Malignant Mesothelioma of the Pleura
1988; Elsevier BV; Volume: 63; Issue: 12 Linguagem: Inglês
10.1016/s0025-6196(12)65411-1
ISSN1942-5546
AutoresRichard J. Pisani, Thomas V. Colby, David E. Williams,
Tópico(s)Medical Imaging and Pathology Studies
ResumoMalignant mesothelioma of the pleura most commonly occurs in persons with a heavy occupational exposure to asbestos. Some patients, however, have no such history of exposure. Clinical features include initial complaints of nonpleuritic chest pain and dyspnea. The most frequent roentgenographic finding is a unilateral pleural effusion. Thrombocytosis and elevated erythrocyte sedimentation rates are common. Pleural effusions are typically exudates, are often hemorrhagic, and are usually insufficient for diagnosing mesothelioma based on cytology alone. Even pleural biopsy may not produce enough tissue to enable the pathologist to make a firm diagnosis. Thoracotomy and open biopsy will confirm the diagnosis in most cases. Pathologic distinction from metastatic adenocarcinoma may be difficult even after the use of special stains and electron microscopy. Clinical deterioration is primarily attributable to local spread of tumor. Several factors seem to predict prolonged survival: (1) epithelial histologic subtype, (2) performance score, (3) age of the patient at the time of diagnosis, and (4) absence of chest pain. Surgical treatment, chemotherapy, and irradiation, alone or in combination, have been used for malignant mesothelioma. Except for the palliative effect of irradiation, most treatment protocols have not altered the dismal median survival of approximately 11 months seen in untreated patients with malignant mesothelioma. Malignant mesothelioma of the pleura most commonly occurs in persons with a heavy occupational exposure to asbestos. Some patients, however, have no such history of exposure. Clinical features include initial complaints of nonpleuritic chest pain and dyspnea. The most frequent roentgenographic finding is a unilateral pleural effusion. Thrombocytosis and elevated erythrocyte sedimentation rates are common. Pleural effusions are typically exudates, are often hemorrhagic, and are usually insufficient for diagnosing mesothelioma based on cytology alone. Even pleural biopsy may not produce enough tissue to enable the pathologist to make a firm diagnosis. Thoracotomy and open biopsy will confirm the diagnosis in most cases. Pathologic distinction from metastatic adenocarcinoma may be difficult even after the use of special stains and electron microscopy. Clinical deterioration is primarily attributable to local spread of tumor. Several factors seem to predict prolonged survival: (1) epithelial histologic subtype, (2) performance score, (3) age of the patient at the time of diagnosis, and (4) absence of chest pain. Surgical treatment, chemotherapy, and irradiation, alone or in combination, have been used for malignant mesothelioma. Except for the palliative effect of irradiation, most treatment protocols have not altered the dismal median survival of approximately 11 months seen in untreated patients with malignant mesothelioma. The incidence of malignant mesothelioma of the pleura is increasing at a rate of 13% per year in American men.1Spirtas R Beebe GW Connelly RR Wright WE Peters JM Sherwin RP Henderson BE Stark A Kovasznay BM Davies JNP Vianna NJ Keehn RJ Ortega LG Hochholzer L Wagner JC Recent trends in mesothelioma incidence in the United States.Am J Ind Med. 1986; 9: 397-407Crossref PubMed Scopus (92) Google Scholar In addition, although formerly seen predominantly in men employed in high-asbestos-exposure occupations, malignant mesothelioma is beginning to occur more frequently in women and in those with no history of work-related exposure to asbestos.2Wolf KM Piotrowski ZH Engel JD Bekeris LG Palacios E Fisher KA Malignant mesothelioma with occupational and environmental asbestos exposure in an Illinois community hospital.Arch Intern Med. 1987; 147: 2145-2149Crossref PubMed Scopus (17) Google Scholar Despite the application of multiple therapeutic approaches, the poor prognosis has not been altered since the initial descriptions of mesothelioma. In this review, we summarize our current understanding of malignant mesothelioma. One of the first clues leading to the eventual link between asbestos and mesothelioma was the observation that tumors occurred more frequently in coastal cities than elsewhere.3Glatzel H Zur Geographie des Pleuracarcinoms.Deutsch Arch Klin Med. 1943; 190: 418-428Google Scholar Subsequently, investigations in South African coal miners confirmed that exposure to asbestos was associated with an increased incidence of mesothelioma.4Wagner JC Sleggs CA Marchand P Diffuse pleural mesothelioma and asbestos exposure in the north western Cape Province.Br J Ind Med. 1960; 17: 260-271PubMed Google Scholar This observation, made in 1960, has been confirmed in numerous studies.5Elmes PC Simpson MJC The clinical aspects of mesothelioma.Q J Med. 1976; 45: 427-449PubMed Google Scholar, 6Selikoff IJ Churg J Hammond EC Relation between exposure to asbestos and mesothelioma.N Engl J Med. 1965; 272: 560-565Crossref PubMed Scopus (243) Google Scholar, 7Whitwell F Rawcliffe RM Diffuse malignant pleural mesothelioma and asbestos exposure.Thorax. 1971; 26: 6-22Crossref PubMed Scopus (118) Google Scholar Although malignant mesothelioma probably was initially described before 1900,8Wagner E Das tuberkelahnliche Lymphadenom.Arch Heilkund (Leipzig). 1870; 11: 497Google Scholar it was not well recognized until 1960.4Wagner JC Sleggs CA Marchand P Diffuse pleural mesothelioma and asbestos exposure in the north western Cape Province.Br J Ind Med. 1960; 17: 260-271PubMed Google Scholar Localized fibrous mesothelioma is unrelated to exposure to asbestos and is discussed only briefly in this report, primarily to illustrate features that distinguish it from diffuse malignant mesothelioma. Three reviews of localized fibrous mesothelioma have been published recently.9Briselli M Mark EJ Dickersin GR Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature.Cancer. 1981; 47: 2678-2689Crossref PubMed Scopus (615) Google Scholar, 10Okike N Bernatz PE Woolner LB Localized mesothelioma of the pleura: benign and malignant variants.J Thorac Cardiovasc Surg. 1978; 75: 363-370PubMed Google Scholar, 11Dalton WT Zolliker AS McCaughey WTE Jacques J Kannerstein M Localized primary tumors of the pleura: an analysis of 40 cases.Cancer. 1979; 44: 1465-1475Crossref PubMed Scopus (173) Google Scholar Approximately two-thirds of the patients with diffuse malignant pleural mesothelioma are between the ages of 50 and 70 years.12Antman KH Clinical presentation and natural history of benign and malignant mesothelioma.Semin Oncol. 1981; 8: 313-320PubMed Google Scholar Rarely, the tumor occurs in children.13Grundy GW Miller RW Malignant mesothelioma in childhood: report of 13 cases.Cancer. 1972; 30: 1216-1218Crossref PubMed Scopus (75) Google Scholar The incidence of malignant mesothelioma is 2 to 6 times higher in men than in women. Wives of men employed in asbestos-related work also have an increased incidence of mesothelioma.14Vianna NJ Polan AK Non-occupational exposure to asbestos and malignant mesothelioma in females.Lancet. 1978; 1: 1061-1063Abstract PubMed Scopus (144) Google Scholar The incidence of malignant mesothelioma in populations considered minimally exposed to asbestos was estimated at one case per million per year in Canada between 1959 and 1968.15McDonald AD Harper A El Attar OA McDonald JC Epidemiology of primary malignant mesothelial tumors in Canada.Cancer. 1970; 26: 914-919Crossref PubMed Scopus (107) Google Scholar Industrialized countries have an increased incidence, and the highest incidence occurs among persons with heavy occupational exposure to asbestos (for example, shipyard workers and insulators). Data from more than 40,000 autopsies performed in various countries show the rate of occurrence of malignant mesothelioma to range from 0.02 to 0.7%;16Shearin Jr, JC Jackson D Malignant pleural mesothelioma: report of 19 cases.J Thorac Cardiovasc Surg. 1976; 71: 621-627PubMed Google Scholar the highest rate was found in Hamburg, a shipbuilding center. One study estimated that a mesothelioma will develop in approximately 2% of workers exposed to one asbestos fiber per cubic centimeter for 50 years.17Peto J The hygiene standard for chrysotile asbestos.Lancet. 1978; 1: 484-489Abstract PubMed Scopus (53) Google Scholar Among a population of asbestos insulation workers from the United States and Canada, 8% of deaths were due to mesothelioma during a decade of observation.18Selikoff IJ Hammond EC Seidman H Latency of asbestos disease among insulation workers in the United States and Canada.Cancer. 1980; 46: 2736-2740Crossref PubMed Scopus (252) Google Scholar These studies reinforce the association of malignant mesothelioma with exposure to asbestos. This relationship has several interesting features. The latency period between the first exposure and the diagnosis of tumor usually ranges from 30 to 45 years.18Selikoff IJ Hammond EC Seidman H Latency of asbestos disease among insulation workers in the United States and Canada.Cancer. 1980; 46: 2736-2740Crossref PubMed Scopus (252) Google Scholar The different types of asbestos, including crocidolite, amosite, tremolite, chrysotile, and anthophyllite, are not equally hazardous. (Table 1) summarizes the risk of mesothelioma that accompanies exposure to each type of asbestos fiber and the settings in which such exposure might occur. The likelihood of developing mesothelioma depends in part on the physical characteristics of the fibers inhaled. Fibers with the greatest length-to-diameter ratio are the most carcinogenic.19Jaurand M-C Fleury J Monchaux G Nebut M Bignon J Pleural carcinogenic potency of mineral fibers (asbestos, attapulgite) and their cytotoxicity on cultured cells.JNCI. 1987; 79: 797-804PubMed Google Scholar, 20Wagner JC Berry G Timbrell V Mesotheliomata in rats after inoculation with asbestos and other materials.Br J Cancer. 1973; 28: 173-185Crossref PubMed Scopus (232) Google Scholar The epidemiologic data presented in (Table 1) confirm this finding, inasmuch as crocidolite, amosite, and tremolite all tend to have high length-to-diameter ratios.21Hillerdal G Malignant mesothelioma 1982: review of 4710 published cases.Br J Dis Chest. 1983; 77: 321-343Abstract Full Text PDF PubMed Scopus (271) Google ScholarTable 1Types of Asbestos Fibers: Environmental Exposure and CarcinogenicityTypeExposureMesothelioma carcinogenicityCrocidolite Miners (South Africa)Factory workersHighAmosite MinersInsulatorsFactory workersHighTremolite Environmental (Greece)As a contaminant in chrysotileHigh (?)Chrysotile Miners (North America)InsulatorsFactory workersLowAnthophylliteMiners (Finland)None Open table in a new tab The epidemiologic data linking crocidolite and amosite with an increased incidence of mesothelioma are widely accepted.4Wagner JC Sleggs CA Marchand P Diffuse pleural mesothelioma and asbestos exposure in the north western Cape Province.Br J Ind Med. 1960; 17: 260-271PubMed Google Scholar, 18Selikoff IJ Hammond EC Seidman H Latency of asbestos disease among insulation workers in the United States and Canada.Cancer. 1980; 46: 2736-2740Crossref PubMed Scopus (252) Google Scholar In comparison, the carcinogenicity of chrysotile is not as great, and increased risk seems to be limited to those directly exposed to chrysotile mine dust.22Nicholson WJ Selikoff IJ Seidman H Lilis R Formby P Long-term mortality experience of chrysotile miners and millers in Thetford Mines, Quebec.Ann NY Acad Sci. 1979; 330: 11-21Crossref PubMed Scopus (56) Google Scholar, 23Churg A Chrysotile, tremolite, and malignant mesothelioma in man.Chest. 1988; 93: 621-628Crossref PubMed Scopus (109) Google Scholar A localized area in Greece with a death rate from mesothelioma of 1% represents a rare instance of exposure to pure tremolite asbestos.24Langer AM Nolan RP Constantopoulos SH Moutsopoulos HM Association of metsovo lung and pleural mesothelioma with exposure to tremolite-containing whitewash.Lancet. 1987; 1: 965-967Abstract PubMed Scopus (75) Google Scholar Occupational exposure to tremolite alone is rare, but tremolite may contaminate chrysotile asbestos and account for some of the cases of mesothelioma reported in workers exposed to chrysotile.23Churg A Chrysotile, tremolite, and malignant mesothelioma in man.Chest. 1988; 93: 621-628Crossref PubMed Scopus (109) Google Scholar No case of mesothelioma has been reported to date among Finnish miners exposed to anthophyllite asbestos.25Huuskonen MS Ahlman K Mattsson T Tossavainen A Asbestos disease in Finland.J Occup Med. 1980; 22: 751-754PubMed Google Scholar Studies vary in estimated percentages of patients with malignant mesothelioma who have well-substantiated antecedent exposure to asbestos. Some of this variation may be due to geographic differences: studies from the eastern coast of the United States,26Borow M Conston A Livornese L Schalet N Mesothelioma following exposure to asbestos: a review of 72 cases.Chest. 1973; 64: 641-646Crossref PubMed Scopus (105) Google Scholar, 27Chahinian AP Pajak TF Holland JF Norton L Ambinder RM Mandel EM Diffuse malignant mesothelioma.Ann Intern Med. 1982; 96: 746-755Crossref PubMed Scopus (299) Google Scholar Great Britain,28Edge JR Choudhury SL Malignant mesothelioma of the pleura in Barrow-in-Furness.Thorax. 1978; 33: 26-30Crossref PubMed Scopus (54) Google Scholar, 29Dorward AJ Stack BHR Diffuse malignant pleural mesothelioma in Glasgow.Br J Dis Chest. 1981; 75: 397-402Abstract Full Text PDF PubMed Scopus (26) Google Scholar and South Africa30Solomons K Malignant mesothelioma—clinical and epidemiological features: a report of 80 cases.S Afr Med J. 1984; 66: 407-412PubMed Google Scholar all reported exposure in 80% or more of the described cases. Studies from the midwestern United States2Wolf KM Piotrowski ZH Engel JD Bekeris LG Palacios E Fisher KA Malignant mesothelioma with occupational and environmental asbestos exposure in an Illinois community hospital.Arch Intern Med. 1987; 147: 2145-2149Crossref PubMed Scopus (17) Google Scholar, 31Oels HC Harrison Jr, EG Carr DT Bernatz PE Diffuse malignant mesothelioma of the pleura: a review of 37 cases.Chest. 1971; 60: 564-570Crossref PubMed Scopus (101) Google Scholar, 32Vogelzang NJ Schultz SM Iannucci AM Kennedy BJ Malignant mesothelioma: the University of Minnesota experience.Cancer. 1984; 53: 377-383Crossref PubMed Scopus (52) Google Scholar confirmed exposure to asbestos in less than 50% of cases. The possibility that exposure to nonasbestos minerals or other factors promote formation of tumors in patients with no occupational exposure to asbestos is confounded by the observation that more than 90% of urban dwellers harbor asbestos mineral fibers in their lungs.33Mollo F Andrion A Bellis D Bertoldo E Screening of autopsy populations for previous occupational exposure to asbestos.Arch Environ Health. 1987; 42: 44-50Crossref PubMed Scopus (10) Google Scholar In addition, residential proximity to primary asbestos manufacturing plants may be a major risk factor. A recent review from a community hospital showed that although less than half the patients with malignant mesothelioma had occupational exposure to asbestos, 84% lived within 2 miles of an asbestos-producing plant.2Wolf KM Piotrowski ZH Engel JD Bekeris LG Palacios E Fisher KA Malignant mesothelioma with occupational and environmental asbestos exposure in an Illinois community hospital.Arch Intern Med. 1987; 147: 2145-2149Crossref PubMed Scopus (17) Google Scholar The role of such environmental exposures remains controversial. Other risk factors such as irradiation,34Stock RJ Fu YS Carter JR Malignant peritoneal mesothelioma following radiotherapy for seminoma of the testis.Cancer. 1979; 44: 914-919Crossref PubMed Scopus (67) Google Scholar exposure to beryllium,35Gold C A primary mesothelioma involving the rectovaginal septum and associated with beryllium.J Pathol Bacteriol. 1967; 93: 435-442Crossref PubMed Scopus (30) Google Scholar and viral illness36Chabot JF Beard D Langlois AJ Beard JW Mesotheliomas of peritoneum, epicardium, and pericardium induced by strain MC29 avian leukosis virus.Cancer Res. 1970; 30: 1287-1308PubMed Google Scholar have been reported, but further studies must be conducted to establish their clinical significance. Cigarette smoking, by increasing the likelihood of death from bronchogenic carcinoma, may actually lower the risk of death from mesothelioma among asbestos-exposed workers who smoke.37Tagnon I Blot WJ Stroube RB Day NE Morris LE Peace BB Fraumeni Jr, JF Mesothelioma associated with the shipbuilding industry in coastal Virginia.Cancer Res. 1980; 40: 3875-3879PubMed Google Scholar The incidence of malignant mesothelioma in the United States has increased most substantially in white men older than 50 years of age at the time of diagnosis. This trend is unlikely to be due to increased recognition of the condition by clinicians and pathologists but rather supports the conclusion that a group exposed to high levels of asbestos in the 1940s and 1950s is reaching the end of a prolonged latency period. The gradual onset of chest pain is the most common (60%) initial manifestation in most series of patients with diffuse malignant mesothelioma.32Vogelzang NJ Schultz SM Iannucci AM Kennedy BJ Malignant mesothelioma: the University of Minnesota experience.Cancer. 1984; 53: 377-383Crossref PubMed Scopus (52) Google Scholar, 38Antman KH Blum RH Greenberger JS Flowerdew G Skarin AT Canellos GP Multimodality therapy for malignant mesothelioma based on a study of natural history.Am J Med. 1980; 68: 356-362Abstract Full Text PDF PubMed Scopus (181) Google Scholar, 39Adams VI Unni KK Muhm JR Jett JR Ilstrup DM Bernatz PE Diffuse malignant mesothelioma of pleura: diagnosis and survival in 92 cases.Cancer. 1986; 58: 1540-1551Crossref PubMed Scopus (144) Google Scholar This pain is typically nonpleuritic. Dyspnea is the next most frequent respiratory complaint (40%). Fever, chills, sweats, or weakness and malaise have been reported in a considerable number of patients. Cough is relatively uncommon (10%). A small percentage of patients have an acute onset of severe pain and dyspnea, usually related to either hemothorax or spontaneous pneumothorax.5Elmes PC Simpson MJC The clinical aspects of mesothelioma.Q J Med. 1976; 45: 427-449PubMed Google Scholar Most patients have experienced symptoms for at least 2 months before diagnosis, and as many as a fourth of the patients have had symptoms for 6 months or longer.27Chahinian AP Pajak TF Holland JF Norton L Ambinder RM Mandel EM Diffuse malignant mesothelioma.Ann Intern Med. 1982; 96: 746-755Crossref PubMed Scopus (299) Google Scholar Rarely, diagnostic evaluation is initiated on the basis of abnormal findings on a chest roentgenogram in an otherwise asymptomatic patient. This type of presentation would be expected to be more common in screening programs of persons with exposure to high levels of asbestos. Most patients with peritoneal mesothelioma complain of abdominal pain and increasing abdominal girth. Other than dullness to percussion and decreased breath sounds, due to either pleural effusion or involvement by tumor, physical examination is unrevealing. Occasionally, metastatic disease is suspected on the basis of the presence of lymphadenopathy (15%) or hepatomegaly (10%). Clubbing is seen in up to 20% of patients with localized fibrous mesothelioma and more frequently in those with large benign tumors,10Okike N Bernatz PE Woolner LB Localized mesothelioma of the pleura: benign and malignant variants.J Thorac Cardiovasc Surg. 1978; 75: 363-370PubMed Google Scholar but it is found in less than 10% of patients with diffuse malignant mesothelioma.12Antman KH Clinical presentation and natural history of benign and malignant mesothelioma.Semin Oncol. 1981; 8: 313-320PubMed Google Scholar The most common chest x-ray finding in patients with malignant mesothelioma is a unilateral pleural effusion; the incidence varies from 30 to 95%.32Vogelzang NJ Schultz SM Iannucci AM Kennedy BJ Malignant mesothelioma: the University of Minnesota experience.Cancer. 1984; 53: 377-383Crossref PubMed Scopus (52) Google Scholar, 38Antman KH Blum RH Greenberger JS Flowerdew G Skarin AT Canellos GP Multimodality therapy for malignant mesothelioma based on a study of natural history.Am J Med. 1980; 68: 356-362Abstract Full Text PDF PubMed Scopus (181) Google Scholar, 39Adams VI Unni KK Muhm JR Jett JR Ilstrup DM Bernatz PE Diffuse malignant mesothelioma of pleura: diagnosis and survival in 92 cases.Cancer. 1986; 58: 1540-1551Crossref PubMed Scopus (144) Google Scholar, 40Solomon A Radiological features of diffuse mesothelioma.Environ Res. 1970; 3: 330-338Crossref PubMed Scopus (18) Google Scholar, 41Wechsler RJ Rao VM Steiner RM The radiology of thoracic malignant mesothelioma.CRC Crit Rev Diagn Imaging. 1984; 20: 283-310Google Scholar, 42Krumhaar D Lange S Hartmann C Anhuth D Follow-up study of 100 malignant pleural mesotheliomas.Thorac Cardiovasc Surg. 1985; 33: 272-275Crossref PubMed Scopus (10) Google Scholar A mediastinal shift toward the affected side, even in the presence of a large amount of fluid, should suggest the possible presence of mesothelioma. Most reported series describe a small number of patients with mesothelioma who have bilateral pleural effusions; thus, this finding should not be used as evidence against the diagnosis. Pleural thickening is present on more than 50% of chest roentgenograms in patients with malignant mesothelioma, but occasionally it is obscured by effusion and will not become evident until thoracentesis has been performed. Diffuse pleural thickening may also be seen in patients with asbestosis, tuberculosis, fungal disease, metastatic cancer, or lymphoma. Lobulation is a feature thought to be highly suggestive of mesothelioma. On the initial chest roentgenogram, less than 25% of patients with malignant mesothelioma have distinct multiple pleural masses without effusions, and even fewer have a solitary pleural mass. Benign pleural plaques, with or without calcifications, may be an accompanying finding. Metastatic pulmonary nodules are commonly found at autopsy,30Solomons K Malignant mesothelioma—clinical and epidemiological features: a report of 80 cases.S Afr Med J. 1984; 66: 407-412PubMed Google Scholar but chest x-ray evidence of lung nodules is uncommon (in less than 15% of patients in most reports). Ipsilateral hilar enlargement is occasionally noted and most often signifies mediastinal pleural involvement rather than metastatic nodal spread. Rib destruction can be present, most often in patients who have far-advanced and bulky tumors. Other imaging modalities are helpful in a variety of situations. Ultrasound scanning is useful for distinguishing pleural effusions from pleural masses. Although gallium scanning has been reported to disclose abnormalities in 88% of patients with malignant mesothelioma,43Wolk RB Gallium-67 scanning in the evaluation of mesothelioma.J Nucl Med. 1978; 19: 808-809PubMed Google Scholar it is being replaced by computed tomography for staging of mesothelioma. Computed tomography can more clearly delineate the extent of involvement of mesothelioma but, like isotope scans, does not distinguish mesothelioma from metastatic adenocarcinoma.44Alexander E Clark RA Colley DP Mitchell SE CT of malignant pleural mesothelioma.AJR. 1981; 137: 287-291Crossref PubMed Scopus (42) Google Scholar One of the most valuable functions of computed tomographic scanning is to assist the surgeon in selecting optimal biopsy sites. Serum chemistries, hemoglobin concentration, and leukocyte counts are typically normal at the time of diagnosis of malignant mesothelioma. Thrombocytosis (more than 400,000 platelets/mm3) was noted in 90% of patients in one series.27Chahinian AP Pajak TF Holland JF Norton L Ambinder RM Mandel EM Diffuse malignant mesothelioma.Ann Intern Med. 1982; 96: 746-755Crossref PubMed Scopus (299) Google Scholar The erythrocyte sedimentation rate can exceed 100 mm in 1 hour. Laboratory features of pleural fluid obtained from patients with mesothelioma have been well described,5Elmes PC Simpson MJC The clinical aspects of mesothelioma.Q J Med. 1976; 45: 427-449PubMed Google Scholar, 12Antman KH Clinical presentation and natural history of benign and malignant mesothelioma.Semin Oncol. 1981; 8: 313-320PubMed Google Scholar, 27Chahinian AP Pajak TF Holland JF Norton L Ambinder RM Mandel EM Diffuse malignant mesothelioma.Ann Intern Med. 1982; 96: 746-755Crossref PubMed Scopus (299) Google Scholar but they are not diagnostic. Half the effusions are bloody. Most are exudates with a specific gravity of more than 1.021, a protein concentration of more than 3.4 g/dl, and elevated lactate dehydrogenase.45Taryle DA Lakshminarayan S Sahn SA Pleural mesotheliomas—an analysis of 18 cases and review of the literature.Medicine. 1976; 55: 153-162Crossref PubMed Scopus (36) Google Scholar The glucose concentration is variable but tends to decrease in inverse proportion to the number of cancer cells present. In one series, malignant cells were found in the pleural fluid in only 32% of patients,39Adams VI Unni KK Muhm JR Jett JR Ilstrup DM Bernatz PE Diffuse malignant mesothelioma of pleura: diagnosis and survival in 92 cases.Cancer. 1986; 58: 1540-1551Crossref PubMed Scopus (144) Google Scholar and the diagnosis of mesothelioma was based solely on the cytologic findings in 10%. Most pathologists prefer a tissue biopsy specimen for diagnosing mesothelioma. A high level of hyaluronic acid in the pleural fluid is found more commonly in mesothelioma than in other processes, and mesothelioma can be suspected with levels in excess of 50 ng/liter. In most patients with a highly suspected diagnosis of mesothelioma, a tissue biopsy is necessary to establish the diagnosis. Among patients with mesothelioma, a needle biopsy specimen of the pleura is usually insufficient to make the diagnosis. Because of its small size, it was considered diagnostic in only 25% of cases in one series12Antman KH Clinical presentation and natural history of benign and malignant mesothelioma.Semin Oncol. 1981; 8: 313-320PubMed Google Scholar and 39% in another.46Prakash UBS Reiman HM Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases.Mayo Clin Proc. 1985; 60: 158-164Abstract Full Text Full Text PDF PubMed Scopus (360) Google Scholar Needle biopsy often fails to provide enough tissue to enable the pathologist to exclude reactive mesothelial proliferations confidently. In addition, needle biopsy does not permit gross inspection and palpation of the pleura, both of which may be helpful in establishing the diffuse nature of malignant mesothelioma and in choosing optimal tissue sampling sites. Finally, one study showed that biopsy needle channels can be invaded by tumor tissue in as many as 20% of cases.29Dorward AJ Stack BHR Diffuse malignant pleural mesothelioma in Glasgow.Br J Dis Chest. 1981; 75: 397-402Abstract Full Text PDF PubMed Scopus (26) Google Scholar At one time, an autopsy was considered necessary for confirmation of the diagnosis of mesothelioma in order to exclude the possibility of metastatic lesions from another site, but open biopsy is now generally considered sufficient in the appropriate clinical setting. In patients suspected of having a mesothelioma (that is, those in whom other entities such as metastatic adenocarcinoma are still possible), open biopsy confirms a mesothelioma approximately 60% of the time.39Adams VI Unni KK Muhm JR Jett JR Ilstrup DM Bernatz PE Diffuse malignant mesothelioma of pleura: diagnosis and survival in 92 cases.Cancer. 1986; 58: 1540-1551Crossref PubMed Scopus (144) Google Scholar In autopsy-proven mesothelioma, previous thoracotomy and biopsy established the diagnosis in 90% of cases.47Ryan CJ Rodgers RF Unni KK Hepper NGG The outcome of patients with pleural effusion of indeterminate cause at thoracotomy.Mayo Clin Proc. 1981; 56: 145-149PubMed Google Scholar Unfortunately, in as many as 40% of patients diagnosed in this fashion, intractable pain develops along the incision line,16Shearin Jr, JC Jackson D Malignant pleural mesothelioma: report of 19 cases.J Thorac Cardiovasc Surg. 1976; 71: 621-627PubMed Google Scholar and metastatic lesions may occur in the thoracotomy wound.28Edge JR Choudhury SL Malignant mesothelioma of the pleura in Barrow-in-Furness.Thorax. 1978; 33: 26-30Crossref PubMed Scopus (54) Google Scholar Although a history of exposure to asbestos is important when the pathogenesis of mesothelioma is considered, it is not a feature that should influence the histologic diagnosis because those persons exposed to asbestos also may have other tumors that involve the pleura (notably, bronchogenic carcinomas), and epidemiologic data have confirmed that primary lung carcinomas occur more frequently than mesotheliomas among the asbestos-exposed population.48Selikoff IJ Hammond EC Seidman H Mortality experience of insulation workers in the United States and Canada, 1943–1976.Ann NY Acad Sci. 1979; 330: 91-116Crossref PubMed Scopus (499) Google Scholar Localized fibrous mesotheliomas (so-called benign mesotheliomas) are probably mesenchymal tumors derived from submesothelial mesenchymal cells rather than tumors of the mesothelial lining cells.11Dalton WT Zolliker AS McCaughey WTE Jacques J Kannerstein M Localized primary tumors of the pleura: an analysis of 40 cases.Cancer. 1979; 44: 1465-1475Crossref PubMed Scopus (173) Google Scholar, 49Dervan PA Tobin B O'Connor M Solitary (localized) fibrous mesothelioma: evidence against mesothelial cell origin.Histopathology. 1986; 10: 867-875Crossref PubMed Scopus (130) Google Scholar They are single masses9Briselli M Mark EJ Dickersin GR Solitary fibrous tumors of the pleura: eight new ca
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