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INTRODUCTION: Pleural mesothelioma (PM) is an aggressive malignancy with no identified predictive biomarkers. We assessed whether tumor BAP1 status is a predictive biomarker for survival in patients receiving first-line combination platinum and pemetrexed therapy.METHODS: PM cases (n = 114) from Aalborg, Denmark, were stained for BAP1 on tissue microarrays. Demographic, clinical, and survival data were extracted from registries and medical records. Surgical cases were excluded. BAP1 status was associated with overall survival (OS) by Cox regression and Kaplan-Meier methods. Results were validated in an independent cohort from Perth, Australia (n = 234).RESULTS: BAP1 loss was found in 62% and 60.3% of all Danish and Australian samples, respectively. BAP1 loss was an independent predictor of OS in multivariate analyses corrected for histological subtype, performance status, age, sex, and treatment (hazard ratio = 2.49, p < 0.001, and 1.48, p = 0.01, respectively). First-line platinum and pemetrexed-treated patients with BAP1 loss had significantly longer median survival than those with retained BAP1 in both the Danish (20.1 versus 7.3 mo, p < 0.001) and Australian cohorts (19.6 versus 11.1 mo, p < 0.01). Survival in patients with BAP1 retained and treated with platinum and pemetrexed was similar as in those with best supportive care. There was a higher OS in patients with best supportive care with BAP1 loss, but it was significant only in the Australian cohort (16.8 versus 8.3 mo, p < 0.01).CONCLUSIONS: BAP1 is a predictive biomarker for survival after first-line combination platinum and pemetrexed chemotherapy and a potential prognostic marker in PM. BAP1 in tumor is a promising clinical tool for treatment stratification.

BACKGROUND The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes. MATERIAL AND METHODS Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value

PURPOSE OF REVIEW: Malignant pleural mesothelioma is an aggressive malignancy with a very poor prognosis. The majority of patients require pleural procedures for diagnostic or fluid management purposes. Damage to the pleura during these procedures can lead to procedure tract metastases (PTMs), with increasing risk from larger interventions. Prophylactic radiotherapy to these sites is a controversial topic with conflicting results from trial data. In this review, we summarize the recent evidence.RECENT FINDINGS: Four RCTs have been published on this topic, with another in follow-up. The earliest, from a cohort of 40 patients, strongly advocated the use of prophylactic radiotherapy. More recent trials, most notably the Surgical and large bore procedures in Malignant pleural mesothelioma And Radiotherapy Trial (SMART) (which randomized over 200 patients) did not demonstrate any benefit, especially when patient report symptoms and cost-effectiveness are considered. Certain subgroups demand further investigation, such as those not receiving systematic chemotherapy or with surgical intervention sites. The soon to be published Prophylactic Irradiation of Tracts (PIT) trial may help to further clarify best practice.SUMMARY: Recent studies have shown that prophylactic radiotherapy should not be routinely used to prevent PTMs in mesothelioma. Instead patients should undergo careful clinical follow-up to ensure PTMs are identified and treated promptly to minimize symptoms.

Paratesticular mesotheliomas are rare tumors with 223 cases described so far. The sole plausible causative factor so far ascertained in the pathogenesis of these tumors is asbestos, which however is found in only around 30% to 40% of such cases. The age range of affected individuals is wide, mostly adults and the elderly, but also includes young people and children. The most common presenting symptom is either hydrocele of unknown origin or intrascrotal mass. When hydrocele is the presenting symptom, these tumors are often clinically overlooked and the diagnosis is delayed. Most paratesticular mesotheliomas arise in the tunica vaginalis, but primary tumors of the spermatic cord and epididymis are also on record. Tumors arising from the peritoneal mesothelium of a hernia sac are excluded from this group. The correct diagnosis is almost always made after histologic examination of the operative specimen. Immunohistochemistry and electron microscopy are always helpful and sometimes necessary tools for diagnosis. So far very few cases have been identified or suspected preoperatively on cytologic examination. Three clinicopathologic types of malignant mesotheliomas of the male genital tract are recognized: diffuse tubulo-papillary mesothelioma, well-differentiated papillary mesothelioma, and multicystic mesothelioma. The histologic subtypes are almost always pure epithelial or biphasic. The differential diagnosis is mainly with serous papillary tumors arising from Mullerian vestiges, but several diverse primary or secondary tumors also need to be considered. A clinicopathologic evaluation of a case of tunical diffuse mesothelioma in a 74-year-old male from the AMR Series is the starting point for this general review.

Malignant mesothelioma is a tumour with increasing incidence due to widespread use of its causative agent, asbestos, in the past decades. The poor survival necessitates a correct differentiation from other lesions at the same site, such as hyperplastic mesothelium and carcinomas metastatic to pleura or peritoneum. Since genetic and immunohistochemical markers are not absolutely differentiating, the diagnosis is based on the histology complemented with (immuno)histochemistry. However, as the tumour presents itself in numerous heterogeneous histological forms, visual evaluation is extremely difficult. In order to evaluate the prognostic and diagnostic performance of syntactic structure analysis (SSA), chromatin texture analysis, densitometry, and morphometry, an automated KNN-classification system has been used to compare Feulgen-stained tissue sections of hyperplastic mesothelium, malignant mesothelioma, and pulmonary adenocarcinoma. In addition, we also studied most discriminative aspects in the differentiation, typing, and prediction of survival. The results indicate that for the diagnosis of malignant mesothelioma, chromatin texture parameters outperform SSA, densitometry, and morphometry (recognition score=96.8 per cent). Most discriminative parameters highlight spatial patterns of the chromatin distribution that are hard to appraise visually and directly show the benefits of a quantitative approach. Typing of the tumour is best described by SSA parameters, relating to the spatial arrangement of the cells in the tissue (recognition score=94.9 per cent). In survival time classifications, chromatin texture yields the highest recognition score (82.9 per cent), although accurate estimations are unreliable due to a large degree of misclassification. ispartof: Journal of Pathology vol:189 issue:4 pages:581-589 ispartof: location:England status: published

The author reported a case of multiple papillary mesothelioma of tunica vaginalis propria testis, differentiated from so-called adenomatoid tumor. In this case, tumor cells were definitely continuous with mesothelial cells of the tunics. Some confusions about mesothelioma and adenomatoid tumor in past reports were discussed and the characteristics of both tumors were defined.

The author reported a case of multiple papillary mesothelioma of tunica vaginalis propria testis, differentiated from so-called adenomatoid tumor. In this case, tumor cells were definitely continuous with mesothelial cells of the tunics. Some confusions about mesothelioma and adenomatoid tumor in past reports were discussed and the characteristics of both tumors were defined.