Gastrointestinal Tract Biopsies Research Articles

T-cells are significantly reduced in the luminal gastrointestinal tract of patients with “complete” 22q11.2 deletion syndrome (DiGeorge syndrome): Utilization of chromogenic multiplex immunohistochemistry to define cellular populations

Patients with 22q11.2 deletion syndrome or DiGeorge syndrome commonly report gastrointestinal symptoms in addition to more widely understood cardiac and immunodeficiency abnormalities. However, the morphologic features of gastrointestinal tract pathology in these patients are poorly understood. We previously reported that plasma cells are essentially absent from the luminal gastrointestinal tract of patients with “complete” DiGeorge syndrome. Herein, we add to the current understanding of the luminal gastrointestinal tract changes in patients with DiGeorge syndrome. Patients with cytogenetically confirmed DiGeorge syndrome were identified after approval from our institutional review board. Gastrointestinal tract biopsies from patients with DiGeorge syndrome that were severely immunosuppressed (complete DiGeorge syndrome, DGS-I), partially immunocompromised (partial DiGeorge syndrome, DGS), and from control patients were reviewed. Two panels of chromogenic multiplex immunohistochemistry (IHC) were performed to evaluate the immune cell infiltrate in the lamina propria of the duodenum and colon. “Panel #1” was composed of antibodies targeting CD3, CD20, and CD68. “Panel #2” was composed of antibodies targeting CD4, CD8, CD56, and TCRϒδ. Assessment of cell types identified by these antibody targets demonstrated a significant reduction of duodenal and colonic T-cells in patients with complete DiGeorge syndrome. In addition to establishing the morphologic phenotype of the luminal gastrointestinal tract of patients with DiGeorge syndrome, we also highlight our chosen technology of chromogenic multiplex IHC as a relatively accessible research and diagnostic tool with wide potential to be utilized across various disease processes.

Graft-versus-host disease-like gastroenteritis after autologous stem cell transplantation with busulfan/thiotepa conditioning for primary central nervous system lymphoma

Graft-versus-host disease (GVHD) is less common in autologous stem cell transplantation (ASCT) recipients than in allogeneic SCT recipients. However, some cases of severe GVHD, especially involving the gastrointestinal (GI) tract, have been documented. We present a patient with primary central nervous system lymphoma (PCNSL) exhibiting severe GI-GVHD after ASCT with busulfan/thiotepa conditioning. A 59-year-old woman with PCNSL in complete remission was admitted for consolidative ASCT. She developed severe diarrhea following busulfan/thiotepa conditioning, which was considered to be neutropenic enterocolitis induced by the conditioning regimen. However, her diarrhea worsened after neutrophil engraftment, and endoscopic findings and GI tract biopsies were suggestive of autologous GVHD. The diarrhea improved markedly with systemic steroid therapy, but she developed cytomegalovirus (CMV) gastroenterocolitis due to severe immunosuppression during systemic steroid therapy for GVHD. After CMV antigenemia negativity was achieved with ganciclovir, pathological examination showed persistent gastrointestinal mucosal edema and erythema with regenerative changes, which indicated a need for continuous GVHD treatment. Treatment with systemic steroids and budesonide for more than 2 months led to remission. It is important to suspect autologous GI-GVHD and consider prompt and aggressive immunosuppressive therapy in patients that manifest persistent diarrhea after engraftment following ASCT with busulfan/thiotepa conditioning.

Multiplexed Tissue Imaging for Immune Cells Profiling During Peanut Allergy Immunotherapy

Oral immunotherapy (OIT) can desensitize food allergic individuals to offending food allergens. However, OIT-induced changes in tissue-resident immune cell subsets remain largely unexplored. We investigated peanut-OIT-induced spatial and temporal changes in gastrointestinal (GI) tract biopsies taken from our phase 2 peanut OIT trial- POISED using Multiplexed Ion Beam Imaging (MIBI).

A histopathological view at the long-term effects of COVID-19 on the gastrointestinal system in children: a single center experience.

Subacute and chronic long-term effects of coronavirus disease 2019 (COVID-19) in different organ systems have been studied in post-COVID patients recently. COVID-19 may cause gastrointestinal (GI) system findings due to the presence of its receptor, angiotensin converting enzyme type 2 (ACE2), which is extensively expressed in the GI tract. In this study, we aimed to evaluate the post-infectious histopathological alterations of COVID-19 in pediatric patients who had GI symptoms. Fifty-six specimens of upper endoscopic biopsies (including esophagus, stomach, bulbus and duodenum) obtained from seven patients and 12 specimens of lower endoscopic biopsies obtained from one patient who had GI symptoms after having COVID-19 (proven by polymerase chain reaction [PCR]) were evaluated as the study group. Forty specimens from five patients presenting with similar complaints but without COVID-19 were selected as the control group. All biopsy materials were immunohistochemically stained with the anti-SARS-CoV-2S1 antibody. In all biopsies of the study group, anti-SARS-CoV-2S1 antibody was detected with moderate cytoplasmic positivity in epithelial cells and inflammatory cells in the lamina propria. No staining was observed in the control group. Epithelial damage, thrombus, or no other specific findings were detected in the GI tract biopsies of any of the patients. The virus antigen was detected immunohistochemically in the stomach and duodenum, but not in the esophagus, even months after infection and causes gastritis and duodenitis. No specific histopathological finding was observed from non-COVID-19 gastritis/duodenitis. Therefore, the post-COVID-19 GI system involvement should be kept in mind in patients presenting with dyspeptic symptoms even if several months have passed.

Endoscopic Surveillance of Esophageal Atresia Population according to ESPGHAN-NASPGHAN 2016 Guidelines: Incidence of Eosinophilic Esophagitis and New Histological Findings.

Follow-up of children born with esophageal atresia (EA) is mandatory due to high incidence of comorbidities. We evaluated endoscopic findings at follow-up of EA patients performed at our Centre according to ESPGHAN-NASPGHAN 2016 guidelines. A retrospective observational study was performed using data from January 2016 to January 2021. We included EA patients (age range: 1-18 years) who were offered a program of endoscopic and histological high gastrointestinal (GI) tract examinations as per ESPGHAN-NASPGHAN 2016 guidelines. Clinical, surgical, auxological, endoscopic, and histological data were reviewed; variables as polyhydramnios, EA type, surgical type, enteral feeding introduction age, growth data, and symptoms were correlated to endoscopic and histological findings. The population included 75 patients (47 males), with mean age of 5 ± 4 years. In 40/75 (53.3%) patients, we recorded oral feeding problems, and upper gastrointestinal or respiratory symptoms suspicious of gastroesophageal reflux. Eosinophilic esophagitis (EoE) incidence was 9/75 (12%), significantly higher than in general population (p < 0.0001), and 10/75 (13.3%) presented non-specific duodenal mucosal lesions. EoE represents a frequent comorbidity of EA, as previously known. EA is also burdened by high, never-described incidence of non-specific duodenal mucosal lesions. Embedding high GI tract biopsies in EA endoscopic follow-up should be mandatory from pediatric age.

Extracardiac Biopsy Sensitivity in Transthyretin Amyloidosis Cardiomyopathy Patients With Positive 99 mTc-Labeled Pyrophosphate Scintigraphy Findings.

The accurate sensitivity of amyloid deposition in extracardiac tissue (subcutaneous tissue and gastrointestinal tract) has not been evaluated in transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients. This study aimed to evaluate the sensitivity of amyloid deposition in obtained endomyocardial and extracardiac biopsies.Methods and Results: This study retrospectively evaluated 175 consecutive ATTR-CM patients (wild-type [ATTRwt]: 134, hereditary [ATTRv]: 41) who had positive findings on 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy and underwent tissue biopsy of at least one organ (subcutaneous tissue, gastrointestinal tract, and endomyocardium). Amyloid deposition was observed in the subcutaneous tissue of 57/150 patients (38%), gastrointestinal tract of 80/131 patients (61%), and endomyocardium of 108/109 patients (99%). Compared to patients with ATTRv, ATTRwt had significantly lower sensitivity in subcutaneous tissue (73% vs. 25%, P<0.01) and tended to be lower in the gastrointestinal tract (74% vs. 57%, P=0.08) biopsies. Among 124 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsies, amyloid was detected in at least 1 specimen in 91 (73%) patients. The sensitivity of the combination of extracardiac biopsies was 66% and 94% in ATTRwt-CM and ATTRv-CM, respectively. Multivariate analysis reveals that ATTRv was the only significant predictor of amyloid deposition in the subcutaneous tissue. Subcutaneous tissue and gastrointestinal tract biopsy sensitivity are inadequate, especially in patients with ATTRwt; however, the combination of these extracardiac biopsies contributes to increased sensitivity in patients with positive 99 mTc-PYP scintigraphy findings.

Abstract 2026: Spatially resolved multiplexed analysisreveals how macrophages adapt to the mantle cell lymphoma microenvironment

Abstract Introduction: Mantle cell lymphoma (MCL) is an incurable disease and we have previously shown that presence of CD163+ cells in the tumor microenvironment in MCL is associated with an adverse outcome. We therefore profiled CD163+ cells to better understand their impact on this tumor and identify possible targetable markers. We hypothesize that, not only the presence of CD163+ cells, a marker of M2 macrophages, in the tumor tissue, but also the spatial context of CD163+ cells might be relevant for MCL development and treatment response. Material and Methods: Sixty-nine protein targets were measured by the Nanostring GeoMx Digital Spatial Profiler. This method allowed for preserved spatial context, in tissue microarrays from a population-based cohort of de novo MCL patients while investigating different markers. A total of 235 cores from 131 different patients were sampled. Regions of interest for CD20+, CD3+ and CD163+ cells were selected, with more than 600 areas of illumination (AOI) collected. From those, 85 AOI, belonging to 61 patients, were from CD163+ cells. These were subsequently classified according to their spatial profile: CD163+ cells within the tumor area and CD163+ cells excluded from the tumor area. Differentially expressed proteins between different tissue types were also explored. Results: Among the highest expressed proteins in the CD163 AOI were CD45, HLA-DR and CD68. The higher expression of both HLA-DR and CD68 suggests that macrophages in MCL microenvironment may display mixed phenotypes between pro- and anti-inflammatory stages, the called M1 and M2 polarization types. Interestingly, p53 and Ki67 were highly correlated among the CD163 AOI collected, which might suggest higher aggressiveness of CD163+ cells. We explored the differently expressed proteins between CD163 AOI sampled located within the tumor and excluded from the tumor/tumor barrier. We identified significant differences in the expressed proteins between the two groups, such as p53, VISTA, ARG1, LAG3 and HLA-DR. p53 was higher in the CD163 AOI within the tumor area, whereas VISTA was highest expressed in CD163 AOI excluded from the tumor cells/tumor barrier. Among the 85 CD163+ AOIs, 47 were sampled from lymph node biopsies, 14 from bone marrow, 10 from tonsil samples, four from the gastrointestinal tract, six from other tissue types and four from unknown origin. Principal component analysis and k-means clustering showed that most of bone marrow and gastrointestinal tract biopsies clustered apart from the remaining samples, with a few differentially expressed proteins, such as NF1 and CD66b. Conclusions: Our study demonstrates that spatial localization within the MCL tumor affects the expression of CD163+ macrophages, adding to the premise that macrophages in tumor are not easily characterized by the concept of M1 and M2 types. Our results shed light on targetable features of the MCL tumor microenvironment. Citation Format: Joana Matos Rodrigues, Lavanya Lokhande, Anna Gerdtsson, Anna Nikkarinen, Peter Hollander, Anna Porwit, Ingrid Glimelius, Mats Jerkeman, Sara Ek. Spatially resolved multiplexed analysisreveals how macrophages adapt to the mantle cell lymphoma microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2026.

Pathologist’s approach to paediatric and neonatal eosinophilic gastrointestinal disorders

SummaryChildren are not simply miniature adults. The evaluation of their gastrointestinal disorders is therefore different from that in full-grown adults and requires a particular clinical/pathologic approach.Different studies have tried to assess the normal eosinophil distribution in the gastrointestinal tract in adults while very few studies have investigated the paediatric population, consequently complicating the pathologist’s ability in identifying an abnormal number of eosinophils in this setting of patients.When evaluating gastrointestinal tract biopsies with eosinophilia, eosinophilic count must be considered along with other histological features like eosinophil distribution in the gastrointestinal wall, their degranulation, cryptitis and crypt abscesses, other accompanying inflammatory cells, apoptotic bodies, foreign material or microorganisms; these findings, although rarely specific, may be a useful aid for diagnosis.Reports should not include a diagnosis of primary eosinophilic gastrointestinal disorders (EoGID) if clinical data and test results do not rule out other forms of gastrointestinal eosinophilia. A more descriptive definition like “with eosinophilic pattern” should be favoured over a specific diagnosis of “eosinophilic disorder” in order to avoid potential confusion between different entities.

Plasma cells are essentially absent in the luminal gastrointestinal tract of patients with “complete” 22q11.2 deletion syndrome (DiGeorge syndrome)

Gastrointestinal symptoms are commonly reported in patients with 22q11.2 deletion syndrome or DiGeorge syndrome (DGS) in addition to the dominant cardiac manifestations and immunodeficiency. But literature providing specific morphologic details of the gastrointestinal tract pathology is very limited. Here, we provide the first comprehensive morphologic description of the luminal gastrointestinal tract changes in patients with DGS. Cytogenetically confirmed DGS patients were identified, clinical and laboratory data were reviewed to determine the severity of immunodeficiency, and patients were stratified into mildly immunocompromised, that is, partial DiGeorge anomaly or severely immunosuppressed, that is, complete DiGeorge anomaly groups. Gastrointestinal tract biopsies from these patients were retrospectively reviewed and compared with those from controls without the history of DGS. Patients with immunosuppressed DGS showed a near complete absence of plasma cells in the stomach, duodenum, and colon lamina propria by hematoxylin and eosin evaluation. Immunohistochemistry for CD138 used to highlight plasma cells confirmed this finding. The notable absence of plasma cells adds to the existing knowledge of the pathophysiology underlying DGSand expands the differential diagnostic considerations for this finding, which has been previously described in common variable immunodeficiency. It also provides a useful morphologic marker observable by the readily accessible light microscopy. Second, patients with DGS showed a mild increase in epithelial cell apoptosis in their colon. This finding is significant because of its overlap with morphologic features of gastrointestinal graft versus host disease as thymus transplantation is being used as a treatment option for patients with complete DGS.

English

BACKGROUND In a developing country like India, vast difference exists in people’s religion, culture, and socio-economic condition and along with it, there exists a significant difference in their dietary habits. This has led to an incidence of a large spectrum of gastrointestinal (GI) diseases which is different in different geographical locations. The study was undertaken for studying the spectrum of various histopathological lesions of gastrointestinal tract with the help of endoscopic biopsy. METHODS This cross-sectional study was carried out in a span of 2 years in the histopathology division. The study included 105 patients who had GI complains and underwent endoscopic biopsies for the same. RESULTS The present study included a total of 105 cases out of which there were 64 cases (61 %) of upper GI tract biopsies and remaining 41 cases (39 %) were of lower GI tract biopsies. Among 64 (100 %) cases of upper GI biopsies, reflux oesophagitis (4.67 %) was the most common in non-neoplastic lesions while well differentiated squamous cell carcinoma (20.31 %) was the most common neoplastic pathology. In gastric biopsies, chronic atrophic gastritis (3.12 %) was the most common condition in a non-neoplastic category, while gastric adenocarcinoma (15.61 %) was the malignant lesion which was found. Among duodenal biopsies, the most common lesion was eosinophilic enteritis / duodenitis (14.06 %). Among 41 (100 %) colonoscopic biopsies, the most common lesion was chronic non-specific inflammation (12.19 %) under non-neoplastic category, while well differentiated adenocarcinoma (46.34 %) was most common entity under malignant category in our study. Non-neoplastic lesions were more common in upper GI endoscopic biopsies whereas, neoplastic lesions were more frequently seen with lower GI endoscopic biopsies. CONCLUSIONS Performing endoscopy alone is an incomplete investigative modality for the diagnosis. While performing endoscopy and simultaneously taking biopsy for histopathological evaluation helps in giving an accurate diagnosis. KEY WORDS GIT, Endoscopy, Endoscopic Biopsy

CORRELATIVE STUDY OF HISTOPATHOLOGICAL DIAGNOSIS WITH CLINICAL &amp; ENDOSCOPIC DIAGNOSIS IN UPPER GASTROINTESTINAL ENDOSCOPIC BIOPSY AT TERTIARY CARE CENTER

Lesions of Upper gastrointestinal tract (GIT) is commonly seen in surgical department patients. These patients are subjected to endoscopic examination and biopsy is taken for further histopathological diagnosis. A clinical, endoscopic and histopathological diagnosis is made. This study was done to compare and correlate the results of histopathological diagnosis with endoscopic and clinical findings.&#x0D; Study Designed: A total 50 Upper Gastrointestinal tract biopsy cases received in histopathology lab were analyzed. &#x0D; Material and Method: All endoscopic biopsies from upper GIT were received and processed. Paraffin blocks were made and sections were cut at 4 microns thickness and stained with routine hematoxylin and eosin stain. Their clinical and endoscopic reports were collected and compared with histopathological diagnosis.&#x0D; Result: After analyzing statistically the data, we found that endoscopy results were better than clinical diagnosis and more closer to histopathological diagnosis.&#x0D; Conclusion: Relation of histopathological diagnosis with endoscopic findings &amp; clinical diagnosis was done in our study. We conclude that endoscopy is incomplete without histopathological examination of biopsy &amp; so, the combinations of both plays an important role in diagnosis &amp; management of upper gastrointestinal tract disorders. Histopathological examination remains the gold standard.&#x0D; Keywords: Histopathology, endoscopy, gastrointestinal lesions.

Clinical and histological features of secondary carcinomas in gastrointestinal tract biopsies.

Secondary carcinoma involving the gastrointestinal (GI) tract is an uncommon finding in biopsy specimens. The diagnosis can be challenging for tumours mimicking a primary carcinoma and when the clinical context is unknown. A multicentre retrospective study was performed to evaluate the clinical and histological features of a series of secondary carcinoma in GI biopsies. A total of 197 cases from 190 patients (median age=67years; 57% females) were reviewed. In 16% of patients, the primary carcinoma was unknown. Most lesions presented endoscopically as mucosal or submucosal masses (58%). In 13%, the endoscopy was non-suspicious for malignancy. The most common tumours were carcinomas of the breast (38%), kidney (13%), lung (12%), prostate (8%) and ovary (7%). The sites of involvement were the stomach (34%), colon (27%), rectum (18%), duodenum (13%), oesophagus (5%), jejunum (3%) and anus (0.5%). Histological patterns of infiltration were mucosal (76%), submucosal (41%), lymphatic (14%), and epithelial colonisation (8%). Submucosal infiltration was found significantly more frequently in carcinomas of the prostate (67%) and lung (62%), compared with carcinomas of the ovary (27%) and breast (23%). Histological obstructive changes were observed in 36% of all cases, with the highest rate in prostate carcinoma (53%) and the lowest rate in kidney carcinoma (8%). Awareness of the main clinical and histological patterns of secondary carcinomas in GI tract biopsies may help pathologists to raise the possibility of this uncommon diagnosis and confirm it with the judicious use of immunohistochemistry.

Histopathological spectrum of lesions in gastrointestinal endoscopic biopsy: A prospective study of 500 cases

Lesion of the gastrointestinal tract is a very common condition encountered in medical science. An endoscopic biopsy is a favourable tool for early diagnosis and management of these conditions. The aim of the work is to study the histopathological spectrum of gastrointestinal endoscopic biopsy. In a prospective study of 500 biopsies, Formalin-fixed tissue was processed and stained with Hematoxylin-Eosin stain and studied under the microscope. A wide spectrum of neoplastic and non-neoplastic lesions was noted with male preponderance in most of the gastrointestinal tract. The commonest age group was 6 decades of life. Mean age being 51.83years. Predominant sample collected was from stomach accounting for 36.6% of total gastrointestinal biopsies. The ratio between non-malignant: malignant lesion was 2.7:1. Majority of the malignancy was Adenocarcinoma seen in 71 out of 135 cases closely followed by Squamous cell carcinoma (62/135). Most of the oesophageal malignancy was squamous cell carcinoma whereas adenocarcinoma was common in rest of the gastrointestinal tract. Gastritis was the commonest non-neoplastic lesion. Celiac disease was common in our study. Eight cases of adenomatous polyp identified, four of them showed high-grade dysplasia. Celiac disease and inflammatory bowel disease need further studies as there were many overlapping features which make a definitive diagnosis difficult. Endoscopy itself is insufficient in the diagnosis and management of gastrointestinal tract disease and biopsy must be performed in all cases of suspected endoscopic finding. Conditions like Barrett’s oesophagus, Celiac disease, Inflammatory Bowel Disease and high-grade dysplasia needs timely intervention to avoid more serious complications.

Upper digestive tract abnormalities in dogs with chronic idiopathic lymphoplasmacytic rhinitis.

BackgroundChronic idiopathic lymphoplasmacytic rhinitis (CILPR) is a common inflammatory disorder of unknown etiology affecting the nasal cavity of dogs. The diagnosis is made by exclusion of other causes of nasal disease and specific therapeutic protocols are lacking. In human medicine, a relationship between CILPR and gastrointestinal clinical signs has been postulated, and remission of respiratory signs after clinical trials with medications for gastrointestinal disorders has been observed.ObjectivesTo describe history, clinical presentation, endoscopic and histopathologic concurrent respiratory and digestive tract abnormalities, and to evaluate improvement of respiratory signs after treatment for gastrointestinal signs.AnimalsTwenty‐five dogs with CILPR.MethodsProspective study. For inclusion, following information had to be available: respiratory and digestive clinical signs, airway and digestive tract endoscopic abnormalities, histologic evaluation of respiratory and gastrointestinal tract biopsy specimens, and clinical response to different treatment strategies.ResultsTwenty‐two dogs had endoscopic gastrointestinal lesions, whereas 13 dogs had concurrent gastrointestinal signs. Most esophageal and duodenal endoscopic abnormalities were classified as moderate or severe. Respiratory and gastrointestinal tract histologic evaluation identified mostly chronic inflammation. Remission or marked improvement of respiratory signs was observed in the majority of dogs treated only for gastrointestinal signs up to 12 months after endoscopy. No significant associations between treatments and follow‐up information were found.Conclusion and Clinical ImportanceNasal and upper digestive tract abnormalities coexist in some dogs with CILPR. Lack of standardized therapeutic protocols suggests caution when interpreting improvement in nasal clinical signs. Additional studies are needed to explore the possibility of a cause‐effect relationship between the 2 processes.

Evaluating the spectrum of histomorphological patterns on endoscopic biopsy in patients with upper gastrointestinal tract disorders

Introduction: The upper gastrointestinal tract (UGT) disorders are more common complaints in clinical practice and have got high degree of mortality and morbidity. Many different types of lesions can affect the upper gastrointestinal tract and can be classified as congenital anomalies, infections, inflammation and neoplastic lesions. Material and Methods: A total of 152 cases of upper gastrointestinal tract biopsies are included in this study, out of which 113 cases were gastric biopsies, 22 cases were esophageal biopsies and the remaining 17 cases were duodenal biopsies. Present study was carried out in the Department of Pathology at Sri Venkateshwaraa Medical College Hospital and Research Centre, Puducherry for a period of one year between March 2018 and February 2019. All the biopsies were performed using fiberoptic endoscopy. Endoscopic biopsy in combination with histopathological examination plays an important role in the early diagnosis of determining UGT lesions. Also, special stains like Giemsa, Warthin starry stain was used to demonstrate Helicobacter pylori. Aim of the study is to evaluate the histomorphological patterns of upper gastrointestinal tract disorders on endoscopic biopsy and to correlate various upper gastrointestinal tract disorders in correspondence to clinical parameters. Results: It is reported among 152 cases of UGT biopsies 137 were non-neoplastic lesions and 15 were neoplastic. Commonly affected age group was 31-40 years followed by 41 to 50 years. As per the present study, males were affected more predominantly than females. Out of the 22 cases from esophageal biopsies, 16 cases showed non-neoplastic lesions and 6 were neoplastic. The most common non-neoplastic lesion was chronic nonspecific esophagitis and neoplastic lesion reported was squamous cell carcinoma. Among 113 gastric biopsies, 104 cases were non-neoplastic lesions and 9 were neoplastic lesions. Adenocarcinoma was the predominant neoplastic lesion of stomach. All the 17 duodenal biopsies showed non -neoplastic lesions.

P897Diagnostic utility of tissue biopsy in transthyretin cardiac amyloidosis diagnosed by non-invasive diagnostic criteria

Abstract Background In the recent past, transthyretin cardiac amyloidosis (TTR-CA) is recognized as an important cause of heart failure with preserved ejection fraction, and diagnostic utility of 99mTc-pyrophosphate (99mTc-PYP) scintigraphy in TTR-CA has been established. However, pathological evaluation is still the basis to confirm diagnosis. Subcutaneous tissue and gastrointestinal tract biopsy are useful examinations alternative to endomyocardial biopsy. Nevertheless, the positive ratio of amyloid deposition in these organs is not fully evaluated based on recent non-invasive diagnostic criteria. Purpose Our aim was to evaluate the diagnostic sensitivity of tissue biopsy in TTR-CA patients diagnosed by 99mTc-PYP scintigraphy. Methods We retrospectively evaluated 124 consecutive TTR-CA patients [wild-type (ATTRwt): 90, hereditary (hATTR): 34] who were diagnosed by positive findings of 99mTc-PYP scintigraphy (visual score 2 or 3) between June 2002 and January 2019 at our institute. Results A total of 114 patients underwent tissue biopsy at least one organ. Amyloid was detected on Congo red staining of subcutaneous tissue (43/97: 44%), gastrointestinal tract (52/78: 67%) and heart (78/79: 99%), respectively. Among 70 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsy, amyloid was detected at least one specimen in 57/70 (81%). Compared to hATTR CA patients, ATTRwt CA patients had lower positive ratio of subcutaneous tissue (81% vs. 27%) and gastrointestinal tract (73% vs. 63%) biopsy. Conclusion Non-invasive diagnostic criteria of TTR-CA had excellent sensitivity of amyloid deposition in heart. The diagnostic sensitivity of subcutaneous tissue and gastrointestinal tract biopsy was lower in ATTRwt CA compared to hATTR CA. Combination of subcutaneous tissue and gastrointestinal tract biopsy was useful for pathological confirmation of amyloid deposition without endomyocardial biopsy.

1246 Patients With Eosinophilic Gastritis and/or Eosinophilic Gastroenteritis Endure a Lengthy Path to Diagnosis and Experience Persistent Symptoms After Diagnosis

INTRODUCTION: Eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE) are chronic diseases characterized by elevated eosinophils in gastrointestinal (GI) tract biopsies. Patients with EG and/or EGE (EG/EGE) suffer from a decreased quality of life due to debilitating GI symptoms, a lengthy path to diagnosis, and lack of safe and effective treatment options. Here we utilize a large, highly representative claims database of ∼300 million US individuals to characterize the real-world diagnosis and management of adult patients with EG/EGE. METHODS: EG/EGE patients were identified by having ≥1 claim with a diagnosis code for EG and/or EGE (ICD-10-CM code K52.81) from Aug 2008 to Oct 2018 from Symphony Health's PatientSource® data. This analysis is focused on 3,458 unique adult patients (≥18 years) who had continuous claims data coverage for ≥3 years before and ≥1 year after EG/EGE diagnosis. RESULTS: Mean time from initial symptom presentation to EG/EGE diagnosis was 46.9 months; factors contributing to delayed diagnosis included delayed gastroenterologist referral, delayed endoscopy (Table 1), failure to diagnose on first endoscopy (39% of patients) and lack of routine biopsy/histopathology (65% of endoscopies). In the 12-month period following EG/EGE diagnosis, a majority of patients (56%) continued to experience GI symptoms, including abdominal pain, diarrhea and vomiting. Symptoms were documented by a healthcare provider at a mean frequency of 3.3 times per year. Overall, 32% of patients were treated with systemic corticosteroids (most commonly prednisone or prednisolone) and 6% received enteric-coated topical steroids (budesonide). Patients treated with systemic corticosteroids received a mean of 3.3 prescriptions per year, with the majority (59%) receiving more than one prescription per year. Persistence of GI symptoms was not related to treatment with systemic corticosteroids (Table 2). CONCLUSION: Patients with EG/EGE endure a lengthy path to diagnosis, and many continue to experience chronic, persistent GI symptoms after confirmed diagnosis despite frequent treatment with systemic corticosteroids. The lack of standard diagnostic processes and therapeutic options may prolong patient suffering due to uncontrolled symptoms. This study highlights the need for heightened disease awareness, standardized diagnostic criteria, and availability of safe and effective treatment options to improve the care of patients with EG/EGE.

Common Etiologies and Clinical Significance of Gastric Intraepithelial Lymphocytosis

Abstract Background Increased intraepithelial lymphocytes or intraepithelial lymphocytosis (IEL) in the upper gastrointestinal (GI) tract is a response to various mucosal injury. However, the frequency of gastric IEL in GI tract biopsy is not well documented, and the etiologies of gastric IEL are yet to be defined. Methods Cases with a diagnosis of “intraepithelial lymphocytosis” and “intraepithelial lymphocytes” were retrieved from 25,074 GI biopsies and 8,921 partial gastrectomies in our departmental database (Powerpath) for a 1-year period. The diagnosis of IEL was confirmed by the report and/or slide review. Possible etiology or causes of gastric IEL were investigated by correlation with clinical information from LIS (EPIC). Results A total of 694 cases with IEL were identified from 33,995 GI tract specimens (biopsy and resection). Among 694 cases, 34 (4.89%) were gastric biopsy and resection cases with IEL, whereas 561 (80.8%), 37 (5.3%), and 62 (8.9%) were duodenal, esophageal, and colonic specimens, respectively. Thirty-four gastric cases with IEL were closely associated with morbid obesity (8, 23.5%), H pylori infection (8, 23.5%), celiac disease (5, 14.7%), lymphocytic gastritis (5, 14.7%), nonspecific gastritis (4, 11.4%), inflammatory bowel disease (3, 8.8%), and gastroesophageal reflux disease (1, 1.9%). Seventeen of 34 (50%) cases had IEL in both gastric and duodenal mucosa. Those 17 cases with gastroduodenal IEL had morbid obesity (n = 5), celiac disease (n = 5), lymphocytic colitis (n = 2), inflammatory bowel disease (n = 2), H pylori gastritis (n = 2), and nonspecific gastritis (n = 1). Five patients with a diagnosis of lymphocytic gastritis were treated with a protein pump inhibitor after pathologic diagnosis. Among them, 4 had a followed-up endoscopy in 12 months, and 3 of them showed persistent IEL in a follow-up biopsy. Conclusion Gastric IEL is less common than duodenal IEL. It is associated with a broad differential diagnosis. Follow-up biopsy may be necessary for some types of gastric IEL. Persistent IEL in follow-up biopsy may be suggestive of a different etiology or requires different treatment strategy.

Osseous Metaplasia: An Unusual and Poorly Understood Finding in Gastric Polyps

Abstract Osseous metaplasia (OM) is an uncommon finding in gastrointestinal tract biopsies. Metaplastic bone formation has been predominantly reported in the lower GI tract in a background of benign and malignant neoplasms, as well as nonneoplastic inflammatory conditions. OM in the stomach is extremely rare, with less than 10 cases reported in the English literature to date. We present two cases of gastric OM encountered at one institution among more than 10,000 stomach polyps examined since 1994. The first is a 46-year-old female with spastic quadriplegia, peptic ulcer disease, and a jejunal feeding tube who had multiple gastric hyperplastic polyps removed over a 13-year period. The most recent polypectomy revealed a 3-cm gastric adenoma with benign bone formation in the stroma. The second case is of a 67-year-old asymptomatic male with a remote history of intestinal metaplasia and atrophy of the stomach who underwent upper endoscopy and removal of a 1-cm polyp. Sections consisted of hyperplastic foveolar epithelium with focal ossification. Both polyps showed acute and chronic inflammation and stromal fibrosis, and they lacked Helicobacter infection. Mechanisms driving gastrointestinal OM have been proposed since the first reported cases in the early 1900s. The most widely accepted theory is that osteogenic factors released by the neoplastic or inflammatory tissue induce undifferentiated stromal mesenchymal cells or fibroblasts to undergo transformation to osteoblasts. However, with gastrointestinal biopsies being one of the most common specimens, the picture remains incomplete as only very rare cases show bone formation, warranting further research. Although gastrointestinal OM appears to be clinically insignificant, long-term studies have yet to be performed. Nevertheless, it is crucial for pathologists to be aware of this phenomenon in order to avoid misdiagnosing OM as a primary mesenchymal neoplasm or bone invasion in cases of OM arising in the background of malignancy.

Evaluation of metabolic profile and C-reactive protein concentrations in brachycephalic dogs with upper airway obstructive syndrome.

BackgroundBrachycephalic dogs have abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome is associated with dyslipidemia, hyperglycemia, and insulin resistance. Despite the fact that anatomic and functional alterations are well described in brachycephalic dogs, little is known about the consequences of upper airway obstruction on systemic inflammatory response and metabolic profile.ObjectivesTo describe history, clinical presentation, and anatomic abnormalities; to evaluate systemic inflammatory response and metabolic profile; and to identify possible associations among clinical signs, anatomic abnormalities, inflammatory response, and metabolic profile in brachycephalic dogs with airway obstruction.AnimalsThirty purebred brachycephalic dogs with brachycephalic airway obstructive syndrome (BAOS).MethodsProspective study. The following information was recorded and studied: respiratory and digestive signs, airway and digestive endoscopic anomalies, presence or absence of tracheal hypoplasia, histologic evaluation of gastrointestinal tract biopsy specimens, serum concentrations of C‐reactive protein (CRP), fructosamine, insulin, glucose, triglyceride, cholesterol, and plasma concentrations of lipoprotein classes.ResultsA high proportion of dogs (76.7%) had gastrointestinal signs. Esophageal deviation, atony of the cardia of the stomach, and distal esophagitis were the most common endoscopic anomalies detected. Twenty‐six (86.6%) dogs had different degrees of laryngeal collapse. Gastrointestinal histologic evaluation identified mostly chronic inflammation. Glucose, fructosamine, triglycerides, cholesterol, CRP, pre‐beta, beta lipoproteins, and chylomicrons were increased to a variable extent. Significant associations among clinical signs, anatomic abnormalities, CRP, and metabolic profile were not found.Conclusion and Clinical ImportanceDespite the presence of inflammation and some mild metabolic derangements, the clinicopathological variables evaluated did not offer valuable information in dogs with BAOS.