Types, differences and prognosis of colonic polyps

Colon polyps might originate from the submucosa including lymphoid aggregates, carcinoids and lipomas. On the other hand, most polyps usually arise from the mucosa and include various types, whether neoplastic or not. The prognosis and treatment of these lesions depend on establishing an adequate diagnosis to rule out the presence of malignancy. Therefore, clinicians should be aware of each subclassification's different types and presentations to achieve the best outcomes. When conducting colonoscopy screening for colorectal cancer, colorectal polyps are commonly discovered. The prevalence of these lesions is high. However, most of them do not have any clinical significance. On the other hand, evidence shows that some polyps might have premalignant characteristics, which are usually challenging to manage in clinical practice. Therefore, evidence shows that the most appropriate approach to managing these lesions and achieving the best prognosis would be identifying and treating them as early as possible before complications appear to intervene against potential morbidities and mortality. Clinicians should consider the wide variations of colorectal cancer to establish the most appropriate diagnosis. A histological diagnosis is essential in these events to exclude malignancy and decide the most appropriate treatment plan.

Rare Case of Gastric Schwannoma Simulating Gastrointestinal Stromal Tumour-A Case Report

Gastric schwannoma (GS) is a rare, benign, slow-growing neoplasm representing 0.2% of all gastric tumors. We report a rare case of Gastric schwannoma in a 56 year old woman who presented with abdominal discomfort and vomiting since few years. Contrast enhanced Computed Tomography showed a well-defined homogeneously attenuating lesion with homogenous enhancement. Wedge gastrectomy was done with a possible diagnosis of Gastrointestinal stromal tumor, but was confirmed to have Gastric schwannoma on histopathology showing spindle cells with peripheral cuff of lymphoid aggregates and S-100 protein positivity on immunohistochemistry. Gastric schwannoma should be included in the differential diagnosis of a gastric intramural or exophytic mass when Computed Tomography shows a well-defined homogeneously attenuating lesion with progressively increasing homogenous enhancement without hemorrhage, necrosis, and degeneration.

38 Spatial immune profiling of human glioblastoma tissue reveals the presence of aggregated lymphoid niches in the tumor microenvironment

BackgroundGlioblastomas (GBM) account for 60% of adult primary brain tumors. With few advances in therapeutics, median overall survival remains 15-months post-diagnosis. Immunotherapies may provide therapeutic benefit in GBM patients; however, no predictive immune features currently inform therapeutic stratification in GBM. We have shown that, independently of known prognosticators, radiographic tumor contact with the lateral ventricle (C-GBM) correlates with 7-months worse survival prognosis compared to patients with ventricle non-contacting GBM (NC-GBM). This study sought to characterize the GBM immune microenvironment and identify targetable mechanisms of immunosuppression correlating with worse outcomes in C-GBM.MethodsTwelve patients presented with pathologically confirmed primary, IDH wildtype C-GBM and thirteen with NC-GBM. Multiplex immunohistochemistry (mxIHC) was performed on formalin-fixed paraffin embedded (FFPE) tissue for each patient interrogating 8 predictive immune markers (CD3, CD4, CD8, FOXP3, CD68, IBA1, PD-1, and PD-L1). Machine learning tools characterized tumor-infiltrating immune populations and identified biomarkers correlating with C-GBM and patient survival. K-means clustering identified immunological neighborhoods within the tissue and a log odds ratio was used to quantify the likelihood of cell-cell interactions in the tissue.ResultsC-GBM tumors were enriched in monocyte-derived macrophages (MDM) compared to NC-GBM (19 ± 8% vs. 6 ± 2%; p<0.001) and depleted in lymphocytes (2.9 ± 1% vs. 7.6 ± 2%; p<0.001) and tissue-resident microglia (1.8 ± 0.3% vs. 7 ± 3%; p<0.001). Further, T cells in C-GBM co-expressed the checkpoint receptors PD-1, suggesting T cell exhaustion in the C-GBM tumor microenvironment. K-means clustering identified 10 immunological niches prevalent in GBM tissue. Macrophage-tumor niches were most common niche in the tissue accounting for 17.93% of all niches, followed by T cell-microglia-tumor niches (17.72%). Conversely, tumor-tumor niches were the least prevalent, accounting for only 2.51% of niches. Within niches, T cell-T cell interactions occurred more frequently than expected by random chance (log odds ratio = 0.90) whereas T cell-macrophage interactions occurred less frequently than expected by random chance (log odds ratio = -1.61). Pathological assessment of the tissue confirmed the presence of lymphoid aggregates in regions of myeloid exclusion in the tissue.ConclusionsThese findings suggest that factors within the periventricular space may influence antitumor immunity within GBM, and have identified clinically targetable immune biomarkers in glioblastoma. The prevalence of T cell niches in GBM tumors suggests the establishment tertiary lymphoid aggregates may be targetable to improve patient outcomes. Lastly, radiologic assessment of lateral ventricle contact by standard-of-care MRI may guide clinical trial design for immunotherapies in neuro-oncology.AcknowledgementsThis study was funded by NIH/NCI grant K00 CA212447 and supported by the Translational Pathology Shared Resource at Vanderbilt University (P30 CA068485).Ethics ApprovalPrimary glioblastoma tumors obtained in accordance with the Declaration of Helsinki and with institutional IRB approval (#131870) along with patient written informed consent.

Mature tertiary lymphoid structures in lung adenocarcinoma are associated with better progression free survival

Introduction/Objective The presence of inducible lymphoid structures known as tertiary lymphoid structures in the tumor microenvironment has been shown to correlate with positive clinical outcome. However, the maturation states of lymphoid aggregates in lung adenocarcinoma are not completely understood. Methods/Case Report Seventy tumor samples from 69 patients diagnosed with lung adenocarcinoma (Stages I to III) between 2013 and 2015 were included in the study. The presence and maturation states of the lymphoid structures within the tumors were evaluated by conventional and 26 samples were further analyzed by multiplexed immunohistochemistry of formalin fixed paraffin embedded tissues and then quantified. Mature lymphoid follicles containing germinal centers were identified by the presence of CD21+ and BCL-6+ cells in an organized configuration within tight clusters of T and B cells. Results (if a Case Study enter NA) Samples with fully mature lymphoid structures (germinal centers) had larger tumors and higher disease stage. The number of mature lymphoid structures correlated with the total number of lymphoid aggregates present in the tumor microenvironment. Additionally, tumor samples with ≥10 mature lymphoid structures had more primary follicles. While there was no difference in overall survival, progression free survival was significantly longer in patients who had ≥10 mature lymphoid structures in comparison with patients who had &lt;10 mature structures. Conclusion In conclusion, a spectrum of lymphoid aggregates in different stages of maturation are present in lung adenocarcinoma. An increase in the number of mature lymphoid structures may be associated with progression free survival in patients with lung adenocarcinoma.

Crohn’s disease of the gallbladder

Crohn’s disease (CD) is a chronic inflammatory condition, which typically involves the small and large bowel but can affect any part of the gastrointestinal tract. Common symptoms include abdominal pain, diarrhoea, fatigue, weight loss and malnutrition. Complications of CD include gallstone formation and cholecystitis. Impaired reabsorption of bile salts in the small bowel and CD-related surgeries are key factors in the development of CD-related gallstones, although other factors are also important. Direct CD-related inflammation of the gallbladder is very unusual and the typical histological features of CD are rarely encountered in cholecystectomy specimens of individuals with CD. We present a case of a man in his early 60s with CD, previous right hemicolectomy and a history of gallstones, who presented with chronic cholecystitis. Following cholecystectomy, pathological examination of the gallbladder unexpectedly demonstrated typical features of CD, including lymphoid aggregates and non-caseating mucosal granulomata.

The 12-CK Score: Global Measurement of Tertiary Lymphoid Structures

There is emerging evidence that the adaptive anti-tumor activity may be orchestrated by secondary lymphoid organ-like aggregates residing in the tumor microenvironment. Known as tertiary lymphoid structures, these lymphoid aggregates serve as key outposts for lymphocyte recruitment, priming and activation. They have been linked to favorable outcomes in many tumor types, and more recently, have been shown to be effective predictors of response to immune checkpoint blockade. We have previously described a 12-chemokine (12-CK) transcriptional score which recapitulates an overwhelming enrichment for immune-related and inflammation-related genes in colorectal carcinoma. Subsequently, the 12-CK score was found to prognosticate favorable survival in multiple tumors types including melanoma, breast cancer, and bladder cancer. In the current study, we summarize the discovery and validation of the 12-CK score in various tumor types, its relationship to TLSs found within the tumor microenvironment, and explore its potential role as both a prognostic and predictive marker in the treatment of various cancers.

Can histopathology of gastric tissue resected in sleeve gastrectomy be informative about serum iron levels?

One of the most common post-operative deficiencies after bariatric surgery is iron deficiency and one of the important determinants of post-operative iron deficiency is the preoperative condition. In this study, it was aimed to investigate the relationship between iron levels and histopathological findings observed in gastric tissue resected in sleeve gastrectomy. Preoperative and postoperative iron levels were compared with the presence of inflammation, atrophy, Helicobacter pylori, intestinal metaplasia, lymphoid follicles, and lymphoid aggregates observed in patients operated due to morbid obesity. The postoperative serum iron levels and preoperative values were compared and a statistically significant increase was found due to the use of iron-containing preparations after the operation. Among the parameters evaluated, inflammation, atrophy, Helicobacter pylori, intestinal metaplasia, and the presence of lymphoid follicles were not found to be associated with iron levels, but it was noted that the presence of lymphoid aggregate in all cases and male cases was correlated with preoperative low iron levels (p values 0.047 and 0.015 respectively). In this study, which investigated the role of histopathological findings in the prediction of iron deficiency in sleeve gastrectomies, the relationship between preoperative iron levels, which was reported to be predictive for post-operative iron deficiency, and the presence of lymphoid aggregates was revealed. It is thought that other histopathological findings such as the presence of lymphoid follicle and Helicobacter pylori are also important in terms of iron levels but could not be revealed due to the limitations of the study.

An analysis of histopathological features of Crohn’s disease in surgical specimens

Background The diagnosis of Crohn’s disease is challenging. This study aimed to compare the histological features of Crohn’s disease and non-Crohn’s disease (i.e., other intestinal inflammatory diseases) in surgical specimens to identify histologic features for differential diagnosis. Methods We evaluated patients who were diagnosed with Crohn’s disease (n = 171) and non-Crohn’s disease (n = 215) between 2010 and 2015 and underwent surgical bowel resection. The frequency of histological features in surgical resection specimens were compared between these two patient groups. Results Transmural inflammation, subserosal lymphoid aggregates, fissures or sinus-like structures, granulomas or granuloma-like nodules, abnormalities of the enteric nervous system, and mucosa structure alterations (i.e., muscularis mucosae thickening or mucosal atrophy with pseudopyloric gland metaplasia) were more frequent in Crohn’s disease than non-Crohn’s disease (p < 0.001 for all). A set of 3 of the above pathological features had a specificity of 93.5% for Crohn’s disease. Some of the above histologic features were further grouped as chronic inflammatory change that includes granulomas or granuloma-like nodules, lymphoid aggregates in the muscularis propria or subserosa, fissures or sinus-like structures, and architectural abnormality (i.e., the presence of abnormal enteric nervous system and/or mucosa structure alterations). A combination of transmural inflammation, chronic inflammatory change, and architectural abnormality had a sensitivity of 92.4% and a specificity of 97.7% for Crohn’s disease. Conclusions A combination of transmural inflammation, chronic inflammatory change, and architectural abnormality in surgical bowel resection specimens is diagnostic for Crohn’s disease.

Pulmonary Histopathology Findings in Patients With STAT3 Gain of Function Syndrome

Introduction and Aim Multiorgan autoimmunity and interstitial lung disease (ILD) are reported in patients with STAT3 GOF syndrome. Results We present lung histopathology findings in 3 such children, two of whom underwent wedge biopsies with adequate diagnostic material. Wedge biopsies showed interstitial cellular expansion with linear and nodular aggregates of CD8 positive T lymphocytes, plasma cells, and histiocytes; consistent with lymphocytic interstitial pneumonia pattern (LIP). CD4+ T cells and CD20+ B cells were present but infrequent in the interstitium. FOXP3 cells ranged from 0-5%. Focal interstitial and intraalveolar histiocytes were also seen. Neutrophils and eosinophils were rare/absent. Non-occlusive peribronchial lymphoid aggregates showed equal T and B cells; likely reactive in nature. Pulmonary vessels appeared normal without vasculitis or hypertensive change. There was no interstitial or subepithelial fibrosis or organizing pneumonia. Interlobular septa and visceral pleura were unremarkable. Conclusion Children with multi-system autoimmune disorders with ILD should be investigated for STAT3 GOF syndrome. Lung wedge biopsies are more informative than transbronchial biopsies, if a tissue sampling is indicated. CD8 dominant T cell inflammation seems to be a key driver of ILD. Although interstitial fibrosis was not seen in our small sample, longer follow up is needed to understand the natural history.