In Search of Nodular Gastric Antral Vascular Ectasia: A Distinct Entity or Simply Hyperplastic Polyps Arising in Gastric Antral Vascular Ectasia?

CONTEXT.­: Nodular gastric antral vascular ectasia (GAVE) is a reported phenotype of GAVE that has histologic features overlapping with gastric hyperplastic polyps (GHPs), with additional features often seen in flat mucosa of GAVE. OBJECTIVE.­: To determine if nodular GAVE and GHPs are distinct lesions by evaluating the prevalence of features reported in nodular GAVE in GHPs with or without associated GAVE. DESIGN.­: A review of all lesions diagnosed as GHPs between 2014 and 2017 was performed. Slides were analyzed for a number of features including established histologic features of GAVE without knowledge of clinical or endoscopic features. RESULTS.­: A total of 90 polyps were analyzed including 18 from patients with GAVE (20%). GAVE polyps were larger than non-GAVE polyps (average size, 1.3 cm versus 0.68 cm; P < .001), with more common extensive ulceration and associated granulation tissue (61.11% [n = 11] versus 4.17% [n = 3]; P = .004), fibrin thrombi (50% [n = 9] versus 15% [n = 11]; P = .003), moderate to marked vascular ectasia (83% [n = 15] versus 35% [n = 11]; P = .001), and fibrohyalinosis (72% [n = 13] versus 28% [n = 20]; P = .001). All polyps showed foveolar hyperplasia and smooth muscle proliferation. There were no features that were exclusively found in GAVE or non-GAVE cases. CONCLUSIONS.­: Nodular GAVE appears to represent GHPs arising in a background of GAVE, with superimposed features found in flat mucosa of GAVE stomachs. The presence of fibrin thrombi, marked vascular ectasia, fibrohyalinosis, and/or ulceration in a GHP is suggestive but not diagnostic of GAVE, and the absence of these features does not rule out GAVE.

Fecal Microbiota Restoration Modulates the Microbiome in Inflammation-Driven Colorectal Cancer.

Chronic inflammation of the colon (colitis) is a known risk factor for inflammatory-driven colorectal cancers (id-CRCs), and intestinal microbiota has been implicated in the etiology of id-CRCs. Manipulation of the microbiome is a clinically viable therapeutic approach to limiting id-CRCs. To understand the microbiome changes that occur over time in id-CRCs, we used a mouse model of id-CRCs with the treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS) and measured the microbiome over time. We included cohorts where the microbiome was restored using cage bedding swapping and where the microbiome was depleted using antibiotics to compare to untreated animals. We identified consistent increases in Akkermansia in mice receiving horizontal microbiome transfer (HMT) via cage bedding swapping, while the control cohort had consistent longitudinal increases in Anaeroplasma and Alistipes. Additionally, fecal lipocalin-2 (Lcn-2), a marker of intestinal inflammation, was elevated in unrestored animals compared to restored and antibiotic-treated counterparts following HMT. These observations suggest a potential role for Akkermansia, Anaeroplasma, and Alistipes in regulating colonic inflammation in id-CRCs.

Successful management of cervical dysgenesis: Case report and review.

Cervical agenesis or dysgenesis is a rare Mullerian anomaly that is usually associated with vaginal aplasia. A literature review revealed reports of 83 cases including ours, of which 57 (68.6%) presented with obstruction of the external OS, 11 (13.2%) had the cervix replaced by a fibrous cord and 5 (6.02%) had a fragmented cervix. A total of 24 (28.9%) were managed by core and drilling technique (CDT), 16(19.2%) patients underwent uterovaginal anastomosis (UVA), 7(8.4%) underwent total abdominal hysterectomy preserving the ovaries and 5 (6.02%) were managed by cervical reconstruction. Unfortunately, 31 failed to return after their clinical and radiological diagnosis was confirmed. Early diagnosis and treatment are necessary to avoid long-term complications.

Effects of COVID-19 pandemic on cytology: specimen adequacy in fine-needle aspiration of palpable head and neck masses.

INTRODUCTION: At our institution, palpation-guided fine-needle aspiration (FNA) is performed by the cytopathology service on an outpatient basis at the request of otolaryngologist surgeons. The aim of this study is to assess the effect of COVID lockdown measures on our FNA service with specific focus on adequacy rates. MATERIALS AND METHODS: All palpation-guided FNA performed in 2019 to 2020 were identified in our pathology database. Adequacy rates were compared for 3 time periods in 2020: pre-COVID, lockdown, and post-lockdown. RESULTS: In 2019, 121 FNAs were performed with 98% (119 of 121) obtained by pathology and only 2% (2 of 121) obtained by surgeons. In 2020, 89 FNAs were performed with 45% (40 of 89) collected by pathologists and 55% (49 of 89) by surgeons. During the pre-COVID period of 2020, 27 FNAs were collected, 85% (23 of 27) by pathologists, 8.7% of these (2 of 23) were nondiagnostic. Of the 4 FNAs performed by surgeons, all were positive for malignancy. During COVID lockdown all 24 FNAs were performed by surgeons with a 50% (12 of 24) nondiagnostic rate. Post-lockdown, with FNA referrals still below pre-COVID levels, surgeons performed 55.3% (21 of 38) of FNAs with 28.6% (6 of 21) non-diagnostic, while pathology performed 44.7% (17 of 38) with an 11.8% (2 of 17) nondiagnostic rate. CONCLUSIONS: Our FNA service noted significant changes in 2020 as a result of the COVID pandemic. Nondiagnostic rates were significantly increased in 2020 compared with 2019, primarily due to a shift to majority surgeon-performed palpation-guided FNA in the absence of cytopathology service during the lockdown period.

Tumour-associated macrophages drive stromal cell-dependent collagen crosslinking and stiffening to promote breast cancer aggression.

Stromal stiffening accompanies malignancy, compromises treatment and promotes tumour aggression. Clarifying the molecular nature and the factors that regulate stromal stiffening in tumours should identify biomarkers to stratify patients for therapy and interventions to improve outcome. We profiled lysyl hydroxylase-mediated and lysyl oxidase-mediated collagen crosslinks and quantified the greatest abundance of total and complex collagen crosslinks in aggressive human breast cancer subtypes with the stiffest stroma. These tissues harbour the highest number of tumour-associated macrophages, whose therapeutic ablation in experimental models reduced metastasis, and decreased collagen crosslinks and stromal stiffening. Epithelial-targeted expression of the crosslinking enzyme, lysyl oxidase, had no impact on collagen crosslinking in PyMT mammary tumours, whereas stromal cell targeting did. Stromal cells in microdissected human tumours expressed the highest level of collagen crosslinking enzymes. Immunohistochemical analysis of biopsies from a cohort of patients with breast cancer revealed that stromal expression of lysyl hydroxylase 2, an enzyme that induces hydroxylysine aldehyde-derived collagen crosslinks and stromal stiffening, correlated significantly with disease specific mortality. The findings link tissue inflammation, stromal cell-mediated collagen crosslinking and stiffening to tumour aggression and identify lysyl hydroxylase 2 as a stromal biomarker.

Optimization of Immunophenotypic Panel to Differentiate Upper From Lower Gastrointestinal Adenocarcinomas: Analysis of New and Traditional Markers.

Adenocarcinomas of the esophagus (EAC), stomach [gastric adenocarcinoma (GAC)], and colorectal carcinoma (CRC) frequently show similar morphology because upper gastrointestinal tumors (GITs) usually evolve from pathologies involving intestinal metaplasia. Upper and lower GIT may also show overlapping immunophenotypes when using the traditional CK7, CK20, and CDX2 panel, which in patients presenting with metastatic disease of unknown origin may lead to misdirected diagnostic workup and/or therapy. We compared the phenotype of upper and lower GIT using an expanded immunohistochemical panel that included the traditional and newer gastrointestinal markers: SATB2, DcR3, MUC5AC, and MUC6. The panel was applied to resection specimens from 40 CRC, 40 GAC, and 40 EAC. A panel using SATB2, CK7, and CDX2 provided the best discriminating power for separating upper from lower GIT and was applied to 101 biopsies including 17 EAC, 17 GAC, 19 CRC, 18 pancreatic adenocarcinomas, 15 cholangiocarcinomas, and 15 lung adenocarcinomas. The phenotype CK7/CDX2/SATB2 was moderately sensitive and highly specific of upper GIT, the phenotype CK7/CDX2/SATB2 was highly sensitive and specific for lower GIT, the phenotypes CK7/CDX2/SATB2 and CK7/CDX2/SATB2 favored pancreatobiliary or lung primaries. Less frequent phenotypes showed substantial overlap. Although strong diffuse expression of SATB2 was characteristic of CRC, weak and/or focal expression was present in one third or more of upper gastrointestinal, cholangiocarcinomas, and lung adenocarcinomas. DcR3, MUC5AC, and MUC6 improved specificity, but showed poor sensitivity, suggesting they should be used as second tier markers.

Performance of Ventana SP263 PD-L1 assay in endobronchial ultrasound guided-fine-needle aspiration derived non-small-cell lung carcinoma samples.

BACKGROUND: Introduction of programmed death-ligand 1 (PD-L1) inhibitors has significantly changed the treatment landscape of non-small-cell lung carcinomas (NSCLC). Since endobronchial ultrasound guided fine-needle aspiration (EBUS FNA) has become the primary diagnostic and staging modality for NSCLC, this study was pursued to determine the adequacy of Ventana SP263 PD-L1 assay in cytology cell blocks. DESIGN: Fifty NSCLC cases with cytology and corresponding histology specimens obtained between 2014 and 2018 were identified. After assessing for adequacy (100 or more tumor cells), forty cases were selected for Ventana SP263 PD-L1 immunohistochemistry (IHC) assay and assessed for tumor proportion scores (TPS) and staining intensity scores (SIS) and analyzed for concordance. RESULTS: Of the 40 matched pairs 33 (82.5%) showed concordant PD-L1 expression. On cytology, 32 cases were positive (8 high-expressors and 24 low-expressors) of which 27 were concordant and 5 discordant with matched histology specimens. On histology, 29 cases were positive (7 high-expressor and 22 low-expressors) while 11 cases were negative for PD-L1 expression of which 6 had concordant negative cytology. The intraclass correlation coefficients (ICC) for TPS was 0.81 with 95% confidence interval (0.68, 0.9) and for the SIS, it was 0.78 with 95% CI (0.62, 0.88), both considered as having excellent agreement. CONCLUSION: With an overall concordance rate of 82.5% between cytology and histology specimen, this study demonstrates the feasibility of PD-L1 IHC with SP263 clone on cytology samples of NSCLC and adds to a growing body of evidence validating the use of cytology cell blocks for PD-L1 expression testing.

Disseminated Hormographiella aspergillata Infection with Lung and Brain Involvement after Allogenic Hematopoietic Stem-Cell Transplantation in a 54-Year-Old Man.

Hormographiella is a rare fungal pathogen in humans; however, case reports have described disseminated infection in immunocompromised hosts. This pathogen has been described to yield poor prognosis in patients who harbor it. Herein, we present a case report of autopsy-proven disseminated Hormographiella aspergillata infection, confirmed by DNA sequencing, in a patient experiencing a relapse of leukemia. This 54-year-old Caucasian man with chronic myelogenous leukemia (CML) that had been diagnosed in 1989, after having received a hematopoietic cell allotransplant from a compatible sibling donor, had B-cell lymphoid-blast phase of CML in April of 2013, with multiple relapses. His most recent relapse was in September of 2016, when bone marrow biopsy showed 90% blasts. The results of bronchoalveolar lavage (BAL) cultures were positive for filamentous fungus infection. The patient developed encephalopathy and worsening respiratory statusand tachycardia with flutter and hypotension, which resulted in his death. At autopsy, bilateral pleural effusions, multiple right pleural nodules, and subarachnoid hemorrhage were noted. Angioinvasive hyphal fungi were found in the right frontal lobe of the brain and the right upper lobe of the lung. Morphologically, the fungi had multiseptate, branching hyphae. The bronchoalveolar lavage specimen grew a fungus for which the colony morphologic characteristics and microscopic features were compatible with a Hormographiella species. H. aspergillata from the bronchoalveolar lavage was further identified by sequencing the D2 hypervariable region of the large-subunit (LSU) ribosomal DNA gene and the full internal transcribed spacer (ITS) regions.

Pulmonary Tumourlets: Case Report and Review of Literature.

We report a case of tumourlets of the lung associated with carcinoid and neuroendocrine cell hyperplasia, found incidentally in a 30-year-old woman, who underwent bullectomy for pneumothorax. These lesions are histologically similar to carcinoid, but differ in molecular pathogenesis about which little is known. Their nature and significance is debated. Here, we point out the importance of histological, clinical, and diagnostic aspects and follow-up to have evidence of eventual malignant evolution.