Pathology International最新文献

Kidney injury molecule-1 (KIM-1) is a potential prognostic marker of advanced-stage clear cell renal cell carcinoma (ccRCC) and is associated with tumor immunogenicity. Little is known about its role in early-stage ccRCC, especially in pathological T1b (pT1b) disease, which shows a higher recurrence rate than pT1a disease. Resected specimens from 112 pT1b ccRCC cases were reviewed and immunohistochemically analyzed for KIM-1 expression. High membranous KIM-1 expression was defined as H score ≥ 140, based on the immunoreactive intensity and area, and cytoplasmic expression in ≥ 10% of cancer cells was considered as high cytoplasmic KIM-1 expression. KIM-1 expression status was compared with clinicopathological variables, including tumor-associated immune cell (TAIC) status. Among the 112 cases, high membranous and cytoplasmic KIM-1 expression was observed in 30 (27%) and 38 (34%) cases, respectively. High membranous KIM-1 expression was significantly associated with a higher nuclear grade, tumor necrosis, hot TAIC status, and shorter recurrence-free survival (RFS) and cancer-specific survival, whereas high cytoplasmic expression was only related to a higher nuclear grade. Multivariate Cox regression analysis revealed that high membranous KIM-1 expression and tumor necrosis were independent predictors of shorter RFS. Our results indicate that membranous KIM-1 expression could be a biomarker for predicting postnephrectomy recurrence in pT1b ccRCC.

Advances in cancer biology have been achieved by the identification of oncogenes and tumor suppressor genes through the remarkable progression of next-generation sequencing. New techniques, such as single-cell analysis, help uncover cancer progression and heterogeneity. Reverse genetic screenings, including methods like random mutagenesis via retroviruses, transposons, RNA interference, and CRISPR, are useful for exploring gene functions and their roles in cancer. Especially in random mutagenesis, CRISPR screening and its modifications have recently emerged as powerful tools due to their comprehensiveness and simplicity in inducing genetic mutations. Initially, CRISPR screening focused on analyzing biological phenotypes in a cell population. It has since evolved to incorporate advanced techniques, such as combining single-cell and spatial analyses. These developments enable the investigation of cell-cell and spatial interactions, which more closely mimic In Vivo microenvironments, offering deeper insights into complex biological processes. These approaches allow for the identification of essential genes involved in cancer survival, drug resistance, and tumorigenesis. Together, these technologies are advancing cancer research and therapeutic development.

Growing experience has correlated the histomorphological characteristics of clear cell renal cell carcinoma (ccRCC), ranging from cytoplasmic features to architectural patterns and tumor immune microenvironment, with clinical outcomes. However, further assessment is needed to determine which of these histologic parameters best correlate with outcomes of interest, especially response to tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Herein, we evaluated four histologic parameters: (i) World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade; (ii) clear and eosinophilic cytological phenotypes; (iii) immunophenotypes; and (iv) vascularity-based architectural classification, using hematoxylin and eosin-stained whole slide images for The Cancer Genome Atlas (TCGA) ccRCC cohort (n = 433). We then correlated these parameters with gene expression signatures associated with TKI and ICI response. Multivariate analysis found that the cytological phenotype and vascularity-based architectural classification were independently associated with an angiogenesis-related gene signature (both p < 0.05). Conversely, WHO/ISUP grade and immunophenotype were independently associated with effector T-cell and immune checkpoint gene signatures (both p < 0.05). In conclusion, histologic parameters, including cytological features, architectural patterns, and tumor immune microenvironment, are associated with gene signatures related to therapy response, with different parameters informative for TKIs versus ICIs. These findings may help guide prospective validation studies.

Adenosquamous carcinoma is an uncommon type of cancer that comprises malignant squamous and glandular components. We present a case of human papillomavirus (HPV)-positive adenosquamous carcinoma of the anorectum, which exhibited extensive pagetoid spread, in a 70-year-old woman. The tumor had spread from the lower rectum to the perianal skin and was removed through a combined endoscopic and transanal surgical procedure. Histological examination revealed three morphologically distinct components: adenocarcinoma in the lower rectum, squamous intraepithelial neoplasia with a minor invasive squamous cell carcinoma component in the anal canal, and pagetoid spread of adenocarcinoma extending to the perianal skin. HPV18 DNA and diffuse p16 expression were detected in all three components, suggesting the integration of HPV and a histogenetic relationship among these morphologically distinct components. This case indicates that HPV-associated adenosquamous carcinoma also occurs in the anal canal, similar to the uterine cervix, and may present as secondary Paget's disease.

This study presents the ultrastructural and immunohistochemical findings of a gastric bizarre leiomyoma arising in the vestibule of a 79-year-old male. Histologically, loosely proliferating tumor cells consist of large, multinucleated, bizarre nuclei with intranuclear inclusions and abundant cytoplasm-containing vacuoles. A murky line was apparent between the tumor cells and eosinophilic and heterogenous stroma-like areas. Immunohistochemically, tumor cells exhibited positively stained dot patterns of α-smooth muscle actin and caldesmon, which were distributed in the cytoplasm of tumor cells and stroma-like regions. Ultrastructurally, tumor cells exhibited extended and complex cytoplasmic processes comprising the fascicles of filamentous fibers. These structures were also detected in the apparent stroma-like regions observed histologically and were consistent with the α-smooth muscle actin- and caldesmon-immunopositive dot structures. The original stromal areas remained as considerably narrow gaps between tumor cells with extended cytoplasmic processes. To the best of our knowledge, this is the first report detailing the unique ultrastructural and immunohistochemical characteristics of tumor cells and the limited stromal composition of an extremely rare primary gastric bizarre leiomyoma.

Several classifications have been proposed to define rare cancers; however, the pathophysiological understanding of tumors evolves rapidly. We propose a New Classification of Rare Cancer (NCRC) using the updated International Classification of Diseases for Oncology 3.2 coding system and World Health Organization Classification of Tumors 5th edition. We applied patient data recorded in the National Cancer Registry of Japan to the new classification, setting a cut-off of a crude incidence rate of 6 cases/100 000/year to define rare cancers, and developed a list of rare cancers in Japan from 2016 to 2019. The NCRC system identified various rare cancers, comprising 20.0% of all cancer diagnoses in this period. To examine this classification system's performance, we compared rare/non-rare labeling of cancers by the Surveillance of Rare Cancers in Europe (RARECARENet) project and NCRC system. Compared with cases using the RARECARENet classification in Europe, 69 351 cases/year (6.8%) switched status with our classification, with 45 293 and 232 109 cases (4 years) switching from rare and non-rare, respectively. Major differences included diffuse large B-cell lymphomas, some thyroid cancers, oral cavity and lip cancers, and squamous cell carcinoma of the uterine cervix. As the NCRC includes newly classified tumor entities, it warrants validation using other diverse cohorts.

Helicobacter pylori is the main pathogenic factor in gastric cancer (GC), and the interleukin (IL)-17-mediated inflammatory response plays a crucial role in both H. pylori infection and gastric carcinogenesis. CMTM4, a subunit of the IL-17 receptor (IL-17R), has been implicated in immune responses, but its role in GC development remains unclear. In this study, we investigate the role of CMTM4 during H. pylori-induced gastric carcinogenesis using Cmtm4 knockout (KO) mice. Our findings indicated that Cmtm4 deficiency inhibited GC development and pseudopyloric metaplasia, while reducing DNA damage in the gastric mucosa. Mechanistically, Cmtm4 deletion downregulated the IL-17 signaling pathway in GC. Specifically, it suppressed the expression of IL-17 receptor RC (IL-17RC) and its downstream signaling molecules, resulting in the inhibition of nuclear factor-κ B (NF-κB) activation and a decrease in NADPH oxidase-1 (NOX1) levels. These results suggest that Cmtm4 deletion suppresses H. pylori-induced gastric carcinogenesis and precancerous lesion formation, potentially through the regulation of IL-17RC/NF-κB/NOX1 signaling, which may represent a new target for the early prevention of GC.