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1.
Clin Transl Gastroenterol ; 12(5): e00360, 2021 05 24.
Article in English | MEDLINE | ID: mdl-34029233

ABSTRACT

INTRODUCTION: Effective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (CRC and advanced adenomas [AA]). However, existing noninvasive screening approaches cannot accurately detect adenomas with high sensitivity. METHODS: Here, we describe a multifactor assay (RNA-FIT test) that combines 8 stool-derived eukaryotic RNA biomarkers, patient demographic information (smoking status), and a fecal immunochemical test (FIT) to sensitively detect advanced colorectal neoplasias and other non-advanced adenomas in a 1,305-patient, average-risk, prospective cohort. This cohort was supplemented with a 22-patient retrospective cohort consisting of stool samples obtained from patients diagnosed with AA or CRC before treatment or resection. Participants within these cohorts were evaluated with the RNA-FIT assay and an optical colonoscopy. RNA-FIT test results were compared with colonoscopy findings. RESULTS: Model performance was assessed through 5-fold internal cross-validation of the training set (n = 939) and by using the model on a hold out testing set (n = 388). When used on the hold out testing set, the RNA-FIT test attained a 95% sensitivity for CRC (n = 22), 62% sensitivity for AA (n = 52), 25% sensitivity for other non-AA (n = 139), 80% specificity for hyperplastic polyps (n = 74), and 85% specificity for no findings on a colonoscopy (n = 101). DISCUSSION: The RNA-FIT assay demonstrated clinically relevant detection of all grades of colorectal neoplasia, including carcinomas, AAs, and ONAs. This assay could represent a noninvasive option to screen for both CRC and precancerous adenomas.


Subject(s)
Biomarkers, Tumor/analysis , Colorectal Neoplasms/diagnosis , Feces/chemistry , Immunochemistry/methods , RNA/analysis , Adult , Aged , Aged, 80 and over , Early Detection of Cancer/methods , Female , Humans , Male , Mass Screening/methods , Middle Aged , Prospective Studies , Retrospective Studies , Sensitivity and Specificity , Smoking , Socioeconomic Factors
2.
Am J Surg Pathol ; 39(12): 1668-72, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26291509

ABSTRACT

Tactile corpuscle-like bodies (TCLB) are microscopic Schwannian structures that simulate the superficial mechanoreceptors of the peripheral nervous system (Wagner-Meissner corpuscles). They have been described nearly exclusively in peripheral nerve sheath tumors, namely diffuse neurofibromas, and schwannomas but also in cellular nevi. There are rare reports of these structures in the gastrointestinal tract (predominantly the lower tract), with the presumption that they are incidental reactive neural proliferations. We compiled 9 cases showing this rare phenomenon in gastrointestinal-type mucosa in nonsyndromic patients to further characterize its features. There were 6 men and 3 women (age range, 39 to 79 y, mean 56 y) with lesions involving esophagus/gastro-esophageal junction (n=7), sigmoid colon (n=1), and gastric heterotopia of the cricopharynx (n=1). Endoscopic examination was abnormal in 6 of the 7 cases (including changes consistent with Barrett esophagus and polypoid/nodular mucosa) and normal in 1 of 7 cases for which this information was available. The histologic features were similar in all cases, with unencapsulated clusters of lamellated and concentrically arranged spindle cells in the lamina propria. The foci of TCLB ranged in size from <0.1 to 1.5 mm in the greatest dimension. Abnormal histopathologic findings were identified in the background mucosa in 6 of 9 cases (including Barrett esophagus, active and inactive chronic gastritis, enterochromaffin-like cell hyperplasia, and gastric intestinal metaplasia). None of the patients showed signs of neurofibromatosis type 1, multiple endocrine neoplasia type 2B, Cowden syndrome, or other inherited syndrome. No morbidity related to TCLB was reported for the patients with available follow-up.


Subject(s)
Gastrointestinal Tract/pathology , Mechanoreceptors/pathology , Schwann Cells/pathology , Adult , Aged , Biomarkers/analysis , Biopsy , Cell Lineage , Diagnosis, Differential , Endoscopy, Gastrointestinal , Female , Gastrointestinal Tract/chemistry , Humans , Immunohistochemistry , Incidental Findings , Male , Mechanoreceptors/chemistry , Middle Aged , Mucous Membrane/chemistry , Mucous Membrane/pathology , Predictive Value of Tests , Regeneration , Schwann Cells/chemistry , United States
3.
Ultrastruct Pathol ; 38(2): 74-82, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24144157

ABSTRACT

Canalicular adenoma (CA) is a rare, benign epithelial neoplasm of the salivary glands. Historically considered to be a variant of basal cell adenoma, this "monomorphic" adenoma has a distinct clinical, morphologic, and immunohistochemical profile. The putative cell of origin remains a topic of debate. A combination of morphology, immunohistochemistry, and ultrastructural analyses have been employed to determine histogenesis, but the interpretations of these studies have implicated multiple different cell types along the salivary gland duct as the cell of origin. The authors sought to further characterize CA using electron microscopy, immunohistochemistry, and special and immuno-stains on 7 cases. Their morphologic, immunohistochemical, and ultrastructural findings support a cell of origin demonstrating features of both the intercalated duct cells and the striated duct luminal epithelial cells.


Subject(s)
Adenoma/ultrastructure , Salivary Gland Neoplasms/ultrastructure , Adenoma/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Female , Humans , Immunohistochemistry , Male , Microscopy, Electron, Transmission , Middle Aged , Salivary Gland Neoplasms/metabolism
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