Histologic Features of Mycobacterial Spindle Cell Pseudotumors: A Multi-institutional Clinicopathologic Analysis of 14 Cases.

Mycobacterial spindle cell pseudotumors (MSPs) are a rare and diagnostically challenging manifestation of non-tuberculous mycobacterial (NTM) infections. Proper recognition of these pseudotumors is important because they are treatable and benign. In this study, we evaluated the morphologic patterns of MSPs to improve their pathologic identification. Clinical and morphologic features of 14 MSPs were analyzed. Histologic factors evaluated included the architectural growth pattern of spindled or epithelioid macrophages, granulomas and their location within the lesion, neutrophilic microabscesses, multinucleated giant cells, necrosis, and effacement of background tissue. The composition of inflammatory infiltrates, organism density by acid-fast staining, and stromal changes were also assessed. In addition, 8 of 14 cases underwent molecular microbiology identification by a clinical amplicon-sequencing assay for non-tuberculous mycobacteria. MSP sites included 2 bowel, 10 lymph nodes, 1 liver, and 1 extremity. Cases with available clinical history (n=10) all occurred in immunocompromised patients. All demonstrated effacement of normal structures with spindled cells arranged in a storiform or fascicular architectural pattern. In addition, all cases showed lymphocytic inflammation, with prominent concurrent neutrophilic inflammation in 50% (7/14) of cases. Other morphologic findings included foamy histiocytes (64%, 9/14), peripherally situated granulomas (21%, 3/14), and neutrophilic microabscesses (21%, 3/14). All tested cases were positive for NTM by PCR methods. Mycobacterium avium was the most commonly isolated pathogen (6/8). Mycobacterial spindle cell pseudotumors show predominantly spindled morphology that may be mistaken as a neoplasm. Surgical pathologists who evaluate lymph nodes, soft tissue, and gastrointestinal tissues should be aware of this spindled tumefactive phenomenon in the setting of immunocompromised patients. Recognition of key morphologic features of neutrophilic inflammation, peripheral granulomas, or foamy histiocytes within a spindled lesion can help guide the pathologist to a correct diagnosis of an inflammatory process secondary to infection rather than a spindle cell neoplasm. Accurate diagnosis to facilitate appropriate antimicrobial and/or surgical therapy requires a comprehensive evaluation combining clinical, histopathologic, and microbiological findings.

Prognostic performance of microscopic size measurements in small invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas.

AIMS: Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication. METHODS: In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes. RESULTS: The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis. CONCLUSIONS: For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis.

Evaluation of fine-needle core biopsy specimens for pancreatic ductal adenocarcinoma: Diagnostic utility and helpful histological features.

AIMS: With the advent of new biopsy devices, fine-needle core biopsy specimens can be obtained from pancreas masses. This study aimed to report the histological spectrum of intrapancreatic adenocarcinoma on fine-needle core biopsy and the accuracy of sampling. METHODS AND RESULTS: We identified 423 SharkCore™ fine-needle core biopsies taken from patients with a high clinical concern for pancreatic adenocarcinoma. For each, we recorded patient age and sex, percentage of diagnostic tissue in each sample and tumour site, size and histological findings. The cases came from 392 patients (193 men, 199 women; mean age 69 years). Median diagnostic tissue amount in the samples was 30%. Common histological findings included desmoplasia (36%), single atypical cells (44%), haphazard glandular growth pattern (68%), nuclear pleomorphism > 4:1 (39%), incomplete gland lumens (18%) and detached atypical epithelial strips (37%). Additional levels were ordered on 143 cases. Final clinical diagnoses associated with the 423 cases were adenocarcinoma (n = 343), pancreatitis (n = 22), intraductal neoplasm or other benign/low-grade process (n = 16) and unknown (n = 42, patients lost to follow-up). Of the adenocarcinoma cases, the diagnosis was established by the evaluated fine-needle core biopsy sample alone in 178, by fine-needle aspiration biopsy alone in 30, by both concurrently in 89 and by subsequent biopsy or resection in 37 cases. Among 68 cases called suspicious on fine-needle core biopsy, 78% ultimately represented adenocarcinoma. CONCLUSIONS: Fine-needle core biopsy allows for histological diagnosis of pancreatic adenocarcinoma, using known histological parameters. Common findings include single atypical cells, desmoplasia, haphazard gland growth and nuclear pleomorphism. Cases interpreted as suspicious often represent malignancy.

Comparative histologic features among liver biopsies with biliary-pattern injury and confirmed clinical diagnoses.

Biliary-pattern injury in the liver (eg, duct injury, ductular reaction, cholestasis) can occur in several conditions, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), large duct obstruction (LDO), and drug-induced liver injury (DILI). While the histologic changes in these conditions have been individually well described, distinguishing among them remains often challenging, particularly when biopsy samples are limited in size, robust clinical information is unavailable, and/or the pathologist does not feel confident in evaluating liver disease. This study evaluated histologic features that could aid the diagnosis of biliary-pattern injury on biopsy. We reviewed 121 liver biopsies from clinically confirmed cases of PBC, PSC, chronic LDO, or DILI for multiple clinical and histologic parameters. The rates of these histologic findings were then compared among different entities. Onion-skin fibrosis was seen in 14% of PSC in comparison to 0%, 5%, and 0% of PBC, DILI, and chronic LDO (P = 0.031). Florid duct lesions were identified in 21% of PBC compared to 2% of PSC and 0% of DILI and LDO (P = 0.0065). Similarly, 42% of PBC showed lobular granulomas, compared to 7% of PSC, 11% of DILI, and 33% of chronic LDO (P = 0.0001). Cholestasis was more commonly seen in DILI (42%) and chronic LDO (83%) than in PBC (4%) and PSC (16%) (P < 0.0001). Lobular chronic inflammation was found in a significantly higher percentage of PBC and LDO than of PSC and DILI (P = 0.0009). There were significantly fewer cases of PBC showing neutrophils in ductular reaction than PSC, DILI, and LDO (P = 0.0063). Histologic findings that can help suggest a diagnosis in liver biopsies with biliary-pattern injury include florid duct lesions, lobular granulomas, lack of neutrophils in ductular reaction, and lobular chronic inflammation in PBC; onion-skin fibrosis in PSC; cholestasis and feathery degeneration in DILI; and lobular granulomas, lobular chronic inflammation, cholestasis, and feathery degeneration in chronic LDO. These findings are likely most helpful when complicating factors interfere with biopsy interpretation.

Oncogenic GNAS Uses PKA-Dependent and Independent Mechanisms to Induce Cell Proliferation in Human Pancreatic Ductal and Acinar Organoids.

IMPLICATIONS: The study identifies an opportunity to discover a PKA-independent pathway downstream of oncogene GNAS for managing IPMN lesions and their progression to PDAC.

Is Social Media Here to Stay?: Survey Results Indicate Increasing Pathologist Interest and Engagement Over Time.

CONTEXT.­: Social media has become widely adopted by pathologists and other physicians for professional purposes. While engagement has likely increased over time, there remain few concrete data regarding attitudes toward its use. OBJECTIVE.­: To assess pathologists' use of and attitudes toward social media over time. DESIGN.­: We created a survey regarding personal and professional use of social media and circulated it via multiple channels in December 2017 and again in February 2022. Results of the 2 surveys were compared for statistically significant differences. RESULTS.­: The 2017 survey was completed by 97 participants, and the 2022 survey by 305 participants. Respondents were predominantly female and academics, included pathologists in all age categories and all time-in-practice length. In both surveys, Twitter (now X) was the most popular platform for professional use and Facebook was the most popular for personal use. Professional barriers to social media use remained consistent between the 2 surveys, including the amount of time required. Education was seen as the main benefit of social media use in both surveys, while other benefits such as networking and increasing professional visibility were endorsed significantly less often in the second survey. While the second survey received more than 3 times as many responses as the first, several aspects of social media use (mainly demographics) remained similar during the timeframe, while other aspects (such as usage and perceived values) decreased. CONCLUSIONS.­: Pathologists continue to find social media valuable. Barriers remain, though overall pathologists of all ages and practice settings appear receptive to using social media to further educational and other opportunities.

Lymphoglandular Complex-Like Colorectal Carcinoma-A Series of 20 Colorectal Cases, Including Newly Reported Features of Malignant Behavior.

Distinguishing colon carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes can be difficult. We assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which we referred to as lymphoglandular complex-like carcinoma (LGCC). We collected clinical and endoscopic features, including lesion size, endoscopic appearance, location, procedure, follow-up, AJCC stage, and mismatch repair status. We recorded the presence of the following histologic features: haphazard gland distribution, gland angulation, gland fusion, solid nest formation, single-cell formation, stromal desmoplasia, presence of lymphovascular invasion and perineural invasion, presence of lamina propria, cytologic atypia as low- or high-grade, presence of goblet cells in the invasive component, and the presence of a surface lesion. Most cases (9 of 13) were described endoscopically as sessile polyps with an average size of 1.56 cm. Most cases (90%) were associated with a surface lesion, of which the majority were tubular adenomas, though a subset was associated with sessile serrated lesions with dysplasia (3 of 18). All cases of LGCC demonstrated haphazard gland distribution and either gland angulation, fusion, or solid nest formation. A portion of cases demonstrated single-cell infiltration (35%) and desmoplasia (50%), and rarely lymphovascular invasion was present (5%). A subset (10%) of cases invaded beyond the submucosa. Deficient mismatch repair was present in 22% (2 of 9) of cases for which it was performed. In cases of colectomy or completion colectomy, nodal metastasis was present in 38% (3 of 8). No cases demonstrated disease recurrence or disease-specific mortality. Overall, LGCC represents an enigmatic subset of carcinomas that is important to distinguish from adenomas involving lymphoglandular complexes due to its varying prognostic outcomes.

Erythrophagocytosis is not a reproducible finding in liver biopsies, and is not associated with clinical diagnosis of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with high mortality. Liver involvement is common (based on elevated liver function tests) with most patients demonstrating acute hepatitis. Liver biopsies are frequently obtained in the setting of suspected HLH for the purpose of identification of erythrophagocytosis, and if present, this finding is thought to suggest or support the diagnosis of HLH. However, there are problems with this approach; in particular, we do not know whether this finding is reproducible or whether it is specific to HLH. Therefore, we conducted a multi-institutional study in which experienced liver pathologists reviewed images taken from liver biopsies from patients with normal liver, acute hepatitis, possible HLH, and clinical HLH to determine if there was agreement about the presence or absence of erythrophagocytosis, and to ascertain whether the finding corresponds to a clinical diagnosis of HLH. Twelve liver pathologists reviewed 141 images in isolation (i.e., no clinical information or diagnosis provided). These came from 32 patients (five normal, 17 acute hepatitis, six HLH, four possible HLH). The pathologists classified each image as negative, equivocal, or positive for erythrophagocytosis. Kappa was .08 (no agreement) for case-level and 0.1 for image-level (1.4% agreement, based on two images which were universally considered negative). There was no difference in the proportion of pathologists who diagnosed erythrophagocytosis among those with different diagnoses at case or image-level (p = 0.82 and p = 0.82, respectively). Thus, erythrophagocytosis is an entirely unreliable histologic parameter in liver, as it is irreproducible and not demonstrably associated with a clinical disease (namely, HLH). Unless and until more reliable guidelines can be established, pathologists should refrain from commenting on the presence or absence of erythrophagocytosis in liver biopsy.

Colorectal Carcinoma With Sarcomatoid Components: Report of 15 Cases and Literature Review of an Exceedingly Rare Carcinoma Subtype.

Colorectal carcinoma with sarcomatoid components (which includes so-called carcinosarcomas and sarcomatoid carcinomas) is a rare subtype with 50 reported cases in the literature and overlapping criteria with undifferentiated carcinoma. We collected and described 15 cases from 10 men and 5 women, with a mean age of 66 years. Symptoms included abdominal pain and gastrointestinal bleeding. Most tumors presented in the rectosigmoid region, with a mean size of 8.2 cm. The sarcomatoid component, on average, represented 58% of the tumors and took many forms, including spindled (10 cases), anaplastic (9 cases), and rhabdoid (3 cases); one case showed osteoid matrix. Tumor budding was usually high, and tumor-infiltrating lymphocytes were usually low. The sarcomatoid component was keratin-positive in 10 cases. One case showed loss of mismatch repair protein expression, and 2 cases showed SMARCA4 loss (1 also with SMARCA2 loss). Molecular testing identified mutations in KRAS (n=1), NRAS (n=2), BRAF (n=2), APC (n=1), and TP53 (n=1) in a few cases. Tumors often presented at advanced stage, with 11 cases pT4, 9 cases with nodal metastases, and 7 cases with distant metastases. Follow-up was available for 10 cases (median: 2 months), with 2 alive without disease, 3 alive with disease, and 5 dead. Our findings roughly corresponded with those in previously reported cases. Colorectal carcinoma with sarcomatoid components is rare and aggressive, with a poor prognosis for many patients. We suggest that spindled cells, anaplasia, heterologous elements, and/or a component with definable sarcomatous lineage be used to distinguish colorectal carcinoma with sarcomatoid components from undifferentiated carcinoma.

Debating Deposits, Redux: Substantial Interobserver Agreement Exists in Distinguishing Tumor Deposits From Nodal Metastases in Small Bowel Neuroendocrine Tumors.

CONTEXT.­: Recent data suggest mesenteric tumor deposits (MTDs) indicate poor prognosis in small bowel well-differentiated neuroendocrine tumors (SB-NETs), including compared to positive lymph nodes, making their distinction crucial. OBJECTIVE.­: To study interobserver agreement in distinguishing SB-NET MTDs from positive nodes. DESIGN.­: Virtual slides from 36 locally metastatic SB-NET foci were shared among 7 gastrointestinal pathologists, who interpreted each as an MTD or a positive node. Observers ranked their 5 preferred choices among a supplied list of potentially useful histologic features, for both options. Diagnostic opinions were compared using Fleiss multirater and Cohen weighted κ analyses. RESULTS.­: Preferred criteria for MTD included irregular shape (n = 7, top choice for 5), perineural invasion/nerve entrapment (n = 7, top choice for 2), encased thick-walled vessels (n = 7), and prominent fibrosis (n = 6). Preferred criteria for positive nodes included peripheral lymphoid follicles (n = 6, top choice for 4), round shape (n = 7, top choice for 2), peripheral lymphocyte rim (n = 7, top choice for 1), subcapsular sinuses (n = 7), and a capsule (n = 6). Among 36 foci, 10 (28%) each were unanimously diagnosed as MTD or positive node. For 13 foci (36%), there was a diagnosis favored by most observers (5 or 6 of 7): positive node in 8, MTD in 5. Only 3 cases (8%) had a near-even (4:3) split. Overall agreement was substantial (κ = .64, P < .001). CONCLUSIONS.­: Substantial interobserver agreement exists for distinguishing SB-NET MTDs from lymph node metastases. Favored histologic criteria in making the distinction include irregular shape and nerve/vessel entrapment for MTD, and peripheral lymphocytes/lymphoid follicles and round shape for positive nodes.

Lobular capillary hemangioma (pyogenic granuloma) of the gastrointestinal tract: Clinicopathologic analysis of 34 cases.

OBJECTIVES: Lobular capillary hemangioma (LCH) rarely involves the gastrointestinal (GI) tract. This study describes clinicopathologic features of LCH in a cohort of GI cases. METHODS: We defined lobular capillary hemangioma as "a proliferation of capillary-sized blood vessels arranged at least focally in a lobular configuration," searched departmental archives for cases, and recorded clinicopathologic findings. RESULTS: We identified 34 GI tract LCHs from 16 men and 10 women; 4 patients had multiple lesions. Mean age was 64 years. Cases arose in the esophagus (n = 7), stomach (n = 3), small bowel (n = 7), and colorectum (n = 17). Twelve patients had anemia or rectal bleeding. No patients had a known genetic syndrome. The lesions manifested as mucosal polyps, with median size of 1.3 cm. Microscopically, 20 lesions were ulcerated, and most involved the mucosa, with 9 extending into the submucosa. Vessel dilation was present in 27 patients, endothelial hobnailing in 13, hemorrhage in 13, and focal reactive stromal atypia in 2. Follow-up information was available for 10 patients, none of whom developed same-site recurrence. Six of the 26 cases (23%) were extradepartmental consultations, including 2 of the multifocal cases. CONCLUSIONS: Gastrointestinal tract LCHs often arise as colorectal polyps. They are typically small but can reach a few centimeters in size and can be multifocal.

Apoptosis, Crypt Dropout, and Equivocal Immunohistochemical Staining May Indicate Cytomegalovirus Infection in Inflammatory Bowel Disease Patients.

Cytomegalovirus (CMV) colitis superimposed on inflammatory bowel disease (IBD) can be challenging to diagnose. This study aimed to determine what histologic clues and immunohistochemistry (IHC) utilization practices, if any, can help diagnose CMV superinfection in IBD. Colon biopsies were reviewed from all patients with CMV colitis with and without IBD between 2010 and 2021 at one institution, along with a separate cohort of IBD patients with negative CMV IHC. Biopsies were assessed for histologic features of activity and chronicity, phlebitis, fibrin thrombi, basal crypt apoptosis, CMV viral cytopathic effect (VCE), and CMV IHC positivity. Features between groups were compared, with statistical significance set at P -value <0.05. The study included 251 biopsies from 143 cases (21 CMV-only, 44 CMV+IBD, 78 IBD-only). Compared with the IBD-only group, the CMV+IBD group was more likely to show apoptotic bodies (83% vs. 64%, P =0.035) and crypt dropout (75% vs. 55%, P =0.045). CMV was detected by IHC in 18 CMV+IBD cases without VCE on hematoxylin and eosin (41%). In the 23 CMV+IBD cases where IHC was performed on all concurrent biopsies, IHC was positive in at least 1 biopsy in 22 cases. Six individual CMV+IBD biopsies with no VCE on hematoxylin and eosin demonstrated equivocal IHC staining. Of these, 5 had evidence of CMV infection. IBD patients with superimposed CMV infection are more likely to demonstrate apoptotic bodies and crypt dropout compared with their noninfected counterparts. Equivocal IHC staining for CMV may indicate true infection in IBD patients, and staining multiple biopsies from the same accession can improve CMV detection.

Learning at a distance: results of an international survey on the adoption of virtual conferences and whole slide imaging by pathologists.

AIMS: This study presents the findings of a global survey of pathologists' views of online conferences and digital pathology. METHODS: An online anonymous survey consisting of 11 questions focusing on pathologists' perceptions of virtual conferences and digital slides was distributed to practising pathologists and trainees across the globe using the authors' social media accounts and professional society connections. Participants were asked to rank their preference for various aspects of pathology meetings on a 5-point Likert scale. RESULTS: There were 562 respondents from 79 countries. Several advantages of virtual meetings were recognised, including that they are less expensive to attend than in-person meetings (mean 4.4), more convenient to attend remotely (mean 4.3) and more efficient due to no loss of time for travel (mean 4.3). The lack of networking was reported as the main disadvantage of virtual conferences (mean 4.0). Most respondents (n=450, 80.1%) preferred hybrid or virtual meetings. About two-thirds (n=356, 63.3%) had no concern regarding the use of virtual slides for educational purposes and viewed them as an acceptable substitute for glass slides. CONCLUSIONS: Online meetings and whole slide imaging are viewed as valuable tools in pathology education. Virtual conferences allow affordable registration fees and flexibility for participants. However, networking opportunities are limited, meaning in-person meetings cannot be entirely replaced by virtual conferences. Hybrid meetings may be a solution to maximise the benefits of both virtual and in-person meetings.

Microvesicular hyperplastic polyp and sessile serrated lesion of the large intestine: a biological continuum or separate entities?

The range of lesions with a serrated appearance within the large intestine has expanded and become more complex over the last 30 years. The majority of these were previously known as metaplastic polyps but are today called hyperplastic polyps (HPs). HPs show two main growth patterns: microvesicular and goblet cell-rich. The former type shows morphological and molecular similarities (eg, BRAF mutations) to the more recently described sessile serrated lesion (SSL). In this review, we debate whether these lesions represent a biological spectrum or separate entities. Whichever view is held, microvesicular HPs and SSLs are distinct from the goblet cell-rich HP and the traditional serrated adenoma (TSA), which may themselves share molecular changes (eg, KRAS mutations), with the goblet cell-rich HP representing a precursor to the TSA. Both SSLs and the goblet cell-rich HP-TSA pathway are routes to colorectal cancer within the serrated pathway and overlaps between them can occur, for example, a (BRAF-mutated) TSA may arise from an SSL.

Submucosal Necrotic Nodule of the Colon: An Enigmatic Entity Potentially Related to Anisakis Infection.

CONTEXT.­: Discrete submucosal necrotic nodules may rarely manifest as colon polyps. OBJECTIVE.­: To characterize the clinical and pathologic features of this lesion, which has been under-studied in the literature. DESIGN.­: We conducted an international search to compile a series. For each potential case, photomicrographs were centrally reviewed to confirm the diagnosis. We gathered clinical and pathologic information on each confirmed case. RESULTS.­: The final cohort included 25 patients, with 23 having 1 lesion and 2 having several (31 lesions total). Mean patient age was 62 years; 13 patients (52%) were male. Symptoms were nonspecific, although 4 patients (16%) had blood in stool; 14 patients were asymptomatic. Patient history and medications appeared noncontributory. Most cases were located in the right colon (n = 18; 58%). Mean lesion size was 0.4 cm (range, 0.1-1.7 cm). Histology typically showed a centrally necrotic nodule with peripheral fibrosis, chronic inflammation, and sometimes palisading granulomatous inflammation. Percent necrosis ranged from 5% to 95% (average, 70%), and percent fibrosis ranged from 3% to 70% (average, 25%). In 3 cases, degenerated parasitic structures consistent with Anisakis could be seen on hematoxylin-eosin and trichrome special stain. No patient experienced disease recurrence. CONCLUSIONS.­: Submucosal necrotic nodules can present as colon polyps. Most cases are unifocal, and patients do well on follow-up. At least some examples appear to be caused by Anisakis, implicating patient diet. Patients are often asymptomatic, and many cases show no histologic evidence of the causative agent.

Practice patterns for reporting digestive system neuroendocrine neoplasms: results from a large, comprehensive international survey.

AIMS: Criteria for the interpretation of digestive system neuroendocrine neoplasms (NENs) continue to evolve. Although there are some literature recommendations regarding workup and diagnosis of these lesions, different practice patterns exist among pathologists when signing out these specimens. The aim of this study was to assess practice trends among pathologists worldwide when reporting these neoplasms. METHODS AND RESULTS: We created an online survey with multiple questions pertaining to digestive NENs. The results were analysed based on type of practice setting, years of sign-out experience, and practice location. Respondents included 384 practicing pathologists: 70% academic, 30% private practice; 63% gastrointestinal (GI) pathology-subspecialised, 37% not; 39% North American, 42% European, 19% others; 45% with ≤10 years in practice; 55% with >10 years. Some question responses were chosen by the majority (e.g. 85% use both mitotic count and Ki67 index for grading NENs, 82% complete a synoptic, and Ki67 stain even for small incidental appendiceal neuroendocrine tumours [NETs], and 96% utilize the diagnosis of grade 3 NET). However, some questions showed varying responses, including counting mitotic figures, Ki67 stain interpretation, and pancreatic grade 3 NEN workup. Pathologists also had some variability in interpreting regional metastatic foci of small bowel NETs and in choosing blocks for Ki67 staining in multifocal lesions. CONCLUSION: There existed scenarios wherein practice patterns varied despite recommendations in the literature, and there were also scenarios lacking clear guidelines wherein pathologists used varying judgement. This survey highlights current key grey areas in digestive system NEN evaluation, leading to variation in practice patterns.

Anal intraepithelial neoplasia: a review of terminology, differential diagnoses, and patient management.

Despite the knowledge of etiological association with high-risk human papilloma viruses and high-risk patient cohorts, the incidence of anal squamous cell carcinoma has continued to rise. The known precursor lesion (in particular, high-grade squamous intraepithelial lesion) makes it amenable to screening and surveillance strategies. However, the diagnosis of anal intraepithelial neoplasia suffers from interpretation challenges leading to high interobserver variability, along with numerous differential diagnoses and lingering terminology issues. Proper treatment of anal lesions requires accurate diagnosis, and while a variety of modalities are available for treatment, the rate of recurrence remains high and each modality has its own set of side effects and complications. The aim of this review article is to outline the diagnostic considerations and provide practical tips for diagnosing anal squamous intraepithelial lesions.

Gastric Histopathologic Findings Are Similar in Portal Hypertension Patients With and Without Endoscopic Portal Hypertensive Gastropathy.

OBJECTIVES: Portal hypertensive gastropathy (PHG) is a diagnosis made based on endoscopic findings in the appropriate clinical setting. Biopsy may be taken during endoscopy for correlation, but the pathologist may encounter a myriad of nonspecific histologic findings. We undertook this study to evaluate contexts where a histologic diagnosis of PHG might be rendered on biopsy. METHODS: Two cohorts were established: stomach biopsy specimens from patients with cirrhosis or undergoing varices screening (n = 188) and stomach biopsy specimens with findings interpreted as PHG in the pathology report (n = 29). RESULTS: In the first cohort, cases with endoscopic varices more frequently displayed foveolar hyperplasia and acute inflammation, with no other histologic differences between cases with and without endoscopic PHG, clinical varices, and clinical cirrhosis. Cases from the second cohort showed no histologic differences when stratified for endoscopic PHG, endoscopic varices, and clinical cirrhosis. Our second cohort displayed the majority of charted histologic findings more frequently than the first. Our results indicate that neither an endoscopic appearance of PHG nor particular clinical diagnoses associated with PHG translate into specific histologic findings. CONCLUSIONS: Although the histologic findings charted displayed increased frequency in pathology reports with an interpretation of PHG, histology should not be used reliably in the diagnosis of PHG.