Background: Mesothelioma of the tunica vaginalis testis (MTVT) is an extremely rare and aggressive cancer. The diagnosis and management of MTVT is complex, and no standard treatment protocol is available. Methods: We conducted a systematic literature review from 1 January 1982 to 14 March 2024 using PubMed to collect all the available case reports and case series. A descriptive analysis of patient characteristics with clinical presentation, diagnostic work-up, therapeutic management, and past asbestos exposure was performed. Survival times of patients treated with different therapeutic approaches were evaluated. Results: Overall, 289 patients with MTVT were included in our analysis. The most common clinical presentations were scrotal/testicular swelling or mass (187 patients, 65%) and the presence of hydrocele (159, 55%). Imaging evaluation, mostly with ultrasonography or CT scan, was reported in two-thirds of cases. Radical surgery (216 patients, 75%) with orchiectomy and, in select cases, hemiscrotectomy and inguinal lymphadenectomy was the most frequent therapeutic approach. A minority of patients (49, 17%) received adjuvant therapy after surgery (radiotherapy, chemotherapy, or a combination of the two), with no evidence of survival improvement. Conclusions: No standard guidelines for MTVT are available so far. Radical surgery following accurate radiological staging should be the mainstay of treatment. The role of adjuvant treatments remains undefined. Due to its rarity, MTVT should be treated in referral centers, and patients’ data should be collected in a dedicated register in order to improve the knowledge of this exceedingly rare disease and establish optimal diagnostic and therapeutic management.

The PRIMATE study is an Italian translational research project, which aims to identify personalized biomarkers associated with clinical characteristics of malignant pleural mesothelioma (MPM). For this purpose, characteristics of MPM patients with different degrees of asbestos exposure will be compared to identify somatic mutations, germline polymorphism, and blood inflammatory biomarkers. In this framework, we assessed exposure to asbestos for 562 cases of MPM extracted from the Lombardy region Mesothelioma Registry (RML), for which a complete interview based on a standardized national questionnaire and histopathological specimens were available. Exposure assessment was performed: (1) through experts' evaluation (considered as the gold standard for the purpose of this study), according to the guidelines of the Italian National Mesothelioma Registry (ReNaM) and (2) using a job-exposure matrix (SYN-JEM) to obtain qualitative (ever/never) and quantitative estimates of occupational asbestos exposure (cumulative exposure expressed in fibers per mL (f/mL)). The performance of SYN-JEM was evaluated against the experts' evaluation. According to experts' evaluation, occupational asbestos exposure was recognized in 73.6% of men and 23.6% of women; furthermore, 29 men (7.8%) and 70 women (36.9%) had non-occupational exposure to asbestos. When applying SYN-JEM, 225 men (60.5%) and 25 women (13.2%) were classified as occupationally exposed, with a median cumulative exposure higher for men (1.7 f/mL-years) than for women (1.2 f/mL-years). The concordance between the two methods (Cohen’s kappa) for occupational exposure assessment was 0.46 overall (0.41 in men, and 0.07 in women). Sensitivity was higher in men (0.73) than in women (0.18), while specificity was higher in women (0.88) than in men (0.74). Overall, both methods can be used to reconstruct past occupational exposure to asbestos, each with its own advantages and limitations.

Background: Malignant pleural mesothelioma (MPM) is a rare highly aggressive tumor strongly associated with asbestos exposure and characterized by poor prognosis. Currently, diagnosis is based on invasive techniques, thus there is a need of identifying non-invasive biomarkers for early detection of the disease among asbestos-exposed subjects. In the present study, we measured the plasmatic concentrations of Mesothelin, Fibulin-3, and HMGB1 protein biomarkers, and of hsa-miR-30e-3p and hsa-miR-103a-3p Extracellular-Vesicles- embedded micro RNAs (EV-miRNAs). We tested the ability of these biomarkers to discriminate between MPM and PAE subjects alone and in combination. Methods: the study was conducted on a population of 26 patients with MPM and 54 healthy subjects with previous asbestos exposure (PAE). Mesothelin, Fibulin-3, and HMGB1 protein biomarkers were measured by the enzyme-linked immunosorbent assay (ELISA) technique; the levels of hsa-miR-30e-3p and hsa-miR-103a-3p EV-miRNAs was assessed by quantitative real-time PCR (qPCR). Results: the most discriminating single biomarker resulted to be Fibulin-3 (AUC 0.94 CI 95% 0.88-1.0; Sensitivity 88%; Specificity 87%). After investigating the different possible combinations, the best performance was obtained by the three protein biomarkers Mesothelin, Fibulin-3, and HMGB1 (AUC 0.99 CI 95% 0.97-1.0; Sensitivity 96%; Specificity 93%). Conclusions: the results obtained contribute to identifying new potential non-invasive biomarkers for the early diagnosis of MPM in high-risk asbestos-exposed subjects. Further studies are needed to validate the evidence obtained, in order to assess the reliability of the proposed biomarker panel.

Cohort studies showed consistently low risks for malignant mesothelioma (MM) among agricultural workers, however the investigated exposures did not include asbestos. Our aim is to describe sources of asbestos exposure of MM in agriculture. Twenty-six MM cases in agricultural or seed trades workers were identified through the MM registry of the Lombardy region, Italy in 2000–2016. Asbestos exposures were investigated through a standardized questionnaire. The most frequent exposure circumstances were recycled jute bags previously containing asbestos (11 cases) and maintenance and repair of asbestos roofs (12 subjects). Three subjects performed maintenance and repair of tractor asbestos brakes and two used asbestos filters for wine production. Our data suggest asbestos exposure opportunities in the agricultural setting, underlining the need to look for this exposure in subjects affected with mesothelioma.

Sinonasal cancers (SNCs) are rare malignancies associated with occupational exposures. The aim of this study was to analyse the survival of SNC patients using data from the population-based SNC registry of the Lombardy region (10 million people), Italy. We included epithelial SNC cases registered in 2008–2020 and followed-up for vital status until 31 July 2023. Multivariate flexible parametric models with time-dependent covariates were fitted to calculate excess hazard ratios (EHRs) and 95% confidence intervals (CIs) of death. Based on 827 cases (553 males, 274 females) and 514 deaths (345 males, 169 females), the 5-year observed survival was 49% and the net survival was 57%. Age had a substantial impact on survival, particularly within the first year (EHR, 1.35; 95% CI, 1.12–1.51 per 10 years). Compared with the nasal cavity, the EHR for paranasal sinuses was 4.70 (95% CI, 2.96–7.47) soon after diagnosis. Compared with squamous cell carcinomas, the EHR was 0.69 (95% CI, 0.52–0.91) for adenocarcinomas, 1.68 (95% CI, 1.20–2.35) for undifferentiated and unspecified carcinomas, and 1.78 (95% CI, 1.07–2.95) for neuroendocrine carcinomas. Age and cancer site showed time-dependent effects on prognosis, especially within the first month after diagnosis. Prognosis was also markedly affected by cancer morphology. No associations were found for gender and period of diagnosis.

Background: Mesothelioma of the tunica vaginalis testis (MTVT) is an exceedingly rare tumor. We performed a registry-based study on MTVT patient management and survival in Italy. Methods: Cases were extracted from the dataset of the Italian National Mesothelioma Registry. A descriptive analysis of patient characteristics, including asbestos exposure, clinical presentation, diagnostic work-up and therapeutic management, was performed. Overall survival was evaluated. We calculated hazard ratios (HR) and 95% confidence intervals (CI) for selected variables by fitting univariate and multivariable Cox models. Results: Overall, 104 patients with MTVT were included. Median age was 72 years (range 17–92). Epithelioid histotype was the most frequent. Previous asbestos exposure was identified in two thirds of cases. Data on diagnostic and therapeutic management were available for 74 patients (71%). The most frequent presentations were scrotal swelling/mass, hydrocele and inguinal pain. All patients underwent surgery, mostly with orchi-funicolectomy. Adjuvant therapy was administered to 15 patients (20%). Overall median survival was 26.2 months (95% CI 22.1–52.1); 3-, 5- and 10-year survival was 49%, 30% and 18%. Older age at diagnosis and presence of distant metastasis (HR 1.91, CI: 0.85–4.26) were negative prognostic factors. Adjuvant therapy was associated with higher mortality (HR 2.54, CI: 1.25–5.15), indicating a more advanced stage at diagnosis. Conclusions: Surgery remains the mainstay of treatment for MTVT; adjuvant therapy in our study did not improve outcome. Data from cancer registries are essential for rare cancers, but they should be integrated routinely with additional diagnostic and therapeutic information.