Aims: Mesothelioma is a malignant neoplasm of the serosal membranes originating from mesothelial cells. Peritoneal mesothelioma is the second most common mesothelial neoplasm after pleural mesothelioma, accounting for approximately 6%–15% of cases. Due to its high morphological variability, often mimicking other lesions, mesothelioma remains a diagnostic challenge. CDKN2A homozygous deletion has been established as a highly accurate biomarker for differentiating mesothelioma from benign mesothelial proliferations. MTAP immunohistochemistry (IHC) has been proposed as a cheaper and more reproducible surrogate for CDKN2A homozygous deletion (HD) detected by FISH in pleural mesothelioma. The aim of our study was to evaluate the reliability of MTAP IHC as a surrogate marker for CDKN2A HD in peritoneal mesothelioma. Methods and results: Thirty‐nine FFPE tissue samples of PeM were analysed for CDKN2A copy number status by FISH. MTAP IHC was performed using antibody clone 2G4, and cytoplasmic positivity was evaluated using two different cut‐offs (1% and 30%). Agreement between IHC and FISH was assessed using Cohen's Kappa. A ROC curve analysis was performed to evaluate the overall diagnostic performance of MTAP IHC. McNemar's test was used to identify statistically significant discordance between the techniques, and a power analysis was conducted to confirm the adequacy of the sample size. Additionally, 14 benign peritoneal lesions were included as external controls and underwent both FISH and IHC. All control samples showed preserved MTAP expression and no CDKN2A deletion. CDKN2A HD was detected in 27/39 cases. MTAP loss was observed in 13 cases, while the remaining 26 cases showed variable levels of MTAP positivity (15%–100%; mean: 36.4%; median: 25%). Cohen's Kappa revealed a low, non‐significant concordance between MTAP IHC and CDKN2A HD (cut‐off 1%: Kappa = 0.091, P = 0.462; cut‐off 30%: Kappa = 0.083, P = 0.326). ROC curve analysis (AUC = 0.569) confirmed the poor discriminatory performance of MTAP IHC. McNemar's test showed a statistically significant discordance between MTAP IHC and CDKN2A FISH results. Power analysis confirmed that the sample size ( n = 39) was adequate. Conclusions: These findings may reflect biological and pathogenetic differences between pleural and peritoneal mesotheliomas. Larger, multicentric studies are needed to validate the diagnostic role of MTAP IHC in peritoneal mesothelioma.

Amyloidosis refers to a group of diseases caused by extracellular deposits of misfolded proteins, which alter tissue function and structure, potentially affecting any organ. The term “amyloid” was introduced in the 19th century and later associated with pathological protein deposits. Amyloid fibrils, which are insoluble and resistant to degradation, originate from soluble proteins that undergo misfolding. This process can be triggered by several factors, such as aging, elevated protein concentrations, or pathogenic variants. Amyloid deposits damage organs both by disrupting tissue architecture and through direct cytotoxic effects, leading to conditions such as heart failure. Amyloidosis can be classified into acquired or inherited forms and can be systemic or localized. Diagnosing cardiac amyloidosis is complex and often requires tissue biopsies, which are supported by Congo Red dye staining. In some cases, bisphosphonate bone scans may provide a less invasive diagnostic option. In this state-of-the-art review, we focus on the most common forms of cardiac amyloidosis, from epidemiology to therapy, emphasizing the differences in molecular mechanisms and the importance of pathological diagnosis for appropriate treatment using a multidisciplinary approach.

Aims: Loss of MTAP expression by immunohistochemistry (IHC) is widely used as a surrogate for CDKN2A homozygous deletion (HD) in pleural mesothelioma (PM), but its diagnostic value in peritoneal mesothelioma (PeM) is less well defined. We investigated whether the observed limited reliability of MTAP IHC in PeM reflects a lower frequency of MTAP/CDKN2A co‐deletion. Methods and results: Twenty‐four PeMs selected from a previously characterized cohort according to CDKN2A and MTAP status underwent MTAP fluorescence in situ hybridization (FISH) using a custom‐made probe. Twenty‐five PMs and 10 reactive mesothelial proliferations (RMPs) were included as external controls. MTAP IHC, CDKN2A FISH and MTAP FISH were evaluated, and concordance was assessed using Cohen's kappa. In PM, MTAP IHC showed perfect concordance with MTAP FISH (kappa = 1.00; p < 0.001) and good concordance with CDKN2A FISH, as did MTAP FISH (kappa = 0.613; p = 0.002). MTAP IHC and FISH showed 100% specificity and 68.8% sensitivity for CDKN2A HD by FISH. In PeM, MTAP IHC remained highly concordant with MTAP FISH (kappa = 0.83; p = 0.001), whereas concordance with CDKN2A FISH was poor and not significant for both MTAP IHC (kappa = 0.21; p = 0.36) and MTAP FISH (kappa = 0.33; p = 0.17). In PeM, MTAP FISH showed 75% specificity and 62.5% sensitivity, MTAP IHC showed 75% specificity and 50% sensitivity for CDKN2A HD by FISH. All RMPs showed complete agreement and full specificity and sensitivity across all assays. Conclusions: Our findings indicate that in PeM, MTAP, although a less reliable surrogate for CDKN2A status, may serve as an independent adjunct diagnostic marker. The low concordance between MTAP and CDKN2A alterations suggests a lower rate of co‐deletion and points to potential site‐specific molecular differences.