Underwater Endoscopic Mucosal Resection Vs Conventional Endoscopic Mucosal Resection for Superficial Nonampullary Duodenal Epithelial Tumors in the Western Setting.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial nonampullary duodenal epithelial tumors (SNADETs), but recently underwater endoscopic mucosal resection (U-EMR) has emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR vs C-EMR for SNADETs in a Western setting. METHODS: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of endoscopic mucosal resection and the occurrence of AEs or RRAs using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤20 mm or >20 mm. RESULTS: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR: n = 201, 69.3%; U-EMR: n = 89, 30.7%). The overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (odds ratio [OR], 4.95; 95% CI, 2.87-8.53), postprocedural bleeding (OR, 7.92; 95% CI, 3.95-15.89), and RRAs (OR, 3.66; 95% CI, 2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions. CONCLUSIONS: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRAs, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs.

Morphologic Heterogeneity of Carcinoma with Signet Ring Cell Features at Different Primary Sites.

INTRODUCTION: Signet ring cells (SRCs) may be observed in carcinomas from multiple primary sites. Elucidating unknown primaries from metastases with SRCs represents a diagnostic challenge. This study examined morphologic characteristics of adenocarcinomas with SRCs from stablished primary sites and described objective features, which can aid in identifying the site of origin. METHODS: The series encompasses 257 cases of adenocarcinomas with SRCs from gastroesophageal junction (GEJ, n = 38), stomach (n = 48), pancreatobiliary system (n = 16), colorectum (n = 40), appendix (n = 32), breast (n = 41), and lung (n = 42). H&E sections were examined and scored using architectural and cytologic criteria. Morphometric analysis was performed using QuPath software. RESULTS: Extracellular mucin was more abundant in GEJ, colorectal, and appendiceal carcinomas. Poorly cohesive morphology was the most frequent pattern in gastric and breast carcinomas. The cytoplasmic mucin/vacuole was predominantly clear and targetoid in breast carcinomas. Breast and gastric carcinomas showed the highest nuclear to cytoplasmic (N/C) ratio, whereas appendiceal carcinoma the lowest. CONCLUSION: Morphological evaluation (extracellular mucin, architectural patterns, and the nature of cytoplasmic mucin/vacuole) represents an important step to determine the cancer site of origin in adenocarcinomas with SRCs and guides further ancillary studies. Cytological morphometry may help further refine morphological criteria and facilitate the construction of digital-pathology algorithms.

Predicting residual neoplasia after a non-curative gastric ESD: validation and modification of the eCura system in the Western setting: the W-eCura score.

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

Gastric polyps in Familial Adenomatous Polyposis Portuguese patients: the first Western cohort with Asian features.

INTRODUCTION: Chronic atrophic gastritis may contribute to gastric polyps (GP) phenotype in familial adenomatous polyposis (FAP). Considering the high prevalence of Helicobacter-pylori (HP) infection in Portugal, we aim to characterise GP in a series of Portuguese patients. METHODS: In a retrospectively-selected series of 53 FAP patients, clinical data and histopathological features of GP and background gastric mucosa were studied. SPSS (27.0) was used for statistical analysis. RESULTS: Thirteen patients (24.5%) developed fundic gland polyps (FGP), seven (13.2%) gastric adenomas (GA) and ten (18.9%) both FGP and GA. Out of 100 GP, four were hyperplastic polyps, 58 FGP (24 with dysplasia), 35 intestinal-type GA (intGA) and three foveolar-type GA (fovGA). IntGA were larger (60% >7mm, p=0.03), occurred predominantly in the distal stomach (66.7%, p=0.024), in patients harbouring gastric intestinal metaplasia (IM) (86.7%, p<0.001) and duodenal adenomas (86.7%, p<0.001) Conclusion: This is the first Western series showing high prevalence of intGA in FAP patients, comparable to Asian cohorts. HP infection and chronic atrophic gastritis/intestinal metaplasia are likely responsible for this difference, with risk of neoplastic transformation and management implications. Biopsy/excision of GP >7mm, in the distal stomach, and in patients harbouring gastric intestinal metaplasia/duodenal adenomas should be considered.

Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study.

INTRODUCTION: Microsatellite instability (MSI) is an important prognostic molecular biomarker for gastric cancer (GC). MSI status may be detected by immunohistochemistry (IHC) for mismatch repair (MMR) proteins and polymerase chain reaction (PCR). Idylla™ MSI assay has not been validated for GC but may prove to be a valid alternative. METHODS: In a series of 140 GC cases, MSI status was evaluated by IHC for MLH1, PMS2, MSH2, and MSH6; gold-standard pentaplex PCR panel (PPP) (BAT-25, BAT-26, NR-21, NR-24, and NR-27); and Idylla. Statistical analysis was performed using SPSS 27.0. RESULTS: PPP identified 102 microsatellite stable (MSS) cases and 38 MSI-high cases. Only 3 cases showed discordant results. Compared with PPP, the sensitivity was 100% for IHC and 94.7% for Idylla. Specificity was 99% for IHC and 100% for Idylla. MLH1 IHC alone showed sensitivity and specificity of 97.4% and 98.0%, respectively. IHC identified three indeterminate cases; all were MSS according to PPP and Idylla. CONCLUSION: IHC for MMR proteins represents an optimal screening tool for MSI status in GC. If resources are limited, isolated MLH1 evaluation may constitute a valuable option for preliminary screening. Idylla may help detect rare MSS cases with MMR-loss and define MSI status in indeterminate cases.

Acute gastrointestinal graft-versus-host disease with cytomegalovirus and Epstein-Barr virus superinfection in a patient with COVID-19.

A 60-year-old female was diagnosed with acute myeloid leukemia. After initial remission with chemotherapy, she relapsed and underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two months later, she presented to emergency department with watery diarrhea, abdominal pain and fever. She also tested positive for SARS-CoV2 on nasopharyngeal swab by polymerase chain reaction (PCR) and both cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were detected in peripheral blood. Flexible sigmoidoscopy showed diffuse edema, erythema and loss of vascular pattern with interspersed segments of mucosal denudation and exudate and bBiopsies revealed epithelial cell apoptosis, diffuse crypt atrophy and dropout, with ulceration and both CMV and EBV were detected in colon mucosa, consistent with acute severe gastrointestinal graft-versus-host disease complicated by CMV and EBV superinfection. Despite starting therapy with methylprednisolone, ganciclovir and rituximab,she presented unfavorable evolution and died after 5 weeks.

Primary small bowel follicular lymphoma: the role of balloon-assisted enteroscopy in diagnosis and follow-up.

An asymptomatic 38-year-old male with no significant previous medical history performed routine laboratory studies that revealed iron-deficiency anemia. Esophagogastroduodenoscopy and colonoscopy were unremarkable and he undergone videocapsule endoscopy that revealed multiple small polyps along jejunum and ileum. Double-balloon enteroscopy confirmed the presence of scattered small whitish nodules and small polyps carpeting segments of jejunal mucosal and sometimes forming conglomerates with a nodular appearance. Histopathological examination showed lamina propria expansion by neoplastic follicles, predominantly composed by small lymphoid cells that, by immunohistochemistry, showed expression of CD20, CD10 and bcl-2. Computed tomography scan of abdomen and pelvis did not reveal systemic involvement, consistent with primary small bowel follicular lymphoma. Chemotherapy was started and, at reevaluation enteroscopy, although nodular jejunal segments persisted, biopsies did not show involvement by lymphoproliferative disease, which was interpreted as complete remission. Periodic clinical and biochemical evaluation and annual enteroscopic surveillance was maintained and, after three years, local recurrence of low-grade follicular lymphoma was detected. As previously, there was no evidence of systemic involvement and the decision was to maintain close surveillance. After one year, the patient remains asymptomatic and without evidence of disease progression. This case illustrates the essential role of balloon-assisted enteroscopy for diagnosis and surveillance of primary small bowel follicular lymphoma.

A practical approach for PD-L1 evaluation in gastroesophageal cancer.

PD-L1 is an established predictive immunohistochemical biomarker of response to immune checkpoint inhibitors. At present, PD-L1 is routinely assessed on biopsy samples of advanced gastroesophageal cancer patients before initiating first-line treatment. However, PD-L1 is still a suboptimal biomarker, due to changing cut-off values and scoring systems, interobserver and interlaboratory variability.This practical illustrated review discusses the range of staining patterns of PD-L1 and the potential pitfalls and challenges that can be encountered when evaluating PD-L1, focusing on gastric and gastroesophageal adenocarcinoma (G/GEA) and esophageal squamous cell carcinoma (ESCC).

Activation of Laminin γ2 by Helicobacter pylori Promotes Invasion and Survival of Gastric Cancer Cells With E-Cadherin Defects.

BACKGROUND: Helicobacter pylori infection induces cellular phenotypes relevant for cancer progression, namely cell motility and invasion. We hypothesized that the extracellular matrix (ECM) could be involved in these deleterious effects. METHODS: Microarrays were used to uncover ECM interactors in cells infected with H. pylori. LAMC2, encoding laminin γ2, was selected as a candidate gene and its expression was assessed in vitro and in vivo. The role of LAMC2 was investigated by small interference RNA (siRNA) combined with a set of functional assays. Laminin γ2 and E-cadherin expression patterns were evaluated in gastric cancer cases. RESULTS: Laminin γ2 was found significantly overexpressed in gastric cancer cells infected with H. pylori. This finding was validated in vitro by infection with clinical isolates and in vivo by using gastric biopsies of infected and noninfected individuals. We showed that laminin γ2 overexpression is dependent on the bacterial type IV secretion system and on the CagA. Functionally, laminin γ2 promotes cell invasion and resistance to apoptosis, through modulation of Src, JNK, and AKT activity. These effects were abrogated in cells with functional E-cadherin. CONCLUSIONS: These data highlight laminin γ2 and its downstream effectors as potential therapeutic targets, and the value of H. pylori eradication to delay gastric cancer onset and progression.

Comparison of East-Asia and West-Europe cohorts explains disparities in survival outcomes and highlights predictive biomarkers of early gastric cancer aggressiveness.

Surgical resection with lymphadenectomy and perioperative chemotherapy is the universal mainstay for curative treatment of gastric cancer (GC) patients with locoregional disease. However, GC survival remains asymmetric in West- and East-world regions. We hypothesize that this asymmetry derives from differential clinical management. Therefore, we collected chemo-naïve GC patients from Portugal and South Korea to explore specific immunophenotypic profiles related to disease aggressiveness and clinicopathological factors potentially explaining associated overall survival (OS) differences. Clinicopathological and survival data were collected from chemo-naïve surgical cohorts from Portugal (West-Europe cohort [WE-C]; n = 170) and South Korea (East-Asia cohort [EA-C]; n = 367) and correlated with immunohistochemical expression profiles of E-cadherin and CD44v6 obtained from consecutive tissue microarrays sections. Survival analysis revealed a subset of 12.4% of WE-C patients, whose tumors concomitantly express E-cadherin_abnormal and CD44v6_very high, displaying extremely poor OS, even at TNM stages I and II. These WE-C stage-I and -II patients tumors were particularly aggressive compared to all others, invading deeper into the gastric wall (P = .032) and more often permeating the vasculature (P = .018) and nerves (P = .009). A similar immunophenotypic profile was found in 11.9% of EA-C patients, but unrelated to survival. Tumours, from stage-I and -II EA-C patients, that display both biomarkers, also permeated more lymphatic vessels (P = .003), promoting lymph node (LN) metastasis (P = .019), being diagnosed on average 8 years earlier and submitted to more extensive LN dissection than WE-C. Concomitant E-cadherin_abnormal/CD44v6_very-high expression predicts aggressiveness and poor survival of stage-I and -II GC submitted to conservative lymphadenectomy.

PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application.

Immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis have brought significant clinical benefit in many solid cancer types, including gastrointestinal malignancies. However, it has been estimated that only 20-40% of patients respond to treatment. The pattern of expression and potential predictive value of PD-L1 as an immunohistochemical biomarker has been extensively studied in gastrointestinal neoplasms. Until now, its predictive value has been demonstrated, and is currently in use only in upper gastrointestinal malignancies (gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma).In this Review, we describe the technical aspects and challenges related to PD-L1 immunohistochemical assays, the current role of PD-L1 as a biomarker in clinical practice and we outline the main studies and clinical trials analyzing the prognostic and predictive value of PD-L1 in gastrointestinal cancers.

Very Early Onset-IBD: evidence for the need of a multidisciplinary approach.

Very early onset inflammatory bowel disease (VEO-IBD) represents approximately 25% of cases of IBD-like colitis occurring during childhood and, by definition, it is characterized by an onset prior to 6 years of age. This subgroup of patients presents significant differences from IBD occurring in older children and in adults, including a more severe clinical course, a reduced responsiveness to conventional IBD therapy, and a greater proportion of cases featuring an underlying monogenic disorder. Histological findings from gastro-intestinal (GI) biopsies are characterized by an IBD-like, apoptotic or enterocolitis-like pattern, complicating the differential diagnosis with other pediatric diseases involving GI tract. Moreover, individuals with monogenic disorders may develop significant comorbidities, such as primary immunodeficiency (PID), impacting treatment options. Without an appropriate diagnosis, the clinical course of VEO-IBD has greater potential for escalated treatment regimens involving extensive surgery, more intensive medical therapies and, even more important, inadequate recognition of underlying monogenic defect that may lead to inappropriate (sometimes fatal) therapy. For these reasons, an adequate context leading to an appropriate diagnosis is imperative, calling for a close collaboration between pediatricians, pathologists, geneticists, and immunologists.

Recent advances in the pathology of heritable gastric cancer syndromes.

Despite the relative rarity of hereditary gastric cancer syndromes, the prompt recognition of their specific clinical features and histopathological characteristics is pivotal in offering patients the most appropriate treatment. In this article, we address the three major inherited syndromes that primarily affect the stomach: hereditary diffuse gastric cancer (HDGC), caused by germline variants in CDH1 and CTNNA1; gastric adenocarcinoma and proximal polyposis of the stomach, caused by germline mutations in promoter 1B of APC; and familial intestinal gastric cancer, which has a poorly defined genetic cause. The main focus will be on HDGC, in light of the recent publication of updated clinical practice guidelines and emerging concepts regarding HDGC histopathology. In particular, we describe the broad morphological spectrum of HDGC lesions, stressing the importance of recognising indolent and aggressive phenotypes. Moreover, we discuss the increased risk of gastric (pre)malignancies developing in patients with other well-defined hereditary cancer syndromes, such as familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis, Li-Fraumeni syndrome, and hereditary breast and ovarian cancer syndrome.

Expression of Thomsen-Friedenreich Antigen in Colorectal Cancer and Association with Microsatellite Instability.

Microsatellite instability (MSI) is a molecular phenotype due to a deficient DNA mismatch repair (dMMR). In colorectal cancer (CRC), dMMR/MSI is associated with several clinical and histopathological features, influences prognosis, and is a predictive factor of response to therapy. In daily practice, dMMR/MSI profiles are identified by immunohistochemistry and/or multiplex PCR. The Thomsen-Friedenreich (TF) antigen was previously found to be a potential single marker to identify MSI-high gastric cancers. Therefore, in this study, we aimed to disclose a possible association between TF expression and MSI status in CRC. Furthermore, we evaluated the relationship between TF expression and other clinicopathological features, including patient survival. We evaluated the expression of the TF antigen in a cohort of 25 MSI-high and 71 microsatellite stable (MSS) CRCs. No association was observed between the expression of the TF antigen and MSI-high status in CRC. The survival analysis revealed that patients with MSI-high CRC showed improved survival when the TF antigen was expressed. This finding holds promise as it indicates the potential use of the TF antigen as a biomarker of better prognosis in MSI-high CRCs that should be validated in an independent and larger CRC cohort.

The Adaptive Immune Landscape of the Colorectal Adenoma-Carcinoma Sequence.

BACKGROUND: The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma-carcinoma sequence (ACS). METHODS: We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). RESULTS: The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. CONCLUSIONS: The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.

Hereditary diffuse gastric cancer: updated clinical practice guidelines.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome that is characterised by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is largely caused by inactivating germline mutations in the tumour suppressor gene CDH1, although pathogenic variants in CTNNA1 occur in a minority of families with HDGC. In this Policy Review, we present updated clinical practice guidelines for HDGC from the International Gastric Cancer Linkage Consortium (IGCLC), which recognise the emerging evidence of variability in gastric cancer risk between families with HDGC, the growing capability of endoscopic and histological surveillance in HDGC, and increased experience of managing long-term sequelae of total gastrectomy in young patients. To redress the balance between the accessibility, cost, and acceptance of genetic testing and the increased identification of pathogenic variant carriers, the HDGC genetic testing criteria have been relaxed, mainly through less restrictive age limits. Prophylactic total gastrectomy remains the recommended option for gastric cancer risk management in pathogenic CDH1 variant carriers. However, there is increasing confidence from the IGCLC that endoscopic surveillance in expert centres can be safely offered to patients who wish to postpone surgery, or to those whose risk of developing gastric cancer is not well defined.

Neoplastic and pre-neoplastic lesions of the oesophagus and gastro-oesophageal junction.

Oesophageal and gastro-oesophageal junction (GOJ) neoplasms, and their predisposing conditions, may be encountered by the practicing pathologist both as biopsy samples and as surgical specimens in daily practice. Changes in incidence of oesophageal squamous cell carcinomas (such as a decrease in western countries) and in oesophageal and GOJ adenocarcinomas (such as a sharp increase in western countries) are being reported globally. New modes of treatment have changed our histologic reports as specific aspects must be detailed such as in post endoscopic resections or with regards to post neo-adjuvant therapy tumour regression grades. The main aim of this overview is therefore to provide an up-to-date, easily available and clear diagnostic approach to neoplastic and pre-neoplastic conditions of the oesophagus and GOJ, based on the most recent available guidelines and literature.

Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes.

Gastric cancer accounts for about 6% of cancers worldwide, being the fifth most frequently diagnosed malignancy and the third leading cause of cancer related death. Gastric carcinogenesis is a multistep and multifactorial process and is the result of the complex interplay between genetic susceptibility and environmental factors. The identification of predisposing conditions and of precancerous lesions is the basis for screening programs and early stage treatment. Furthermore, although most gastric cancers are sporadic, familial clustering is observed in up to 10% of patients. Among them, hereditary cases, related to known cancer susceptibility syndromes and/or genetic causes are thought to account for 1-3% of all gastric cancers. The pathology report of gastric resections specimens therefore requires a standardized approach as well as in depth knowledge of prognostic and treatment associated factors.

New insights into the inflamed tumor immune microenvironment of gastric cancer with lymphoid stroma: from morphology and digital analysis to gene expression.

BACKGROUND: Gastric cancer with lymphoid stroma (GCLS) is characterized by prominent stromal infiltration of T-lymphocytes. The aim of this study was to investigate GCLS biology through analysis of clinicopathological features, EBV infection, microsatellite instability (MSI), immune gene-expression profiling and PD-L1 status in neoplastic cells and tumor immune microenvironment. METHODS: Twenty-four GCLSs were analyzed by RNA in situ hybridization for EBV (EBER), PCR/fragment analysis for MSI, immunohistochemistry (PD-L1, cytokeratin, CD3, CD8), co-immunofluorescence (CK/PD-L1, CD68/PD-L1), NanoString gene-expression assay for immune-related genes and PD-L1 copy number alterations. CD3+ and CD8+ T-cell densities were calculated by digital analysis. Fifty-four non-GCLSs were used as control group. RESULTS: GCLSs displayed distinctive clinicopathological features, such as lower pTNM stage (p = 0.02) and better overall survival (p = 0.01). EBV+ or MSI-high phenotype was found in 66.7 and 16.7% cases, respectively. GCLSs harbored a cytotoxic T-cell-inflamed profile, particularly at the invasive front of tumors (p < 0.01) and in EBV+ cases (p = 0.01). EBV+ GCLSs, when compared to EBV- GCLSs, showed higher mRNA expression of genes related to Th1/cytotoxic and immunosuppressive biomarkers. PD-L1 protein expression, observed in neoplastic and immune stromal cells (33.3 and 91.7%, respectively), and PD-L1 amplification (18.8%) were restricted to EBV+/MSI-high tumors and correlated with high values of PD-L1 mRNA expression. CONCLUSIONS: This study shows that GCLS has a distinctive clinico-pathological and molecular profile. Furthermore, through an in-depth study of tumor immune microenvironment-by digital analysis and mRNA expression profiling-it highlights the role of EBV infection in promoting an inflamed tumor microenvironment, with putative therapeutic implications.

Perianal purpuric plaques revealing an amyloid light-chain amyloidosis: case report and review of the literature.

Systemic immunoglobulin light chain amyloidosis is the most common and severe type of amyloidosis. There is an abnormal fibrillary protein deposition in tissues that leads to progressive and irreversible organ dysfunction. The most commonly affected organs are kidney and heart. Although rare, cutaneous manifestations may be the first clinical sign of the disease and usually present as hemorrhagic lesions, such as purpura, petechiae, and ecchymosis. We present a 71-year-old man that presented to our department because of exuberant purpuric plaques in the anogenital area as the first manifestation of an amyloid light-chain (AL) amyloidosis. The multi-organ involvement in addition to rapid clinical deterioration precipitated the patient's death four months later.