Document wgybKMJEbnzb5dV2n3jJ3megE

in ph 4oert- Malignant Mesothelioma in Young Adults Michael J. Kane, MD,* A. Philippe Chahinian, MD,f and James F. Holland, MD Ten cases of malignant mesothelioma presenting in patients 40 years old or younger at diagnosis were reviewed. Seven cases had a documented history of asbestos exposure of which live were household exposures. The median age at first exposure to asbestos was 10 years and the median duration of exposure was 120 months. The median latency period (time between initial asbestos exposure and diagnosis of malignant mesothelioma) was 19 years. The median interval from initial symptoms to definitive diagnosis was 5.5 months. The case history of each patient is presented. A significant delay in diagnosis in this age group compared with an ageunrestricted series is noted. The significance of nonoccupational exposure to asbestos is emphasized as a probable causative factor in the development of malignant mesothelioma. In addition, a possible genetic predisposition is briefly discussed. Cancer 65:1449-1455,1990. 1 PLAINTIFFS EXHIBIT he incidence of malignant mesothelioma, once an Materials and Methods T uncommon neoplasm, is increasing.1 After the Departmental and hospital records were examined for landmark epidemiologic study by Wagner el al.,2 its asall patients seen by one of us (A.P.C.) with a diagnosis of sociation with asbestos exposure has been well docu mented.3*6 There have been additional data to implicate malignant mesothelioma of the pleura or peritoneum be tween the years 1974 and 1987. The charts of all patients nonoccupational risk factors.7'13 as well as other etiologic diagnosed before reaching 41 years of age were reviewed agents such as zeolites.14'13 radiation,16-17 chronic serosal in detail. Particular attention was directed toward expo irritation,18 and other agents.19 sure history with emphasis on asbestos; age at first ex The majority of patients presenting with malignant posure and duration of exposure, if applicable; latency mesothelioma are older than 40 years at diagnosis.1U(U1 period (time from first exposure to diagnosis), ifapplicable; There are a few reports of childhood presentations with duration and type of symptoms; extent of prediagnostic only 49 cases in the literature summarized by Brenner et evaluation; method ofdefinitive diagnosis; histopathologic al.22 in 1981 and several subsequent case reports.33-24 A subtype; treatment modalities; and, survival from diag comprehensive review of patients with presentations in the third and fourth decades of life has not been published. nosis. We report our experience with malignant mesothelioma Results in ten adults presenting at age 40 years or younger and prospectively evaluated in the Department of Neoplastic Diseases. Mount Sinai Medical Center, New York, from 1974 through 1987. One hundred eighty-one patients with malignant me sothelioma were seen during the 13-year period, 1974 through 1987. Nine patients including one younger than 40 years were seen in consultation only without any fol From the Department ot' Neoplastic Diseases. Mount Sinai Medical Center. New York. New York. * Current address: Jetferson Medical College. Department ol'Medicine, Division of Medical Oncology, 1025 Walnut Street. Philadelphia. PA 19107. t Current address: St. Luke's--Roosevelt Medical Center. Division of Medical Oncology, Amsterdam Avenue at 114th Street. New York. NY 10025. Address for reprints: Michael J. Kane. MD. Jetferson Medical College. Department of Medicine. Division of Medical Oncology, 1025 Walnut Street. Philadelphia. PA 19107. Accepted for publication September I. 1989. low-up available. Age distribution of the remaining 172 cases is depicted in Figure 1. Ten patients (Table 1) were age 40 years or younger at diagnosis of mesothelioma. There were six cases of pleural and four cases of peritoneal mesothelioma. Six of the ten patients were women. Me dian age at diagnosis was 33.3 years (range, 24--10 years) for all patients: 34.3 years for pleural mesothelioma (range, 24--40 years); 30.0 years for peritoneal mesothelioma (range, 26-39 years). Women comprised four of the six cases of pleural mesothelioma and two of the four cases 1449 1450 Cancer March 15 1990 Vol. 65 70 X *7 <21 21*30 11*40 41-M (1*00 01*70 X. 71 Fig. 1. Age distribution ofl72 patients with malignant mesothelioma at Mount Sinai Medical Center. New York (1974-1987). of peritoneal mesothelioma. Distribution of cell types in cluded the following: biphasic (four), epithelial (three), and fibrosarcomatous (three). Seven of the ten patients admitted a history of asbestos exposure whereas three (Cases 4, 7, and 8) had no such exposure documented (Table 2). Household exposure to asbestos was prominent in this age group and was present in five cases. Case 1, an only child, was likely exposed to asbestos from age 11 to 21 years through her father who delivered the product while working for a construction firm. At the time of diagnosis, both of her parents were aiive and well. Case 2, an only child, was probably exposed initially at age 6 years and for the next 4 years through his father who worked at a glass factory which also produced an asbestos product Case 3, one of three sisters, has already been reported.23 She was exposed to asbestos beginning at birth through her father who worked as a shipyard pipe insulator. Throughout her childhood she lived approxi mately 6 kilometers from the shipyard. This case is also noteworthy in that the patient's mother was diagnosed with malignant mesothelioma of the pleura at age 50 years and her father with adenocarcinoma of the lung at age 71. Her sisters had no evidence of cancer at the time of her evaluation and treatment. Case 5 was exposed at age 6 years to asbestos dust through her brother-in-law who worked in an asbestos plant and frequently spent time after work at the patient's home in his dusty work clothing. In addition, she lived within 2 kilometers of a factory using asbestos in manu facturing for fourteen years. Case 6, one of seven children, was 10 years old when exposed to asbestos over a 12month period through his father's dusty work clothing. His older sister died of "lung cancer" 18 years after the same exposure. Unfortunately, pathology slides of the sis ter could not be obtained to verify this diagnosis. There is. of course, a possibility that this also may have been a mesothelioma. Overall, five of the seven cases probably were exposed to asbestos nonoccupationally. Cases 9 and 10 each had occupational exposure to asbestos. Case 9 worked for 5 weeks at age 20 fin a warehouse handling asbestos. Case 10 had worked as a school teacher for 14 years in a building later cited for asbestos. The median age at first exposure to asbestos was 10 years for all patients (range, birth-25 years). The median duration of exposure was 120 months (range, 1.25-216 months). Case 7 denied asbestos exposure. She admitted exposure to fiberglass dust throughout childhood because her father would return home from work in clothing cov ered with fiberglass fibers. The median latency period (time between probable ini tial asbestos exposure and diagnosis of malignant meso thelioma) was 19 years for all seven patients with asbestos exposure by history (range, 13-34 years); 13.5 years for peritoneal and 30.0 years for pleural mesothelioma. The median interval from onset of symptoms to defin itive diagnosis was 5.5 months (range, 1-13 months) for all patients; 7.5 months for pleural (range, month to thir teen months) and 4.8 months for peritoneal mesothelioma (range, 1-12 months). The clinical presentation for all patients is depicted in Table 3. Pain (five of six) or dyspnea (three of six) were the most common presenting com plaints in patients with pieund mesothelioma, whereas patients with peritoneal mesothelioma had a diverse group of symptoms without a predominant presenting com plaint. The diagnostic workup in each case of malignant me sothelioma varied greatly not only in length but also in number and type of studies performed. A brief summary of each case is presented to highlight frequent delays in diagnosis. Case Reports Case 1: Case 1 presented to an orthopedic surgeon with back pain first noted during participation in a sporting event. Anal gesics were prescribed for "muscle strain" but symptoms wors ened. The patient was hospitalized elsewhere for workup 1 year after initial symptoms when a spine roentgenogram revealed marked scoliosis. A chest roentgenogram was not done at that Table 1. Malignant Mesothelioma Patient Characteristics Case no. Age at diagnosis (yr) Site Histopathologic Sex subtype i 24 Pleural Female Biphasic ? 25 Pleural Male Epithelial 3 34 Pleural Female Biphasic 4 35 Pleural Female Fibrosarcomatous 5 36 Pleural Female Biphasic 6 40 Pleural Male Biphasic 7 26 Peritoneal Female Epithelial 8 27 Peritoneal Male Epithelial 9 33 Peritoneal Male Fibrosarcomatous 10 39 Peritoneal Female Fibrosarcomatous No. 6 Mesothelioma in Young adults Kaneetal. 1451 Case 00. i 2 3 4 5 6 7 8 9 10 Asbestos exposure Yes Yes Yes No Yes Yes No No Yes Yes Method of exposure Household (father) Household (father) Household (father) Household (brother-in-law) Household (father) Age of first exposure (yr) Length of exposure (yr) " " ' - Time from first exposure to diagnosis (yr) ,......... 11 6 0 . .... , - 10 4 , 18 - 13 ........ - 19 -- - , 34 ........... 6 10 14 1 30 30 Occupational ' Occupational ........ 20 25 0.1 . 14 13 14 time. Myelography was unremarkable. A computerized tomo graphic (CT) scan of the abdomen and laparoscopy were done to evaluate a pelvic mass discovered during the hospitalization. Laparoscopy was unremarkable but the abdominal CT scan revealed a right pleural effusion. A chest roentgenogram con firmed the effusion and suggested pleural thickening (Fig. 2). A CT scan of the thorax (Fig. 3) revealed significant volume loss in the right hemithorax with pleural effusion and pleural thick ening. Thoracentesis and bronchoscopy were not diagnostic. Limited thoracotomy with pleural biopsy yielded a diagnosis of malignant mesothelioma. The patient was referred to Mount Sinai Hospital (MSH) where she underwent a right thoracotomy revealing tumor involvement of the entire parietal and portions of the visceral pleura. The extent of disease permitted only a partial decortication. A portion of lung parenchyma analyzed by electron microscopic study for mineral fiber identified tremolite asbestos. The patient was begun on chemotherapy and is alive 15 months after diagnosis. Case 2: One month of malaise and dyspnea was the chief complaint of Case 2. Upon hospitalization, a chest roentgeno gram revealed a right pleural effusion. Thoracentesis yielded class III cytologic results. Bronchoscopy and a percutaneous needle biopsy of the pleura were not diagnostic. The patient was em pirically placed on antibiotics and discharged from the hospital with a chest tube in place. Two months later the patient was readmitted for a diagnostic and therapeutic thoracotomy to per- mit reexpansion ofa "trapped lung." An extensive decortication was performed revealing malignant mesothelioma. The patient was then seen at MSH 5 months after symptom onset and began a course of experimental chemotherapy. Disease progression was noted, however, and the patient died 3 months later. Case 3: Case 3 presented with dyspnea and chest pain. A chest roentgenogram revealed a right pleural effusion and the patient was hospitalized. Thoracentesis was not diagnostic. A limited right thoracotomy with pleural biopsy performed within I month of the onset of symptoms yielded the diagnosis. The patient began chemotherapy with doxorubicin, dacarbazine. and cyclo phosphamide and exhibited a clinical complete response after 6 months of treatment She received an additional 2 months of chemotherapy before treatment was stopped. Two months later Table 3. Duration and Character of Initial Symptoms and Length of Survival Case no. Symptoms Duration of symptoms (mol before diagnosis Survival (mo) from diagnosis i Back pain 2 Malaise, dyspnea 3 Dyspnea, chest pain 4 Cough, chest pain 5 Subscapular pain 6 Dyspnea, chest pain, fever 7 Infertility 8 Abdominal pain, ascites 9 Anorexia, ascites, scapular pain 0 Weight loss, fever, ni&ht sweats 12 3 1 13 13 2 i 12 1.5 8 15+ 7 17 11 II 15 225 48 3 9 Fig. 2. Chest roentgenogram demonstrating scoliosis and right pleural # etfusion. 1452 Cancer March 15 1990 VoL65 Fig. 3. Computerized tomographic scan of the thorax revealing marked volume loss of the right hemithorax, pleural eifusion, and the suggestion of pleural thickening. she recurred in the initial site of disease and was first seen at MSH. Subsequent treatment with the same chemotherapeutic agents was unsuccessful as were radiation and surgical debulking. The patient died of progressive disease 7 months after recurrence. Case 4: Case 4 presented elsewhere with a productive cough and chest pain. A lingular lesion was noted on chest roentgen ogram. Despite a history of Bacillus Calmette-Guerin (BCG) vaccination as a child, the patient was started on isoniazid and rifampin because of a positive tuberculin skin test Three months later the lingular lesion had tripled in volume. Thoracotomy was performed with resection of the lingula and a wedge resection of the left lower lobe and adjacent pericardium. Histopathologic diagnosis was reported as malignant mesothelioma or heman giopericytoma. Six months later the patient developed a pleural friction rub and pleural effusion. A transthoracic percutaneous needle biopsy performed at that time was interpreted as probable malignant mesothelioma. Eleven months after the onset of symptoms, the patient was seen at MSH and underwent a second thoracotomy and pleurectomy confirming the diagnosis of ma lignant mesothelioma. Case 5: Case 5 developed right subscapular pain which pro gressed over 8 weeks to involve the entire right hemithorax. A chest roentgenogram was interpreted as "pleurisy" and steroids were prescribed. The patient's symptoms waxed and waned for 8 months when pain became acutely worse. Spine roentgeno grams were unremarkable. A liver/spleen scan and intravenous pvelogram were done to rule out subdiaphragmatic etiologies and both studies were normal. The following month a repeat chest roentgenogram showed a right pleural based mass. Two months later, a thoracotomy and pleural biopsy yielded a di agnosis of malignant mesothelioma. Fourteen monthsafterinitial symptoms the patient was referred to MSH where she was treated with chemotherapy and radiotherapy with progression of disease until her death 11 months later. Case 6: Case 6 presented with fever, dyspnea, and right pleu ritic chest pain of 2 months duration. A chest roentgenogram demonstrated a pleural effusion and diffuse pleural thickening Thoracentesis was not diagnostic. A pleural biopsy was "suspi cious for mesothelioma." One month later a right thoracotomy yrifti decortication confirmed the ^diagnosis.-Four months after the onset of symptoms the patient was referred to MSH where he was treated with chemotherapy and radiotherapy until pro gression of disease resulted ip his death 1. year later. .....- Case 7: Case 7 presented elsewhere forevaluation of infertility. She had a history of familial granular ceil myoblastoma, which also affected her mother and brother, resected from her left shoulder 6 years previously and a second resection for local re currence 2 years before presentation. A bimanual pelvic ex amination revealed multiple masses. Culdoscopy was unre markable. One month later, a laparotomy with biopsy yielded the diagnosis of malignant mesothelioma. Case 8: Over a 12-month period Case 8 developed increasing abdominal girth. Three months before presentation the patient developed right upper quadrant pain exacerbated by fatty foods. Sudden, severe abdominal pain prompted his presentation else where. An abdominal roentgenogram suggested ascites which was confirmed by abdominal sonography. A paracentesis was not diagnostic as were upper gastrointestinal series, barium enema, and computerized abdominal tomogram. Results of a bone marrow aspirate and biopsy were unremarkable. An ex ploratory laparotomy with partial omentectomv was performed 3 weeks after presentation yielding the diagnosis of malignant mesothelioma. Fourteen months after symptom onset and, 1 month after diagnosis, the patient was seen at MSH and began chemotherapy. He developed progressive disease and died 48 months from the time of diagnosis. Case 9: A 4-week period of anorexia, right scapular pain, and increasing abdominal girth led Case 9 to his family physician. A barium enema and upper gastrointestinal series were normal. Upon hospitalization elsewhere for further evaluation an ab dominal ultrasound revealed ascites and an anterior abdominal mass. Paracentesis was not diagnostic. A liver/spleen scan was normal. An abdominal arteriogram revealed omental neovas cularization "consistent with a primary omental tumor." Eleven days after admission an exploratory laparotomy with omental biopsy yielded the diagnosis. The patient was seen at MSH l month after diagnosis and began chemotherapy. His disease progressed rapidly and he died 2 months later. Case 10: Case 10 developed weight loss, night sweats, and anemia over an 8-month period. Chest roentgenogram and mammography were normal. A bone marrow evaluation was remarkable only for mild plasmacvtosis. A urinalysis revealed microscopic hematuria. This led to an intravenous pvelogram which demonstrated a pelvic mass. Computerized tomography of the pelvis revealed that it was 10 cm in diameter, it was gal lium-avid on scan. Exploratory laparotomy performed within 1 month of presentation revealed a poorly differentiated neoplasm initially interpreted as malignant fibrous histiocytoma. Reeval uation of the slides at another institution 1 month later suggested a diagnosis of malignant mesothelioma which was subsequently confirmed at MSH. The patient was treated elsewhere with che motherapy and radiotherapy but rapidly progressed.. Upon re ferral to MSH 14 months after initial symptoms, she failed to respond to surgical debulking and chemotherapy and died 3 months later. No. 6 Mesothelioma in Young adults Kane et al. 1453 Summary ofCases v,, .......... Discussion ?- In summary, all cases ofpleural mesothelioma had chest roentgenograms. Thoracentesis was performed in four cases but was not diagnostic, as was bronchoscopy in the two cases in which it was performed. Three cases under went percutaneous pleural biopsy but in only one was the specimen suggestive of mesothelioma. No patient under went thoracoscopy. All six cases of pleural mesothelioma ultimately required thoracotomy for diagnosis. A wide variety of diagnostic studies were performed before laparotomy for diagnosis in peritoneal mesotheli oma. In no instance was the diagnosis made without lap arotomy. Nine of ten patients have died (Table 3). Median sur vival from diagnosis was 13.0 months (range, 3-226 months). Case 1 is alive with residual disease 13 months after a thoracotomy and debulking procedure followed by chemotherapy and radiotherapy. Case 7 died of another cancer and is unique. Her treatment has been reported26 but is summarized and updated here. She was treated in 1969 with 60 mg of intraperitoneal thiotepa and abdominal strip radiotherapy at 1000 cGy per strip over a 12-week period. Procarbazine was given oraily (50-100 mg per day) over a 5-month period, the first month overlapping with radiotherapy. A repeat lap arotomy in August 1970 revealed persistent, unresectable mesothelioma in the cul-de-sac and right lower quadrant of the abdomen. An additional 3000 cGy of whole ab dominal radiotherapy was administered over 2 months. Because of an increase in the size of masses in the posterior vaginal fornix and right lower abdominal quadrant in May 1971, doxorubicin (30 mg/m2/day for 3 days) and bleo mycin (20 mg/m2/day for 4 days) were administered in travenously in combination for two courses followed by one course of doxorubicin alone. Local progression was noted in October 1971 and the patient was treated with methyl-CCNU (100-125 mg/m2/day once every 6 to 8 weeks) until June 1972. No progression of disease was evident for the next 13 years. She then developed a Clark's level IV melanoma of the left leg which was excised. Computerized abdominal tomography suggested a renal cyst but no evidence of me sothelioma. One year later a renal sonogram revealed that the right kidney mass was solid. This led to a partial ne phrectomy for renal oncocytoma. Regional nodal metastases of malignant melanoma developed 3 months later. After multiple surgical resections that disease was con trolled, but in 1987 (18 years alter diagnosis of mesothe lioma) she developed adenocarcinoma of the bladder which was rapidly fatal. This tumor was compared with the patient's mesothelioma slides and independent his tologic types were confirmed. Mesothelioma in young adults is uncommon. Hochberg27 noted 12.4% of 192 cases presenting at an age younger than 30 years. Elmes and Simpson11 found only five cases younger than 40 years in a series of 327 patients (1.5%), whereas McDonald et al.23 reported 22 of 165 cases (13.3%) and Brenner and associates29 noted 20 of 123 cases (16.3%). In a review of 5778 death certificates in Great Britain listing mesothelioma as a cause of death, Jones and Thomas20 reported 298 cases (5.2%) between the ages of 15 and 44 years at the time of death. In our series, ten of 172 cases (5.8%) were 40 years old or younger at diagnosis. The largest percentage of patients present in the sixth and seventh decades. This finding is consistent with other reports.20,2* The sex distribution in our series revealed a male:female ratio of 0.7:1.0. This contrasts to the male predominance in other published series of mesothelioma not age re stricted in which the male:female ratio ranged from 1.8:1.0 to 5.0:1.0.11,21,29,31 In our current updated group of 172 patients with malignant mesothelioma seen at MSH the male:female ratio is 4.0:1.0.J2 A study by McDonald et al.23 has shown a male:female ratio of 0.8:1.0 for 22 patients diagnosed in the third and fourth decades of life. Additionally, Archer and Rom33 have shown an equal sex incidence in patients younger than 45 years of age but a male predominance in older age groups. Surprisingly, a comprehensive review of childhood mesothelioma22 demonstrated a male:female ratio of 1.6:1.0 on a total of 49 cases approximating that seen in age unrestricted series. The difference in sex ratio rather than reflecting a difference in susceptibility to malignant mesothelioma, probably is related to different degrees of occupational exposure to asbestos.7-13 Although most series report a predominance of pleural over peritoneal mesothelioma.1*-I-SJl including the re view by Brenner et al. of childhood disease.-- and some have suggested that peritoneal disease is associated with a more "intense" asbestos exposure history9,11-21 our small series presents an almost equal distribution. In this regard, it may not be fortuitous that both patients with "occu pational" exposure (Cases 9 and 10) presented with peri toneal disease. The intensity of exposure, however, is purely subjective and the question of whether intensity of exposure is a significant risk factor remains unan swered.34 Case 7 recalled household fiberglass exposure through her father for several years during childhood. In addition to asbestos exposure, peritoneal mesothelioma has been reported as a sequela of therapeutic radiation16,33,36 thorotrast17 pneumoperitoneum.37 and recurrent peritoni tis.1* To our knowledge, fiberglass has not been shown to 1454 Cancer March IS 1990 Vol. 65 be a risk factor for malignant mesothelioma, although McDonald et al.29 did notice that nine of 19 patients with malignant mesothelioma who did not report definite or probable asbestos exposure had been exposed to copper, nickel, rubber, or fiberglass. In a subsequent study they noted that a history of fiberglass exposure was more fre quently found in cases of mesothelioma than in controls.3* The latter study failed to show a statistically significant increase in fiberglass exposure when allowance for coin cidental asbestos exposure was made. Unfortunately, we have no quantitative data detailing intensity of exposure. Of interest is the report by Hueper39 implicating polyure thane as an inducer of experimental mesothelioma. Poly mer resins are often used to cover fiberglass insulation. The chest roentgenogram in peritoneal mesothelioma is often abnormal. Elmes and Simpson11 showed that 13 of 27 cases demonstrated pleural plaques and/or paren chymal lesions consistent with asbestos exposure. None of our cases demonstrated these findings on chest roent genograms or on computerized axial tomography of the chest. The distribution of histopathologic subtypes is remark able for the small number of epithelial tumors. This has previously been noted in children19-22 and varies from the epithelial predominance in age-unrestricted series.21-40 We have previously reported that the median interval from initial symptom to diagnosis for a series of 69 pa tients was 2 months but 25% of patients had symptoms for greater than 6 months before diagnosis.21 The longer symptomatic period before diagnosis in our current series probably reflects the fact that cancer and, in particular mesothelioma, is generally not considered high in the list of differential diagnostic possibilities in this age group. Another factor might be the possibility that young patients may delay seeking professional medical advice for a longer time period after initial symptoms. Clinical investigations may therefore be not only misdirected but also delayed. The diagnosis of mesothelioma is difficult and requires a high index of suspicion. An appropriate medical history with emphasis on exposure(s) is crucial. Adequate tissue must be available for diagnostic studies that include not only light microscopy41 but also special stains20-39 and, on occasion, electron microscopic study.42 For these reasons, it is not unexpected that our series of cases required tho racotomy or laparotomy in all cases for definitive diag nosis. It is also not unusual that slides required review at several institutions before a definitive diagnosis of malig nant mesothelioma. The median survival of our series is in the range of most larger series. The single long-term survivor (Case 7) had progressed despite a combination of surgery, radio therapy, and both intraperitoneal and systemic chemo therapy until a new investigational chemotherapeutic agent was used. Few animal or human studies to date have addressed the question of whether young age at first exposure to asbestos predisposes to development of mesothelioma at a shorter latent period. Wagner43 inoculated rats intra pleurally with asbestos fibers at either 2 or 10. months of age. Nineteen of 48 animals (39.6%) developed mesothe lioma when injected at 2 months, whereas 17 of90 (18.9%) developed mesothelioma when inoculated at 10 months. Peto et al.** examined the influence of age at first ex posure and duration of exposure to asbestos with respect to the cumulative probability of dying of malignant me sothelioma by age 80 years in 17800 asbestos workers. The youngest age group evaluated was 15 to 24 years of age at first exposure. The risk of death secondary to me sothelioma was independent of age at first exposure but clearly a function of duration of time since initial expo sure. The high incidence of likely household exposure to as bestos which occurred in five of ten cases reported here is remarkable. AH of our household exposures with one exception (Case 5) were father to child. There is no way of quantifying exposure retrospectively. It has been shown that asbestos dusts can remain airborne for days before settling; epidemiologic evidence supports the concept that asbestos may promote the development of mesothelioma after only short-duration occupational exposure.45 Similar evidence in household exposures is not available. Host susceptibility to asbestos or other, as yet unap preciated, carcinogens may be important.46 The finding of tremolite in Case 1 is interesting. The association of malignant pleural mesothelioma and tremolite asbestos in Greece has recently been reported.47 Martensson et al.4* reported two pairs of siblings that developed mesothelioma after asbestos exposure. One set of "identical" twins were exposed during the same time period and with the same intensity of exposure from ages 16 to 23. Within months of each other at age 42 they both developed pleural me sothelioma. Karyotypes were not reported however. Nonrandom deletion of a segment of the short arm of chromosome 3 has recently been cited49 as a common chromosomal abnormality in malignant mesothelioma and such studies, as well as HLA subtyping, would be useful to determine if karyotypic changes are induced by asbestos exposure or if they represent increased suscep tibility to asbestos associated illnesses. The possibility exists that in the first four decades of life mesothelioma is more common than ordinarily be lieved. A detailed occupational and nonoccupational his tory may help in suspecting this diagnosis as well as un covering additional risk factors unrecognized previously. No. 6 Mesothelioma in Young Adults Kane et al. 1455 The diagnosis must be considered whenever pleural or peritoneal disease of unknown etiology presents. REFERENCES . 1. Spinas R. Beebe GW. Connelly RR. Recent trends in mesothelioma incidence in the United States. Am J Ind Med 1986: 9:397-407. 2. Wagner JC Sleggs CA. Marcnand P. Diffuse Pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med I960: 17:260-271. 3. Selikolf U. Churg J, Hammond EC. Asbestos exposure and neo plasia. JAMA 1964: 188:22-26. 4. SelikotFU, Churg J, Hammond EC. Relation between exposure to asbestos and mesothelioma. N Engl J Med 1965: 272:560-565. 5. Selikotf U. Hammond EC. Community etfects of nonoccupational environmental asbestos exposure. Am J Public Health 1968: 58:1658 1666. 6. Wagner JC. Epidemiology ofdiffuse mesotheliai tumors: Evidence ofan association from studies in South Africa and the United Kingdom. Ann NY Acad Sci 1965; 132:575-578. 7. Anderson HA. Lilis R. Daum SM. Fischbein AS. Selikolf U. Household-contact asbestos neoplastic risk. Ann NYAcad Sci 1976; 271: 311-323. 3. Elmes PC. The epidemiology and clinical features ofasbestosis and related diseases. Postgrad Med J 1966; 42:623-635. 9. Selikotf IJ. Cancer risk of asbestos exposure. In: Hiatt HH. Watson JD, Winston JA, eds. Origins of Human Cancer Book C. Human Risk Assessment. New York: Cold Spring Harbor Laboratory, 1977; 1765 1784. 10. Vianna NJ. Polan AK. Nonoccupational exposure to asbestos and malignant mesothelioma in females. Lancet 1978; 1:1061-1063. 11. Elmes PC. Simpson MJC. The clinical aspects of mesothelioma. QJ Med 1976: 179:427-449. 12. Epler GR. Gerald MXF. Gaensier EA. Carrington CB. Asbestos- related disease from household exposure. Respiration 1980; 39:229-240. 13. Chen W. Mottel NK. Malignant mesothelioma with minimal as bestos exposure. Hum Pathol 1973: 9:253-258. 14. Kelsey KT, Yano E. Liber HL. Little JB. The in vitro genetic etfects of fibrous erionite and crocidolite asbestos. Br J Cancer 1986; 54: 107-114. ' 15. Baris YI. Artvinli M. Sahin AA. Environmental mesothelioma in Turkey. Ann NY Acad Sci 1979: 330:423-432. 16. Stock RJ, Fu YS, Carter JR. Malignant peritoneal mesothelioma following radiotherapy for seminoma of the testis. Cancer 1979; 44:914 919. 17. Maurer R. Eglotf B. Malignant peritoneal mesothelioma after cholangiography with thorotrast. Cancer 1975: 36:1381-1385. 18. Riddell RH. Goodman MJ. Moossa AR. Peritoneal malignant mesothelioma in a patient with recurrent peritonitis. Cancer 1981; 48: 134-139. 19. Peterson JT, Greenberg SD. Buifler PA. Non asbestos-related ma lignant mesothelioma. Cancer 1984; 54:951-960. 20. Lesha SS. Muggia FM. Pleural mesothelioma: Clinical features and therapeutic implications. Ann intern Med 1977; 37:613-621. 21. Chahinian AP. Pajak TF. Holland JF. Norton L, Ambinder RM, Mandel EM. Diffuse malignant mesothelioma: Prospective evaluation of 69 patients. Ann intern Med 1982: 96:746-755. 22. Brenner J. Sordillo PP. Magill GB. Malignant mesothelioma in children: Report of seven cases and review of the literature. Med Pediair Oncol 1981:9:367-373. 23. Kovaiivker M. Motovic A. Malignant peritoneal mesothelioma in children: Description of two cases and review of the literature. J Pediatr Sure 1985: 20:3:274-275. 24. Berry PJ. Favara BE. Odom LF. Malignant peritoneal mesothe lioma in a child. Pediatr Pathoi 1986: 5:397-409. -. . .. .. " 25. Li FP. Lokich J, Lapey J. Neptune WB. Wilkins EW. Familial mesothelioma after intense asbestos exposure at home. JAMA 1978; 240: 467. " 26. Chahinian AP. Holland JF. Treatment of diffuse malignant me sothelioma: A review. Mt Sinai J Med 1978: 45:54-67. 27. Hochberg LA. Endothelioma (mesothelioma) of the pleura. Am Rev Tuberc 19513 63:150-175. 28. McDonald AD. Harper A, -El Attar OA. McDonald JC. Epide miology of. primary malignant mesotheliai tumors in Canada. Cancer 1970:26:914-919. 29. Brenner J. Sordillo PP, Magill GB. Golbey RB. Malignant me sothelioma ofthe pleura. Review of 123 patients. Cancer 1982; 49:2431 2435. 30. Jones B, Thomas P. Incidence of mesothelioma in Britain (Letter). Lancet 1986: 1:1275. 31. Amman 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: 68:356-362. 32. Kane MJ, Chahinian AP. Unpublished data. 1988. 33. Archer VE. Rom WN. Trends in mortality of diffuse malignant mesothelioma of pleura (Letter). Lancet 1983: 2:112-113. 34. McDonald JC. Health implications of environmental exposure to asbestos. Environ Heaith Perspect 1985: 62:319-328. 35. Babcock TL. Powell DH. Bothwell RS. Radiation induced peri toneal mesothelioma. J Surg Oncol 1976: 8:369-372. 36. Amman KH, Corson JM. Li FP et al. Malignant mesothelioma following radiation exposure. J Clin Oncol 1983; 1:695-700. 37. Brown JW, Kristensen KAB. Monroe LS. Peritoneal mesothelioma following pneumoperitoneum maintained for twelve years. Am J Dig Disease 1963; 13:830-835. 38. McDonald AD, McDonald JC. Malignant mesothelioma in North America. Cancer 1980: 46:1650-1656. 39. Hueper WC. Cancer induction by polyurethane and polysilicone plastics. JNCI 1964; 33:1005-1027. 40. Oels HC. Harrison EG. Carr DT. Bematz PE Diffuse malignant mesothelioma of the pleura: A review of 37 cases. Chest 1971; 60:564 570. 41. Planteydt HT. Observer variation and reliability ofthe histopathological diagnosis of mesothelioma. Ann NY Acad Sci 1979; 330:761 764. 42. Wang N. Electron microscopy in the diagnosis of pleural me sotheliomas. Cancer 1973: 31:1046-1054. 43. Wagner JG Animal experiments using the pleural cavity in studies of fibrous mineral dusts. In: Chretian J. Hirsh A eds. Diseases of the Pleura. Pans: Masson Publishing, 1983: 208-212. 44. Peto J, Seidman H, Selikolf U. Mesothelioma mortality in asbestos workers: Implications for models of carcinogenesis and risk assessment. Br J Cancer 1982; 45:124-135. 45. Browne K. Asbestos-related mesothelioma: Epidemiological ev idence for asbestos as a promoter. Arch Environ Heaith 1983: 38:261 266. 46. Mulvihill JJ. Miller RW, Fraumeni JF Jr. Genetics of human cancer. In: Mulvihill JJ. Miller RW, Fraumeni JF Jr. eds. Progress in Cancer Research and Therapv. Volume 3. New York: Raven Press. 1977; 391-399. ' 47. Langer AM. Nolan RP. Constantoooulos SH. Moutsopoulos HM. Association of metsovo lung and pleural mesothelioma with exposure to tremolite-contaimng whitewash. Lancet 1987: 1:965-967. 48. Martensson G. Larsson S. Zettergren L Malignant mesothelioma in two pairs of siblings: Is there a hereditary predisposing factor? Eur J Respir Dts 1984; 65:179-184. 49. Popescu NC. Amsbaugh SC. Chahinian PA. Dipaolo JA. Non random deletions of chromosome 3 (pi 4-21) in human malignant me sothelioma (Abstr). Proc Am Assoc Cancer Res 1987; 28:37.