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Background: The American Joint Committee on Cancer (AJCC) 8th edition TNM staging manual for non-small cell lung cancer (NSCLC) M1a descriptors includes tumors presenting with malignant pleural or pericardial effusion (ie, M1a-Effusion), pleural or pericardial nodule(s) (ie, M1a-Pleural), or separate tumor nodule(s) in a contralateral lobe (ie, M1a-Contralateral)., Research Question: Is M1a NSCLC presenting with malignant pleural or pericardial effusion associated with worse survival compared with other types of M1a NSCLC?, Study Design and Methods: Patients with cT1-4, N0-3, M1a NSCLC (satisfying a single M1a descriptor of M1a-Effusion, M1a-Pleural, or M1a-Contralateral), according to AJCC eighth edition staging criteria, in the National Cancer Database from 2010 to 2015 were included. Overall survival was evaluated by using Kaplan-Meier analysis, multivariable-adjusted Cox proportional hazards modeling, and propensity score matching., Results: Of the 25,716 patients who met study eligibility criteria, 12,756 (49.6%) presented with M1a-Effusion tumors, 3,589 (14.0%) with M1a-Pleural tumors, and 9,371 (36.4%) with M1a-Contralateral tumors. In multivariable-adjusted analysis, compared to M1a-Effusion tumors, both M1a-Pleural tumors (hazard ratio, 0.68; 95% CI, 0.64-0.71; P < .001) and M1a-Contralateral tumors (hazard ratio, 0.66; 95% CI, 0.64-0.69; P < .001) were associated with better overall survival. No significant differences were found in overall survival between patients with M1a-Pleural tumors vs M1a-Contralateral tumors. In a propensity score-matched analysis of 5,581 patients with M1a-Effusion tumors and 5,581 patients with other M1a tumors (ie, M1a-Contralateral or M1a-Effusion), those with M1a-Effusion tumors had worse 5-year overall survival than patients with other M1a tumors (M1a-Effusion 6.4% [95% CI, 5.7-7.1] vs M1a-Other 10.6% [95% CI, 9.7-11.5]; P < .001)., Interpretation: In this national analysis of AJCC 8th edition cT1-4, N0-3, M1a NSCLC, tumors with malignant pleural or pericardial effusion were associated with worse overall survival than tumors with either pleural or contralateral pulmonary nodules. These findings may be taken into consideration for the upcoming ninth edition of the AJCC lung cancer staging guidelines., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Case Presentation: A 57-year-old man with history of stage IIIB right-sided malignant pleural mesothelioma was admitted from his oncologist's office for progressive dyspnea of two weeks duration. He had associated dyspnea at rest and a new dry cough. He denied sputum production, hemoptysis, or fevers, but he did endorse chills, fatigue, and weight loss. The patient was a veteran of the Navy and had extensive international travel in his 20s. He had never been incarcerated and denied any sick contacts or recent travels. He had received a diagnosis of mesothelioma 11 months earlier after presenting to his physician's office with complaints of shortness of breath on exertion. Initial imaging revealed a large right-sided pleural effusion with irregular pleural thickening. He underwent right-sided thoracoscopy, and the pleural biopsy result was consistent with epithelioid mesothelioma. Because of invasion of his seventh rib, he was not a candidate for surgery and underwent palliative radiation and chemotherapy with cisplatin, pemetrexed, and bevacizumab. He was undergoing his eighth cycle of chemotherapy at the time of presentation., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Most patients with malignant pleural mesothelioma (MPM) seek treatment with malignant pleural effusion (MPE). In vitro evidence suggests that MPE may not be a simple bystander of malignancy, but rather potentially has biological properties that improve cancer cell survival and promote cancer progression. If this is the case, MPE management may need to shift from current symptomatic strategies to aggressive fluid removal to impact survival., Research Question: Is there an association between pleural fluid exposure and survival in MPM?, Study Design and Methods: Data from 761 patients who received a diagnosis of MPM between 2008 and 2018 were collected from patient medical records in three UK pleural units. Data included factors previously identified as influencing prognosis in MPM. Medical imaging was reviewed for presence, size, and duration of pleural effusion. Time-dependent covariate analysis of pleural fluid exposure and survival (model included weight loss, serum albumin, hemoglobin, MPM subtype, performance status, chemotherapy, and age) and multivariate Cox regression analysis of pleurodesis and survival were conducted., Results: Median overall survival was 278 days (interquartile range, 127-505 days; 95% CI, 253-301 days). Pleural fluid exposure duration showed no association with survival (hazard ratio, 1.0; 95% CI, 1.0-1.0). Median survival was 473, 378, and 258 days with complete, partial, and no pleurodesis (P = .008)., Interpretation: Pleurodesis success seems to be associated with improved survival; however, it is unclear whether duration of MPM exposure to pleural fluid is associated with survival within the limitations of this retrospective study. Future prospective studies are required to assess this potentially important mechanism., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sclerosing pneumocytoma (SP) is a rare primary lung tumor. Typical carcinoids (TCs) count for 2% of lung malignancies. A description of a combined neoplasm of SP with a nodal and pleural metastasized TC has, to our knowledge, never been published. A 57-year-old actively smoking woman received a diagnosis of a lesion in the left lower lobe via a screening CT scan for rheumatoid arthritis. A fluorodeoxyglucose-PET scan confirmed a 21 × 26 × 16 mm (standardized uptake maximum value, 3.0), well-circumscribed round lesion with calcification, which was thought to be most probably benign. No mediastinal lymph node enlargement or fluorodeoxyglucose uptake was detected. The results of routine laboratory tests, respiratory function tests, and physical examination were unremarkable. In diagnostic thoracoscopy pleural, diaphragmatic, and pericardial lesions were discovered and biopsied in addition to a wedge resection. After diagnosis of a pleural metastasized TC mixed with SP, radical resection and systemic lymph node dissection were performed. The patient is in remission after 36 months of follow-up., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Case Presentation: A man in his 20s presented to the ED after several months of progressive dyspnea, dry cough, and night sweats. He had no chest pain, fevers, weight loss, or sick contacts. He was previously healthy and took no medications. Social history was notable for 5 pack-years of tobacco use. The patient was sexually active with male partners and had a recent partner infected with human T-lymphotropic virus. The patient worked in set design and window installations, and wore a respirator when working around solvents and resins. From ages 2 to 7 years, he frequently visited buildings at his parents' workplace that were undergoing asbestos abatement. From ages 7 to 24 years, he frequently visited pottery studios where talc-containing products were used. He frequently visited northern Massachusetts, and infections with Borrelia burgdorferi and Bartonella henselae were common in family members. His stepfather had recently been infected with Anaplasma. There was no family history of cancer., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Pleural biopsies in patients with suspected malignant pleural mesothelioma (MPM) are often inconclusive resulting in repeat diagnostic procedures. Confocal laser endomicroscopy (CLE) enables real-time imaging on a cellular level. We investigated pleural CLE imaging as a biopsy guidance technique to distinguish malignant from benign pleural disease., Methods: Prospective, multicenter study in patients with (suspected) MPM based on PET-CT imaging who were scheduled for pleural biopsies. Patients received 2.5 mL fluorescein intravenously preceding the procedure. In vivo through-the-needle CLE imaging of the pleura and ex vivo CLE imaging of the biopsies were correlated with histology. CLE characteristics for various pleural entities were identified, and their interpretability was tested by CLE video scoring by multiple blinded raters., Results: CLE imaging was successfully obtained in 19 of 20 diagnostic pleural biopsy procedures (thoracoscopy: n = 4, surgical excision: n = 3, CT scan: n = 3, ultrasound: n = 9, esophageal ultrasound guided: n = 1) in 15 patients. CLE videos (n = 89) and corresponding pleural biopsies (n = 105) were obtained. No study-related adverse events occurred. Tumor deposits of MPM were distinguished from areas with pleural fibrosis based on CLE imaging and recognized by raters (n = 3) (interobserver agreement, 0.56; 95% CI, 0.49-0.64)., Conclusions: CLE imaging was feasible and safe regardless of the biopsy method. Real-time visualization of pleural abnormalities in epithelial and sarcomatoid MPM could be distinguished from pleural fibrosis. Therefore, CLE has potential as a guidance biopsy tool to reduce the current substantial rate of repeat biopsy procedures by identification of areas with malignant cells in vivo (smart needle)., Trial Registry: ClinicalTrials.gov; No.: NCT02689050; URL: www.clinicaltrials.gov., (Copyright © 2019. Published by Elsevier Inc.)

Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis with a median survival of < 12 months from diagnosis. Biomarkers have been proposed as a cost-effective means of cancer management, and the search for a mesothelioma biomarker has been ongoing for the last 30 years. Many traditional soluble (glyco)protein biomarkers have been evaluated over this time, and an ever-increasing list of new biomarkers, including messenger RNA, DNA, microRNA, and antibodies, is being reported from biomarker discovery projects. To date, soluble mesothelin is the only tumor biomarker to receive US Food and Drug Administration approval for clinical use in mesothelioma. Mesothelin is a glycoprotein normally expressed on the surface of mesothelial cells, and in the cancerous state it can be present in circulation. Mesothelin has a limited expression on normal, nonmalignant tissue and is thus an attractive therapeutic target for mesothelin-positive tumors. In this review we will focus on the discovery and clinical usages of mesothelin and provide an update on other mesothelioma biomarkers and show how such biomarker studies might impact on the management of this deadly tumor in the future., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Myiasis refers to a parasitic infestation of vertebrate mammals by dipterous larvae (maggots) of higher flies. Infections in humans typically occur in tropical and subtropical regions, regions with limited medical access, and areas with poor hygiene and living conditions. Infestations in humans have been described in subcutaneous, nasal, ocular, oropharyngeal, and orotracheal cases; however, reports of pulmonary myiasis in humans in the United States and other developed countries are extremely rare. We describe a patient with recently diagnosed primary pleural angiosarcoma who presented to our clinic for the management of a thoracostomy tube and was diagnosed with pleural myiasis., (Copyright © 2016 American College of Chest Physicians. All rights reserved.)

Background: Indwelling pleural catheters (IPCs) are commonly used to manage malignant effusions. Tumor spread along the catheter tract remains a clinical concern for which limited data exist. We report the largest series of IPC-related catheter tract metastases (CTMs) to date, to our knowledge., Methods: This is a single-center, retrospective review of IPCs inserted over a 44-month period. CTM was defined as a new, solid chest wall lesion over the IPC insertion site and/or the tunneled subcutaneous tract that was clinically compatible with a malignant tract metastasis., Results: One hundred ten IPCs were placed in 107 patients (76.6% men; 60% with mesothelioma). CTM developed in 11 cases (10%): nine with malignant pleural mesothelioma and two with metastatic adenocarcinoma. CTM often developed late (median, 280 days; range, 56-693) post-IPC insertion. Seven cases had chest wall pain, and six received palliative radiotherapy to the CTM. Radiotherapy was well tolerated, with no major complications and causing no damage to the catheters. Longer interval after IPC insertion was the sole significant risk factor for development of CTM (OR, 2.495; 95% CI, 1.247-4.993; P = .0098) in the multivariate analyses., Conclusions: IPC-related CTM is uncommon but can complicate both mesothelioma and metastatic carcinomas. The duration of interval after IPC insertion is the key risk factor identified for development of CTM. Symptoms are generally mild and respond well to radiotherapy, which can be administered safely without removal of the catheter.

Immunohistochemistry has come to occupy a key position among the armamentarium of tools pathologists apply to the evaluation of lung and pleural neoplasms. This technique uses antibodies that bind to specific antigens, usually proteins, enabling microscopic detection of the antigens. Over the last several decades, an impressive array of antibodies has become commercially available, and many of these antibodies have become integrated into the routine practice of pathology. Evaluation of tissue or cytology samples with these antibodies can facilitate determination of tumor type and site of origin. Comments citing results of immunohistochemical staining with these antibodies frequently appear in pathology reports and may be difficult to translate for those less familiar with the technique. This review presents, in two parts, common diagnostic applications of immunohistochemistry, with information about strategies taken for frequently encountered differential diagnostic scenarios. This, the first of two parts, offers a basic overview of the technique and discusses its applications in the diagnosis of common primary lung carcinomas.

Background: Malignant pleural mesothelioma (MPM) is an incurable cancer with a rising incidence. MPM is often perceived as a locally invasive cancer, and the exact cause of death is poorly understood.This two-center study describes the anatomic features of patients with MPM at postmortem., Methods: The Western Australia Mesothelioma Registry (Australia) and Coroner’s Office reports from the Avon region (England) were interrogated for the postmortem records of confirmed mesothelioma cases., Results: Postmortem records of 318 patients with pleural mesothelioma (169 from Western Australia and 149 from Avon) were identified. Most patients (91.5%) were men (mean age, 68.4 ± 11.5 years), and MPM was right-sided in 55.3%. Extrapleural dissemination of tumor was found in 87.7% of cases and lymph node involvement in 53.3%. Tumor dissemination in extra thoracicsites was common (55.4% of patients), and almost all organs were involved, including liver(31.9%), spleen (10.8%), thyroid (6.9%), and the brain (3.0%). Pulmonary emboli were found in 6% of cases and considered as directly contributing to death in 13 patients (4.1%). The precise cause of death could only be determined in 63 (19.8%) cases even after postmortem. The BMI was significantly lower in cases that had no identifiable anatomic cause of death at postmortem(18.8 ± 4.3 vs 21.0 ± 4.7, P = .034)., Conclusions: In this largest, to our knowledge, postmortem series on MPM, extrathoracic dissemination of mesothelioma was common and often under recognized. No anatomic cause of death was identified in the majority of patients even at autopsy, raising the possibility of physiologic and metabolic causes of death.

Immunohistochemistry has come to occupy a key position among the armamentarium of tools pathologists apply to the evaluation of lung and pleural neoplasms. This technique uses antibodies that bind to specific antigens, usually proteins, enabling microscopic detection of the antigens. Over the last several decades, an impressive array of antibodies has become commercially available, and many of these antibodies have become integrated into the routine practice of pathology. Evaluation of tissue or cytology samples with these antibodies can facilitate determination of tumor type and site of origin. Comments citing results of immunohistochemical staining with these antibodies frequently appear in pathology reports and may be difficult to translate for those less familiar with the technique. This review presents, in two parts, common diagnostic applications of immunohistochemistry with information about strategies taken for frequently encountered differential diagnostic scenarios. This article is the second of the two parts and focuses on immunohistochemical approaches to differentiating primary pulmonary from metastatic adenocarcinomas, mesotheliomas from carcinomas, and various types of spindle cell neoplasms. Potential future directions involving therapeutic and prognostic biomarkers are also discussed.

Background: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study examined the effect of clinical covariates on biomarkers levels and their diagnostic and prognostic value., Methods: Five hundred ninety-four participants were enrolled in a multicenter study, including 106 patients with mesothelioma and 488 control subjects. Multiple linear regression analyses were used to identify which covariates were independently associated with SM and MPF levels. The effect of these covariates on the diagnostic accuracy was evaluated with receiver operating characteristics curve analysis. In patients with mesothelioma, survival analysis was performed with Cox regression., Results: SM and MPF levels were independently associated with age, glomerular filtration rate (GFR), and BMI in control subjects and with GFR and tumor stage in patients with mesothelioma. The diagnostic accuracy of SM and MPF was significantly affected by the distribution of these covariates in the study population. The patients with mesothelioma were best discriminated from the control subjects with either the youngest age, the highest GFR, or the largest BMI. Furthermore, the control subjects were significantly better differentiated from stage II to IV than from stage I mesothelioma. MPF, not SM, was an independent negative prognostic factor, but only if adjusted for the biomarker-associated covariates., Conclusions: SM and MPF levels were affected by the same clinical covariates, which also had a significant impact on their diagnostic and prognostic value. To improve the interpretation of biomarker results, age, GFR, and BMI should be routinely recorded. Approaches to account for these covariates require further validation, as does the prognostic value of SM and MPF.

Background: Spontaneous pneumothorax (SPTX) is an uncommon phenomenon in the general population and is most commonly associated with prior bulbous emphysema, cystic parenchymal lung disease, and tuberculous lung disease. A rare cause of SPTX is malignant disease, either in the form of primary lung or pleural cancers, or in metastatic disease to the lungs. The purpose of this investigation was to compile patient characteristics, treatments received, and outcomes of patients with SPTX complicating sarcomatous cancer., Methods: Case reports and series published in the medical literature were identified through a MEDLINE search and compiled to determine similarities among patient characteristics, treatments received, and outcomes., Results: One hundred fifty-three cases representing 20 different sarcoma cell types were included; 126 (82.3%) had received some form of treatment prior to the development of pneumothorax, and 70 (45.7%) experienced recurrence of pneumothorax at an average of 61 (+/- 112) days. Patients had poor survival, with only seven of 81 subjects remaining alive 2 years after the initial diagnosis of SPTX., Conclusions: SPTX complicating sarcoma is associated with most cell types and is associated with increased mortality compared with patients without this complication.

Although the insulating properties of asbestos have been known for millennia, the link between asbestos exposure and mesothelioma was not recognized until 1960, when it was first described in South African asbestos miners. The incidence of mesothelioma parallels asbestos usage with a latency of 20 to 40+ years; thus, patient numbers are declining in the United States but rising in the developing world. Radiation, genetics, and possibly simian virus 40 are less common causes. Diagnosis can be challenging, since the results of pleural fluid cytology testing are often negative despite repeated sampling. No staging system adequately predicts prognosis in the unresected patient. Newly described biomarkers, including soluble mesothelin-related peptide, megakaryocyte potentiation factor, and osteopontin, may predict which asbestos-exposed individuals will develop mesothelioma, and may prove useful in assessing response to treatment. Since surgery cannot eradicate all residual microscopic disease, a multimodality approach is encouraged. Metaanalysis suggests that pleurectomy/decortication may achieve outcomes similar to those of extrapleural penumonectomy. The standard first-line chemotherapy for unresectable disease is pemetrexed plus cisplatin. This combination improves response, survival, time to progression, pulmonary function, and disease-related symptoms. Carboplatin is often substituted, with similar results. Other active agents include raltitrexed, gemcitabine, and vinorelbine. Novel agents in clinical trials include inhibitors of the epidermal growth factor receptor, vascular endothelial growth factor, mesothelin, and histone deacetylases. Although disappointing results of early trials did not confirm promising preclinical data, recent studies have suggested that some novel agents may be effective. As we learn more about mesothelioma biology, molecularly targeted agents may become treatment options.

Background: The T2 descriptor for staging non-small cell lung cancer (NSCLC) contains several non-size-based criteria. It remains unknown whether the prognostic significance of these non-size-based criteria is dependent on tumor size., Methods: A total of 10,545 patients with stage IB NSCLC from the California Cancer Registry between 1989 to 2003 were categorized into the following three nonoverlapping criteria: (1) tumor size (T2S); (2) visceral pleura invasion, hilar atelectasis, or obstructive pneumonitis (T2P); and (3) main bronchus involvement > or = 2 cm from the carina (T2C). Univariate survival analyses were performed using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios., Results: A total of 51.1% of patients with stage IB NSCLC were staged by T2S, 43.2% by T2P, and 5.7% by T2C; 2,224 stage IB patients (total, 21.1%; 18.9% T2P + 2.2% T2C) had tumors < or = 3 cm in size. The 5-year survival rate and the median survival time of these stage IB patients with tumors < or = 3 cm in size were as follows: T2P, 51.2% and 64 months, respectively; T2C, 49.0% and 58 months, respectively. These values were similar to the 53.2% 5-year survival rate and 67-month median survival time for patients with stage IA NSCLC (p = 0.40). Cox proportional hazards model revealed T2P of > 3 cm was a poor prognostic factor for survival (vs T2S; hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.08 to 1.24). Conversely, T2P < or = 3 cm was a favorable prognostic factor for survival (vs T2S; HR, 0.89; 95% CI, 0.82 to 0.96). T2C was not an independent prognostic factor for survival., Conclusions: Prognostic significance of the non-size-based T2 descriptor T2P is dependent on tumor size.

We report a case of a 65-year-old male patient who presented with gradually worsening dyspnea over 2 years. History was significant for smoking and the absence of any hazardous occupational exposure. The clinical findings at presentation included absent breath sounds and stony dullness on the left side, with tracheal deviation contralaterally and clubbing. A chest roentgenogram showed a left-sided opacity occupying almost the entire left hemithorax. A subsequent CT scan of the chest revealed an intrathoracic, extrapulmonary lesion producing a mediastinal shift. Surgical resection of the mass was performed, and pathology, along with immunohistochemical studies positive for CD34 and negative for epithelial markers, confirmed the diagnosis of solitary fibrous tumor of the pleura (SFTP). SFTP is a rare neoplasm, and diagnosis is often difficult. Suspicion of SFTP should arise in the setting of a patient presenting with a paucity of symptoms (except in the case of an accompanying paraneoplastic syndrome), the absence of exposure to asbestos, and a large mass with sharp margins and encapsulation seen on a chest radiograph.

Study Objective: Dynamic contrast-enhanced MRI (DCE-MRI) followed by pharmacokinetic analysis has been successfully used in a variety of solid tumors. The aims of this study were to evaluate the feasibility of DCE-MRI in malignant pleural mesothelioma (MPM), to differentiate benign from pathologic tissue and compare pharmacokinetic with clinical parameters and survival in order to map out its microcirculation; and to compare pharmacokinetic with clinical parameter and survival in order to improve our understanding of the in vivo biology of this malignancy., Methods: Nineteen patients with a diagnosis of MPM who were scheduled to receive chemotherapy with gemcitabine were enrolled in the study. DCE-MRI was performed before treatment (n = 19) and after the third cycle (n = 12) and sixth cycle (n = 7) of chemotherapy. An established pharmacokinetic two-compartment model was used to analyze DCE-MRI. Tumor regions were characterized by the pharmacokinetic parameters amplitude (Amp), redistribution rate constant (kep), and elimination rate constant (kel). Kinetic parameters of tumor tissue and normal tissue were compared using the Student t test. Patients were classified as clinical responders or nonresponders according to clinical outcome, and these groups were compared with the pharmacokinetic parameters derived from DCE-MRI., Results: Normal and tumor tissue could be distinguished by the pharmacokinetic parameters Amp and kel (p

The diagnosis and management of malignant pleural mesothelioma are major challenges that often frustrate both patient and clinician alike. Occupational asbestos exposure to crocidolite or amosite forms of the fiber is the most important known risk factor in North America and Western Europe. Other mineral fibers such as erionite, a naturally occurring fibrous zeolite crystal, are associated with mesothelioma in volcanic tuffs of the Cappadocia region of central Anatolia in Turkey. In addition, other possible factors such as the presence of simian virus 40 and genetic susceptibility have been associated recently with the development of mesothelioma in animal models. These latter findings are increasing our understanding of this disease. In addition, the discovery of elevated levels of various markers such as folic acid receptor alpha, cyclooxygenase 2, and multidrug resistance proteins 1 and 2 in mesothelioma tissue have opened up new areas of potential diagnostic and therapeutic importance. However, traditional treatment modalities--surgery, radiotherapy, and chemotherapy--have evolved slowly, and few gains in therapeutic efficacy have occurred. Recently, however, continuing research efforts have led to novel treatment strategies that are changing the way clinicians view a disease that has traditionally been managed with almost universal therapeutic nihilism. This review explores our current knowledge of this disease and presents current and novel therapeutic strategies.

Study Objectives: To study the ability of positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG) to distinguish between benign and malignant disease in exudative pleural effusions and pleural thickening., Design: Prospective study of 98 consecutive patients presenting with either pleural thickening or an exudative pleural effusion., Setting: Department of pulmonary medicine of a university hospital., Methods: FDG-PET was performed on each subject before invasive procedures were used to determine the etiologic diagnosis. FDG-PET data were analyzed by visual interpretation., Results: Sixty-three of 98 patients were found to have malignant pleural disease after histologic analysis. Sixty-one of 63 patients with histologically confirmed malignant disease showed FDG uptake within the area of pleural thickening. Uptake was graded as intense in 51 cases and moderate in 10 cases. Only two patients with malignant pleural disease did not show increased FDG uptake. FDG-PET imaging showed an absence of FDG uptake, and correctly classified 31 of 35 benign lesions. For the remaining four lesions, intense FDG uptake was seen in one case of parapneumonic effusion, while moderate and localized uptake was observed in one parapneumonic, one tuberculous, and one uremic pleurisy. The sensitivity of the method to identify malignancy was 96.8% with a negative predictive value of 93.9%, while its specificity was 88.5% and its positive predictive value was 93.8%., Conclusions: Our results suggest that FDG-PET is an effective tool for differentiating between benign and malignant pleural diseases.

Objectives: Malignant mesothelioma (MM) is a fatal tumor of increasing incidence related to asbestos exposure. Microscopic tumor necrosis (TN) is a poor prognostic factor in solid tumors, but it has not been characterized in MM. We wished to evaluate the incidence of TN in MM and its correlations with clinicopathologic factors, angiogenesis, and survival., Methods: TN was graded in 171 routine formalin-fixed, paraffin-embedded hematoxylin-eosin-stained tumor sections by two independent observers. Angiogenesis was assessed by the microvessel count (MVC) of CD34 immunostained sections. TN was correlated with survival by Kaplan-Meier and log-rank analysis, and stepwise, multivariate Cox models were used to compare TN with angiogenesis and established prognostic factors and prognostic scoring systems., Results: TN was identified in 39 cases (22.8%) and correlated with low hemoglobin (p = 0.01), thrombocytosis (p = 0.04), and high MVC (p = 0.02). TN was a poor prognostic factor in univariate analysis (p = 0.008). Patients with TN had a median survival of 5.3 months vs 8.3 months in negative cases. Independent indicators of poor prognosis in multivariate analysis were nonepithelioid cell type (p = 0.0001), performance status > 0 (p = 0.007), and increasing MVC (p = 0.004) but not TN. TN contributed independently to the European Organisation for Research and Treatment of Cancer (EORTC) [p = 0.03] and to the Cancer and Leukemia Group B (CALGB) [p = 0.03] prognostic groups in respective multivariate Cox analyses., Conclusions: TN correlates with angiogenesis and is a poor prognostic factor in MM. TN contributes to the EORTC and CALGB prognostic scoring systems.

Study Objectives: Intrapleural immunotherapy has shown some activity in patients with malignant mesothelioma. We conducted a multicentric pilot phase II study to evaluate the tolerance and the activity of intrapleurally infused autologous human activated macrophages (AM Phi) in patients with stage IA, IB, and IIA malignant pleural mesothelioma (MPM)., Design: AM Phi derived from in vitro monocyte culture were infused into the pleura of patients every week for 8 consecutive weeks. Each infusion was followed 3 days later by an intrapleural injection of 9 millions units of gamma-interferon (gamma-IFN) in an attempt to prolong the in vivo activation of infused AM Phi. Response was assessed by CT scan and thoracoscopy when possible. If the patient's disease progressed after AM Phi treatment, an additional treatment was left to the choice of the investigator., Patients: Nineteen patients with histologically proven stage IA, IB, or IIA MPM were enrolled. Two patients were excluded before any AM Phi infusion because of complications impeding infusion. Seventeen patients were actually treated. After completion of the AM Phi cellular therapy, 10 patients were treated with chemotherapy as their diseases progressed., Results: The overall response rate of patients actually treated was 14%. When including the two patients enrolled but not treated, the overall response "in intention to treat" was 11%; two patients had a partial response, with a duration of response of 30 months and 3 months, respectively. One patient, who could not be evaluated by thoracoscopy because of pleural symphysis, is still alive without any clinical or radiologic sign of disease 69 months after treatment. No major adverse effects were observed during the infusion of either AM Phi or gamma-IFN, and there was no interruption of treatment because of toxicity. However, symphysis was observed in 7 of 14 patients who received the complete treatment. The median survival of patients actually treated, including those who received chemotherapy after AM Phi, was 29.2 months., Conclusion: Combined infusion of AM Phi and gamma-IFN was well tolerated in patients with MPM; however, it had limited antitumor activity.

Study Objectives: Pleural fluid cytology and non-image-guided Abrams or Cope biopsies have sensitivities of approximately 30% for detecting malignant mesothelioma, and thoracoscopic biopsy has a sensitivity of approximately 90%. The difference between these two probably relates to obtaining adequate tissue. The use of immunohistochemical stains allows a firm diagnosis to be made from relatively small samples. This study explores whether percutaneous image-guided cutting needle biopsy (CNB) combined with immunohistochemistry is accurate in diagnosing pleural thickening due to mesothelioma., Design: Retrospective review of image-guided CNB of pleural thickening performed on consecutive patients over 7 years by a single radiologist., Setting: Teaching hospital chest radiology department., Patients: Twenty-one adult patients with a final diagnosis of malignant mesothelioma were identified from 53 consecutive patients who underwent percutaneous image-guided CNB. All 21 patients had pleural thickening identified on contrast-enhanced CT, and all had a final histologic diagnosis of mesothelioma confirmed by postmortem examination or thoracoscopy., Interventions: Fourteen-gauge and 18-gauge cutting needles were used. Biopsy guidance was by ultrasound in 6 patients and by CT in 15 patients., Measurements and Results: A correct histologic diagnosis of malignant mesothelioma was made by CNB in 18 patients (86% sensitivity and 100% specificity). Complications included one chest wall hematoma and a small hemoptysis. Four patients with a pleural thickness of < or = 5 mm underwent biopsy, and all specimens were diagnostic for mesothelioma., Conclusions: Image-guided percutaneous CNB of pleural thickening is a safe procedure, with 86% sensitivity for detecting malignant mesothelioma. Pleural thickening of < or = 5 mm may be successfully sampled.

Objective: To determine the optimal administered dose of meta-tetrahydroxyphenylchlorin (mTHPC) for intraoperative photodynamic therapy (IPDT) in resected malignant pleural mesothelioma (MPM). The primary objective of this combination treatment was to improve local tumor control., Design: Phase I/II dose escalation study., Setting: Two Dutch cancer centers., Patients: The study included 28 patients (2 women, 26 men), with pathologically confirmed MPM. The mean age was 57 years (age range, 37 to 68 years), and the World Health Organization performance score was 0 to 1. Epithelial mesotheliomas were found in 17 patients, a sarcomatous mesothelioma was found in 1 patient, and mixed epithelial sarcomatous mesotheliomas were found in 10 patients., Methods: Patients were injected with 0.075 mg/kg (4 patients), 0.10 mg/kg (19 patients), or 0.15 mg/kg (5 patients) mTHPC 4 or 6 days before undergoing surgery and IPDT. Complete surgical resection (i.e., pleuropneumonectomy) was followed by integral illumination with monochromatic light of 652 nm (10 J/cm(2)). The real-time fluence rate measurements were performed using four isotropic detectors in the chest cavity to calculate the total light dose., Results: Dose-limiting toxicity was reached at the level of 0.15 mg/kg mTHPC. Three patients died in the perioperative period, and one death was directly related to photodynamic therapy. Real-time dosimetry identified 12 patients in whom additional illumination had to be given to the diaphragmatic sinuses, which were unavoidably shielded during integral illumination. In two patients, illumination was cancelled due to the insufficient resectability of the tumor. The median survival time for all 28 patients was 10 months. Local tumor control, 9 months after treatment, was achieved in 13 of the 26 patients treated with IPDT., Conclusion: IPDT using mTHPC, combined with a pleuropneumonectomy, resulted in local control of disease in 50% of the treated cases. The considerable toxicity associated with the procedure, however, precludes its recommendation for widespread use. Stricter patient selection and improvements of the IPDT technique may reduce the toxicity.

Study Objectives: Asbestos fibers have not been reported in tissues from the peritoneal cavity. Therefore, omentum, mesentery, and lung tissues from 20 individuals in whom mesothelioma was diagnosed were analyzed for asbestos bodies and asbestos fibers., Design: Tissue was digested and prepared filters were analyzed by light microscopy and analytical transmission electron microscopy., Results: Asbestos bodies were found in the lungs of 18 individuals, mesentery samples from 5, and omentum samples from 2. Uncoated asbestos fibers were found in lungs of 19 patients, 17 of whom had fibers in at least one extrapulmonary site. The most common asbestos in the omentum and mesentery was amosite. Several features of asbestos found in lung influenced the likelihood of amphibole fibers being found in the omentum or mesentery. Lung features included total amphibole fiber burden, length, aspect ratio, and ferruginous body burden. An increased total ferruginous body burden was strongly associated with increased likelihood of detecting amphiboles in the omentum (p < 0. 05)., Conclusion: Asbestos fibers reach areas in the peritoneal cavity where some mesotheliomas develop. This study suggests their presence can be predicted based on concentrations and characteristics of fiber burdens in lung tissue.

Study Objectives: Malignant pleural mesothelioma (MPM) is predominantly a local/regional disease that results in a survival time that ranges from 4 to 12 months without treatment. Single-modality therapy using surgery, chemotherapy, or radiotherapy alone is largely ineffective. The objective of the study was presentation of the use of pleuropneumonectomy in a multimodality treatment setting and the results., Design: Didactic presentation., Setting: Academic tertiary-care hospital., Patients: One hundred eighty-three patients who underwent multimodality therapy., Interventions: Of all the single-modality treatment approaches, pleuropneumonectomy has been associated most consistently with long-term disease-free survival and has provided the greatest amount of tumor cytoreduction. The technique of pleuropneumonectomy traditionally has been linked with high perioperative mortality and morbidity when compared with that of other cytoreductive techniques such as pleurectomy/decortication. Recently, improvements in operative mortality (< 5%) have been reported, largely due to improvements in patient selection and perioperative management. Multimodality therapy, including chemotherapy, radiotherapy, and extrapleural pneumonectomy, was used to treat patients., Results: Outcomes were presented for 183 patients with MPM who underwent multimodality therapy., Conclusions: With the development of multimodality therapy, pleuropneumonectomy followed by sequential chemotherapy and radiotherapy has demonstrated a significant survival benefit, especially for patients who have epithelial tumor histology, tumor-free resection margins, and tumor-free extrapleural node status.

Malignant diffuse mesothelioma is the most common type of mesothelioma, with a median survival ranging from 8.5 to 18 months after diagnosis. Good performance status, absence of chest pain, age < 50 years, and epithelial histology are all associated with improved survival. Several investigators have described staging systems for this tumor and have emphasized the importance of thoracoscopy in the diagnosis and staging of the disease. Pleurectomy is the most common surgery employed to manage patients with diffuse mesothelioma, and this procedure is associated with minimal postoperative morbidity and mortality. Because mesothelioma usually recurs locally after surgery, efforts at optimizing local control have included both intraoperative phototherapy and chemotherapy. However, neither of these techniques has demonstrated any significant benefit to date and thus should not be considered as standards of care. No studies have compared pleurectomy to extrapleural pneumonectomy (EPP) in randomized trials. However, nonrandomized series suggest a significant improvement in disease-free survival for those undergoing EPP versus pleurectomy. Other data suggest that EPP may improve local control but may predispose the patient to distant metastases. A randomized comparison of these techniques may be beneficial in identifying the most effective procedure for patients with malignant diffuse mesothelioma.

Treatment of malignant pleural mesothelioma continues to be frustrating regardless of the modality employed. Numerous trials of chemotherapeutic agents have been performed, but until recently, these studies were small and subject to inaccuracies of disease measurement. To our knowledge, no chemotherapeutic regimen has emerged as a standard of care. A review of the literature reveals that small activity against this disease has been shown by the anthracyclines, platinum compounds, and alkylating agents, whereas higher activity has been reported with the antimetabolites. The plant alkaloids have not demonstrated any activity against mesothelioma. Dose-escalated chemotherapeutic regimens may offer an advantage, whereas combination chemotherapy has not shown any benefit over single-agent therapy. Favorable responses have been reported with the administration of intrapleural biological response modifiers. Further trials and the investigation of new agents in the treatment of this disease are necessary.

In this article, we explain the current trimodality approach used to treat malignant pleural mesothelioma. Our current approach employs extrapleural pneumonectomy as the cytoreductive procedure followed by combination chemoradiotherapy. Trimodality therapy was performed at the Dana-Farber Cancer Institute/Brigham and Women's Hospital Thoracic Oncology Program. From 1980 to 1995, we prospectively followed up a series of 120 patients with confirmed malignant pleural mesothelioma who underwent trimodality therapy. Two- and 5-year survival rates for the entire cohort were 45% and 22%, respectively. Survival rates were 65% and 27%, respectively, at 2 and 5 years for patients with epithelial histology. Patients with sarcomatous or mixed histology had the poorest prognosis, with 2- and 5-year survival rates of 20% and 0%, respectively. For patients with epithelial tumors and negative nodes, survival at 2 and 5 years was 74% and 39%, respectively. Extrapleural pneumonectomy in the context of trimodality therapy is a potential surgical option for a selected group of patients with malignant pleural mesothelioma.

Five patients had a solitary fibrous tumor of the pleura; a well-known but rare entity. In all cases, biopsy by a transthoracic cutting needle (Tru-Cut; Travenol; Deerfield, IL) yielded specimens adequate for histologic analysis and gave the clue to the diagnosis. In four patients, surgical resection confirmed the diagnosis. The opportunity for and interest in diagnosing these tumors by transthoracic cutting needle biopsy before surgery are discussed. An accurate diagnosis of solitary fibrous tumors of the pleura can be made by a minimally invasive procedure; this allows for a more informed allocation of surgical resources.

A 57-year-old man with a history of exposure to silica for 32 years presented with pleural thickening of the lower lobe of the left lung and a chronic right-sided pleural effusion without any radiographic evidence of parenchymal nodules in either lung. Light microscopic examination of a left visceral pleural biopsy specimen revealed markedly thickened pleura with fibrosis and macrophages containing birefringent silica and silicates. Occasional rounded intrapleural silicotic nodules were present. The underlying lung tissue did not show fibrosis or silicotic nodules. An energy-dispersive x-ray analysis confirmed the presence of silica. In the absence of lung involvement, this case represents a very unusual pathologic reaction caused by silica and silicates and adds to the clinical differential diagnosis of chronic pleuritis and malignant mesothelioma.

Mesothelioma is a rare disease for which neither single modality nor bimodality therapy improves survival. For this reason, from 1980 to 1995, we used trimodality therapy in an attempt to improve survival in selected patients at Brigham and Women's Hospital and Dana-Farber Cancer Institute. One hundred twenty patients underwent trimodality treatment involving extrapleural pneumonectomy followed by combination chemoradiotherapy. Twenty-seven women and 93 men (mean age, 56 years) were evaluable for response and treatment-related morbidity. The operative mortality rate was 5%, and 22% of patients experienced major morbidity. Cell type and nodal status were significant prognostic variables. The respective 2- and 5-year survival rates were 45% and 22% overall, 70% and 37% for patients with epithelial cell type, 20% and 0% for patients with sarcomatous or mixed-histologic-type tumors, and 74% and 39% for patients who were node-negative with epithelial histologic type. Positive resection margins impacted survival only in the case of full-thickness, transdiaphragmatic invasion. A revised staging system stratified survival with median intervals of 22, 17, and 11 months for stages I, II, and III disease, respectively (p=0.04). Thus, extrapleural pneumonectomy with adjuvant therapy is appropriate and effective treatment for patients with stage I disease according to the revised staging system.

Study Objective: Treatment of malignant mesothelioma (MM) at an early stage results in increased survival. Cytologic examination of pleural effusions is one of the first diagnostic techniques attempted in these patients. The objective of this study was to define the role of cytologic examination of pleural fluid in facilitating early diagnosis., Design: The medical records and cytologic slides of patients with pleural MM were reviewed., Setting: Medical records were reviewed from two institutions: a large general hospital and a cancer hospital., Patients: Twenty-nine patients ranging in age from 32 to 81 years (mean, 59 years) met the study criteria., Interventions: All patients had at least one cytologic pleural fluid examination., Measurements and Results: The median time from initial symptoms to the diagnosis of MM was 8 weeks for all patients. For patients with a positive or suspicious cytologic result, the median was 4 weeks, and in those with a negative cytologic result, it was 12 weeks. The overall sensitivity of cytologic examination for the diagnosis of MM was 32%. Cytogenetic analysis of pleural fluid had a sensitivity of 56%, and was positive in 1 case in which results of cytologic examination were negative. Patients in whom the time from presentation to diagnosis was greater than 1 year all had negative cytologic results followed by long periods without further workup, despite a history of exposure to asbestos., Conclusions: A positive or suspicious cytologic result was associated with a decreased median time to diagnosis. Unfortunately, the sensitivity of cytologic examination for a diagnosis of MM was only 32%. Until better diagnostic techniques are developed, we recommend immediate pleural biopsy in patients in whom MM is suspected and cytologic evaluation of pleural fluid gives negative results.

We report a case of malignant pleural mesothelioma in a patient who presented with pleural effusion and reticulonodular shadow on chest radiograph. Pulmonary metastases were diagnosed by transbronchial lung biopsy specimen and the patient died of extensive pulmonary metastases. This pattern of clinical and radiographic presentation is seldom reported for malignant pleural mesothelioma.

Background: The prognosis of patients with pleural mesothelioma is more dependent on "pretreatment factors" than on the effect of therapeutic interventions. Histopathologic subtype is one of several important prognostic factors in pleural mesothelioma, and several studies indicate that the epithelial subtype of pleural mesotheliomas has a more favorable prognosis than the sarcomatoid. In this study, we retrospectively evaluated qualitative and quantitative aspects of the tissue specimens used for histopathologic diagnosis in 85 patients with pleural mesothelioma., Materials and Methods: The prognostic roles of two different histopathologic classification systems were evaluated in 85 consecutive cases of pleural mesotheliomas. Efficiency of different diagnostic procedures, influence of the size of the biopsy specimens on the histopathologic diagnosis, and immunohistochemical profiles for histopathologic subtypes of mesotheliomas were also evaluated., Results: Patients with pure epithelial mesotheliomas (n = 35), and especially those with the tubulopapillary subtype (n = 18) of epithelial mesotheliomas, survived significantly longer than those with a sarcomatoid component (n = 50). With larger biopsy specimens (surgical biopsy, autopsy), more tumors were classified as biphasic (36/78 vs 9/44, p < 0.005). The sarcomatoid mesotheliomas comprised about 20% of the tumors regardless of type of biopsy. Staining intensity for cytokeratin CAM 5.2 was equal in all types of mesotheliomas, while intensity with cytokeratin AE1/AE3 decreased from the epithelial to the sarcomatoid mesotheliomas. Staining with vimentin was most intense among the sarcomatoid mesotheliomas, while with epithelial membrane antigen it was most intense among the epithelial mesotheliomas., Conclusions: The quality of the biopsy specimens has considerable impact on the possibility to arrive at a correct histopathologic diagnosis. Based on our results, we suggest tubulopapillary mesotheliomas be regarded as "low-grade mesotheliomas" and other types, including the epithelioid type of epithelial mesotheliomas, as "high-grade mesotheliomas." This should be taken into account when designing clinical trials.

Study Objective: Investigation of the behavior and treatment of the diffuse malignant pleural mesothelioma (MPM) is hindered by the lack of an accurate universally accepted staging system. To address this problem, the International Mesothelioma Interest Group (IMIG) has developed a new TNM-based staging system., Methods: The staging system was developed at a consensus meeting of IMIG members involved in clinical research in MPM, including the originators of previously proposed staging systems. The new staging system is based on the analysis of emerging information about the impact of T and N status on survival., Results: In contrast to five previous staging systems, the T descriptors designated as T1, T2, T3, and T4, provide precise anatomic definitions of the local extent of the primary tumor. The N descriptors, designated as N0, N1, N2, and N3, are virtually identical to those used in the International Lung Cancer Staging System. The stage groupings recognize new data about the better prognosis of T1 and N0 tumors and classify those tumors into stages I and II. The adverse impact of nodal metastases on survival noted in some recent surgical series warrants placing node-positive tumors in stage III. Locally advanced unresectable (T4) tumors and extrathoracic disease (N3 or M1) are classified as stage IV., Conclusion: This proposed staging system reconciles and updates several earlier systems, and can provide the framework for analyzing the results of prospective clinical trials aimed at improving the currently dismal prognosis of MPM.

The purpose of this randomized prospective study was to assess the efficacy of local radiotherapy in preventing malignant seeding along invasive diagnostic procedures (cytology, needle biopsy, thoracoscopy, or chest tube placement) in patients with malignant pleural mesothelioma. Forty consecutive patients with histologically proven malignant mesothelioma were enrolled. Twenty patients received three daily sessions of radiotherapy at a dosage of 7 Gy 10 to 15 days after thoracoscopy. The other 20 patients did not receive radiotherapy. None of the 20 patients treated developed entry tract metastasis. In contrast, 8 of the 20 (40%) patients who were not treated developed metastases. These findings confirm the efficacy and safety of early local radiotherapy in preventing malignant seeding after invasive diagnostic procedures in patients with malignant pleural mesothelioma.

Malignant mesothelioma of the pleura occurs primarily in individuals who were exposed to asbestos either in the workplace or home. The incidence of malignant mesothelioma is rising and, reflective of the malignancy's long latency period, is expected to continue to increase into the next century. Current treatment measures, including surgery, radiation therapy, chemotherapy, intrapleural therapy, and combined-modality therapies, have had varying impacts on survival. This paper explores current trends in the treatment of malignant pleural mesothelioma.

Localized pleural mesotheliomas are rare tumors that have a variety of clinical presentations, from an asymptomatic solitary nodule to a massive, highly symptomatic neoplasm filling most of the pleural cavity. Two cases are reported which show the clinical spectrum of the more common benign variant. The clinical differentiation between the benign tumor as well as the less frequent malignant neoplasms of localized mesotheliomas has been disappointing. Complete surgical resection is the preferred treatment for both types and is usually curative with the benign mesothelioma.

Metastases in pleural mesothelioma usually occur late in the disease process. Diffuse involvement of the lung parenchyma is rare. A patient with miliary pulmonary parenchymal involvement with malignant mesothelioma is described. To our knowledge, this represents the first such case reported.

We report a case of pleural dissemination of invasive thymoma, which was successfully treated with intrathoracic chemothermotherapy following panpleuropneumonectomy. Intrathoracic chemothermotherapy in combination with surgery may be a hopeful adjuvant treatment to control pleural disseminated lesions of invasive thymoma.

A 35-year-old male homosexual, a former intravenous drug abuser, was found to be human immunodeficiency virus (HIV) positive in 1984. He developed AIDS in 1987 and began treatment with zidovudine in 1989. One year later he developed left apical pleural blebs, a pneumothorax and an exudative pleural effusion. A malignant mesothelioma developed at the pleural blebs in the left apex. He was treated with adriamycin but rapid progression of the malignancy occurred and he died three months later. At autopsy, a malignant mesothelioma, causing respiratory failure and death, was found. The patient had no exposure to asbestos and asbestosis was not present at autopsy. We postulate that the development of malignant mesothelioma was probably related to HIV immune suppression or HIV and/or cytomegalovirus or zidovudine and is a complication of AIDS similar to the development of other malignant neoplasms in patients with AIDS.