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Widespread screening colonoscopy procedures and advances in definitive endoscopic therapy call for precise and reproducible criteria for the evaluation of superficially invasive colorectal adenocarcinoma (CRC) in endoscopic resections. Submucosa-invasive CRC [...], * Context.--Recent data support that low-risk submucosally invasive (pT1) colonic adenocarcinomas (ie, completely resected tumors that lack high-grade morphology, tumor budding, and lymphovascular invasion) are considered cured via endoscopic resection, provided that the submucosal invasion is less than 1000 [micro]m. Hence, the pathologists' assessment of depth of submucosal invasion may guide further management (ie, surveillance versus colectomy). Objective.--To assess interobserver concordance among gastrointestinal pathologists in measuring submucosal depth of invasion in colonic endoscopic resections. Design.--Six gastrointestinal pathologists from 5 academic centers independently measured the greatest depth of submucosal invasion in micrometers on 52 hematoxylineosin-stained slides from colonic endoscopic specimens with pT1 adenocarcinomas, per published guidelines (round 1 scoring). Two separate measurements (round 2 scoring) were subsequently performed by each pathologist following a consensus meeting, (1) from the surface of the lesion and (2) from the muscularis mucosae, and pathologists were asked to choose their (3) "real-life (best)" assessment between the first 2 measurements. Interobserver agreement was assessed by the intraclass correlation coefficient (ICC) and Cohen [kappa] statistics. Results.--Round 1 had poor ICC (0.43; 95% CI, 0.31-0.56). Round 2 agreement was good when measuring from the surface (ICC = 0.83; 95% CI, 0.76-0.88) but moderate (ICC = 0.59; 95% CI, 0.47-0.70) when measuring from the muscularis mucosae and became poor (ICC = 0.49; 95% CI, 0.36-0.61) for the best-assessment measurement. Conclusions.--Our findings indicate that clearer and reproducible guidelines are needed if clinical colleagues are to base important management decisions on pathologists' estimate of the depth of submucosal invasion in colonic endoscopic resections. doi: 10.5858/arpa.2021-0598-OA

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P 10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

Helicobacter pylori infects approximately 50% of the global H H population and is classified as a class I carcinogen by the World Health Organization owing to the increased risk of [...], * Context.--Helicobacter pylori-associated and autoimmune gastritis may coexist in a subset of patients who require treatment for both disorders. Objective.--To delineate findings that identify autoimmune gastritis in the background of H pylori infection. Design.--We examined cases of (1) patients with H pylori-associated gastritis who had successful eradication therapy and subsequent biopsies diagnostic of autoimmune gastritis and (2) H pylori-associated gastritis wherein pathologists noted features of autoimmune gastritis during original interpretation. Control patients underwent H pylori eradication but lacked evidence of autoimmune gastritis or H pylori infection after 10 years of follow-up. Results.--Eight subjects had H pylori-associated gastritis followed by H pylori-negative sampling that showed autoimmune gastritis. Review of original samples showed full-thickness inflammation of oxyntic mucosa in 8 of 8 and oxyntic gland loss in 7 of 8 cases. Enterochromaffin-like (ECL) cell hyperplasia, pyloric metaplasia, and intestinal metaplasia were present in 4 of 8 (80% of 5 tested cases), 4 of 8, and 3 of 8 cases, respectively. Features of autoimmune gastritis were noted at the time of their original H pylori diagnosis in 11 study subjects. Ten of 11 samples displayed full-thickness inflammation of oxyntic mucosa and/or partial loss of oxyntic glands, 8 of 11 had ECL cell hyperplasia (all tested cases), 6 of 11 showed pyloric metaplasia, and 4 of 11 harbored intestinal metaplasia. Except for full-thickness oxyntic mucosa inflammation, these features were absent in control cases. Conclusions.--Full-thickness inflammation combined with oxyntic gland loss and ECL cell hyperplasia may help to identify autoimmune gastritis in patients with concomitant H pylori infection.

Pancreatic cystic lesions (PCLs) comprise a broad spectrum of entities and can be categorized into neoplastic and nonneoplastic. They differ greatly in their clinical behavior and malignant potential. Neoplastic cystic [...], * Context.--Pancreatic cystic lesions (PCLs) are very common, and their detection is increasing with the advances in imaging techniques. Because of the major implications for management, distinguishing between neoplastic and nonneoplastic PCLs is critical. Neoplastic cysts with potential to progress into cancer include mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) and nonmucinous cysts (solid pseudopapillary tumors, serous cystic neoplasms, and neuroendocrine tumors with cystic degeneration). Nonneoplastic cysts with no risk of malignant transformation include pseudocysts, retention cysts, lymphoepithelial cysts, cystic pancreatic lymphangioma, and duplication cyst/ciliated foregut cysts. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology with cyst fluid analysis in the diagnosis of PCLs has evolved during the last decade; however, a definitive diagnosis on cytologic specimens is hampered by the sparse cellularity and can be challenging. EUS-FNA can play an important role to differentiate low-risk from high-risk pancreatic cysts and to distinguish between patients with cysts who need clinical follow-up versus those who require surgery. Objective.--To provide an integrative approach to diagnose pancreatic cystic lesions using EUS-FNA cytology and cyst fluid analysis, along with clinical, radiologic, histologic, genetic, and molecular characteristics. Data Sources.--The review and analysis of the latest literature describing pancreatic cystic lesions. Conclusions.--Accurate diagnosis of PCLs requires a multidisciplinary and multimodal team approach, including the integration of clinical findings, imaging, cytology, cyst fluid analysis, and molecular testing. (Arch Pathol Lab Med. 2020;144:47-61; doi: 10.5858/arpa.2019-0308-RA)

Primary appendiceal tumors are found in less than 2% of surgically removed appendices, but still pose a variety of diagnostic and therapeutic challenges. In particular, the classification and management of [...], * Context.--Appendiceal mucinous neoplasms are considered enigmatic tumors of unpredictable biologic potential. Their importance lies in their potential to spread to the peritoneum and viscera in the form of gelatinous mucin deposits. Extra-appendiceal spread of these tumors is the most common etiology of pseudomyxoma peritonei, which is a descriptive term encompassing a number of neoplastic and nonneoplastic peritoneal disorders. Many studies aimed at evaluating the biologic importance of appendiceal mucinous neoplasms and pseudomyxoma peritonei have employed inconsistent histologic criteria for their diagnosis and descriptive terminology for their classification. As a result, appendiceal mucinous neoplasms and associated peritoneal disease represents one of the most confusing and controversial areas in gastrointestinal pathology. Objectives.--To summarize the literature regarding the biologic potential of appendiceal mucinous neoplasms and pseudomyxoma peritonei and to discuss the similarities and differences between proposed systems for their classification. Data Sources.--Literature review and case-derived material. Conclusions.--Many studies have contributed to an increased understanding of the natural progression of mucinous neoplasms of the appendix and peritoneum, and the adoption of a uniform reporting system, as advocated by the American Joint Committee on Cancer and the World Health Organization, will facilitate clear communication among pathologists and clinical colleagues. doi:10.5858/arpa.2011-0034-RA