Hornick

Pagetoid spread in esophageal squamous epithelium associated with underlying esophageal adenocarcinoma (EAC) has been well studied. Case reports describing pagetoid spread of esophageal squamous cell carcinomas (ESCC) also exist in the literature. The latter, however, has not been systematically studied. In this study, we report seven cases of pagetoid spread associated with ESCC. The clinical, morphologic, and immunophenotypic profiles of pagetoid spread in the context of ESCC and EAC are compared. Cases of pagetoid spread of ESCC were identified through computerized search of pathology archives at five institutions...

Standard methods of variant assessment in hereditary cancer susceptibility genes are limited by the lack of availability of key supporting evidence. In cancer, information derived from tumors can serve as a useful source in delineating the tumor behavior and the role of germline variants in tumor progression. We have previously demonstrated the value of integrating tumor and germline findings to comprehensively assess germline variants in hereditary cancer syndromes. Building on this work, herein, we present the development and application of the INT2 GRATE|HPPGL platform...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. nab -Sirolimus is approved in the United States for the treatment of metastatic or locally advanced malignant perivascular epithelioid cell tumor (PEComa) on the basis of the primary analysis results of the phase II Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT) trial (ClinicalTrials...

BACKGROUND: People with cystic fibrosis (CF) are at increased risk for bronchiectasis, and several reports suggest that CF carriers may also be at higher risk for developing bronchiectasis. The purpose of this study was to determine if CF carriers are at risk for more severe courses or complications of bronchiectasis. METHODS: Using MarketScan data (2001-2021), we built a cohort consisting of 105 CF carriers with bronchiectasis and 300 083 controls with bronchiectasis but without a CF carrier diagnosis...

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PURPOSE: ERBB2 amplified colorectal cancer (CRC) is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic RAS/RAF alterations are not known. EXPERIMENTAL DESIGN: Dana-Farber and Foundation Medicine Inc. CRC cohorts with genomic profiling were used to identify ERBB2 amplified cases (Dana-Farber, n = 47/2,729 [1.7%]; FMI, n = 1857/49,839 [3.7%]). Outcomes of patients receiving HER2-directed therapies are reported (Dana-Farber, n = 9; Flatiron Health-Foundation Medicine clinicogenomic database, FH-FMI CGDB, n = 38)...

BACKGROUND: The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. METHODS: 305 newly-diagnosed EoE patients received standard (omeprazole 20mg daily), once-daily moderate (40mg daily), twice-daily moderate (20mg twice daily), or high (40mg twice daily) dose PPI for ≥8 weeks. RESULTS: 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate:52...

Immune suppression within tumor microenvironments (TME) have been implicated in limited efficacy of immune check point inhibitors (ICIs) against solid tumors. Down-regulated VentX expression in tumor associated macrophages (TAMs) underlies phagocytotic anergic phenotype of TAMs, which govern immunological state of TME. In this study, using a tumor immune microenvironment enabling model system (TIME-EMS) of non-small cell lung cancer (NSCLC), we found that PD-1 antibody modestly activates cytotoxic T lymphocytes (CTLs) within the NSCLC-TME but not the status of TIME...

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...

Soft tissue tumors form part of a challenging domain in diagnostic pathology owing to their comparative rarity, astonishing histologic diversity, and overlap between entities. Many of these tumors are now known to be defined by highly recurrent, or, in some instances, unique molecular alterations. Insights from gene profiling continue to elucidate the wider molecular landscape of soft tissue tumors; many of these advances have been co-opted by immunohistochemistry (IHC) for diagnostic applications. There now exists a multitude of antibodies serving as surrogate markers of recurrent gene fusions, amplifications, and point mutations, which, in certain settings, can replace the need for more resource and time-intensive cytogenetic and molecular genetic analyses...

BACKGROUND: Accurate diagnosis of pancreatic lesions by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy can be challenging. Although surrogate immunohistochemical markers for genetic alterations associated with pancreatic ductal adenocarcinoma (PDAC) have been identified, they have modest sensitivity. Biallelic loss of CDKN2A occurs in up to 46% of PDACs, and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) has been identified as a reliable surrogate marker for this alteration...

A survey was carried out on 356 breeders in the Department of the Menoua Region of West Cameroon to characterize guinea pig breeding systems, using descriptive analysis, factorial analysis of multiple correspondences (AFCM), and upward hierarchical classification (CAH). Three types of guinea pig breeders have been identified, discriminated according to the size of the herd and the professional character of the breeding. Most of the housing systems were of the traditional type, free-ranging on the ground. Feed generally was based on fodders and food residues, and hygiene conditions were considered as good...

Human poxvirus infections have caused significant public health burdens both historically and recently during the unprecedented global Mpox virus outbreak. Although vaccinia virus (VACV) infection of mice is a commonly used model to explore the anti-poxvirus immune response, little is known about the metabolic changes that occur in vivo during infection. We hypothesized that the metabolome of VACV-infected skin would reflect the increased energetic requirements of both virus-infected cells and immune cells recruited to sites of infection...

Lakes worldwide are affected by multiple stressors, including climate change. This includes massive loading of both nutrients and humic substances to lakes during extreme weather events, which also may disrupt thermal stratification. Since multi-stressor effects vary widely in space and time, their combined ecological impacts remain difficult to predict. Therefore, we combined two consecutive large enclosure experiments with a comprehensive time-series and a broad-scale field survey to unravel the combined effects of storm-induced lake browning, nutrient enrichment and deep mixing on phytoplankton communities, focusing particularly on potentially toxic cyanobacterial blooms...

AIMS: Angiofibroma of soft tissue (AFST) is a benign, morphologically distinctive tumour type that harbours recurrent AHRR::NCOA2 fusions in 60-70% of cases and shows a non-specific immunophenotype, expressing EMA in roughly half of cases. The AHRR::NCOA2 fusion results in increased expression of cytochrome P450 1A1 (CYP1A1); a recent study demonstrated CYP1A1 immunohistochemistry (IHC) to be moderately sensitive and highly specific for AFST. METHODS AND RESULTS: In this study, we sought to validate these findings in a larger independent cohort of 30 AFST, as well as 215 morphological mimics, including 30 solitary fibrous tumours, 29 myxoid liposarcomas, 28 low-to-intermediate grade myxofibrosarcomas (MFS), 20 atypical spindle cell lipomatous tumours (ASCLT), 20 cellular angiofibromas, 10 cases each of spindle cell lipoma, neurofibroma, malignant peripheral nerve sheath tumour, superficial angiomyxoma, cellular myxoma, soft tissue perineurioma and deep fibrous histiocytoma, and nine cases each of low-grade fibromyxoid sarcoma and mammary-type myofibroblastoma...

C-reactive protein (CRP) is an acute phase, predominantly hepatically synthesized protein, secreted in response to cytokine signaling at sites of tissue injury or infection with the physiological function of acute pro-inflammatory response. Historically, CRP has been classified as a mediator of the innate immune system, acting as a pattern recognition receptor for phosphocholine-containing ligands. For decades, CRP was envisioned as a single, non-glycosylated, multi-subunit protein arranged non-covalently in cyclic symmetry around a central void...

Thymic epithelial neoplasms are morphologically diverse and can pose a diagnostic challenge that is complicated by a lack of immunohistochemistry (IHC) markers that are entirely sensitive and specific for thymic epithelium. Polyclonal PAX8 is often used in this context, but it is not a specific marker. The PAX1 transcription factor shares significant homology with PAX8 and plays an integral role in thymic development in humans and murine models. This study evaluated the role of PAX1 IHC in differentiating thymic epithelial neoplasms from morphologic mimics on whole slide tissue sections...

BACKGROUND: Myxoid liposarcoma (LPS) has a unique tendency to spread to extrapulmonary sites, including osseous sites such as the spine, and adjacent sites such as the paraspinous tissue. No clear consensus exists to guide the approach to imaging in these patients. OBJECTIVE: The aim of this study was to investigate the rate and distribution of spine metastases in patients with myxoid LPS and detection modality. METHODS: Records of all patients with myxoid LPS evaluated at our sarcoma center were retrospectively reviewed...

Neuroendocrine tumors (NETs) are rare cancers that most often arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP)-NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation, and fate determination stages...

Sorghum Bicolor is a cereal used for grains as feed and food, mainly cultivated in dry areas. To study the possibilities of increasing its cultivation for feed purposes, ecological, morpho-agronomical, and bromatological characterization of some local ecotypes was conducted as the first steps toward selecting better cultivars. Indeed, twenty-one ecotypes were collected from farms in Northern Morocco in 2018. The edapho-climatic parameters of the collection sites were evaluated. The ecotypes were cultivated in 2019 in an experimental field with a randomized complete block design with three replicates...