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Despite efforts to ban asbestos mining and manufacturing, mesothelioma deaths in the United States have remained stable at approximately 2500 cases annually. This trend is not unique to the United States but is also a global phenomenon, associated with increased aging of populations worldwide. Although geoeconomic factors such as lack of regulations and continued asbestos manufacturing in resource-poor countries play a role, it is essential to consider biological factors such as immune senescence and increased genetic instability associated with aging. Recognizing that mesothelioma shares genetic instability and immune system effects with other age-related cancers is crucial because the impact of aging on mesothelioma is frequently assessed in the context of disease latency after asbestos exposure. Nevertheless, the long latency period, often cited as a reason for mesothelioma's elderly predominance, should not overshadow the shared mechanisms. This communication focuses on the role of immune surveillance in mesothelioma, particularly exploring the impact of immune escape resulting from altered TSG function during aging, contributing to the phylogenetic development of gene mutations and mesothelioma oncogenesis. The interplay between the immune system, TSGs, and aging not only shapes the immune landscape in mesothelioma but also contributes to the development of heterogeneous tumor microenvironments, significantly influencing responses to immunotherapy approaches and survival rates. By understanding the complex interplay between aging, TSG decline, and immune senescence, health care professionals can pave the way for more effective and personalized immunotherapies, ultimately offering hope for better outcomes in the fight against mesothelioma., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21 st century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.

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., Competing Interests: Declaration of competing interest Dr. Roggli has consulted with plaintiff and defense attorneys in asbestos litigation cases. Dr. Pavlisko and Dr. Carney have consulted with defense attorneys in asbestos litigation cases. Drs. Glass and Pina-Oviedo have no disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This paper summarizes recent insights into causal biological mechanisms underlying the carcinogenicity of asbestos. It addresses their implications for the shapes of exposure-response curves and considers recent epidemiologic trends in malignant mesotheliomas (MMs) and lung fiber burden studies. Since the commercial amphiboles crocidolite and amosite pose the highest risk of MMs and contain high levels of iron, endogenous and exogenous pathways of iron injury and repair are discussed. Some practical implications of recent developments are that: (1) Asbestos-cancer exposure-response relationships should be expected to have non-zero background rates; (2) Evidence from inflammation biology and other sources suggests that there are exposure concentration thresholds below which exposures do not increase inflammasome-mediated inflammation or resulting inflammation-mediated cancer risks above background risk rates; and (3) The size of the suggested exposure concentration threshold depends on both the detailed time patterns of exposure on a time scale of hours to days and also on the composition of asbestos fibers in terms of their physiochemical properties. These conclusions are supported by complementary strands of evidence including biomathematical modeling, cell biology and biochemistry of asbestos-cell interactions in vitro and in vivo, lung fiber burden analyses and epidemiology showing trends in human exposures and MM rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BTM has participated as an expert witness in asbestos-related litigation. S Moolgavkar has served as a consulting and testifying expert in asbestos and talc litigation. V Roggli has consulted with plaintiff and defense attorneys in asbestos litigation cases., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We reviewed 354 cases of malignant diffuse mesothelioma (MM) in women from a database of 2858 histologically confirmed MM cases. There was a pleural predominance with 78% pleural MM and 22% peritoneal MM. The pleural tumors consisted of 72% epithelioid, 19% biphasic, and 9% sarcomatoid variant. The peritoneal tumors consisted of 82% epithelioid, 13% biphasic, and 5% sarcomatoid. The immunohistochemical profile was typical of what is well-accepted and previously described for MM. When examining tumor subtype and location, there was a trend toward epithelioid subtype and peritoneal location; however, this did not reach statistical significance. Age at the time of diagnosis ranged from 19 to 93 years with a mean of 60 years. The median age at time of diagnosis for pleural MM was 65 years and for peritoneal MM was 52 years. A further look at age and histologic subtype showed no statistically significant difference in age between MM subtypes. Survival was greatest for epithelioid variant, and this was magnified in the peritoneum. A majority of our cases were exposed to asbestos through a household contact. Asbestosis and parietal pleural plaque were present in 5% and 50% of cases with data, respectively. Fiber analysis data was available in 67 cases; 38 cases had elevated asbestos fiber burden, and tremolite was the most common asbestos fiber type detected. Commercial and noncommercial amphibole asbestos fibers were elevated in nearly equal numbers of cases.

Neurofibromatosis type 2 (NF2), an inherited disorder associated with multiple inherited schwannomas, meningiomas and ependymomas is caused by an autosomal dominant, likely loss of function germline mutation of the NF2 gene. Interestingly, biallelic NF2 gene inactivation is one of the most common mutations associated with the development of malignant mesothelioma (MM), a highly fatal malignancy that arises in the pleura and less frequently in the pericardium, peritoneum, and tunica vaginalis. It has been proposed that NF2 patients could potentially be at increased risk of developing MM. However, patients with inherited NF2 rarely develop MM. To date, only 2 cases describing patients diagnosed with both have been reported in the literature. Here, we describe the third case and for the first time, also provide molecular evidence that a "second hit" involving a somatic mutation is likely required to trigger the development of MM in this rare cohort. In our patient diagnosed with NF2 at age 25 who developed an aggressive peritoneal MM 15 years later, we identified a germline NF2 mutation and somatic mutations including BAP1. Of clinical relevance, our case supports a germline NF2 mutation may not necessarily be more susceptible to develop mesothelioma without a "second hit" mutation.

Malignant mesothelioma (MM) arising from the serosal membranes of the tunica vaginalis testis (TVT) is rare. Most examples in the published medical literature are individual case reports. This study presents the clinicopathological findings of mesothelioma of the TVT in one of the largest series to date. Individuals with mesothelioma of the TVT were identified from a database of more than 4000 mesothelioma cases, and their clinicopathological features were recorded. Eighteen men with MM and 2 with well-differentiated papillary mesothelioma of the TVT were identified, which represented 0.6% of males with mesothelioma in study population. The median age at diagnosis was 72 years (range, 32-85 years). A neoplasm was not suspected preoperatively in 12 of the 17 (71%) men whose clinical presentation was known, 7 of whom presented with hydrocele and 5 with inguinal hernia. The other 5 had a clinically recognized mass. Seven of the men underwent herniorrhaphy; 7, radical orchiectomy; 3, hydrocelectomy; and 3, paratesticular mass biopsy or excision as the initial diagnostic procedure. Twelve of the MM cases were epithelioid and 6 were biphasic. Among the 6 men with MM who had ≥6 months of follow-up, 1 was alive with no evidence of disease at 6 months, and 5 were known to have died of disease 8-74 months (median = 31.5 months) following diagnosis. Three men with MM had received either chemotherapy or radiation therapy. Of the 2 men initially diagnosed with well-differentiated papillary mesothelioma, 1 was alive without evidence of disease 5 years after diagnosis, while the other had findings more compatible with MM with peritoneal involvement 2 years following initial diagnosis. In 15 of the 18 cases of MM (83%), there was documented occupational or paraoccupational exposure to asbestos, the average duration of which was 33 years (range, 2-46 years). Information regarding the presence or absence of pleural plaques was available in 5 of the MM cases, and pleural plaques had been found in 4. Lung tissue was not available for fiber analysis in any of the cases. One additional case originally diagnosed at another institution as MM of the TVT was reclassified as adenocarcinoma following performance of additional immunohistochemical testing. TVT is a rare site of MM, the diagnosis of which is often unsuspected preoperatively. Like its counterparts at other serosal sites, MM of the TVT is an aggressive tumor with a poor prognosis that evidence would suggest is etiologically associated with asbestos in at least some cases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Florid mesothelial hyperplasia is known to result from endometriosis. Well-differentiated papillary mesothelioma and multiloculated peritoneal inclusion cysts have also been described in women with endometriosis. To our knowledge, peritoneal diffuse malignant mesothelioma (MM) arising in the setting of endometriosis has not been reported. The purpose of this study is to report the clinicopathological characteristics of women with MM and endometriosis., Methods: The surgical pathology files of a tertiary academic medical centre and the consultation files of one of the study authors were reviewed for cases of MM in females with and without endometriosis., Results: Six women with MM and endometriosis ranging in age from 29 to 55 years (median=45 years) were identified. All had peritoneal MM and endometriosis involving the peritoneum and/or adnexa. Five had epithelioid MM and one had biphasic MM. Two had paraoccupational exposure to asbestos. The median age of women with MM and endometriosis (44.5 years) was significantly less than the median age of cases without endometriosis (58.0 years) (p value=0.01)., Conclusions: To our knowledge, this is the first report of MM in women with endometriosis. Interestingly, MM in the setting of endometriosis has only been observed in the peritoneum and not in other serosal cavities. The findings in the present study suggest that chronic serosal inflammation secondary to endometriosis may be an inducing factor in rare cases of MM of the peritoneum., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Asbestos exposure is the main etiology of malignant mesothelioma, but there are conflicting data on whether the intensity of exposure modulates the development of this disease. This study considered 594 patients with malignant mesothelioma for whom count data on asbestos bodies and fibers (per gram of wet lung tissue) were available. The relationships between age at diagnosis (a time-to-event outcome variable) and these two measures of internal asbestos exposure, along with other possible modulating factors (sex, tumor location, histological subtype and childhood exposure), were assessed on multivariable Cox proportional hazard models, stratifying by decade of birth year. For both measures of asbestos in lung tissue, younger age at diagnosis was associated with higher internal measures of exposure to asbestos. Stratified Cox analyses showed that for each doubling in asbestos body count patients were 1.07 times more likely to be diagnosed at a younger age [hazard ratio (HR) = 1.07; 95% confidence interval (CI), 1.04-1.09; P = 2.2 × 10-7] and for each doubling in asbestos fiber count patients were 1.13 times more likely to be diagnosed at a younger age (HR = 1.13; 95% CI, 1.09-1.17; P = 8.6 × 10-11). None of the other variables considered were associated with age at diagnosis. Our finding that tumors become clinically apparent at a younger age in heavily exposed subjects suggests that asbestos is involved not only in the malignant mesothelioma tumor initiation but, somehow, also in the progression of the disease.

Objectives: The aim of the study was to reanalyze an updated database of lung asbestos fiber levels for 21 brake repair workers who died of mesothelioma using robust maximum likelihood-based regression methods to address nondetectable measurements., Methods: We applied bivariate normal regression to address the doubly left-censored situation where both the lung fiber concentration of noncommercial (TAA) and commercial amphiboles (AC) were subject to detection limits. For the single left-censored situation, we applied censored normal regression to study the relationship between duration of employment (DOE) and TAA., Results: We found a statistically significant positive relationship between TAA and AC (β = 0.49, 95% confidence interval [CI], 0.11 to 0.86) and a not statistically significant relationship between DOE and TAA (β = 0.02, 95% CI, -0.03 to 0.06)., Conclusions: Our results provide additional support for the conclusion that exposure to commercial amphibole asbestos, and not chrysotile, is related to the occurrence of mesothelioma among some brake workers.

Context: - Malignant mesothelioma (MM) is a component of the BAP1 tumor predisposition syndrome. Other than in BAP1 familial studies, nonmesothelial neoplasms in individuals with MM has not been comprehensively assessed., Objective: - To assess the spectrum and prevalence of nonmesothelial neoplasms in individuals with MM., Design: - Individuals with MM and second neoplasms were identified from a database of 3900 MM cases. The expected prevalence of each type of neoplasm was calculated and compared with the actual prevalence in the study population using available Surveillance, Epidemiology, and End Results data and other published data., Results: - Two hundred seventy nonmesothelial neoplasms were identified in 241 individuals (6% of the study population) with MM. Prostate adenocarcinoma was most common. Non-Hodgkin lymphoma, Hodgkin lymphoma, lung carcinoma, urothelial carcinoma, breast carcinoma, chronic lymphocytic leukemia, clear cell renal cell carcinoma, head and neck squamous cell carcinoma, papillary renal cell carcinoma, multiple myeloma/plasmacytoma, meningioma, pleomorphic undifferentiated sarcoma, chronic myelogenous leukemia, ocular melanoma, hepatocellular carcinoma, liposarcoma, and Wilms tumor all were more prevalent than expected., Conclusions: - Nonmesothelial neoplasms are uncommon in individuals with MM, but certain tumor types are increased in prevalence. In an unselected study population with respect to BAP1 status, the prevalence of several tumor types described in BAP1 mutation carriers, including lung carcinoma, clear cell renal cell carcinoma, breast carcinoma, meningioma, pleomorphic undifferentiated sarcoma, and ocular melanoma, was increased.

Context: - Although many mesotheliomas are related to asbestos exposure, not all are, and there is increasing information on other causes of mesothelioma., Objective: - To provide a review of non-asbestos causes for malignant mesothelioma., Data Sources: - Review of relevant published literature via PubMed and other search engines., Conclusions: - Currently, most pleural mesotheliomas (70% to 90%) in men in Europe and North America are attributable to asbestos exposure; for peritoneal mesothelioma the proportion is lower. In North America few mesotheliomas in women at any site are attributable to asbestos exposure, but in Europe the proportion is higher and varies considerably by locale. In certain geographic locations other types of mineral fibers (erionite, fluoro-edenite, and probably balangeroite) can induce mesothelioma. Therapeutic radiation for other malignancies is a well-established cause of mesothelioma, with relative risks as high as 30. Carbon nanotubes can also induce mesotheliomas in animals but there are no human epidemiologic data that shed light on this issue. Chronic pleural inflammation may be a cause of mesothelioma but the data are scanty. Although SV40 can induce mesotheliomas in animals, in humans the epidemiologic data are against a causative role. A small number of mesotheliomas (probably in the order of 1%) are caused by germline mutations/deletions of BRCA1-associated protein-1 ( BAP1) in kindreds that also develop a variety of other cancers. All of these alternative etiologies account for a small proportion of tumors, and most mesotheliomas not clearly attributable to asbestos exposure are spontaneous (idiopathic).

A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.

Aims: Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD., Methods: A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD., Results: Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65 years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3 years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure., Conclusions: Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Epidemiological studies indicate that 80-90% of mesotheliomas are asbestos related. This suggests that 10-20% are not. Lung fiber burden analysis provides objective information about past exposures to asbestos. We have performed lung fiber burden analysis on a large cohort of mesothelioma cases and compared the findings with a reference population. Herein we report our findings along with demographic and exposure data.

Objectives: To examine the clinicopathologic characteristics of individuals with diffuse malignant mesothelioma (DMM) occurring concurrently with lung cancer (LC)., Materials and Methods: A database of approximately 3800 patients with DMM was reviewed, from which 18 patients (0.5%) who had synchronous LC were identified. The clinicopathologic features, as well as the occupational exposure history and fiber burden analysis data were examined., Results: The patient median age was 68 years (range 58-84 years). Of the 18 patients (14 male, 4 female), 11 (61%) had epithelial, 5 (28%) had biphasic, and 2 (11%) had sarcomatoid DMM, with the majority (16 cases; 89%) originating in the pleura and only 2 were peritoneal. Among the histologic types of LC, adenocarcinoma was most frequent (12 cases; 67%), while 5 cases of squamous cell carcinoma, and 1 case of small cell carcinoma were observed. Three patients also had a history of prior malignancy (1 with testicular seminoma and bladder carcinoma and 2 with prostate carcinoma). Fifteen patients had a positive smoking history. All but 3 had documented asbestos exposure. Three had histologic features of asbestosis. Mineral analysis performed in 8 showed an elevated asbestos fiber burden in 4 (22%). Amosite was detected in 4 patients, crocidolite in 3, and non-commercial amphiboles in 5., Conclusion: The finding of simultaneous carcinoma of the lung and DMM is distinctly unusual. The majority of patients are male smokers with pleural epithelial DMM and lung adenocarcinoma. This study represents the largest cohort of patients reported to date with synchronous malignant mesothelioma and lung cancer, and we propose guidelines for making a diagnosis of synchronous malignant mesothelioma and primary lung cancer., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Lung tissue from 42 peritoneal mesothelioma cases was analyzed by light microscopy and scanning electron microscopy/energy dispersive spectrometry. There were 34 men and 8 women with a mean age of 61 ± 10 years. Also, 17% of cases had histologically confirmed asbestosis, and 26% had only parietal pleural plaques. The asbestos body count exceeded our normal range in 22 of 42 cases (52%). Cases with asbestos-related pulmonary disease had higher fiber burdens than those without. The vast majority of fibers were commercial amphiboles (amosite with lesser amounts of crocidolite). These findings concur with previously published epidemiological observations.

Peritoneal mesothelioma is rare, and the sarcomatoid variant is more infrequent, with <30 cases reported to date in the literature. Several case series have described the morphologic features of sarcomatoid peritoneal mesothelioma (SPe); however, the clinicopathologic features are not well characterized. To our knowledge, this is the first large series reporting the clinicopathologic features of SPe. We reviewed our database of 3106 malignant mesothelioma cases. Of 248 peritoneal mesotheliomas, 15 (4%) were sarcomatoid variant (0.5% of all mesotheliomas). Only cases with 100% sarcomatoid morphology diagnosed by open surgical biopsy and/or autopsy were included. Thus, 4 cases were excluded leaving 11 cases of SPe. Two additional cases of SPe previously published by 1 of the authors (V.L.R.), not included in the database, are added yielding 13 cases total. The median age at diagnosis was 66 years (range=48 to 85 y), and there was a male predominance (M:F=3.25:1). Survival from date of diagnosis to date of death was 5 months (range=0 to 12 mo). The most common presenting symptom was abdominal pain, and 3 of 4 women were suspected to have cholecystitis/cholelithiasis. All cases stained positive for cytokeratins, and 2 contained heterologous elements. Seven cases had objective markers of asbestos exposure, and 2 additional cases had occupations strongly associated with mesothelioma. Two cases with alleged household contact exposures could not be confirmed to be asbestos related by lung fiber analysis. SPe is a rare variant of mesothelioma attributed to asbestos exposure in 69% of our cases.

Context: Ionizing radiation has a role in the development of malignant mesothelioma, in several epidemiologic studies, including patients with hematologic malignancies., Objective: To study the clinicopathologic characteristics of patients with malignant mesothelioma and hematologic malignancies with and without a history of radiotherapy., Design: From a database of approximately 3600 patients with malignant mesothelioma, we identified 45 patients (1%) who also had hematologic malignancies. We examined clinicopathologic features and noted whether the patient had received radiotherapy for malignancy, comparing those with and those without such exposure., Results: Among the 45 cases, 18 (40%) had Hodgkin lymphoma, 15 (33%) had non-Hodgkin lymphoma, 10 (4%) had chronic lymphocytic leukemia, and 2 (22%) had chronic myelogenous leukemia; 20 patients (44%) had a history of radiotherapy, and 23 (51%) did not. Most patients with Hodgkin lymphoma (16 of 18; 90.0%) received radiation, whereas none of the patients with leukemia (0 of 12) and only 20% (3 of 15) of the patients with non-Hodgkin lymphoma did so. Patients without radiation were older than patients who received radiotherapy (median, 73 versus 54 years, respectively; P < .001), had a shorter interval from diagnosis of hematologic malignancy to that of mesothelioma (median, 2 versus 24 years, respectively; P < .001), and had a shorter survival period (median, 6.0 versus 14.0 months, respectively; P = .02). Epithelial mesotheliomas were proportionately more common in patients with a history of radiotherapy., Conclusions: Patients with mesothelioma and hematologic malignancies with a history of radiation tended to be younger, had a longer interval from diagnosis of hematologic malignancy to that of mesothelioma, had a longer survival period, and were more likely to have the epithelial variant compared with patients without radiotherapy.

The mechanism for biological effects after exposure to particles is incompletely understood. One postulate proposed to explain biological effects after exposure to particles involves altered iron homeostasis in the host. The fibro-inflammatory properties of mineral oxide particles are exploited therapeutically with the instillation of massive quantities of talc into the pleural space, to provide sclerosis. We tested the postulates that (1) in vitro exposure to talc induces a disruption in iron homeostasis, oxidative stress, and a biological effect, and (2) talc pleurodesis in humans alters iron homeostasis. In vitro exposures of both mesothelial and airway epithelial cells to 100 μg/ml talc significantly increased iron importation and concentrations of the storage protein ferritin. Using dichlorodihydrofluorescein, exposure to talc was associated with a time-dependent and concentration-dependent generation of oxidants in both cell types. The expression of proinflammatory mediators was also increased after in vitro exposures of mesothelial and airway epithelial cells to talc. Relative to control lung tissue, lung tissue from patients treated with sclerodesis demonstrated an accumulation of iron and increased expression of iron-related proteins, including ferritin, the importer divalent metal transport-1 and the exporter ferroportin-1. Talc was also observed to translocate to the parenchyma, and changes in iron homeostasis were focally distributed to sites of retention. We conclude that exposure to talc disrupts iron homeostasis, is associated with oxidative stress, and results in a biological effect (i.e., a fibro-inflammatory response). Talc pleurodesis can function as a model of the human response to mineral oxide particle exposure, albeit a massive one.

We report 9 patients with pleural biopsies referred because of concern about infiltration of what appeared to be chest wall fat by pan-keratin-positive spindled cells, a finding that led to a consideration of desmoplastic mesothelioma. All patients showed pleural effusions/pleural thickening on computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic paucicellular pleura with circular fat-like spaces and, sometimes, adjacent oblate spaces mostly deep in the fibrotic area. Indistinct, keratin-positive, spindle cells arranged parallel to the pleural surface coursed between these fat-like spaces. S-100 stains were negative around the fat-like spaces. Vimentin stains showed that the spaces did not have a cellular lining of any kind. Sometimes the spaces contained faintly hematoxyphilic material that was Alcian blue positive, and similar material was seen in the fibrotic stroma. Follow-up with periods ranging from 6 to 30 months revealed that 8 cases had stable disease on chest imaging or by clinical findings. One case had slowly progressive pleural thickening. These observations suggest that spaces resembling fat may be encountered in fibrotic pleurae and that horizontally oriented keratin-positive spindled cells between the fat-like spaces deep in the fibrotic portion of a thickened pleura represent a benign finding seen in some cases of organizing pleuritis/fibrothorax. The spaces themselves are probably artifacts derived from the biopsy procedure and/or cutting artifacts. In contrast, in true desmoplastic mesotheliomas there is downward, rather than horizontal, growth of keratin-positive spindled cells running between clearly definable fat cells.

Sarcomatoid mesothelioma is the least common, but most aggressive of the three major histological types of mesotheliomas. This study comprises 326 cases of sarcomatoid mesotheliomas among 2000 consecutive malignant mesothelioma cases received in consultation (16%). Patients included 312 men (96%) and 14 women (4%), with a median age of 70 years (range 41-94 years). Most tumors were pleural (319; 98%), and 7 were peritoneal (2%). Some desmoplastic features were identified in 110 cases (34%), and 70 (21%) were classified as desmoplastic. Rare subtypes included two cases with a lymphohistiocytoid pattern (<1%) and eight heterologous mesotheliomas (2%). Labeling for cytokeratins (CKs) was observed in 261/280 cases (93%), and for calretinin and vimentin in 31 and 91%, respectively. Pleural plaques were present in 79% of cases for which information was available, and asbestosis was diagnosed in 34/127 cases (27%). Median survival was 3.5 months. Fiber analysis was performed in 61 cases. The median asbestos body count was 1640/g wet lung tissue (by light microscopy). Amosite fibers were the most commonly identified fibers using energy-dispersive X-ray analysis and were significantly higher in the sarcomatoid cases, as were uncoated fibers using scanning electron microscopy. This study represents the largest series of sarcomatoid and desmoplastic malignant mesotheliomas to date and confirms the diagnostic usefulness of CK immunohistochemistry. The relationship with asbestos exposure--particularly amosite--and an association with pleural plaques and less often asbestosis is confirmed.

Context: Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose., Objective: To develop practical guidelines for the pathologic diagnosis of MM., Data Sources: A pathology panel was convened at the International Mesothelioma Interest Group biennial meeting (October 2006). Pathologists with an interest in the field also contributed after the meeting., Conclusions: There was consensus opinion regarding (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the differential diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. The International Mesothelioma Interest Group recommends that markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

This study reports changes in the frequency of detection of various asbestos fiber types between 1982 and 2005. Crocidolite is increasingly detected in U.S. mesothelioma patients. The percentage of crocidolite fibers detected in lung tissue has risen from 4 to 10%, and the percentage of cases in which crocidolite was detected increased from 19 to 37%. Meanwhile, the frequency of detection of amosite and chrysotile has decreased. The authors performed a detailed analysis of cases in which crocidolite was identified in the absence of amosite. Most of such cases were identified in recent years, a finding of concern since crocidolite is considered the most potent fiber type with respect to the pathogenesis of mesothelioma.

Only a small number of malignant mesotheliomas with heterologous elements have been described. There are currently no criteria for diagnosis and little data regarding prognosis. We suggest that the term heterologous mesothelioma should be reserved for tumours that show malignant heterologous elements, notably osteosarcomatous, chondrosarcomatous, or rhabdomyoblastic elements but have immunohistochemical and clinical characteristics of mesothelioma. We identified 27 such cases and characterized the clinical and pathological characteristics of these tumours. In our series, 89% originated in the pleura, and 11% from the peritoneal cavity. The median age at diagnosis was 68 years, ranging from 27 to 85 years. Of these cases, 93% occurred in males and 7% in women. Of the 27 mesothelioma cases 16 (59%) were sarcomatoid, 10 (37%) were biphasic, and one was reported as epithelioid; 40% (11 cases) showed osteosarcomatous elements only, 19% showed areas of rhabdomyosarcoma only, 19% contained areas of chondrosarcoma only, and 22% exhibited osteochondromatous elements. Immunohistochemical labelling for cytokeratins was present in the majority of cases. Exposure to asbestos was identified in all the 17 cases for which an exposure history was available (63%). Median survival was 6 months after diagnosis, similar to the survival seen in sarcomatoid mesotheliomas. The differential diagnosis includes primary and secondary pleural sarcomas, including osteosarcomas and chondrosarcomas. Immunohistochemical labelling for cytokeratins is helpful in the distinction, but lack of labelling for cytokeratins in a spindle cell/sarcomatoid tumour does not exclude the diagnosis of mesothelioma, irrespective of the presence of heterologous elements. We suggest that if the anatomical distribution conforms to that of mesothelioma, a diagnosis of heterologous mesothelioma should be made in preference to a diagnosis of primary pleural osteosarcoma or chondrosarcoma, regardless of cytokeratin positivity, as for conventional non-heterologous sarcomatoid mesothelioma.

The causative relationship between asbestos exposure and mesothelioma is firmly established. Some information in this regard comes from analysis of the fiber content of lung tissue by means of analytical electron microscopy. The author has had the opportunity to study the lung asbestos content of 396 cases of mesothelioma, including 28 peritoneal cases, by means of analytical scanning electron microscopy. The highest fiber levels occurred in patients who also had asbestosis, which was found in 12% of pleural and 43% of peritoneal cases. Elevated tissue asbestos content was identified in 87% of pleural and 75% of peritoneal cases. Peritoneal cases that are asbestos related have on average a higher lung fiber burden than pleural cases. Mesotheliomas in women have elevated tissue asbestos content in about 60% of cases, and many of these had a history of exposure as a household contact of an asbestos worker. The main fiber type identified in our series was amphibole, predominantly amosite. These fibers have been demonstrated to reach the target tissue, the pleura.

Objective: We address the current classifications and new changes regarding uncommon primary pleural tumors. Primary pleural tumors are divided according to their behavior and are discussed separately as benign tumors, tumors of low malignant potential, and malignant neoplasms., Data Sources: Current literature concerning primary pleural neoplasms was collected and reviewed., Study Selection: Studies emphasizing clinical, radiological, or pathologic findings of primary pleural neoplasms were obtained., Data Extraction: Data deemed helpful to the general surgical pathologist when confronted with an uncommon primary pleural tumor was included in this review., Data Synthesis: Tumors are discussed in 3 broad categories: (1) benign, (2) low malignant potential, and (3) malignant. A practical approach to the diagnosis of these neoplasms in surgical pathology specimens is offered. The differential diagnosis, including metastatic pleural neoplasms, is also briefly addressed., Conclusions: Uncommon primary pleural neoplasms may mimic each other, as well as mimic metastatic cancers to the pleura and diffuse malignant mesothelioma. Correct diagnosis is important because of different prognosis and treatment implications for the various neoplasms.

Of putative specific markers for diffuse malignant mesothelioma, nuclear staining with Zymed polyclonal calretinin antibody has shown the best specificity to date for epithelial diffuse malignant mesothelioma versus adenocarcinoma. We compared specificity and sensitivity of this polyclonal antibody for diagnosis of diffuse malignant mesothelioma with a new monoclonal antibody from DAKO. One hundred eighteen adenocarcinomas and 111 diffuse malignant mesotheliomas-70 epithelial, 22 sarcomatous, and 19 biphasic-were immunostained with calretinin antibodies from Zymed (polyclonal rabbit, prediluted, PAD:DC8) and DAKO(monoclonal mouse, 1:100, clone DAK Calret 1) using manufacturer-recommended procedures. Cases were blinded and assessed for nuclear versus cytoplasmic staining, percent positive cells, and background. Both antibodies showed similar positive predictive values for diffuse malignant mesothelioma by nuclear staining (Zymed=95%; DAKO=97%). False positives in 4 (3.4%) and 2 (1.7%) adenocarcinomas, respectively, stained greater than 10% of cells. Sensitivity for epithelial malignant mesothelioma was slightly less for DAKO antibody (Zymed=80%; DAKO=73%). Neither antibody performed well on sarcomatous malignant mesothelioma (Zymed=2/22; DAKO=1/22). Both antibodies are useful in the diagnosis of epithelial malignant mesothelioma, although monoclonal antibody is slightly less sensitive.

A remaining uncertainty in the U.S. cohort study of man-made vitreous fiber (MMVF) workers is whether asbestos exposure contributed to 10 questionable cases of mesothelioma. We report further details on one case from our previous mesothelioma investigation, including results of a recent lung tissue analysis. Case is a 68 year-old white male employed 1951-54 in a rock/slag wool plant where asbestos-containing products were manufactured. Cause of death was recorded as "mesothelioma, malignant, right pleural cavity" (ICD9: 163.9). Analysis for presence of asbestos bodies identified 18,300 asbestos bodies per gram of wet lung tissue (AB/gm), which greatly exceeds the normal range of 0-20 AB/gm. No MMVFs were identified in this sample. We conclude that this patient's tumor was not a mesothelioma, but a carcinoma possibly arising in the lung or mediastinum, and that this case supports the view that the few suspected mesotheliomas found in the U.S. cohort may have been caused by asbestos exposure.

Objectives: A large number of workers in the USA are exposed to chrysotile asbestos through brake repair, yet only a few cases of malignant mesothelioma (MM) have been described in this population. Epidemiologic and industrial hygiene studies have failed to demonstrate an increased risk of MM in brake workers. We present our experience of MM in individuals whose only known asbestos exposure was to brake dust and correlate these findings with lung asbestos fiber burdens., Methods: Consultation files of one of the authors were reviewed for cases of MM in which brake dust was the only known asbestos exposure. Lung fiber analyses were performed using scanning electron microscopy (SEM) in all cases for which formalin-fixed or paraffin-embedded lung tissue was available., Results: Ten cases of MM in brake dust-exposed individuals were males aged 51-73 yr. Nine cases arose in the pleura and one in the peritoneum. Although the median lung asbestos body count (19 AB/g) is at our upper limit of normal (range 0-20 AB/g), half of the cases had levels within our normal range. In every case with elevated asbestos fiber levels by SEM, excess commercial amphibole fibers were also detected. Elevated levels of chrysotile and non-commercial amphibole fibers were detected only in cases that also had increased commercial amphibole fibers., Conclusions: Brake dust contains exceedingly low levels of respirable chrysotile, much of which consists of short fibers subject to rapid pulmonary clearance. Elevated lung levels of commercial amphiboles in some brake workers suggest that unrecognized exposure to these fibers plays a critical role in the development of MM.

Background: Exposure to chrysotile dust has been associated with the development of mesothelioma and recent studies have implicated contaminating tremolite fibers as the likely etiological factor. Tremolite also contaminates talc, the most common non-asbestos mineral fiber in our control cases., Methods: We examined 312 cases of mesothelioma for which fiber burden analyses of lung parenchyma had been performed by means of scanning electron microscopy to determine the content of tremolite, non-commercial amphiboles, talc and chrysotile. The vast majority of these patients were exposed to dust from products containing asbestos., Results: Tremolite was identified in 166 of 312 cases (53%) and was increased above background levels in 81 cases (26%). Fibrous talc was identified in 193 cases (62%) and correlated strongly with the tremolite content (P < 0.0001). Chrysotile was identified in only 32 cases (10%), but still correlated strongly with the tremolite content (P < 0.0001). Talc levels explained less of the tremolite deviance for cases with an increased tremolite level than for cases with a normal range tremolite level (22 versus 42%). In 14 cases (4.5%) non-commercial amphibole fibers (tremolite, actinolite and/or anthophyllite) were the only fiber types found above background., Conclusions: We conclude that tremolite in lung tissue samples from mesothelioma victims derives from both talc and chrysotile and that tremolite accounts for a considerable fraction of the excess fiber burden in end-users of asbestos products.

Asbestos exposure is indisputably associated with development of mesothelioma. However, relatively few studies have evaluated the type of occupational exposure in correlation with asbestos fiber content and type. This study reports findings in 1445 cases of mesothelioma with known exposure history; 268 of these also had fiber burden analysis. The 1445 cases of mesothelioma were subclassified into 23 predominant occupational or exposure categories. Asbestos body counts per gram of wet lung tissue were determined by light microscopy. Asbestos fiber content and type were determined by scanning electron microscopy and energy dispersive x-ray analysis. Results were compared with a control group of 19 lung tissue samples. Ninety-four percent of the cases occurred among 19 exposure categories. Median asbestos body counts and levels of commercial and noncommercial amphibole fibers showed elevated levels for each of these 19 categories. Chrysotile fibers were detectable in 36 of 268 cases. All but 2 of these also had above-background levels of commercial amphiboles. When compared to commercial amphiboles, the median values for noncommercial amphibole fibers were higher in 4 of the 19 exposure groups. Most mesotheliomas in the United States fall into a limited number of exposure categories. Although a predominant occupation was ascertained for each of these cases, there was a substantial overlap in exposure types. All but 1 of the occupational categories analyzed had above-background levels of commercial amphiboles. Commercial amphiboles are responsible for most of the mesothelioma cases observed in the United States.

Malignant mesothelioma is strongly associated with prior asbestos exposure. Recently there has been interest in the role of talc exposure in the pathogenesis of mesothelioma. We have analyzed lung tissue samples from a large series of malignant mesothelioma patients. Asbestos bodies were counted by light microscopy and mineral fiber concentrations for fibers 5 µm or greater in length were determined by scanning electron microscopy equipped with an energy dispersive spectrometer. The values were compared with 20 previously published controls. Among 609 patients with mesothelioma, talc fibers were detected in 375 (62%) and exceeded our control values in 65 (11%). Elevated talc levels were found in 48/524 men (9.2%) and 17/85 women (20%). Parietal pleural plaques were identified in 30/51 informative cases (59%) and asbestosis in 5/62 informative cases (8%). Commercial amphiboles (amosite and/or crocidolite) were elevated in 52/65 (80%) and noncommercial amphiboles (tremolite, actinolite or anthophyllite) in 41/65 (63%). Both were elevated in 34/65 (52%). Asbestos body counts by light microscopy were elevated in 53/64 informative cases (83%). A history of working in industries associated with asbestos exposure and increased mesothelioma risk was identified in 36/48 cases in men, and a history of exposure as household contacts of an occupationally exposed individual was identified in 12/17 cases in women. We conclude that among patients with mesothelioma, the vast majority have talc levels indistinguishable from background. Of the remaining 11% with elevated talc levels, the vast majority (80%) have elevated levels of commercial amphibole fibers. [ABSTRACT FROM AUTHOR]

Context.--Numerous articles in the scientific literature indicate that pathogenic fibers with respect to asbestos-related diseases are those that exceed 5 lm in length. Nonetheless, some authors have expressed concerns regarding pathogenicity of shorter fibers. Objective.--To review the scientific evidence regarding pathogenicity (or lack thereof) of fibers less than or equal to 5 lm in length, with particular attention to publications indicating that such fibers might be hazardous. Data Sources.--The scientific literature was reviewed for experimental animal studies and human studies that address the role of fiber size in causation of disease. Sources included original studies, as well as review articles related to the topic. Conclusions.--Experimental animal studies involving inhalation of fibers have demonstrated that fibers greater than 5 lm in length are associated with both pulmonary fibrosis (ie, asbestosis) and malignancies (carcinoma of the lung and mesothelioma). There is no convincing evidence for a pathogenic effect for fibers that are 5 lm or less in length. Fiber analyses of human lung tissue samples provide further support for pathogenicity of long fibers, particularly the more biopersistent amphibole fibers. Similar observations have been reported for nonasbestos mineral fibers. Concerns expressed by some authors (eg, the greater abundance of short fibers) do not alter these conclusions. Similarly, in vitro studies demonstrating biological activity of short fibers do not override inhala-tional studies of whole animals or the epidemiological findings in humans. [ABSTRACT FROM AUTHOR]

Context: A detailed evaluation of the correlation and linearity of industrial hygiene retrospective exposure assessment (REA) for cumulative asbestos exposure with asbestos lung burden analysis (LBA) has not been previously performed, but both methods are utilized for case-control and cohort studies and other applications such as setting occupational exposure limits. Objective: (a) To correlate REA with asbestos LBA for a large number of cases from varied industries and exposure scenarios; (b) to evaluate the linearity, precision, and applicability of both industrial hygiene exposure reconstruction and LBA; and (c) to demonstrate validation methods for REA. Methods: A panel of four experienced industrial hygiene raters independently estimated the cumulative asbestos exposure for 363 cases with limited exposure details in which asbestos LBA had been independently determined. LBA for asbestos bodies was performed by a pathologist by both light microscopy and scanning electron microscopy (SEM) and free asbestos fibers by SEM. Precision, reliability, correlation and linearity were evaluated via intraclass correlation, regression analysis and analysis of covariance. Plaintiff's answers to interrogatories, work history sheets, work summaries or plaintiff's discovery depositions that were obtained in court cases involving asbestos were utilized by the pathologist to provide a summarized brief asbestos exposure and work history for each of the 363 cases. Results: Linear relationships between REA and LBA were found when adjustment was made for asbestos fiber-type exposure differences. Significant correlation between REA and LBA was found with amphibole asbestos lung burden and mixed fiber-types, but not with chrysotile. The intraclass correlation coefficients (ICC) for the precision of the industrial hygiene rater cumulative asbestos exposure estimates and the precision of repeated laboratory analysis were found to be in the excellent range. The ICC estimates were performed independent of specific asbestos fiber-type. Conclusions: Both REA and pathology assessment are reliable and complementary predictive methods to characterize asbestos exposures. Correlation analysis between the two methods effectively validates both REA methodology and LBA procedures within the determined precision, particularly for cumulative amphibole asbestos exposures since chrysotile fibers, for the most part, are not retained in the lung for an extended period of time. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the impact of extreme data points in Finkelstein's 2009 findings of no association between lung levels of commercial and non-commercial amphiboles (principally tremolite as a marker for chrysotile asbestos) in brake repair workers with mesothelioma. Methods: We first identified potential outliers, high leverage points, and influential points among lung levels of commercial amphiboles and tremolite among 15 persons whose only known exposure to asbestos was through brake repair work. We used sensitivity analysis and quantile regression to account for extreme data points and model commercial amphibole levels as a predictor of tremolite levels. We also used quantile regression to evaluate whether case-reported duration of employment as a brake repair worker predicted lung levels of commercial amphiboles or tremolite. Results: We found lung levels of commercial amphiboles are a statistically significant predictor of tremolite levels via sensitivity analysis ( r == 0.82, slope estimate P-value == 0.001, R2 == 0.68) and quantile regression (slope estimate P-value <0.0001). Our data provide no evidence that duration of employment as a brake repair worker was a predictor of lung levels of tremolite or commercial amphiboles. Conclusions: Our findings suggest that elevated lung levels of tremolite in the lungs of brake repair workers with elevated levels of amphiboles arose from concurrent exposures to commercial amphibole and chrysotile asbestos in occupational settings other than brake repair work. These findings are supported by five new cases. The weight of the scientific evidence does not support a role for occupational exposure to brake dust and other friction products in the development of mesothelioma. [ABSTRACT FROM AUTHOR]

Summary: Asbestos exposure has resulted in a variety of diseases, including asbestosis, carcinoma of the lung (LC), pleural plaques, and malignant mesothelioma (MM). We hypothesized that there have been significant changes in the mineral fiber content of lung tissue from individuals with these diseases over the past 25 years. Asbestos content was measured in lung tissue samples from 819 individuals using light microscopy (to measure asbestos body concentrations) and scanning electron microscopy (to measure types and concentrations of mineral fibers). Cases were divided chronologically according to those occurring in the first half (group 1) versus those occurring in the second half (group 2). The study included 419 cases of MM, 206 cases of asbestosis, and 340 cases of LC. The median asbestos body count (in asbestos bodies per gram) decreased from group 1 to group 2 for each disease: MM, 480 to 350; asbestosis, 24700 to 19200; and LC, 1600 to 174 (reference range, 0-20). A similar trend was observed for fiber counts by scanning electron microscopy. Amosite was the most frequently detected asbestos fiber type and decreased in frequency of detection and median concentration from group 1 to group 2. Crocidolite showed an increased detection frequency from group 1 to group 2 across all 3 disease categories. The decrease in asbestos body and amosite concentrations over time is consistent with the banning of asbestos from insulation products in 1972. The source for the increased detection of crocidolite was not identified and needs further investigation. [Copyright &y& Elsevier]

Studies the various sub-areas of pleural pathology. Comparison between mesothelial hyperplasia and mesothelioma; Elements of asbestos body and asbestos fiber analysis in mesothelioma patients; Primary solid tumors of the pleura other than diffuse malignant mesothelioma; Characteristics of lymphoreticular malignancies of the pleura; Unusual metastases to and from the pleura.

Context.— Ionizing radiation has a role in the development of malignant mesothelioma, in several epidemiologic studies, including patients with hematologic malignancies. Objective.— To study the clinicopathologic characteristics of patients with malignant mesothelioma and hematologic malignancies with and without a history of radiotherapy. Design.— From a database of approximately 3600 patients with malignant mesothelioma, we identified 45 patients (1%) who also had hematologic malignancies. We examined clinicopathologic features and noted whether the patient had received radiotherapy for malignancy, comparing those with and those without such exposure. Results.— Among the 45 cases, 18 (40%) had Hodgkin lymphoma, 15 (33%) had non-Hodgkin lymphoma, 10 (4%) had chronic lymphocytic leukemia, and 2 (22%) had chronic myelogenous leukemia; 20 patients (44%) had a history of radiotherapy, and 23 (51%) did not. Most patients with Hodgkin lymphoma (16 of 18; 90.0%) received radiation, whereas none of the patients with leukemia (0 of 12) and only 20% (3 of 15) of the patients with non-Hodgkin lymphoma did so. Patients without radiation were older than patients who received radiotherapy (median, 73 versus 54 years, respectively; P < .001), had a shorter interval from diagnosis of hematologic malignancy to that of mesothelioma (median, 2 versus 24 years, respectively; P < .001), and had a shorter survival period (median, 6.0 versus 14.0 months, respectively; P = .02). Epithelial mesotheliomas were proportionately more common in patients with a history of radiotherapy. Conclusions.— Patients with mesothelioma and hematologic malignancies with a history of radiation tended to be younger, had a longer interval from diagnosis of hematologic malignancy to that of mesothelioma, had a longer survival period, and were more likely to have the epithelial variant compared with patients without radiotherapy. [ABSTRACT FROM AUTHOR]

Context-The development of successful chemotherapeutic agents directed against the Kit receptor tyrosine kinase protein has generated intense interest in the Kit (CD117) immunoreactivity of various neoplasms. Immunoreactivity for Kit in small cell lung carcinoma (SCLC) has been well established. However, data on Kit immunostaining in other lung tumors is limited, likewise, while solitary fibrous tumors of the gastrointestinal tract have been examined for Kit expression, the Kit staining characteristics of their counterpart in the pleura, namely, localized fibrous tumor, are not well known. Objective.-To characterize the Kit immunohistochemical profiles of major types of lung and pleural tumors. Design.-We stained 60 lung carcinomas, including 11 SCLCs, 4 large cell neuroendocrine carcinomas, 22 squamous cell carcinomas, 23 adenocarcinomas, 11 pulmonary carcinoid tumors, 19 pleural malignant mesotheliomas, and 6 localized pleural fibrous tumors with a commonly used polyclonal Kit antibody. Results.-Small cell lung carcinomas demonstrated Kit staining in 82% of cases, nearly all of which demonstrated moderate to intense immunoreactivity. Immunostaining was observed in 25% of large cell neuroendocrine carcinomas. Focal staining was observed in 9% of squamous cell carcinomas and 17% of adenocarcinomas. None of the pulmonary carcinoid tumors were immunoreactive. Moderately intense immunostaining was present in 50% of localized fibrous tumors. Malignant mesotheliomas were nonimmunoreactive for Kit in 95% of cases. Conclusion.-Non-small cell lung carcinomas showed very limited expression of Kit. Lung tumors with neuroendocrine differentiation exhibited a wide spectrum of Kit immunoreactivity, ranging from rare in pulmonary cardnoid tumors to frequent in SCLC. The high frequency of Kit immunostaining in SCLC has important potential therapeutic implications. Demonstration of Kit positivity in some localized fibrous tumors in this study contrasts with absent immunoreactivity in solitary fibrous tumors of the gastro- intestinal tract. The paucity of Kit staining in malignant mesothelioma suggests these tumors are unlikely to respond to currently available tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]