Malignant mesothelioma in south east England: clinicopathological experience of 272 cases [published erratum appears in Thorax 1997 Nov;52(11):1018]

BACKGROUND: Malignant mesothelioma is a rare pleural tumour associated with asbestos exposure. The proportion of malignant mesothelioma unrelated to asbestos exposure, and any differentiating features between exposed and unexposed cases, are not well described. This study describes occupational, clinical, and pathological features in a large cohort of cases of malignant mesothelioma from south east England. METHODS: All 272 cases from this region were studied, either in life or after death when necropsy examination suggested malignant mesothelioma. Detailed information was gathered regarding the occupational history, clinical course, and mode of death. Necropsies were performed in 98% of cases. Lung tissue was examined histologically to confirm the diagnosis, subtype of tumour, presence or absence of asbestosis and asbestos bodies. RESULTS: Exposure to asbestos was documented in 87% of cases, while in the remainder, no asbestos exposure was found nor were asbestos bodies seen; 94.5% were pleural, 5.1% peritoneal, and 0.4% pericardial. Right sided tumours were more common than left sided tumours (ratio 1.6:1). Patients usually presented with breathlessness and chest pain, but 33% presented with pleural effusion in the absence of chest pain. The mean (SD) time from first exposure to asbestos to symptoms was 40 (12) years with a median (interquartile range (IQR) survival of 14 (12.5) months. The median (IQR) survival time in sarcomatous, epithelial, and mixed cell type malignant mesothelioma was 9.4 (10) months, 12.5 (18) months, and 11 (14) months, respectively, and was significantly greater in cases detected by chance. Clinical features were similar in asbestos related and non-asbestos related malignant mesothelioma. CONCLUSIONS: In south east England most cases of malignant mesothelioma are associated with asbestos exposure. Clinical features do not differentiate between asbestos related and non- asbestos related disease.


     

Epithelial mesothelioma with deciduoid features: report of four cases

Deciduoid mesothelioma is the designation given to an unusual morphologic variant of epithelial mesothelioma that closely simulates exuberant ectopic decidual reaction. Because all four previously reported cases involved the peritoneum and occurred in young women without a history of asbestos exposure, it was suggested that deciduoid mesothelioma was a subtype of epithelial mesothelioma characterized by its unique morphology, that it affects a distinct patient population, and that it is unrelated etiologically to asbestos. The author reports four cases of mesothelioma with deciduoid features, all of which originated in the pleura. Three of the patients were men and one was a woman. Their ages ranged from 46 to 78 years (mean age, 67 yrs). Two of the patients had a history of asbestos exposure. These findings indicate that this morphologic variant of mesothelioma is not limited to a specific patient population nor is it restricted to the peritoneum.     

Well-differentiated papillary mesothelioma.

Well-differentiated papillary mesothelioma is an unusual variant of epithelial mesothelioma considered to be of low malignant potential. The majority of previously reported cases developed in the peritoneum of young women without a history of asbestos exposure. The authors report 14 cases of well-differentiated papillary mesothelioma, seven of which originated in the pleura, six in the peritoneum, and one in the tunica vaginalis. Eleven of the patients were male and three were female, with an average age at presentation of 58 years (range 32-82 years). Six of the patients had a quantifiable history of asbestos exposure. Of the nine cases with complete follow-up, six had clinically indolent disease, one showed resolution after adjuvant chemotherapy, one pursued an aggressive course, and one died of other causes. These findings indicate that well-differentiated papillary mesothelioma is a rare variant of mesothelioma with a variable clinical prognosis that is etiologically related to asbestos exposure in some cases.     

Laparoscopy and mesothelioma.

Malignant mesothelioma is a well-recognized long-term sequela of chronic asbestos exposure. Asbestos use in the United States began in the 1950s and was widespread until the mid-1970s. Although currently only 2.2 cases per million population per year are diagnosed, disease incidence is increasing because of the long latency of this neoplasm. A latency of 15-50 years means that a higher incidence of this neoplasm can be anticipated in the future. The authors report a patient with peritoneal mesothelioma and no known prior exposure to asbestos. The diagnosis was confirmed by exploratory laparoscopy, which entailed biopsies of the diaphragm and of the peritoneal and abdominal walls, and by cytologic evaluation of 700 ml ascitis fluid. At present, exploratory laparoscopy offers the quickest, safest, and least invasive way to confirm the clinical diagnosis of peritoneal malignant mesothelioma.     

Asbestos-induced malignant mesothelioma of the tunica vaginalis testis

Since 1977 the diffuse malignant mesothelioma of the pleura and peritoneum caused by asbestos represents one of the most often compensated occupational cancers in Germany. Because of the probability of an asbestos-related etiology, it is considered as a "signal tumour", mainly indicating exposure to asbestos dust at the workplace. Two cases of histologically confirmed rare malignant mesothelioma of the tunica vaginalis testis are presented. Previous exposure to asbestos at the workplace is to be considered as a causal factor in both tumors. If cases of mesothelioma occur the criteria for indicating an occupational disease (No. 4105 of the German Law of Occupational Diseases, BKV) are fulfilled.     

Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma

BACKGROUND: Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed. METHODS: To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content. RESULTS: Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years. CONCLUSIONS: Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.     

Malignant peritoneal mesothelioma

Mesothelioma is a neoplasm originating from the mesothelial surface lining cells of the serous human cavities. It may involve the pleura, less frequently the peritoneum rarely, the pericardium, the tunica vaginalis testis and ovarian epithelium. Asbestos has been widely used in industry. A causal relationship between asbestos exposure and pleural, peritoneal and pericardial malign mesothelioma was suggested, the risk of cancer being correlated to cumulate exposure. Studies from National Cancer Institute, USA, show that the malignant mesothelioma is a rare and aggressive asbestos related malignancy. The symptomatology is insidious and poses difficult problems in diagnosis and treatment. This paper presents the case of a 59 year old patient with malignant peritoneal mesothelioma who worked almost 40 years as an electrician, exposed to asbestos fibers. He was hospitalized for important weight loss, abdominal pain and tiredness being diagnosed after imaging tests with a giant tumor, localized at the abdominal upper level, which seems to originate from the spleen's superior pole. During surgery we discovered a tumor with cystic parts, intense vascularized, which turn to be adherent in the upper side to the lower face of the left midriff cupola, to the spleen superior pole and 1/3 middle level of the great gastric curve. It was performed surgical ablation of the tumor, splenectomy with favorable postoperative evolution, the patient being now under chemotherapy treatment.     

Peritoneal malignant mesothelioma: case report

Our study reports peritoneal diffuse malignant mesothelioma (DMM) in a 43 years old male patient, with no exposure to asbestos in his medical history; the partner of the patient was also not exposed to asbestos. The exposure to X-rays was also excluded. Different pathogenic mechanisms for the pathogenesis of a peritoneal diffuse malignant mesothelioma in this patient can be hypothesized, for example, SV40 infection and genetic susceptibility; a minimal domestic exposure to asbestos can be not excluded. Therefore, further studies in a larger number of subjects are necessary to determine whether one or all of these hypothetic pathogenic mechanisms are more significant for the development of malignant mesothelioma.     

Well-differentiated papillary mesothelioma of the pleura: a series of 24 cases

Well-differentiated papillary mesothelioma (WDPM) of the pleura represents a distinct mesothelial tumor presenting with unilateral pleural effusion and superficial spreading of stout papillary formations with myxoid cores, lined by bland, flattened, or epithelioid cells, without or with limited invasion of the submesothelial layer. The majority of cases have been reported in the peritoneum in women of reproductive age with no history of asbestos exposure and also in the tunica vaginalis of men. We report 24 cases of pleural WDPM and compared their histologic, epidemiologic, and clinical features with those of classic mesothelioma. Men and women were equally affected, with a mean age of 60 years. Half of the patients had a history of occupational asbestos exposure. In 11 patients with a minimal follow-up period of 24 months, the survival ranged from 36 to 180 months with an average of 74 months as compared with 9.89 months for 1248 paired patients with diffuse malignant mesothelioma. Ten-year survival was 30.8%. We conclude that WDPM is a rare and unusual mesothelial tumor, characterized by a lack of deep invasion and associated with an indolent clinical course and long survival. For these reasons, WDPM is best considered as a specific clinico-pathologic entity distinct from conventional diffuse malignant mesothelioma.     

Malignant mesothelioma of tunica vaginalis testis

Malignant mesothelioma of the tunica vaginalis is rare, but sometimes curable. It is similar to malignant mesothelioma of the peritoneum and of the pleura, and is likewise associated with asbestos exposure. We report a case, with correlative computed tomography, ultrasound, and gross pathology images that demonstrate tiny tumor implants studding the vaginalis testis. The literature is reviewed.     

Peritoneal nesothelioma.

Two patients with primary peritoneal mesothelioma are reported. They had abdominal symptoms, no symptoms referable to the respiratory system and normal chest X-rays. There was no clinical evidence of impaired respiratory function. One of the patients had a history of brief asbestos exposure over 20 years before diagnosis. The procedure for obtaining compensation is outlined and the protean uses of, and hence possible exposure to, asbestos are noted. In screening programmes consideration should be given to both pulmonary and abdominal symptoms. Laparoscopy may have a part to play in earlier diagnosis of peritoneal mesothelioma.     

Aristolochic acid nephropathy and the peritoneum: Functional, structural, and molecular studies

BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy linked to the exposure to aristolochic acid (AA) and characterized by extensive fibrosis and urothelial atypia. Although the fibrotic process has been documented in extrarenal tissues, the involvement of the peritoneum, as well as the efficacy of peritoneal dialysis in AAN patients, remain uncertain. METHODS: The structure of the peritoneal membrane and the expression of basic fibroblast growth factor (bFGF), collagen type III, endothelial nitric oxide synthase (eNOS), and aquaporin-1 (AQP1) were investigated in peritoneal biopsies from an index AAN patient, four other AAN patients, four regular peritoneal dialysis patients, and two controls. Similar methods were used to investigate a rabbit model of AAN after intraperitoneal exposure to high-dose AA. AA-DNA adducts were screened by 32P-postlabeling analysis. RESULTS: The AAN patients had renal failure, renal fibrosis, and urothelial atypia. The peritoneum of AAN patients had a normal structure, lacked cellular atypia, and, in comparison with regular peritoneal dialysis patients and controls, did not show abnormal regulation of fibrotic and endothelial markers. Furthermore, specific AA-DNA adducts were not identified in the peritoneum of AAN patients. In contrast, AA-DNA adducts were detected in peritoneal and kidney tissues of all exposed rabbits, and one of them developed a malignant mesothelioma. CONCLUSION: These data demonstrate the lack of fibrotic and vascular alterations and the absence of cellular atypia in the peritoneum from AAN patients. Thus, peritoneal dialysis should not be discouraged in these patients. Nevertheless, studies in a rabbit model of high-dose AA exposure may suggest a potential risk of peritoneal malignancy.     

Malignant mesothelioma of the peritoneum presenting as an inflammatory lesion: a report of four cases

Most cases of malignant mesothelioma present with obvious diffuse tumor, and the presence of grossly visible diffuse tumor is usually cited as an important criterion for making the diagnosis. We report four cases of unsuspected malignant mesothelioma of the peritoneum presenting as localized acute inflammatory lesions. The clinical diagnoses were acute appendicitis in two cases, acute cholecystitis in the third case, and incarcerated umbilical hernia in the fourth case. In all cases tumor was not evident at initial surgical exploration or on gross pathologic examination, and the diagnosis was only made on microscopic examination of the resected specimens. All cases showed a tubulopapillary form of epithelial mesothelioma with obvious tissue invasion, but the foci of tumor were too small to be seen grossly or were present deep in fibrous tissue. On follow-up all patients developed grossly evident tumor, and one of these patients is alive without evidence of disease 5 years after presentation. We conclude that peritoneal mesotheliomas may occasionally present as inflammatory processes without grossly evident tumor and can be diagnosed by microscopic findings alone.     

Radiologic findings of mesothelioma at the tunica vaginalis

Malignant mesothelioma of the tunica vaginalis testis is a rare, but often fatal, malignancy that usually appears during the fourth decade and has a strong relationship with occupational exposure to asbestos and long-lasting hydrocele. We present a case involving a 36-year-old man without a history of hydrocele, trauma, or exposure to asbestos who developed malignant mesothelioma.     

胸膜间皮瘤的诊断与治疗

经手术病理证实的胸膜间皮瘤１８例，其中良好性１５例，恶性１３例，局限型７例，弥漫型１１例。本病术前误诊率高，本组误诊８例。１９例均行手术治疗，术后３例失访。本病诊断主要依靠胸水的检查和胸膜活检；局限型胸膜间皮瘤一经确诊，主张早期手术；弥漫型确诊后如患者全身情况允许，应行广泛手术切除及术后综合治疗，以利于延长患者生命。     

Malignant mesothelioma in women.

BACKGROUND: Malignant mesothelioma reportedly shows different epidemiology and pathology in females, and a proportion are believed to arise spontaneously. METHODS: One hundred and seventy seven cases of malignant mesothelioma in females were reviewed, examined by histochemistry and immunohistochemistry, assessed for asbestosis and lung fibre burden by transmission electron microscopy with energy dispersive x ray analysis, and compared with 31 female controls. RESULTS: Two of one hundred and three cases tested for carcinoembryonic antigen were positive and were excluded from further analysis. Tumour cases showed increased amphibole burdens; in those in whom exposure information was known, 74 (80%) of 93 patients had a history of exposure to asbestos. Seventy two (47%) of 152 patients had lung fibrosis. Tumour site and histological type were little different from those reported in adult males. Mixed type histological pattern, lung fibrosis, and peritoneal site were associated with heavier lung asbestos burdens, but not exclusively. Thirty five (30%) of 117 patients had amphibole burdens of less than 2 x 10(6) fibres/g; the sites affected and the histological pattern of tumours in this group were similar to those in cases with amphibole fibre counts of > or = 2 x 10(6)/g lung. A higher lung amphibole burden than the mean burden in control females was found in 115 (98%) of 117 patients tested. CONCLUSIONS: The pathology of malignant mesothelioma appears to be similar in women and in men, and in cases associated and unassociated with asbestos.     

Mesotheliomas with deciduoid morphology: a morphologic spectrum and a variant not confined to young females

Deciduoid mesotheliomas are rare with only four previously reported cases, all affecting the peritoneum of young females. We describe another six cases (three men and three women; age range 52-65 yrs, median 55 yrs; five peritoneal and one pleural). Three patients had an occupational history of asbestos exposure. The deciduoid appearance predominated in four cases, whereas in two it represented a minor component within conventional tubulopapillary epithelioid mesothelioma. All tumors were strongly cytokeratin-positive (including CK5/6) and all showed at least focal staining for thrombomodulin, HBME-1, and calretinin. All were negative for epithelial mucin (D/PAS), CEA, BerEP4, LeuM1 (CD15), CD21, CD35, and S100 protein. Five of six cases (83%) were vimentin-positive and two (33%) were focally positive for alpha-smooth muscle actin. A differential diagnosis of gastrointestinal autonomic nerve tumor (GANT) had been initially considered from the morphology of one case, and we found positivity for some of the "neuronal" markers described in GANTs. This prompted us to apply such a panel to the other five tumors, accepting that the cytokeratin positivity encountered in all of our cases would exclude GANT. All cases of deciduoid mesothelioma (100%) were positive for PGP 9.5 and NSE and four of six (66%) were positive for NKI/C3. Weak focal staining (<5% cells) for synaptophysin was seen in two of six tumors. All cases were chromogranin-negative. All cases examined by electron microscopy showed desmosomes and smooth microvilli without rootlets but no neuroendocrine granules. In conclusion, a deciduoid morphology appears to be part of the histopathologic spectrum encountered in epithelioid mesothelioma. This variant is not confined to female patients and occurs over a wider age range than previously recognized. The overlapping immunophenotype with GANTs illustrates that caution should be exercised when interpreting positivity for "neuronal" markers in this context. An immunohistochemical panel that includes cytokeratins should always be used.     

Surgical treatment of asbestos-related disease of the chest

Thoracic surgeons are asked to evaluate various diseases related to asbestos, including benign pleural plaques, malignant mesothelioma, and lung cancer. The benign localized mesothelioma is usually considered in the differential diagnosis of pleural tumors, but it is not related to asbestos exposure. Benign pleural plaques can be diagnosed by history and radiologic studies, and surgery offers no therapeutic benefit. Diffuse malignant mesothelioma is currently an incurable tumor, but pleurectomy can afford some palliation. Extrapleural pneumonectomy can be accomplished with an acceptable mortality, but long-term results do not justify its routine use. Lung cancer in those exposed to asbestos fibers is treated no differently than when it occurs in the general population.     

Diagnosis of Mesothelioma

Mesothelioma is a rare neoplasm that arises from mesothelial cells lining body cavities including the pleura, pericardium, peritoneum, and tunica vaginalis. Most malignant mesotheliomas occur in the chest and are frequently associated with a history of asbestos exposure. The diagnosis of malignant mesothelioma is challenging and fraught with pitfalls, particularly in small biopsies. This article highlights what the pathologist needs to know regarding the clinical and radiographic presentation of mesothelioma, histologic features including subtypes and variants, and recent advances in immunohistochemical markers and molecular testing.