Identifying malignant mesothelioma by a pathological survey using the São Paulo state hospital cancer registry, Brazil

ABSTRACT Objective: To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry database in the state of São Paulo, Brazil. Methods: Possible cases were retrieved by assessing the database. Inclusion criteria were being older than 30 years of age and having ICD-O-3 topography and morphology codes related to MM. A board of expert pathologists reviewed the pathology reports and requested paraffin blocks in cases that demanded revision. After staining with calretinin, D2-40, WT-1 (as positive MM markers) and Ber-EP4 and MOC31 (as negative MM markers), cases were divided and studied independently by a pair of pathologists to confirm or discard the diagnosis of MM. Results: Our sample comprised 482 cases from 25 hospitals, and 130 needed further histological revision. We received 73 paraffin blocks with adequate material. After board analysis, there were 9 cases with a definitive diagnosis of MM, improving the diagnostic rate in 12%. Two cases of previously diagnosed MM were discarded by review. Conclusions: Our results confirm that part of MM underdiagnosis and underreporting in Brazil is due to incomplete or mistaken pathological diagnosis.

Mesothelioma in a developing country: a retrospective analysis of the diagnostic process / Mesotelioma em um país em desenvolvimento: análise retrospectiva do processo diagnóstico

ABSTRACT Objective: To evaluate the process of diagnosing patients with malignant pleural mesothelioma (MPM) at a tertiary care hospital. Methods: This was a retrospective study involving patients referred to a tertiary-care cancer center in Brazil between 2009 and 2020. The diagnostic process was divided into four steps: onset of symptoms, referral to a specialist visit, histopathological diagnosis, and beginning of treatment. The intervals between each phase and the factors for delays were evaluated. Data including clinical status, radiological examinations, staging, treatment modalities, and survival outcomes were collected. Results: During the study period, 66 patients (mean age = 64 years) were diagnosed with MPM and underwent treatment. Only 27 (41%) of the patients had knowledge of prior exposure to asbestos. The median number of months (IQR) between the onset of symptoms and the first specialist visit, between the specialist visit and histopathological characterization, and between definite diagnosis and beginning of treatment was, respectively, 6.5 (2.0-11.4), 1.5 (0.6-2.1), and 1.7 (1.2-3.4). The knowledge of prior asbestos exposure was associated with a shorter time to referral to a specialist (median: 214 vs. 120 days; p = 0.04). A substantial number of nondiagnostic procedures and false-negative biopsy results (the majority of which involved the use of Cope needle biopsy) were found to be decisive factors for the length of waiting time. The mean overall survival was 11.9 months. Conclusions: The unfamiliarity of health professionals with MPM and the patient's lack of knowledge of prior asbestos exposure were the major factors to cause a long time interval between the onset of symptoms and beginning of treatment. An overall survival shorter than 1 year is likely to have been due to the aforementioned delays.

RESUMO Objetivo: Avaliar o processo de diagnóstico de pacientes com mesotelioma pleural maligno (MPM) em um hospital terciário. Métodos: Estudo retrospectivo envolvendo pacientes encaminhados a um centro oncológico terciário no Brasil entre 2009 e 2020. O processo diagnóstico foi dividido em quatro etapas: início dos sintomas, encaminhamento para consulta especializada, diagnóstico histopatológico e início do tratamento. Foram avaliados os intervalos entre as etapas e os fatores de atraso. Os dados coletados incluíram estado clínico, exames radiológicos, estadiamento, modalidades de tratamento e resultados de sobrevida. Resultados: Durante o período do estudo, 66 pacientes (média de idade = 64 anos) foram diagnosticados com MPM e submetidos a tratamento. Apenas 27 (41%) dos pacientes tinham conhecimento de exposição prévia ao amianto. A mediana de meses (IIQ) entre o início dos sintomas e a primeira consulta especializada, entre a consulta especializada e a caracterização histopatológica e entre o diagnóstico definitivo e o início do tratamento foi, respectivamente, de 6,5 (2,0-11,4), 1,5 (0,6 -2,1) e 1,7 (1,2-3,4). Conhecimento de exposição prévia ao amianto associou-se a menor tempo para encaminhamento a um especialista (mediana: 214 vs. 120 dias; p = 0,04). O número substancial de procedimentos não diagnósticos e as biópsias falso-negativas (a maioria envolvendo o uso de biópsia com agulha de Cope) foram considerados fatores decisivos para o tempo de espera. A sobrevida global média foi de 11,9 meses. Conclusões: A falta de familiaridade dos profissionais de saúde com o MPM e o desconhecimento dos pacientes em relação à exposição prévia ao amianto foram os principais fatores que ocasionaram um longo intervalo de tempo entre o início dos sintomas e o início do tratamento. A sobrevida global inferior a 1 ano provavelmente se deve aos atrasos supracitados.

Malignant Mesothelioma Diagnosed by Bronchoscopic Biopsy / 결핵및호흡기질환

Malignant mesothelioma is a rare malignant neoplasm that arises from mesothelial surfaces of the pleural cavity, peritoneal cavity, tunica vaginalis, or pericardium. Typically, pleural fluid cytology or closed pleural biopsy, surgical intervention (video thoracoscopic biopsy or open thoracotomy) is conducted to obtain pleural tissue specimens. However, endobronchial lesions are rarely seen and cases diagnosed from bronchoscopic biopsy are also rarely reported. We reported the case of a 77-year-old male who was diagnosed as malignant mesothelioma on bronchoscopic biopsy from obstructing masses of the endobronchial lesion.

A Case of Advanced Malignant Pleural Mesothelioma Treatment with Chemotherapy and Photodynamic Therapy / 결핵및호흡기질환

Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant, and generally fatal disease. A 68-year-old male who was diagnosed with MPM at another hospital came to our hospital with dyspnea. We advised him to take combination chemotherapy but he refused to take the treatment. That was because he had already received chemotherapy with supportive care at another hospital but his condition worsened. Thus, we recommended photodynamic therapy (PDT) to deal with the dyspnea and MPM. After PDT, the dyspnea improved and the patient then decided to take the combination chemotherapy. Our patient received chemotherapy using pemetrexed/cisplatin. Afterwards, he received a single PDT treatment and then later took chemotherapy using gemcitabine/cisplatin. The patient showed a survival time of 27 months, which is longer than median survival time in advanced MPM patients. Further research and clinical trials are needed to demonstrate any synergistic effect between the combination chemotherapy and PDT.

Knockdown of Bcl-xL Enhances Growth-Inhibiting and Apoptosis-Inducing Effects of Resveratrol and Clofarabine in Malignant Mesothelioma H-2452 Cells

Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhibition of Bcl-xL influences cell growth and apoptosis against simultaneous treatment of resveratrol and clofarabine in the human malignant mesothelioma H-2452 cells. Resveratrol and clofarabine decreased Mcl-1 protein levels but had little effect on Bcl-xL levels. In the presence of two compounds, any detectable change in the Mcl-1 mRNA levels was not observed in RT-PCR analysis, whereas pretreatment with the proteasome inhibitor MG132 led to its accumulation to levels far above basal levels. The knockdown of Bcl-xL inhibited cell proliferation with cell accumulation at G2/M phase and the appearance of sub-G0/G1 peak in DNA flow cytometric assay. The suppression of cell growth was accompanied by an increase in the caspase-3/7 activity with the resultant cleavages of procaspase-3 and its substrate poly (ADP-ribose) polymerase, and increased percentage of apoptotic propensities in annexin V binding assay. Collectively, our data represent that the efficacy of resveratrol and clofarabine for apoptosis induction was substantially enhanced by Bcl-xL-lowering strategy in which the simultaneous targeting of Mcl-1 and Bcl-xL could be a more effective strategy for treating malignant mesothelioma.