The histological spectrum of ARB-induced gastritis.

AIMS: Olmesartan, an angiotensin receptor blocker (ARB) used for hypertension management, is known to cause a sprue-like enteropathy in a subset of patients. Rare cases of gastritis occurring with ARB use have also been reported, but the histological features of ARB-induced gastritis and the response to drug cessation have not been examined in a dedicated case-series. METHODS AND RESULTS: Cases of suspected ARB-induced gastritis were identified from the pathology archives of four institutions. Haematoxylin and eosin (H&E) slides from gastric biopsies were reviewed. Fifteen patients (14 female, one male) were identified. The most common presenting symptoms were diarrhoea (10) and weight loss (six). Gastric biopsies commonly showed a full-thickness active chronic gastritis with surface epithelial injury involving the antrum and body. Glandular atrophy, intra-epithelial lymphocytosis and/or subepithelial collagen thickening were also present in some cases. Duodenal involvement, including villous atrophy, intra-epithelial lymphocytosis and/or collagenous sprue, was identified in 11 of 13 cases with concurrent duodenal biopsies. Following drug cessation, symptomatic improvement occurred in all 11 cases for which follow-up data were available. Histological resolution occurred in five of eight cases with follow-up gastric biopsies, with improvement seen in the remaining three biopsies. CONCLUSION: ARB-induced gastritis typically presents as active chronic gastritis, frequently with associated surface epithelial injury. Glandular atrophy, intra-epithelial lymphocytosis and/or subepithelial collagen thickening may also be present. These gastric changes can be seen without associated duodenal injury in rare cases, and they should alert the pathologist to the possibility of ARB-induced injury. Drug cessation results in marked symptomatic and histological improvement.

Oncocytoma-Like Angiomyolipoma of the Kidney: A Closer Look into the Clinicopathologic, Immunohistochemical, and Molecular Characteristics of a Rare Entity with Review of the Literature.

Introduction. Angiomyolipoma (AML) is a mesenchymal neoplasm that belongs to the perivascular epithelioid cell tumor family (PEComa). AMLs can be subtyped into several patterns dependent on cell type, morphology, and tissue composition. One of the patterns, oncocytoma-like AML is a rare entity with only three cases published in the literature. Case presentation. We present a case of a previously healthy 29-year-old woman who underwent a left partial nephrectomy secondary to a 4.6 cm heterogeneous renal neoplasm. Gross examination demonstrated a well-circumscribed renal mass. Modified Giemsa stain preparation showed oncocytic cells in syncytial pattern with ample granular cytoplasm and round nuclei with prominent nucleoli. Histology assessment showed an oncocytic neoplasm with interspersed adipose tissue. The tumor exhibited tubular architecture with the tubules lined by eosinophilic epithelioid cells with nuclear atypia and prominent nucleoli. Thick blood vessels with emanating epithelioid cells were present. High-grade histology features were not identified. The tumor cells were positive for HMB-45 and SMA and negative for PAX8, keratins, KIT, and vimentin. A diagnosis of oncocytoma-like AML was rendered. Next-generation sequencing (NGS) and RNA fusion were performed. NGS revealed no pathogenic variants and RNA fusion identified no rearrangements. Chromosomal copy number alterations were present in the long arm of chromosome 1 (1p) and chromosome 22. Conclusions. We describe and discuss the clinical, cytomorphologic, histologic, and molecular findings of oncocytoma-like AML, a rare renal neoplasm, and provide a review of the literature.

The utility of the dilute prothrombin time in the interpretation of antiphospholipid syndrome testing.

OBJECTIVES: To evaluate the utility of the dilute prothrombin time (DPT) in diagnosing antiphospholipid syndrome (APS), alone and when paired with the dilute Russell viper venom time (DRVVT). METHODS: Dilute prothrombin time and DRVVT testing was performed on plasma samples spiked with apixaban or rivaroxaban, or depleted of vitamin K-dependent clotting factors. A retrospective analysis of all functional APS testing results over a 44-month period at the University of Chicago Medical Center was performed. RESULTS: In spiking studies, the screening clotting time in the DPT (DPTS) is more sensitive to deficiency of vitamin K-dependent factors than is the screening clotting time in the DRVVT (DRVVTS). The converse is true for factor Xa direct oral anticoagulant (DOAC)-spiked plasma. In a 44-month retrospective analysis, only 2.6% of clinical APS panels showed isolated positivity in the DPT-based system. Comparing the DPT-based system with the DRVVT-based system showed utility in identifying false-positive DRVVT results due to anticoagulation. A DRVVTS/DPTS ratio of 0.785 or lower predicted an international normalized ratio of 1.5 or higher (sensitivity, 86.3%; specificity, 60.4%; likelihood ratio, 2.18). Conversely, a DRVVTS/DPTS ratio of 1.165 or higher was the optimal cutoff for predicting the identification of factor Xa DOAC (sensitivity, 61.8%; specificity, 77.8%; likelihood ratio, 2.78). Within the data set that had full DRVVT and DPT results, parameters were identified that could further improve identification of samples with anticoagulation interference. CONCLUSIONS: Dilute prothrombin time lupus anticoagulant assay is rarely the sole laboratory functional evidence for APS, but when combined with the DRVVT, the DPT can serve as an effective screen for common anticoagulant interference.

Fate of nondiagnostic thyroid fine needle aspirations.

BACKGROUND: Thyroid nodules may be detected during the workup of thyroid hormone abnormalities and as incidental findings during unrelated imaging studies. The diagnosis of a thyroid nodule is mainly established by performing fine needle aspiration (FNA) under ultrasound guidance. Thyroid nodules are classified as nondiagnostic, defined in the Bethesda System for Reporting Thyroid Cytopathology as samples with excess blood, cyst fluid only, and lack of thyroid follicular cells. The current study evaluates a series of nondiagnostic FNAs to assess whether repeat sampling improves yield and what patient management, and outcomes are after a nondiagnostic FNA. METHODS: Thyroid FNAs from 2016 to 2023 were retrieved from our institution archives. All cases were performed under ultrasound guidance and with rapid on-site evaluation. Cases were assigned the Bethesda System Category. Nondiagnostic FNAs were further reviewed for repeat FNA procedures, potential molecular testing, or diagnostic resections. RESULTS: In total 3104 thyroid FNAs were reviewed, with 153 (4.9%) being nondiagnostic. Of the 154 FNAs, there were 129 patients with an average age of 60 and a male-to-female ratio of 1:3.2. Of the 130 patients, there were 50 patients who underwent 55 repeat FNAs. Thirty-seven (67%) of the repeats were benign, 13 (24%) were nondiagnostic again, and 5 (9%) were atypia of undetermined significance (AUS). Molecular testing was performed on repeat FNAs diagnosed AUS. Four cases showed no mutations and had a high likelihood of being benign. One case did have an NRAS Q61R mutation, and resection revealed a noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Seventeen (13% of all cases) with nondiagnostic FNA were resected. Twelve (71%) thyroidectomies showed benign adenomatous nodules. The remainder showed incidental papillary thyroid microcarcinoma (0.1 cm), an infarcted follicular adenoma, a noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and metastatic renal cell carcinoma (2×). CONCLUSION: Thyroid nodules with nondiagnostic cytology are reassuring of being highly likely a benign nodule. Only 5 of the 55 (9%) repeat FNAs yielded abnormalities, with only one of those being truly a follicular neoplasm (confirmed by molecular testing and resection). No primary thyroid malignancies have been identified in follow-up (repeat FNA or surgery). Clinical and ultrasound follow-up may be more appropriate management for nondiagnostic thyroid FNAs.

Dysplasia Detected in Patients With Serrated Epithelial Change Is Frequently Associated With an Invisible or Flat Endoscopic Appearance, Nonconventional Dysplastic Features, and Advanced Neoplasia.

The significance of serrated epithelial change (SEC), defined as endoscopically invisible hyperplastic polyp (HP)-like mucosal change identified in patients with inflammatory bowel disease (IBD), remains unclear. Although some studies reported an increased risk of synchronous and/or metachronous colorectal neoplasia in patients with SEC, including advanced neoplasia (high-grade dysplasia or colorectal cancer), the development of SEC is not significantly associated with increased colonic inflammation. This contrasts with the reported positive correlation between increased colonic inflammation and the risk of colorectal neoplasia in ulcerative colitis, arguing against the notion that SEC may represent a form of dysplasia. As such, this study aimed to characterize the features of synchronous and metachronous dysplasia detected in patients with SEC to identify factors contributing to the increased risk of colorectal neoplasia, including advanced neoplasia, observed in a subset of these patients. Clinicopathologic features of 46 IBD patients with SEC (n=109) and synchronous and/or metachronous dysplasia (n=153) were analyzed. All dysplastic lesions were subtyped as either conventional or nonconventional dysplasia. As controls, 45 IBD patients with endoscopically visible or polypoid HP (n=75) and synchronous and/or metachronous dysplasia (n=87) were analyzed. The SEC group included 28 (61%) men and 18 (39%) women with a mean age of 58 years and a long history of IBD (mean duration: 23 years). The majority of patients (n=34; 74%) had ulcerative colitis, and 12 (26%) had Crohn's disease. Thirty-nine (85%) patients had a history of pancolitis, and 2 (4%) had concomitant primary sclerosing cholangitis. Twenty-seven (59%) patients had multifocal SEC. SEC was predominantly found in the left colon (n=52; 48%) and rectum (n=34; 31%). Dysplasia in the SEC group was often endoscopically invisible or flat (n=42; 27%) and demonstrated nonconventional dysplastic features (n=49; 32%). Six nonconventional subtypes were identified in the SEC group, including 17 (11%) dysplasia with increased Paneth cell differentiation, 12 (8%) hypermucinous dysplasia, 8 (5%) crypt cell dysplasia, 7 (5%) goblet cell deficient dysplasia, 3 (2%) sessile serrated lesion-like dysplasia, and 2 (1%) traditional serrated adenoma-like dysplasia. Advanced neoplasia was detected in 11 (24%) patients. The SEC group was more likely to have nonconventional dysplasia (32%, P<0.001), invisible/flat dysplasia (27%, P<0.001), and advanced neoplasia (24%, P<0.001) than the control group (7%, 2%, and 0%, respectively). High-risk nonconventional subtypes (ie, hypermucinous, crypt cell, and goblet cell deficient dysplasias) accounted for 18% of all dysplastic lesions in the SEC group, which were not seen in the control group (P<0.001). The SEC group (n=35; 76%) also had a higher rate of concordance between the location of SEC and the area of synchronous/metachronous dysplasia than the control group (n=22; 49%) (P=0.007). In conclusion, dysplasia detected in patients with SEC is often endoscopically invisible/flat (27%), nonconventional (32%, including the high-risk subtypes), and found in the same colonic segment as SEC (76%), which may in part explain why some patients with SEC are associated with an increased risk of colorectal neoplasia, including advanced neoplasia. The finding of SEC may warrant a careful follow-up colonoscopy with increased random biopsy sampling, especially in the segment of colon with SEC.