Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 2.364
Filter
1.
Methods Cell Biol ; 186: 25-49, 2024.
Article in English | MEDLINE | ID: mdl-38705603

ABSTRACT

One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.


Subject(s)
Flow Cytometry , Gastrointestinal Neoplasms , Genomic Instability , Humans , Flow Cytometry/methods , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Genomic Instability/genetics , Precancerous Conditions/genetics , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , Tissue Fixation/methods , Paraffin Embedding/methods , DNA/genetics , DNA/analysis , Gastrointestinal Tract/pathology , Gastrointestinal Tract/metabolism , Barrett Esophagus/genetics , Barrett Esophagus/pathology , Barrett Esophagus/diagnosis
2.
Cell ; 187(8): 2010-2028.e30, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38569542

ABSTRACT

Gut inflammation involves contributions from immune and non-immune cells, whose interactions are shaped by the spatial organization of the healthy gut and its remodeling during inflammation. The crosstalk between fibroblasts and immune cells is an important axis in this process, but our understanding has been challenged by incomplete cell-type definition and biogeography. To address this challenge, we used multiplexed error-robust fluorescence in situ hybridization (MERFISH) to profile the expression of 940 genes in 1.35 million cells imaged across the onset and recovery from a mouse colitis model. We identified diverse cell populations, charted their spatial organization, and revealed their polarization or recruitment in inflammation. We found a staged progression of inflammation-associated tissue neighborhoods defined, in part, by multiple inflammation-associated fibroblasts, with unique expression profiles, spatial localization, cell-cell interactions, and healthy fibroblast origins. Similar signatures in ulcerative colitis suggest conserved human processes. Broadly, we provide a framework for understanding inflammation-induced remodeling in the gut and other tissues.


Subject(s)
Colitis, Ulcerative , Colitis , Animals , Humans , Mice , Colitis/metabolism , Colitis/pathology , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Fibroblasts/metabolism , Fibroblasts/pathology , In Situ Hybridization, Fluorescence/methods , Inflammation/metabolism , Inflammation/pathology , Cell Communication , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/pathology
3.
Radiologie (Heidelb) ; 64(5): 392-399, 2024 May.
Article in German | MEDLINE | ID: mdl-38598006

ABSTRACT

BACKGROUND: Developmental disorders of the gastrointestinal tract comprise a broad spectrum of congenital malformations of different etiologies and locations from the mouth to the anus. METHODS: The authors present the most important malformations of the gastrointestinal tract on the basis of basic and current reviews. RESULTS: Gastrointestinal developmental disorders occur both sporadically and in connection with malformation syndromes. Symptoms are highly variable and range from postnatal emergencies to asymptomatic abnormalities, which may be incidental radiological findings. Prenatal ultrasound examinations can often identify gastrointestinal developmental disorders at an early stage. Here, fetal magnetic resonance imaging can be a useful addition to the diagnostic process. In the first few days of life, simple X­ray overview images, supplemented by images after the administration of contrast medium, are often sufficient. CONCLUSION: Many patients with a malformation of the gastrointestinal tract require lifelong medical care, so that not only pediatric radiologists need specific knowledge about this group of diseases.


Subject(s)
Gastrointestinal Tract , Humans , Gastrointestinal Tract/abnormalities , Gastrointestinal Tract/diagnostic imaging , Gastrointestinal Tract/pathology , Gastrointestinal Diseases/diagnostic imaging , Gastrointestinal Diseases/diagnosis , Magnetic Resonance Imaging , Infant, Newborn , Digestive System Abnormalities/diagnostic imaging , Digestive System Abnormalities/diagnosis , Digestive System Abnormalities/complications , Female , Ultrasonography, Prenatal/methods
4.
BMC Pediatr ; 24(1): 203, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519924

ABSTRACT

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.


Subject(s)
Histiocytosis, Langerhans-Cell , Hypoalbuminemia , Child , Humans , Hypoalbuminemia/complications , Hypoalbuminemia/pathology , Histiocytosis, Langerhans-Cell/complications , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/pathology , Gastrointestinal Tract/pathology , Biopsy , Diarrhea/complications
5.
Sci Rep ; 14(1): 6468, 2024 03 18.
Article in English | MEDLINE | ID: mdl-38499629

ABSTRACT

Linear endoscopic ultrasonography (EUS) has been extensively utilized as a novel diagnostic and therapeutic modality across various fields. However, there have been relatively few studies focusing on lower gastrointestinal lesions. The aim of our study was to investigate the feasibility, safety and clinical value of linear EUS in the lower gastrointestinal subepithelial lesions. This was a retrospective study involving patients with lower gastrointestinal subepithelial lesions diagnosed by linear EUS from August 2019 to April 2023 at the Second Affiliated Hospital of Anhui Medical University. The data, including basic clinical information, linear EUS features, technical success rate, complications, and follow-up, were retrospectively collected and analyzed. A total of 69 patients with lower gastrointestinal subepithelial lesions underwent examination by linear EUS. Excluding the rectum, the technical success rate of linear EUS was 90.6% (29/32). Apart from the 7 patients whose diagnosis remained unknown, 3 patients with no abnormal EUS findings, and 3 patients failed the procedure, 56 patients were included in the final diagnostic performance analysis. The most common locations of the lesions were the rectum (37/56, 66.1%) and sigmoid colon (7/56, 12.5%). Based on endoscopy findings and pathological results, the most prevalent types of subepithelial lesions in the lower gastrointestinal tract were neuroendocrine tumor (NET) (12/56, 20.3%), lipoma (8/56, 13.6%) and extraluminal compression (8/56, 13.6%). The majority of lesions ranged in diameter from 1 to 3 cm (χ2 = 18.750, p < 0.001). After undergoing linear EUS examination, 36 patients received EUS-FNA (3/36), biopsy (5/36), endoscopic resection (25/36), or surgical excision (3/36) respectively. The pathological results of 29 patients were entirely consistent with the diagnosis made using linear EUS, with an 80.6% (29/36) diagnostic accuracy rate. Follow-up indicated that the lesions remained unchanged within 6-36 months. All patients tolerated the procedure well without any complications. In conclusion, linear EUS demonstrates technical feasibility, safety, and a high diagnostic accuracy for subepithelial lesions in the lower gastrointestinal tract.


Subject(s)
Endosonography , Gastrointestinal Tract , Humans , Endosonography/methods , Retrospective Studies , Feasibility Studies , Gastrointestinal Tract/diagnostic imaging , Gastrointestinal Tract/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration
6.
Am J Surg Pathol ; 48(5): 623-631, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38525823

ABSTRACT

NTRK-rearranged spindle cell neoplasm occurs predominantly in the superficial or deep soft tissues of extremities or trunk. Occurrence in the visceral organs is extremely rare. Herein, we describe 8 cases of NTRK-rearranged spindle cell neoplasm that arose primarily in the gastrointestinal tract. Patients included 5 males and 3 females with age at presentation ranging from 6 to 63 years (median: 29.5 years). Tumors occurred in the colon (n=3), small intestine (n=2), rectum (n=2), and stomach (n=1). Tumor size ranged from 3.5 to 9 cm (median: 5 cm). Morphologically, 4 tumors were low-grade, composed of haphazard or intertwining fascicles of spindle cells, with prominent interstitial collagen fibers and ring-like perivascular hyalinization being present in 2 tumors. The other 4 tumors were histologically high-grade sarcomas, consisting of sweeping fascicles of atypical spindle cells showing increased cellularity and brisk mitotic activity. Immunohistochemically, 6/6 cases (100%) showed diffuse and strong cytoplasmic staining of pan-TRK. Variable expression of TrkA, CD34, and S100 was noted in 5/5 (100%), 5/8 (62.5%), and 4/7 (57.1%) cases, respectively. Fluorescence in situ hybridization analysis showed NTRK1 rearrangement (n=7) and NTRK2 rearrangement (n=1). In cases with available materials, RNA sequencing identified LMNA::NTRK1 (n=3), TPM3::NTRK1 (n=2), and STRN::NTRK2 (n=1) fusions. At follow-up (range: 4 to 30 months; median: 12.5 months), 6 of 7 patients who underwent surgery had no evidence of disease at last follow-up. One patient was succumbed to the disease at 12 months despite adjunctive treatment with TRK inhibitor larotrectinib after surgery. One patient was treated with larotrectinib alone. He showed significant response at 7 months after treatment. NTRK-rearranged spindle cell neoplasm represents an exceptionally rare entity in the gastrointestinal tract. The presence of interstitial collagen fibers and ring-like perivascular hyalinization and co-expression of CD34 and S100 are diagnostic clues to low-grade neoplasms. However, high-grade sarcomas pose a considerable diagnostic challenge to pathologists owing to the lack of specific features. The final diagnosis relies on molecular assays. Patients with advanced disease may benefit from TRK inhibitor treatment.


Subject(s)
Receptor, trkA , Sarcoma , Male , Female , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Receptor, trkA/genetics , In Situ Hybridization, Fluorescence , Sarcoma/genetics , Gastrointestinal Tract/pathology , Collagen , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Oncogene Proteins, Fusion/genetics
8.
Radiat Res ; 201(5): 406-417, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38319684

ABSTRACT

The purpose of this investigation was to characterize the natural history of a murine total-abdominal-irradiation exposure model to measure gastrointestinal acute radiation injury. Male CD2F1 mice at 12 to 15 weeks old received total-abdominal irradiation using 4-MV linear accelerator X-rays doses of 0, 11, 13.5, 15, 15.75 and 16.5 Gy (2.75 Gy/min). Daily cage-side (i.e., in the animal housing room) observations of clinical signs and symptoms including body weights on all animals were measured up to 10 days after exposure. Jejunum tissues from cohorts of mice were collected at 1, 3, 7 and 10 days after exposure and radiation injury was assessed by histopathological analyses. Results showed time- and dose-dependent loss of body weight [for example at 7 days: 0.66 (±0.80) % loss for 0 Gy, 6.40 (±0.76) % loss at 11 Gy, 9.43 (±2.06) % loss at 13.5 Gy, 23.53 (± 1.91) % loss at 15 Gy, 29.97 (±1.16) % loss at 15.75 Gy, and 31.79 (±0.76) % loss at 16.5 Gy]. Negligible clinical signs and symptoms, except body weight changes, of radiation injury were observed up to 10 days after irradiation with doses of 11 to 15 Gy. Progressive increases in the severity of clinical signs and symptoms were found after irradiation with doses >15 Gy. Jejunum histology showed a progressive dose-dependent increase in injury. For example, at 7 days postirradiation, the percent of crypts, compared to controls, decreased to 82.3 (±9.5), 69.2 (±12.3), 45.4 (±11.9), 18.0 (±3.4), and 11.5 (± 1.8) with increases in doses from 11 to 16.5 Gy. A mucosal injury scoring system was used that mainly focused on changes in villus morphology damage (i.e., subepithelial spaces near the tips of the villi with capillary congestion, significant epithelial lifting along the length of the villi with a few denuded villus tips). Peak levels of total-abdominal irradiation induced effects on the mucosal injury score were seen 7 days after irradiation for doses ≥15 Gy, with a trend to show a decline after 7 days. A murine multiple-parameter gastrointestinal acute-radiation syndrome severity-scoring system was established based on clinical signs and symptoms that included measures of appearance (i.e., hunched and/or fluffed fur), respiratory rate, general (i.e., decreased mobility) and provoked behavior (i.e., subdued response to stimulation), weight loss, and feces/diarrhea score combined with jejunum mucosal-injury grade score. In summary, the natural-history radio-response for murine partial-body irradiation exposures is important for establishing a well-characterized radiation model system; here we established a multiple-parameter gastrointestinal acute-radiation syndrome severity-scoring system that provides a radiation injury gastrointestinal tissue-based assessment utility.


Subject(s)
Acute Radiation Syndrome , Animals , Mice , Male , Acute Radiation Syndrome/pathology , Acute Radiation Syndrome/etiology , Dose-Response Relationship, Radiation , Jejunum/radiation effects , Jejunum/pathology , Disease Models, Animal , Severity of Illness Index , Gastrointestinal Tract/radiation effects , Gastrointestinal Tract/pathology , Body Weight/radiation effects , Radiation Injuries, Experimental/pathology
9.
Lab Invest ; 104(4): 102028, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38382808

ABSTRACT

Primary gastrointestinal (GI) T-cell and natural killer (NK)-cell lymphomas/lymphoproliferative disorders (LPD) are uncommon, and they are usually aggressive in nature. However, T-cell and NK-cell lymphoma/LPD of the GI tract with indolent clinical course has been reported over the past 2 decades. Indolent T-cell LPD was formally proposed a decade ago in 2013 and 4 years later recognized as a provisional entity by the revised fourth edition of WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in 2017. Indolent T-cell LPD of the GI tract has been changed to indolent T-cell lymphoma of the GI tract as a distinct entity by the fifth edition of WHO Classification of Haematolymphoid Tumours, but the International Consensus Classification of mature lymphoid neoplasms prefers indolent clonal T-cell LPD of the GI tract instead. In the past decade, indolent lymphoma/LPD of the GI tract has been expanded to NK cells, and as such, indolent NK-cell LPD of the GI tract was recognized as an entity by both the fifth edition of WHO Classification of Haematolymphoid Tumours and the International Consensus Classification. The underlying genetic/molecular mechanisms of both indolent T-cell lymphoma/LPD of the GI tract and indolent NK-cell LPD of the GI tract have been recently discovered. In this review, we describe the history; salient clinical, cytohistomorphologic, and immunohistochemical features; and genetic/genomic landscape of both entities. In addition, we also summarize the mimics and differential diagnosis. Finally, we propose future directions with regard to the pathogenesis and clinical management.


Subject(s)
Lymphoma, T-Cell , Lymphoma , Lymphoproliferative Disorders , Humans , Lymphoma/diagnosis , Lymphoma/pathology , Gastrointestinal Tract/pathology , Killer Cells, Natural , Lymphoma, T-Cell/diagnosis , T-Lymphocytes/pathology , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/pathology
10.
Histopathology ; 84(7): 1079-1091, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38362762

ABSTRACT

Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta-analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle-Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta-analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21-5.04]), gastric adenocarcinoma (2.03 [1.38-2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02-3.25]), and biliary tract adenocarcinoma (3.11 [2.46-3.93]) with high-grade tumour budding. Additionally, high-grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility.


Subject(s)
Gastrointestinal Neoplasms , Pancreatic Neoplasms , Humans , Prognosis , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/mortality , Biliary Tract Neoplasms/pathology , Biliary Tract Neoplasms/mortality , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Gastrointestinal Tract/pathology
11.
Brasília; CONITEC; fev. 2024.
Non-conventional in Portuguese | BRISA/RedTESA, Inca | ID: biblio-1551260

ABSTRACT

INTRODUÇÃO: Os tumores neuroendócrinos (TNE) são neoplasias, com origem mais comum no trato gastrointestinal, que podem cursar com liberação de hormônios associado a sintomas, levando a síndrome carcinoide, com incidência anual estimada em 0,25/1.000.000 na Europa (ano de 2008). As manifestações clínicas mais comuns incluem diarreia secretória e rubor súbito, mas a diarreia é considerada mais debilitante com potencial risco de morte. Quando o tratamento curativo com ressecção completa não é viável pela presença de doença metastática, o tratamento é direcionado para o controle dos sintomas da síndrome carcinoide e os análogos da somatostatina (octreotida ou lanreotida) são considerados terapia de primeira linha na SC. PERGUNTAS DE PESQUISA: O acetato de octreotida de liberação prolongada (octreotida LAR) e o acetato de lanreotida de liberação prolongada (lanreotida LP) são eficazes, seguros e custo-efetivos para o tratamento dos sintomas relacionados à SC associados ao TNE gastroenteropancreático funcional em pacientes adultos? EVIDÊNCIAS CLÍNICAS: Foram selecionados três ensaios clínico


Subject(s)
Humans , Sincalide/analogs & derivatives , Octreotide/therapeutic use , Endocrine Gland Neoplasms/etiology , Gastrointestinal Tract/pathology , Intestinal Diseases/pathology , Malignant Carcinoid Syndrome/drug therapy , Unified Health System , Brazil , Efficacy , Cost-Benefit Analysis/economics
13.
Am J Surg Pathol ; 48(3): 275-283, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38062799

ABSTRACT

Occurrence of extraskeletal Ewing sarcoma (ES) in the gastrointestinal (GI) tract is extremely rare. Here, we report 25 cases of ES arising primarily in the GI tract with a focus on the clinicopathological and molecular features, differential diagnosis, and biological behavior. Thirteen patients (52%) were male, and 12 (48%) were female with age ranging from 9 to 59 years (mean: 36.2 years; median: 38 years). Twenty-one tumors (84%) occurred in the small intestine, 3 (12%) in the stomach, and 1 (4%) in the anal canal. At operation, 8/18 (44.4%) patients presented with abdominopelvic disseminated disease. Tumor size measured from 2 to 25 cm (mean: 8.2 cm; median: 6 cm) in maximum size. Microscopically, the tumors were composed of infiltrative small round, ovoid, or short spindle cells arranged mostly in lobular and solid sheet-like patterns with a rich capillary vasculature. Focal formation of Homer Wright-type rosettes and pseudoalveolar architecture was noted each in 2 (8%) cases and 3 (12%) cases. Besides CD99 (25/25; 100%), Fli-1 (15/15, 100%), and NKX2.2 (14/16; 87.5%), the tumor cells also showed variable staining of CD117 (14/17; 82.4%). Of 25 cases, 23 (92%) demonstrated EWSR1 rearrangement by fluorescence in situ hybridization analysis. The 2 cases with negative fluorescence in situ hybridization results were found to harbor EWSR1::ERG and EWSR1::FLI1 fusion by further RNA sequencing, respectively, with a median follow-up of 12 months (range: 1 to 42 months), 5/19 (26.3%) patients developed visceral metastasis and 12/19 (63.2%) patients died of the disease (range:1 to 33 months; median: 9 months). This study showed that GI ES had a predilection for the small intestine, although other sites of the GI tract could also be involved. GI ES had a poor prognosis with a high rate of mortality, particularly in patients with abdominopelvic disseminated disease. In light of appropriate therapeutic strategies and prognostic considerations, it is essential not to misdiagnose GI ES as gastrointestinal stromal tumor owing to the expression of aberrant CD117.


Subject(s)
Sarcoma, Ewing , Humans , Male , Female , Child , Adolescent , Young Adult , Adult , Middle Aged , Sarcoma, Ewing/genetics , Sarcoma, Ewing/therapy , Sarcoma, Ewing/pathology , In Situ Hybridization, Fluorescence , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , RNA-Binding Protein EWS/genetics , Gastrointestinal Tract/pathology , Molecular Biology
14.
Neuroendocrinology ; 114(2): 120-133, 2024.
Article in English | MEDLINE | ID: mdl-37690447

ABSTRACT

Practice of neuroendocrine neoplasms (NENs) of the digestive tract, which comprise of a highly diverse group of tumors with a rising incidence, faces multiple biological, diagnostic, and therapeutic issues. Part of these issues is due to misuse and misinterpretation of the classification and terminology of NENs of the digestive tract, which make it increasingly challenging to evaluate and compare the literature. For instance, grade 3 neuroendocrine tumors (NETs) are frequently referred to as neuroendocrine carcinomas (NECs) and vice versa, while NECs are, by definition, high grade and therefore constitute a separate entity from NETs. Moreover, the term NET is regularly misused to describe NENs in general, and NETs are frequently referred to as benign, while they should always be considered malignancies as they do have metastatic potential. To prevent misconceptions in future NEN-related research, we reviewed the most recent terminology used to classify NENs of the digestive tract and created an overview that combines the classification of these NENs according to the World Health Organization (WHO) with location- and functionality-based classifications. This overview may help clinicians and researchers in understanding the current literature and could serve as a guide in the clinic as well as for writing future studies on NENs of the digestive tract. In this way, we aim for the universal use of terminology, thereby providing an efficient foundation for future NEN-related research.


Subject(s)
Carcinoma, Neuroendocrine , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Neuroendocrine Tumors/pathology , Carcinoma, Neuroendocrine/pathology , World Health Organization , Gastrointestinal Tract/pathology , Pancreatic Neoplasms/pathology
15.
Arch Pathol Lab Med ; 148(2): e25-e35, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37450346

ABSTRACT

CONTEXT.­: Mast cells are essential components of the immune system and play crucial pathogenetic roles in several digestive diseases, including mastocytic enterocolitis and eosinophilic gastrointestinal disorders. Pathologists have rarely been asked to evaluate the distribution and density of mast cells in gastrointestinal (GI) biopsy specimens. However, such requests are becoming more common because of an increasing awareness of the role of mast cells in functional GI disease and in both esophageal and nonesophageal eosinophilic gastrointestinal disorders. OBJECTIVE.­: To provide pathologists with tools to incorporate the assessment of mast cells in the evaluation of esophageal, gastric, and intestinal specimens by developing a systematic approach to their evaluation, counting, and reporting. DESIGN.­: This study consisted of a review of the literature followed by multiple consensus sessions to decide where to count mast cells and what a countable mast cell is. RESULTS.­: We reviewed 135 papers addressing the content of mast cells in the digestive tract, selected 21 that detailed how cells were counted (microscope lens, area of high-power fields, locations evaluated, type of cells considered as countable), and summarized their data in a table. Then, drawing from both the acceptable literature and our own extensive experience, we reached a tentative consensus on: (1) the normal numbers in the different segments of the GI tract; (2) the morphology of countable mast cells; and (3) the locations and strategies for counting them. CONCLUSIONS.­: The result is a set of suggestions for reporting mast cell counts, their distribution, and their location in a way clinicians can understand and use for management decisions.


Subject(s)
Gastrointestinal Diseases , Mastocytosis , Humans , Mast Cells/pathology , Pathologists , Gastrointestinal Tract/pathology , Mastocytosis/diagnosis , Mastocytosis/pathology , Gastrointestinal Diseases/pathology
17.
J Allergy Clin Immunol Pract ; 12(2): 472-481, 2024 02.
Article in English | MEDLINE | ID: mdl-37918653

ABSTRACT

BACKGROUND: Current data on the normal quantity of mast cells throughout the adult gastrointestinal tract are limited in several domains. These include microanatomic localization of mast cells, standardization of staining and counting methods, and reporting of microscope field of view. OBJECTIVE: To address this lack of reliable reference ranges to facilitate the study of and diagnosis of emerging mast cell-mediated diseases. METHODS: We examined biopsies obtained from the esophagus, stomach, duodenum, and colon from an unselected cohort. Mean and peak mast cell density were determined on slides stained for tryptase and CD117, and were expressed per high power field (hpf) and surface area (mm2), thus deriving reference ranges (average ± 2 SDs). RESULTS: For the most common hpf surface area (0.238 mm2), upper limits of the derived reference ranges for average/peak mast cells were 0.15/3.67 (esophagus, tryptase), 0.70/5.98 (esophagus, CD117), 22.56/35.30 (stomach, tryptase), 31.32/53.10 (stomach, CD117), 30.28/49.77 (duodenal crypts, tryptase), 41.96/65.26 (duodenal crypts, CD117), 4.98/11.56 (duodenal villi, tryptase), 8.38/14.17 (duodenal villi, CD117), 26.58/41.08 (colon, tryptase), and 35.57/57.92 (colon, CD117). Interobserver variability was moderate to good. There was significant correlation between average and peak mast cell counts. CONCLUSIONS: These data help standardize mast cell reference ranges throughout the gastrointestinal tract in adults, which can be used to determine whether abnormal levels of mast cells are present in patients with suspected mast cell-mediated disease. Our data show that the commonly used cutoff of 20 mast cells per hpf irrespective of the gastrointestinal tract segment is an underestimate of an appropriate cutoff in stomach, duodenum (crypt area), and colon.


Subject(s)
Mast Cells , Mastocytosis , Adult , Humans , Mast Cells/pathology , Tryptases/metabolism , Gastrointestinal Tract/pathology , Duodenum/pathology , Mastocytosis/pathology
19.
Am J Surg Pathol ; 48(3): 302-308, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38145407

ABSTRACT

Amyloidosis can involve the gastrointestinal (GI) tract, and deposition can present with varied histologic patterns that make recognition challenging. This retrospective observational study aimed to characterize the deposition patterns in the GI tract and evaluate key quality metrics, including discrepant cases, to improve recognition and provide insight for accurate diagnosis. Sixty-two patients (195 biopsies) with amyloid involvement of the luminal tract were reviewed. Amyloid subtyping by mass spectrophotometry was available for 59 patients. Immunoglobulin light chain (AL) was the most commonly identified subtype (60%), followed by serum amyloid A (AA; 19%) and transthyretin (ATTR; 16%). 150/195 biopsies (77%) were positive for amyloid deposition, with an average of 2.4 positive biopsies per every 3.1 taken per patient. The sites with the highest yield were duodenum (37/37, 100%) and colon (63/74, 85%). Gastric biopsies were most likely to involve the lamina propria (41/45, 91%, P < 0.001), with the background mucosa showing reactive epithelial changes in almost half of the biopsies (20/45, 44%). Several distinct histologic patterns of interstitial deposition were identified, including muscularis mucosae deposition (n = 40, 27% of positive biopsies), peri-Brunner gland (n = 6, 17% of duodenal biopsies), mass-forming (n = 4, 2.7% of positive biopsies, including 3 suspected cases with localized involvement), collagenous colitis-like (n = 3, 4.8% of positive colonic biopsies), and globular (n = 19, 12.7% of positive biopsies). Congo Red was ordered in 81% of cases in which it was requested clinically, with a positivity rate of 30%. Of the 34 cases in which an amyloid workup was requested (but Congo Red was not performed), 14 were positive on reevaluation. Several missed cases had deposition in multiple biopsies, and almost half were missed by subspecialist GI pathologists. Nine misinterpretations were from the stomach, with seven initially diagnosed as chemical or reactive gastropathy. Additional discrepant cases were identified from the duodenum (n = 2) and colon (n = 3), with the vascular-only deposition pattern (n = 3), muscularis mucosae-only deposition (n = 3), and globular pattern (n = 1) identified. Given the challenges of identifying amyloid on hematoxylin and eosin staining, Congo Red ordering percentage should be 100% in clinically suspicious cases unless deposition is definitively seen on hematoxylin and eosin staining.


Subject(s)
Amyloidosis , Congo Red , Humans , Amyloid , Amyloidosis/diagnosis , Eosine Yellowish-(YS) , Gastrointestinal Tract/pathology , Hematoxylin , Retrospective Studies
20.
Viruses ; 15(12)2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38140656

ABSTRACT

Enteric viruses are significant human pathogens that commonly cause foodborne illnesses worldwide. These viruses initiate infection in the gastrointestinal tract, home to a diverse population of intestinal bacteria. In a novel paradigm, data indicate that enteric viruses utilize intestinal bacteria to promote viral replication and pathogenesis. While mechanisms underlying these observations are not fully understood, data suggest that some enteric viruses bind directly to bacteria, stabilizing the virion to retain infectivity. Here, we discuss the current knowledge of these viral-bacterial interactions and examine the impact of these interactions on viral transmission.


Subject(s)
Enterovirus Infections , Enterovirus , Viruses , Humans , Gastrointestinal Tract/pathology , Bacteria/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...