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Background: Colorectal carcinoma is the second most common cause of cancer-related deaths in North America. Invasion of tumor cells into lymphatic and blood vessels is an imperative step in the metastatic progression of colorectal carcinoma., Objectives: This is a before-and-after study conducted by the Department of Pathology and Laboratory Medicine of Mount Sinai Medical Center of Florida to assess the impact on venous invasion (VI) detection by implementing routine elastin staining on all tumor-containing blocks per case, where feasible, in colorectal carcinoma (CRC) resection specimens., Methods: Clinicopathological parameters of CRC specimens were collected from January until December 2021 (n = 93) for the pre-implementation cohort and from January until December 2022 (n = 61) for the post-implementation cohort., Results: VI detection was significantly increased in the post-implementation cohort at a rate of 50.8 % compared to only 18.6 % in the pre-implementation cohort. The majority of VI identified in the pre-implementation cohort was extramural (61.5 %), whereas in the post-implementation cohort it was intramural (41.9 %). On univariate analysis, implementation of routine elastin stain was associated with strikingly increased VI detection rates (OR = 4.5, p-value < 0.001). On multivariate analysis, after adjusting for other clinicopathologic variables, elastin staining retained its independent statistically significant impact on VI detection (OR = 2.6, p-value = 0.034). Of note, there were no significant differences in the pre- and post-implementation cohorts in the frequency of nodal metastases, tumor extent, histologic grade, perineural invasion, T stage or M stage., Conclusion: Based on our results and what has been published recently, we confirm an increase in the VI detection rate after implementing routine elastin staining on all tumor-containing blocks in CRC resection specimens., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to poor prognosis and adverse outcomes in various malignant neoplasms; nevertheless, it can also be seen in benign pathologic conditions. In this review article, we discuss various signaling pathways and neurotrophic factors implicated in the development and progression of PNI. We also describe the methodology, benefits, and limitations of different in vitro, ex vivo, and in vivo models of PNI. The spectrum of presentation for PNI can range from diffuse spread within large nerves ("named" nerves) all the way through localized spread into unnamed microscopic nerves. Therefore, the clinical significance of PNI is related to its extent rather than its mere presence or absence. In this article, we discuss the guidelines for the identification and quantification of PNI in different malignant neoplasms based on the College of American Pathologists (CAP) and World Health Organization (WHO) recommendations. We also describe benign pathologic conditions and neoplasms demonstrating PNI and potential mimics of PNI. Finally, we explore avenues for the future development of targeted therapy options via modulation of signaling pathways involved in PNI.

Ganglioneuromas (GNs) are rare, benign tumors composed of ganglion cells, nerve fibers, and glial cells. Three types of colonic GN lesions exist: polypoid GNs, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. Less than 100 cases of GN are documented in the literature. A 10-year retrospective search of the pathology database at our institution identified eight cases of colonic GNs. All cases were incidental. Seven of the eight cases presented with colonoscopy findings of small sessile polyps (ranging between 0.1 and 0.7 cm) treated with polypectomy, whereas one case showed a 4 cm partially circumferential and partially obstructing mass in the ascending colon, treated with right hemicolectomy. Almost two-thirds of the cases (5/8) demonstrated associated diverticulosis. All cases were positive for S100 protein and Synaptophysin via immunohistochemistry (IHC). No syndromic association was identified in any of the cases. We also conducted a comprehensive review using PubMed to identify cases of colonic GN reported in the literature. In total, 173 studies were retrieved, among which 36 articles met our inclusion criteria (35 patients and 3 cases on animals). We conclude that while most GNs are incidental and solitary small sessile lesions, many can be diffuse and associated with syndromes. In these cases, the tumor can result in bowel obstruction simulating adenocarcinoma.

Prostate cancer (PCa) is the second-most commonly diagnosed cancer in men around the world. It is treated using a risk stratification approach in accordance with the National Comprehensive Cancer Network (NCCN) in the United States. The main treatment options for early PCa include external beam radiation therapy (EBRT), brachytherapy, radical prostatectomy, active surveillance, or a combination approach. In those with advanced disease, androgen deprivation therapy (ADT) is considered as a first-line therapy. However, the majority of cases eventually progress while receiving ADT, leading to castration-resistant prostate cancer (CRPC). The near inevitable progression to CRPC has spurred the recent development of many novel medical treatments using targeted therapies. In this review, we outline the current landscape of stem-cell-targeted therapies for PCa, summarize their mechanisms of action, and discuss avenues of future development.

Brenner tumors (BTs) are surface-epithelial stromal cell tumors that are categorized by the World Health Organization as benign, borderline, and malignant. Due to the rarity of BTs, the published literature on these tumors is comprised primarily of case reports and small retrospective studies. We performed a pathology database review spanning the last ten years at our institution revealing nine reported benign BTs. We collected the clinical and pathological data of patients associated with those BTs, describing the clinical presentation and imaging results, and assessing the possible risk factors associated with them. The average age at diagnosis was 58 years. BTs were discovered incidentally in 7/9 cases. The tumor was multifocal and bilateral in 1/9 cases and ranged in size from 0.2 cm to 7.5 cm. Associated Walthard rests were found in 6/9 cases and transitional metaplasia of surface ovarian and/or tubal epithelium was found in 4/9 cases. One patient had an associated mucinous cystadenoma in the ipsilateral ovary. Another patient had an associated mucinous cystadenoma in the contralateral ovary. In conclusion, we found that Walthard rests and transitional metaplasia are common findings in association with BTs. Additionally, pathologists and surgeons need to be aware of the association between mucinous cystadenomas and BTs.

T cells in the tumor microenvironment (TME) have diverse roles in anti-tumor immunity, including orchestration of immune responses and anti-tumor cytotoxic attack. However, different T cell subsets may have opposing roles in tumor progression, especially in inflammation-related cancers such as colorectal cancer (CRC). In this study, we phenotypically characterized CD3 + CD4 - (CD8 + ) T cells in colorectal tumor tissues (TT), normal colon tissues (NT) and in circulation of CRC patients. We investigated the expression levels of key immune checkpoints (ICs) and Treg-related markers in CD8 + T cells. Importantly, we investigated associations between different tumor-infiltrating CD8 + T cell subpopulations and disease-free survival (DFS) in CRC patients. We found that FoxP3 expression and ICs including PD-1, CTLA-4, TIM-3, and LAG-3 were significantly increased in tumor-infiltrating CD8 + T cells compared with NT and peripheral blood. In the TME, we found that TIM-3 expression was significantly increased in patients with early stages and absent lymphovascular invasion (LVI) compared to patients with advanced stages and LVI. Importantly, we report that high levels of certain circulating CD8 + T cell subsets (TIM-3-expressing, FoxP3 - Helios - TIM-3 + and FoxP3 - Helios + TIM-3 + cells) in CRC patients were associated with better DFS. Moreover, in the TME, we report that elevated levels of CD25 + and TIM-3 + T cells, and FoxP3 + Helios - TIM-3 + Tregs were associated with better DFS.

Introduction: Although it usually involves extranodal sites such as the gastrointestinal tract in more than 80% of cases, mantle cell lymphoma is considered a rare cause of gastrointestinal bleeding, especially severe and life-threatening bleeding., Patient Concern: A 60-year-old man with peptic ulcer disease, who presented with severe upper gastrointestinal (GI) bleeding and large gastric ulcer., Diagnosis: Primary gastric mantle cell lymphoma., Interventions: He was treated conservatively with blood transfusion and started on Traneximic acid for 3 days. Then, the patient underwent urgent hemostatic radiotherapy., Outcomes: The patient became stable and kept in the hospital for monitoring with a definite diagnosis of stage IV Mantle cell lymphoma is made., Conclusion: Mantle cell lymphoma should be kept in mind when assessing massive upper GI bleeding, as an unusual cause of bleeding gastric ulcer, given that bleeding is an uncommon presenting feature of GI lymphoma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Tissue-resident macrophages are receptive to specific signals concentrated in cellular niches that direct their cell differentiation and maintenance genetic programs. Here, we found that deficiency of the cytokine RANKL in lymphoid tissue organizers and marginal reticular stromal cells of lymph nodes resulted in the loss of the CD169 + sinusoidal macrophages (SMs) comprising the subcapsular and the medullary subtypes. Subcapsular SM differentiation was impaired in mice with targeted RANK deficiency in SMs. Temporally controlled RANK removal in lymphatic endothelial cells (LECs) revealed that lymphatic RANK activation during embryogenesis and shortly after birth was required for the differentiation of both SM subtypes. Moreover, RANK expression by LECs was necessary for SM restoration after inflammation-induced cell loss. Thus, cooperation between mesenchymal cells and LECs shapes a niche environment that supports SM differentiation and reconstitution after inflammation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Microenvironment and activation signals likely imprint heterogeneity in the lymphatic endothelial cell (LEC) population. Particularly LECs of secondary lymphoid organs are exposed to different cell types and immune stimuli. However, our understanding of the nature of LEC activation signals and their cell source within the secondary lymphoid organ in the steady state remains incomplete. Here we show that integrin alpha 2b (ITGA2b), known to be carried by platelets, megakaryocytes and hematopoietic progenitors, is expressed by a lymph node subset of LECs, residing in medullary, cortical and subcapsular sinuses. In the subcapsular sinus, the floor but not the ceiling layer expresses the integrin, being excluded from ACKR4+ LECs but overlapping with MAdCAM-1 expression. ITGA2b expression increases in response to immunization, raising the possibility that heterogeneous ITGA2b levels reflect variation in exposure to activation signals. We show that alterations of the level of receptor activator of NF-κB ligand (RANKL), by overexpression, neutralization or deletion from stromal marginal reticular cells, affected the proportion of ITGA2b+ LECs. Lymph node LECs but not peripheral LECs express RANK. In addition, we found that lymphotoxin-β receptor signaling likewise regulated the proportion of ITGA2b+ LECs. These findings demonstrate that stromal reticular cells activate LECs via RANKL and support the action of hematopoietic cell-derived lymphotoxin.