A diagnostic stewardship approach to prevent unnecessary testing of an enteric bacterial molecular panel.

IMPORTANCE: Testing for enteric bacterial pathogens in patients hospitalized for more than 3 days is almost always inappropriate. Our study validates the utility of the 3-day rule and the use of clinical decision support tools to decrease unnecessary testing of enteropathogenic bacteria other than C. difficile. Overriding the restriction was very low yield. Our study highlights the importance of diagnostic stewardship and further refines the criteria for allowing providers to override the restriction while monitoring the impact of the interventions.

Inflammation and tissue remodeling contribute to fibrogenesis in stricturing Crohn's disease: image processing and analysis study.

BACKGROUND: Inflammation and structural remodeling may contribute to fibrogenesis in Crohn's disease (CD). We quantified the immunoexpression of calretinin, CD34, and calprotectin as a surrogate for mucosal innervation, telocytes (interstitial cells playing a role in networking), and inflammation, respectively, and correlated them with bowel alterations in stricturing CD. METHODS: Primary resection specimens for ileal CD (n = 44, 31 stricturing CD, 13 inflammatory CD) were identified. Left-sided ulcerative colitis and trauma cases were used as controls. Proximal and distal margin and middle (diseased) sections were stained for calretinin, CD34, and calprotectin. Microscopic images were captured from the mucosa (calretinin), submucosa (calprotectin), and myenteric plexus (CD34), and the immunostaining was quantified using image processing and analysis. Bowel thickness at the corresponding sections were measured and correlated with the amount of immunoexpression. RESULTS: A total of 2,037 images were analyzed. In stricturing CD, submucosal alteration/thickening at the stricture site correlated with calprotectin staining and inversely correlated with calretinin staining at the proximal margin. Muscularis propria alteration/thickening at the stricture site correlated with mucosal calretinin staining at the proximal margin. Submucosal alteration/thickening at the proximal margin correlated with calretinin and CD34 staining at the proximal margin and inversely correlated with CD34 staining at the stricture site. Calretinin immunostaining at the distal margin was significantly higher in stricturing CD than the controls. CONCLUSIONS: Inflammation and tissue remodeling appear to contribute to fibrogenesis in stricturing CD. Increased mucosal calretinin immunostaining distal to the diseased segment could be helpful in diagnosing CD in the right clinical context.

Low-grade non-intestinal-type sinonasal adenocarcinoma: a histologically distinctive but molecularly heterogeneous entity.

Although low-grade non-intestinal-type sinonasal adenocarcinoma (SNAC) is formally a diagnosis of exclusion defined by the absence of salivary or intestinal differentiation, most tumors in this category comprise a distinctive histologic group that are increasingly thought to derive from seromucinous glands. However, the molecular underpinnings of SNAC remain poorly understood, and it is unclear if diverse genetic alterations recently reported in isolated cases should delineate separate subgroups. This study aims to perform comprehensive evaluation of gene fusions and mutations and their histologic correlates in low-grade SNAC to clarify its pathogenesis and classification. We identified 18 non-intestinal-type SNAC that all displayed characteristic tubulopapillary architecture and low-grade cytology, although several cases had other unique histologic features and 3 showed intermixed high-grade areas. Among tumors stained with S100 protein, SOX10, and DOG1, 86% expressed at least one of these seromucinous markers. Of 17 cases with sufficient RNA or DNA available for analysis, likely oncogenic molecular alterations were identified in 76% of cases, most notably including CTNNB1 p.S33F mutations in 2 cases, concomitant BRAF p.V600E and AKT1 p.E17K mutations in 2 cases, and ETV6::NTRK3, PRKAR1A::MET, FN1::NRG1, and DNAJB1::PRKACA fusions in 1 case each. While tumors with most genetic alterations were histologically indistinguishable, cases with CTNNB1 mutations had intermixed squamoid morules and cases with BRAF and AKT1 mutations showed a myoepithelial cell population and prominent papillary to micropapillary architecture. Overall, these findings confirm previous reports of frequent seromucinous differentiation in low-grade SNAC. However, these tumors display striking molecular diversity with involvement of multiple kinase fusions, leading to frequent activation of signaling cascades including the MAPK pathway. While most genetic alterations are not associated with sufficiently distinctive histologic features to suggest separate classification, biphasic tumors with BRAF p.V600E mutations are more unique and may represent a distinctive subgroup.

COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.

BACKGROUND: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). METHODS: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. RESULTS: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). CONCLUSIONS: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.

Pyloric gland metaplasia: Potential histologic predictor of severe pouch disease including Crohn's disease of the pouch in ulcerative colitis.

Crohn's disease of the pouch (CDP) is seen in a subset of ulcerative colitis (UC) patients following ileal pouch-anal anastomosis (IPAA). Histologic or clinical predictors of CDP are unknown. UC patients with subsequent CDP diagnosis were identified. The rationales for the diagnosis, the interval from the initial signs of CDP to the diagnosis, family history and smoking history were reviewed. Archived pathology materials were reviewed for the presence of pyloric gland metaplasia (PGM) and compared with those from UC with similar severity of pouchitis with CDP (matched UC controls), random UC controls, and ileocolectomies from primary CD patients. CDP diagnosis was made in 26 (18.1%) of 144 patients; all of them met commonly used diagnostic criteria for CDP. The diagnosis was rendered on average 15 months after the initial CD-like signs. PGM was found in 58% of CDP, more common than random UC controls but no different from primary CD and matched UC controls. PGM preceded first signs of CD in a subset. Patients with a family history of CD were more likely to develop CDP than those without a family history of any type of inflammatory bowel disease. Smoking status did not affect the likelihood of developing CDP. Finding PGM in proctocolectomy, ileostomy and follow-up biopsies in UC patients post IPAA may warrant close follow up for the potential development of pouchitis. Some of these patients, especially those with family history of CD, may further progress and develop severe disease meeting the clinical diagnostic criteria for CDP.

Increased Cytoplasmic Yes-associated Protein (YAP) Expression in Mismatch Repair Protein-Proficient Colorectal Cancer With High-grade Tumor Budding and Reduced Autophagy Activity.

Yes-associated protein (YAP) is a transcriptional coactivator regulated by autophagy that stimulates colorectal cancer (CRC) progression through activation of epithelial-mesenchymal transition (EMT), represented by tumor budding. The associations between these components in CRC are unknown. Archived surgically resected CRCs with known mismatch repair protein (MMR) status were retrieved (n=81; 2010 to 2016). Electronic medical records were reviewed for clinicopathologic variables including pathologic TNM stage and clinical stage. Tumor budding was graded according to consensus guidelines. Cytoplasmic and nuclear YAP and p62 (autophagy substrate) immunoreactivity were semiquantitatively scored within tumor samples. The Student t test, Fisher exact test, χ2 test, and Spearman correlation coefficient were performed with P<0.05 as a significance level. MMR proficiency (MMR-P) status correlated with high-grade tumor budding. The extent of cytoplasmic YAP staining and pathologic N stage was associated with tumor budding in multivariate analysis. Cytoplasmic YAP expression correlated with higher cytoplasmic p62 expression, suggesting an inverse correlation between autophagy activation and cytoplasmic YAP expression. Nuclear YAP expression correlated with pathologic N stage and clinical stage. A correlation between MMR-P status and tumor budding, combined with correlations between cytoplasmic YAP, tumor budding and p62 raise the possibility of 2 distinct neoplastic pathways concerning autophagy and YAP; one displaying relative activation of YAP and EMT, being commonly observed in MMR-P, and another with less active YAP and EMT, but active autophagy, being commonly seen in MMR-deficient CRC. Nuclear YAP staining could be useful in prognostication.