity, a diagnosis of LE requires intraepithelial lymphocytosis without significant granulocytic inflammation and some evidence of epithelial damage; the rationale for and studies supportive of these histologic criteria are discussed within. Clinically, the majority of patients who present with histologically confirmed LE are older women or patients with underlying immunologic abnormalities, such as Crohn disease, rheumatologic disorders, or common variable immunodeficiency. The most common presenting symptom of LE is dysphagia, and the endoscopic findings can vary from normal mucosa to mucosal changes that resemble eosinophilic esophagitis: edema, rings, furrows, and plaques. The incidence of luminal strictures and the persistent dysphagia and/or lymphocytosis present in some patients provide evidence that LE is a chronic inflammatory disorder, at least within a subset of individuals. Several histologic mimics of LE are examined, as are disagreements surrounding the LE diagnosis.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"e55-e63"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38782873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lichen Sclerosus et Atrophicus With Histopathologic Features Mimicking Mycosis Fungoides: A Large Series of Cases Comparing Genital With Extragenital Lichen Sclerosus.","authors":"Eleonora Leoni,&nbsp;Werner Kempf,&nbsp;Lorenzo Cerroni","doi":"10.1097/PAS.0000000000001738","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001738","url":null,"abstract":"<p><p>Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory dermatosis of unknown etiology involving the genital and/or extragenital area, showing histopathologically a characteristic homogeneization and sclerosis of the superficial collagen with variably dense lymphoid infiltrates. Intraepidermal lymphocytes may be observed, and in some cases may pose differential diagnostic problems with mycosis fungoides (MF). We studied the histopathologic features of 121 cases of LSA with dense lymphoid infiltrates (genital: 94; male:female: 93:1; age range: 2 to 87 y; median age: 11 y; extragenital: 27; male:female: 0.1:1; age range: 11 to 79 y; median age: 59 y), to better characterize the intraepidermal lymphoid infiltrate and to compare genital with extragenital cases. Epidermotropic lymphocytes mimicking the histopathologic features of MF were present in 93.6% of the genital specimens but none of the extragenital cases. Interestingly, typical features of LSA were mssing in 39.4% of genital LSA, and in a further 25.5% were present only focally. Immunohistochemical analyses showed a predominance of CD8+ T-lymphocytes within the epidermis. Molecular studies of the T-cell receptor genes revealed a monoclonal population of T-lymphocytes in nearly half of the cases. Our study shows that MF-like histopathologic features are extremely common in genital LSA but are never encountered in extragenital cases. A diagnosis of MF in the genital area should be made only upon compelling features, keeping in mind the frequent pseudolymphomatous aspects of LSA.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"83-88"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39030176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Frontiers of Appendiceal Controversies: Mucinous Neoplasms and Pseudomyxoma Peritonei.","authors":"Erika Hissong,&nbsp;Rhonda K Yantiss","doi":"10.1097/PAS.0000000000001662","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001662","url":null,"abstract":"<p><p>Appendiceal mucinous neoplasms show a range of morphologic features and biological risk. At one end of the spectrum, high-grade adenocarcinomas are cytologically malignant with infiltrative invasion, lymph node metastases, and behavior similar to that of extra-appendiceal mucinous adenocarcinomas. At the other end, mucinous neoplasms confined to the mucosa are uniformly benign. Some cases lying between these extremes have potential risk to metastasize within the abdomen despite a lack of malignant histologic features. They show \"diverticulum-like,\" pushing invasion of mostly low-grade epithelium through the appendix with, or without, concomitant organizing intra-abdominal mucin. The latter condition, widely termed \"pseudomyxoma peritonei,\" tends to pursue a relentless course punctuated by multiple recurrences despite cytoreductive therapy, culminating in death for many patients. The combination of bland histologic features and protracted behavior of peritoneal disease has led some authors to question whether these metastatic tumors even represent malignancies. The World Health Organization and its cadre of experts widely promote usage of \"low-grade appendiceal mucinous neoplasm\" as an umbrella term to encompass benign and malignant conditions, as well as those that have uncertain biological potential. Although this practice greatly simplifies tumor classification, it causes confusion and consternation among pathologists, clinical colleagues, and patients. It also increases the likelihood that at least some patients will undergo unnecessary surveillance for, and treatment of, benign neoplasms and non-neoplastic conditions. The purpose of this review is to critically evaluate the relevant literature and discuss a practical approach to classifying appendiceal mucinous neoplasms that more closely approximates their biological risk.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"e27-e42"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38796993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal Abnormalities in Patients With SARS-CoV-2 Infection: Histopathologic Changes Reflect Mechanisms of Disease.","authors":"Rhonda K Yantiss,&nbsp;LiHui Qin,&nbsp;Bing He,&nbsp;Carl V Crawford,&nbsp;Surya Seshan,&nbsp;Sanjay Patel,&nbsp;Nabeel Wahid,&nbsp;Jose Jessurun","doi":"10.1097/PAS.0000000000001755","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001755","url":null,"abstract":"<p><p>Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"89-96"},"PeriodicalIF":5.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39057364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}