Adverse Prognostic Impact of Transitional and Pleomorphic Patterns in Pleural Nonepithelioid Mesothelioma: Insights From Comprehensive Analysis and Reticulin Stain.

CONTEXT.­: Mesothelioma subtyping into epithelioid and nonepithelioid categories plays a crucial role in prognosis and treatment selection, with emerging recognition of the impact of various histologic patterns. OBJECTIVE.­: To investigate the prognostic implications of transitional and pleomorphic patterns in sarcomatoid mesothelioma. DESIGN.­: A total of 132 mesothelioma cases (87 biphasic, 45 sarcomatoid) were analyzed. Histologic slides were assessed, treatment data collected, and cases categorized into predominant epithelioid or sarcomatoid patterns. The sarcomatoid mesotheliomas were classified into usual, pleomorphic, and transitional patterns, with reticulin staining for the latter. Statistical analysis included Cox regression and Kaplan-Meier methods. RESULTS.­: Younger age (P = .02) and receiving therapy (P < .001) correlated with improved survival for both histotypes. Advanced stage was associated with shorter survival in sarcomatoid cases (P = .02). Predominant epithelioid pattern in biphasic cases led to longer survival (P < .001). Transitional and pleomorphic patterns were indicative of worse prognosis, with significantly lower survival in cases with both patterns than with usual sarcomatoid (P = .046). Multivariate analysis identified independent survival factors, including predominant epithelioid component in biphasic mesothelioma (P = .001) and chemotherapy (P < .001). CONCLUSIONS.­: Histologic subtyping in mesothelioma plays a pivotal role in prognosis. Transitional and pleomorphic patterns, even in low percentages, indicate poorer outcomes. This study highlights the need for standardized diagnostic support and suggests the potential utility of histochemical staining in identifying more aggressive morphologic aspects. Recognizing the significance of these patterns can guide treatment decisions and patient care strategies.

Case report: Mesothelioma and BAP1 tumor predisposition syndrome: Implications for public health.

BRCA-1 associated protein 1 (BAP1) tumour predisposition syndrome (TPDS) is a hereditary condition characterised by germline mutation of the tumour suppressor BAP1. This disorder is associated with the development of various benign and malignant tumours, mainly involving the skin, eyes, kidneys, and mesothelium. In this article, we report the case of a man recruited through the Apulia (Southern Italy) Mesothelioma Regional Operational Centre of the National Register of Mesotheliomas, who suffered from uveal melanoma, renal cancer, and mesothelioma, and a familial cluster of BAP1 germline mutations demonstrated by molecular analyses. The family members of the proband developed multiple malignancies. As tumours arising in this context have specific peculiarities in terms of clinical behaviour, identification of this condition through appropriate genetic counselling should be considered for adequate primary, secondary, and tertiary prevention measures for offspring.

Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation.

There is evidence that asbestos could play a role in the carcinogenesis of digestive cancers. The presence of asbestos fibres in histological samples from gastric, biliary, colon cancers has been reported, but the mechanism is still controversial. It has been hypothesised that asbestos reaches these sites, especially through contaminated water; however, some experimental studies have shown that the inhaled fibres are mobile, so they can migrate to many organs, directly or via blood and lymph flow. We report four unusual cases of colorectal cancers in patients with a long history of asbestos exposure who also developed synchronous or metachronous mesothelioma. We evaluated the roles of BRCA associated protein-1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) in colon cancer and mesothelioma to support the hypothesis that BAP-1 and CDKN2A are tumour suppressor genes involved in disease progression, recurrence, or death in both digestive cancers and mesothelioma. Potentially, these markers may be used as predictors of worse prognosis, but we also stress the importance of clinical surveillance of exposed patients because asbestos could induce cancer in any organ.

Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights.

Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.