Identification of Thrombosis-Related Genes in Patients with Advanced Gastric Cancer: Data from AGAMENON-SEOM Registry

Advanced gastric cancer is one of the most thrombogenic neoplasms. However, genetic mechanisms underlying this complication remain obscure, and the molecular and histological heterogeneity of this neoplasm hinder the identification of thrombotic biomarkers. Therefore, our main objective was to identify genes related to thrombosis regardless of Lauren subtypes. Furthermore, in a secondary exploratory study, we seek to discover thrombosis-associated genes that were specific to each TCGA molecular subtype. We designed a nested case-control study using the cohort of the AGAMENON national advanced gastric cancer registry. Ninety-seven patients were selected—48 with and 49 without venous thromboembolism (using propensity score matching to adjust for confounding factors)—and a differential gene expression array stratified by Lauren histopathological subtypes was carried out in primary tumor samples. For the secondary objective, the aforementioned differential expression analysis was conducted for each TCGA group. Fifteen genes were determined to be associated with thrombosis with the same expression trend in both the intestinal and diffuse subtypes. In thrombotic subjects, CRELD1, KCNH8, CRYGN, MAGEB16, SAA1, ARL11, CCDC169, TRMT61A, RIPPLY3 and PLA2G6 were underexpressed (adjusted-p < 0.05), while PRKD3, MIR5683, SDCBP, EPS8 and CDC45 were overexpressed (adjusted-p < 0.05), and correlated, by logistic regression, with lower or higher thrombotic risk, respectively, in the overall cohort. In each TCGA molecular subtype, we identified a series of genes differentially expressed in thrombosis that appear to be subtype-specific. We have identified several genes associated with venous thromboembolism in advanced gastric cancer that are common to Lauren intestinal and diffuse subtypes. Should these genetic factors be validated in the future, they could be complemented with existing clinical models to bolster the ability to predict thrombotic risk in individuals with advanced gastric adenocarcinoma.

Biomarkers for Prognosis in Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (PNETs) encompass a diverse group of malignancies marked by histological heterogeneity and highly variable clinical outcomes. We performed a systematic review on potential prognostic biomarkers in PNETs by searching the PubMed database. A total of 472 manuscripts were reviewed in detail and 52 multivariate studies met the inclusion criteria proposed by the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK). These altogether analyzed 53 unique targets and 36 of them were statistically associated with survival.

Histological Heterogeneity of Primary Liver Cancers: Clinical Relevance, Diagnostic Pitfalls and the Pathologist’s Role

Primary liver cancers (PLCs) mainly comprise hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and cHCC-CCA. Combined HCC-CCA and small duct type iCCA show similar clinical presentations, and their histological features are more complex than seen in HCC. Therefore, while their treatment strategy differs, it is difficult to properly diagnose these tumors. Currently, HCC is the only tumor that can be treated by liver transplantation. In addition, small duct type iCCA harbors IDH1/2 mutations and FGFR2 fusions, which can be used for targeted therapy. Thus, improving diagnostic accuracy is crucial. A further point to note is that PLCs often present as multiple liver tumors, and they can be a combination of different types of PLCs or HCCs. In the case of HCCs, two different scenarios are possible, namely intrahepatic metastasis, or multicentric occurrence. Therefore, it is essential to characterize the type of multiple liver tumors. This review aims to clarify the pathological features of HCC, iCCA and cHCC-CCA, including their diagnostic pitfalls and clinical relevance. It is designed to be of use to clinicians who are dealing with PLCs, to provide a better understanding of the pathology of these tumors, and to enable a more accurate diagnosis and optimal treatment choice.

Pulmonary Sclerosing Pneumocytoma: A Pre and Intraoperative Diagnostic Challenge. Report of Two Cases and Review of the Literature

Pulmonary sclerosing pneumocytoma is a rare benign pulmonary tumor of primitive epithelial origin. Because of the unspecific radiological features mimicking malignancies and its histological heterogeneity, the differential diagnosis with adenocarcinoma and carcinoid tumors is still challenging. We report our experience of two cases of sclerosing pneumocytoma, as well as a review of the literature. Immunohistochemical findings showed intense staining of the cuboidal epithelial cells for cytokeratin-pool and TTF-1, with focal positivity for progesterone receptors. Round and spindle cells expressed positivity for vimentin, TTF-1 and focally for the progesterone receptor. Cytologic diagnosis of pulmonary pneumocytoma requires the identification of its dual cell population, made up of abundant stromal cells and fewer surface cells. Since the pre- and intraoperative diagnosis should guide surgical decision making, obtaining a sufficient specimen size to find representative material in the cell block is of paramount importance.

Dedifferentiated liposarcoma with abrupt transition of low-grade and high-grade dedifferentiated components: A case report

BackgroundDedifferentiated liposarcoma (DDLPS) is a unique subtype of liposarcoma, which has obvious histological heterogeneity. In affected patients, the condition typically manifests as the dedifferentiation of high-grade histological morphology, but it may also manifest as the dedifferentiation of low-grade histological morphology. In some cases, unique histological or immunophenotypic characteristics are observed. We describe, herein, a rare case of dedifferentiated liposarcoma, in which the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology.Case presentationA 69-year-old woman with severe abdominal pain lasting for 1 hour presented to our hospital. Physical examination revealed a mobile large left abdominal mass, Magnetic resonance imaging (MRI) scan showed a huge mass with typical fat components and the non-fatty nodule in the left retroperitoneal cavity. After laparotomy, histologic analysis of the specimens could find the atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and DDLPS components. Fluorescence in situ hybridization (FISH) analysis suggested the presence of MDM2 gene amplification. These findings supported a diagnosis of DDLPS.ConclusionIn our case, the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology. We hypothesize that low-grade dedifferentiation may be a precursor to high-grade dedifferentiation. MRI images cannot distinguish the two components.

Dedifferentiated liposarcoma with abrupt transition of low-grade and high-grade dedifferentiation: A rare case report

Dedifferentiated liposarcoma is a unique subtype of liposarcoma, which has obvious histological heterogeneity. In affected patients, the condition typically manifests as the dedifferentiation of high-grade histological morphology, but it may also manifest as the dedifferentiation of low-grade histological morphology. In some cases, unique histological or immunophenotypic characteristics are observed. We describe, herein, a rare case of dedifferentiated liposarcoma, in which the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology.

Comparison of Clinical and Histopathological Parameters amongst Microsatellite Unstable and Microsatellite Stable Cases of Colorectal Carcinomas in an Indian Setting

Introduction:Inthiseraofprognosisbasedmedicine,itisimportant to identify microsatellite unstable Colorectal Cancers (CRCs) as they offer good prospects to the patient and they respond poorly to 5-fluorouracil and platinum based chemotherapeutic regime. Aim: To find out the prevalence of Microsatellite Instability-High (MSI-H) in CRC, to identify clinicopathological features associated with Microsatellite Instability (MSI) and assess the value of surgical pathology in predicting MSI-H. Materials and Methods: The present study was a case-control study conducted in a tertiary care centre of Pune in Western India from January 2013 to December 2020. Thirty-five CRCs deficient in Mismatch Repair (MMR) proteins contrasted with 206 Microsatellite Stable (MSS) CRCs were studied and analysed for a given set of clinical and histopathological parameters to find out any correlation between the occurrence of microsatellite unstable tumours and these variables were presented as percentages. Results: In the present study, the prevalence rate of MSI-H was found to be 14.5% and the statistical analysis was carried out using the software Statistical Package for the Social Sciences (SPSS) version 27.0. Univariate analysis revealed that right-sided/proximal location of tumours, age at diagnosis less than 50 years, no lymph node deposits (N0 disease), presence of Tumour Infiltrating Lymphocytes (TILs), peri-tumoural reaction, mucinous component, increased stromal plasma cells, histological heterogeneity, signet ring/medullary component and Crohn-like reaction were all statistically significant predictors of microsatellite instability (p-value <0.05). Multivariate analysis of these significant parameters revealed right-sided location of tumours, age at diagnosis less than 50 years, N0 disease, and presence of TILs, increased stromal plasma cells, histological heterogeneity and Crohn-like reaction to be independent predictors. Conclusion: Clinical parameters and histological evaluation is handy in screening for the MSI-H colorectal carcinomas. This would go a long way in selecting the patients who will require confirmatory molecular testing and thus precluding the need of Immunohistochemistry (IHC), which will be helpful in day-to-day practice as it is uncomplicated, cost-effective and easy to replicate.

Novel Approaches in Surgical Management: How to Assess Surgical Margins

The concept of surgical margins was born a long time ago but still lacks a univocal and sound understanding. The current biological rationale behind the recommendations on margins management relies on two pillars: (1) the observation that groups of cancer cells can leave the macroscopic tumor and disseminate throughout adjacent tissues with different degrees of aggressiveness; (2) the belief that removal of all (or most of) cancer cells can cure the patient. However, this background is undermined by some pieces of evidence. For instance, it has been proven that tissues surrounding cancer often bear precancerous traits, which means that cutting through non-cancerous tissues does not equate to cut through healthy tissues. The head and neck exquisitely poses a number of challenges in the achievement of negative margins, with special reference to anatomical complexity, high density in relevant structures, and unique histological heterogeneity of cancers. Currently, intraoperative margins evaluation relies on surgeons’ sight, palpation, ability to map tumor extension on imaging, and knowledge of anatomy, with some optical imaging technologies aiding the delineation of the mucosal margins of excision. Frozen sections are currently used to intraoperatively evaluate margins, yet with debate on whether and how this practice should be performed. Future perspectives on improvement of margins control are threefold: research is oriented towards refinements of understanding of cancers local progression, implementation of technologies to intraoperatively render tumor extension, and employment of optical imaging modalities capable of detecting foci of residual tumor in the surgical bed.

Dedifferentiated Liposarcoma with Abrupt Transition of Low-Grade and High-Grade Dedifferentiated Components ：A Case Report

Background: Dedifferentiated liposarcoma (DDLPS) is a unique subtype ofliposarcoma, which has obvious histological heterogeneity. In affected patients, the condition typically manifests as the dedifferentiation of high-grade histological morphology, but it may also manifest as the dedifferentiation of low-grade histological morphology. In some cases, unique histological or immunophenotypic characteristics are observed. We describe, herein, a rare case of dedifferentiated liposarcoma, in which the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology.Case presentation: A 69-year-old woman with severe abdominal pain lasting for 1 hour presented to our hospital. Physical examination revealed a mobile large left abdominal mass, Magnetic resonance imaging (MRI) scan showed a huge mass with typical fat components and the non-fatty nodule in the left retroperitoneal cavity. After laparotomy, histologic analysis of the specimens could find the ALT/WDLPS and DDLPS components. Fluorescence in situ hybridization (FISH) analysis suggested the presence of MDM2 gene amplification. These findings supported a diagnosis of DDLPS.Conclusion: In our case, the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology. We hypothesize that low-grade dedifferentiation may be a precursor to high-grade dedifferentiation. MRI images cannot distinguish the two components.