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

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.

Pleural Effusion Caused by an Unusual Mass in the Right Hemithorax.

CASE PRESENTATION: An 80-year-old woman presented with complaints of weakness and dizziness. She had a medical history of subacute cerebral ischemia, vertigo, hypertension, and thalassemia minor. The patient was born and raised in Turkey and has lived in Switzerland for 50 years. Her sister died of a mesothelioma caused by asbestos exposure at the age of 60 years but had lived in Turkey until her death. The patient had neither a history of TB nor B symptoms. She has never smoked.

Nonmesothelial Spindle Cell Tumors of Pleura and Pericardium.

Spindle cell lesions of the pleura and pericardium are rare. Distinction from sarcomatoid mesothelioma, which has a range of morphologic patterns, can be difficult, but accurate diagnosis matters. This article provides practical guidance for the diagnosis of pleural spindle cell neoplasms, focusing on primary lesions.

Diagnostic performance of immunohistochemistry markers for malignant pleural mesothelioma diagnosis and subtypes. A systematic review and meta-analysis.

BACKGROUND: Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several immunohistochemistry markers have been employed to aid in accurate diagnosis. METHODS: The present systematic review and meta-analysis aimed to assess the diagnostic performance of various immunohistochemistry markers in malignant pleural mesothelioma diagnosis and its histological subtypes. Following the PRISMA guidelines, we systematically searched the literature for articles on using different immunohistochemical markers in MPM and its histological subtypes. EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to August 2023. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to assess the quality of the included articles. Meta-analyses were performed to determine prevalence using a random-effects model. RESULTS: 103 studies met the inclusion criteria, comprising a diverse range of immunohistochemistry markers. EMA and desmin-loss exhibited high sensitivity (96% and 92%, respectively) in distinguishing malignant pleural mesothelioma from benign pleural pathologies. Specificity was notably high for both BAP1-loss and survivin expression at 100%. Subtype-specific analyses demonstrated that EMA and HEG1 were sensitive markers for epithelioid mesothelioma, while GLUT1 showed high sensitivity for sarcomatoid mesothelioma. In cases comparing epithelioid mesothelioma and lung adenocarcinoma, CAM5.2 and calretinin displayed high sensitivity, while WT1 and BAP1-loss demonstrated exceptional specificity for malignant epithelioid mesothelioma. In the case of sarcomatoid mesothelioma and sarcomatoid lung carcinoma, GATA3 exhibited the most heightened sensitivity, while GATA3 and D2-40 displayed the best specificity for sarcomatoid malignant mesothelioma diagnosis. CONCLUSION: Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes.

Extrapleural pneumonectomy for sarcoma: Outcomes of adult patients at a specialized center.

BACKGROUND: Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral diaphragm. Small case series of pleural-based sarcoma of predominantly pediatric patients suggest EPP may be a life-prolonging surgical option. We aimed to describe the characteristics and outcomes of adults who underwent EPP at a specialized sarcoma center. METHODS: Clinicopathologic variables, surgical details, and follow-up information were extracted for patients undergoing EPP for pleural-based sarcoma between August 2017 and December 2020. Primary outcomes were event-free survival (EFS) and overall survival (OS) from the date of EPP. Secondary outcomes were disease-free interval (DFI) prior to EPP, and early and late postoperative complications. RESULTS: Eight patients were identified, seven with soft tissue sarcoma and one with bone sarcoma. Patients had either localized disease with a primary thoracic sarcoma, sarcoma recurrent to the thorax, or de novo metastatic disease. All patients underwent resection of their pleural-based sarcoma by an experienced cardiothoracic surgeon, and some patients had pre or postoperative treatment. The perioperative morbidity was comparable with previously published reports of EPP performed in mesothelioma patients. At median follow-up of 22.5 months, median EFS was 6.0 months and OS was 20.7 months. Six patients (75%) had disease recurrence; five (62.5%) died of progressive disease. Two patients (25%) had not recurred: one died of a radiation-related esophageal rupture, and one was alive with no evidence of disease at 37.0 months. Characteristics of those with the longest EFS included low-grade histology and achieving a metabolic response to preoperative chemotherapy. CONCLUSIONS: In adults with pleural-based sarcoma, EPP is rarely curative but appears to be a feasible salvage procedure when performed at specialized centers. Patient selection is critical with strong consideration given to multimodal therapy to optimize patient outcomes. In the absence of a confirmed response to neoadjuvant treatment, long term survival is poor and EPP should not be recommended.

Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Solitary pleural fibroma causing IGF-2-mediated hypoglycaemia in a non-diabetic patient.

A patient without a diagnosis of diabetes mellitus presented to the hospital due to a fall and hypoglycaemia on admission. The patient was found to have recurrent nocturnal fasting hypoglycaemia. CT revealed a large lung mass consistent with a solitary pleural fibroma, a rare tumour associated with insulin-like growth factor 2 (IGF-2) production. This case is an important reminder that potential causes of hypoglycaemia should be considered in non-diabetic patients.

Comparison of Immunohistochemistry, Next-generation Sequencing and Fluorescence In Situ Hybridization for Detection of MTAP Loss in Pleural Mesothelioma.

9p21 deletions involving MTAP/CDKN2A genes are detected in diffuse pleural mesotheliomas (DPM) but are absent in benign mesothelial proliferations. Loss of MTAP expression by immunohistochemistry (IHC) is well accepted as a surrogate for 9p21 deletion to support a diagnosis of DPM. Accurate interpretation can be critical in the diagnosis of DPM, but variations in antibody performance may impact interpretation. The objectives of this study were to compare the performance of MTAP monoclonal antibodies (mAbs) EPR6893 and 1813 and to compare MTAP expression by IHC with 9p21 copy number status in DPM. Cytoplasmic expression of MTAP IHC with mAbs EPR6893 (ab126770; Abcam) and 1813 (NBP2-75730, Novus Biologicals) was evaluated in 56 DPM (47 epithelioid, 7 biphasic, and 2 sarcomatoid) profiled by targeted next-generation sequencing. 9p21 Copy number status was assessed by Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) analysis and also by CDKN2A fluorescence in situ hybridization in discrepant cases when material was available. MTAP mAb 1813 showed stronger immunoreactivity, more specific staining, and no equivocal interpretations compared to mAb EPR6893 which showed equivocal staining in 19 (34%) of cases due to weak or heterogenous immunoreactivity, lack of definitive internal positive control, and/or nonspecific background staining. MTAP expression with mAb 1813 showed near perfect agreement with 9p21 copy number by combined FACETS/fluorescence in situ hybridization calls (κ = 0.85; 95% CI, 0.71-0.99; P < .001). MTAP IHC with mAb 1813 was 96% sensitive, 86% specific, and 93% accurate for 9p21 homozygous deletion. The findings of this study suggest that interpretation of MTAP IHC is improved with mAb 1813 because mAb EPR6893 was often limited by equivocal interpretations. We show that MTAP IHC and molecular assays are complementary in detecting 9p21 homozygous deletion. MTAP IHC may be particularly useful for low tumor purity samples and in low-resource settings.

[Interdisciplinary diagnostics and therapy of malignant mesothelioma]. / Interdisziplinäre Diagnostik und Therapie von malignen Mesotheliomen.

The asbestos-related malignant mesothelioma (MM) is one of the common occupational cancers in Germany with approximately 1000 new cases per year. Provided that the appropriate diagnostic criteria are fulfilled, MM can be diagnosed with high specificity from both histological and cytological specimens. However, many MM are detected cyto-/histologically only at advanced stages. Clinical/radiological aspects complement each other and enable interdisciplinary assessment of tumor stage and individualized decisions on the best possible therapeutic options. Diagnostically, video-assisted thoracoscopy (VATS) has the highest priority. Therapy planning is based on the MM subtype, tumor spread and stage, and the patient's clinical condition. MM has generally a very unfavorable prognosis. Accordingly, the standard therapy aims at a macroscopic radical tumor resection in terms of cytoreduction within the framework of a suitable multimodal therapy concept (chemotherapy, radiotherapy, psychooncology). The aim of palliative measures should be primarily symptom control. Overall, interdisciplinary diagnosis and therapy of MM is crucial for the best possible care of MM patients.

The over diagnosis of diffuse mesothelioma: An analysis of 311 cases with recommendations for the avoidance of pitfalls.

BACKGROUND: The diagnosis of mesothelioma may be challenging. We investigated a large database of cases in order to determine the frequency with which a diagnosis of mesothelioma was made incorrectly and the most frequent causes of error. DESIGN: A database including more than 4000 consultation cases of histologically confirmed mesothelioma was examined to identify cases in which mesothelioma was diagnosed by at least one pathologist when the available information pointed towards a different diagnosis. RESULTS: There were 311 cases misdiagnosed as mesothelioma. The most common category was metastatic carcinoma to the pleura or peritoneum (129 cases: 73 lung carcinomas, 15 renal cell carcinomas). The next most common category was primary lung cancer (111 cases: 55 sarcomatoid carcinoma, 56 pseudomesotheliomatous carcinoma). The third most common category was primary malignancies arising from or near the serosal membranes (33 cases). The fourth most common category was fibrous pleurisy (38 cases). The most common errors were failure to consider important radiographic information regarding the gross distribution of tumor, lack of awareness or consideration of another malignancy, overreliance on certain immunohistochemical results, and failure to perform certain diagnostic histochemical, immunohistochemical, or ultrastructural studies. CONCLUSIONS: There are a number of diagnostic pitfalls that can lead to the over diagnosis of mesothelioma. Careful attention to clinical and radiographic information as well as performance of appropriate ancillary tests can help to prevent such misdiagnoses. Detailed examples will be presented to assist in the avoidance of these pitfalls with emphasis on the most commonly observed errors.

Psychosocial well-being among patients with malignant pleural mesothelioma.

OBJECTIVES: The investigators conducted a psychosocial needs assessment of mesothelioma patients through self-report measures of quality of life (QOL), coping, depression, and social support. METHODS: Patients with malignant pleural mesothelioma (MPM) (N = 67) completed a battery of assessments at a single timepoint after being approached during routine medical oncology clinic appointments or by letter. RESULTS: Participants were predominately male (70.0%; n = 47) and ranged in age from 35 to 83 years old (M = 65.61, SD = 9.71). Most participants were white (88.0%; n = 59), and 10.0% (n = 7) were identified as Hispanic. The majority were married or living with a partner (93.0%; n = 62) and had some college or more education (64.0%; n = 43). Fourteen percent of participants (n = 11) endorsed significantly elevated depression symptoms. No significant demographic or clinical differences in depressed compared to nondepressed participants were observed, with a trend toward those identifying as Hispanic and those who were divorced as being more likely to be depressed. For the total sample, the most frequently endorsed coping strategies were active coping, emotional support, and acceptance. SIGNIFICANCE OF RESULTS: The present study did not identify any clear correlates of depression or QOL among patients with MPM. This research contributes to the small literature on psychosocial functioning in patients with MPM and provides putative directions for future larger studies and the development of interventions to provide appropriate support to diverse patients with MPM.

A Rare Presentation of Minimally Invasive Mesothelioma as a Large Tension Pneumothorax.

Development of mesothelioma is associated with asbestos exposure. Common presentations are with pleural-based plaques invading the chest wall and/or pleural effusion on chest imaging. The intent of this case report is to describe a rare presentation of mesothelioma, which presented atypically as a large tension pneumothorax. A 93-year-old male presented with a history of dyspnea that started after a coughing episode. On physical examination he was hemodynamically stable, but was hypoxic requiring 2L of supplemental oxygen. Computed tomography of the chest revealed a large right tension pneumothorax. A chest tube was placed and connected to suction (-20cmH20), but he continued to have an unresolving air leak over the following 2-week period. Upon video-assisted thoracotomy there were no blebs or adhesions seen. Right apical wedge resection and talc pleurodesis were performed. Pathologic examination revealed an atypical mesothelial cell proliferation with minimal, focal invasion into the pulmonary parenchyma. Tumor spread along the visceral pleura was thought to be the underlying cause of the pneumothorax. The surgical margins were uninvolved by the tumor, and the patient was later discharged home in stable condition. This was a rare presentation of what could best be described as minimally invasive mesothelioma arising in a background of probable mesothelioma in situ, which presented atypically as a large tension pneumothorax. This case highlighted the importance of establishing a pathologic diagnosis from pleural effusion cytology and/or pleural biopsy in persons presenting with spontaneous pneumothorax, and the difficulty in confirming a pathologic diagnosis of early mesothelial neoplasia.

Updates on grading mesothelioma.

Mesothelioma is a rare disease with an historically poor prognosis. Over the past decade, a grading system has been developed that is a powerful prognostic tool in epithelioid mesothelioma. Grading of epithelioid mesothelioma is now required or strongly recommended by expert consensus, the College of American Pathologists, the World Health Organization, and the International Mesothelioma Interest Group. The original nuclear grading system for epithelioid mesothelioma, developed in the United States, split epithelioid mesotheliomas into three prognostic groups with marked differences in survival. Now, this three-tiered nuclear grading system has been combined with the presence or absence of necrosis to form the currently recommended two-tiered grading system of low- and high-grade epithelioid mesothelioma. This review will focus on the development of this grading system in mesothelioma, the grading system's shortcomings, and the application of the grading system to cytology specimens and other extra-pleural sites. Lastly, this review will briefly discuss alternative grading systems and future considerations.

[Research progress on immunohistochemical diagnostic markers for malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, characterized by insidious onset, strong local invasiveness, short survival period, and poor prognosis. Clinical diagnosis is of paramount importance for the treatment and prognosis of MPM. Currently, the gold standard for diagnosing MPM is the results of histopathological examinations. Immunohistochemistry (IHC) is an effective auxiliary method in pathological diagnosis. Preliminary examinations can use two positive markers and two negative markers to distinguish pleural metastatic tumors, with additional antibodies selected based on differential diagnosis. The combined use of IHC markers plays a crucial role in the differential diagnosis between MPM and other tumors. This article primarily introduces commonly used IHC markers in MPM and the research progress of novel IHC markers in screening and differential diagnosis, aiming to provide reference for the clinical diagnosis and treatment of MPM.

Methylthioadenosine Phosphorylase and Breast Cancer 1 Protein-Associated Protein 1 as Biomarkers for the Peritoneal Mesothelioma.

OBJECTIVES: Combination of Breast Cancer 1 protein-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) in the peritoneal mesothelioma (PeM) has yet to be explored. We aim to assess the diagnostic value of combined BAP1 and MTAP to distinguish biphasic mesothelioma (BM) from epithelioid mesothelioma (EM) with reactive stroma in peritoneum, as well as its prognostic value in PeM. METHODS: This is a retrospective study from June 2014 to December 2021. This study included 18 cases of BM and 27 cases of EM with reactive stroma, excluded sarcomatoid, and EM without reactive stroma cases, and clinicopathological information was collected. The associations between MTAP and BAP1 levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and univariate/multivariate Cox proportional hazards regression models. RESULTS: Loss/decrease of BAP1/MTAP was observed in 6 (33.3%) BM cases and 12 (44.4%) EM cases. In 5 (27.8%) cases, loss of or decreased BAP1/MTAP expression was observed in both EC and SC of BM. BAP1/MTAP loss/decrease was observed in 12 (44.4%) cases of only EC of EM but not in reactive stroma. Compared with histology alone, a combination of BAP1 and MTAP immunohistochemistry (IHC) in spindled PeM provides a more objective mean to distinguish BM from EM with reactive stroma. Loss/decrease of BAP1/MTAP was associated with peritoneal cancer index (PCI) score (P = 0.047) and completeness of cytoreduction (CC) score (P = 0.038). BM patients have worse overall survival (OS) than EM with reactive stroma (P = 0 .007). CONCLUSIONS: Combination of BAP1/MTAP by IHC is helpful for differential diagnosis of peritoneal BM from EM with reactive stroma. Nevertheless, BAP1/MTAP may help to evaluate the biological behavior of PeM.

Updates in Management of Malignant Pleural Mesothelioma.

OPINION STATEMENT: Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated thoracic malignancy that is usually incurable. As demonstrated in the landmark MARS2 trial, surgical resection does not improve survival outcomes and its role in managing MPM is limited. Whilst platinum-pemetrexed chemotherapy in combination with bevacizumab was the standard first-line approach for unresectable disease, landmark phase 3 trials have now established the role of immune checkpoint inhibitors (CPIs) in the upfront management of unresectable disease: either nivolumab-ipilimumab or carboplatin-pemetrexed-pembrolizumab. Patient selection for optimal strategy remains an ongoing question. For relapsed disease novel genomic-based therapies targeting a range of aberrations including losses of the tumour suppressor genes BAP1, CDKN2A and NF2, are being evaluated. Nonetheless, the future of MPM therapeutics holds promise. Here we overview current treatment strategies in the management of MPM.