Case Report
Pleural mesothelioma in a couple of brothers Abstract Malignant mesotheliomas of the pleura, epithelial type, were observed in two brothers. Both the patients had histories of severe exposure to asbestos, having worked as insulators. The latency periods in the two cases were 26 and 38 years, respectively. Available literature data suggest that mesothelioma occurrence among blood‑related people is favored by a genetic predisposition. Key words: Asbestos, cofactors, familial mesothelioma, insulators
INTRODUCTION A number of reports have been devoted to familial mesothelioma.[1‑5] The meaning of such an occurrence remains controversial. The recent International Agency for Research on Cancer (IARC) monograph on asbestos suggests that familial mesothelioma is a rather rare event.[6] However, various data are at odds with such view. We describe a couple of brothers with pleural mesothelioma. Both the patients had histories of severe occupational exposure to asbestos.
CASE REPORT Case 1 A 45‑year‑old man was admitted to a hospital in central Italy in August 2000 for right pleural effusion. Three‑months later, a diagnosis of malignant mesothelioma, epithelial type, was made on the basis of multiple pleural biopsies obtained at right thoracotomy. Hyaline pleural plaques were also visible. Partial right pleurectomy was performed on December 2000. In the following years, the patient was treated by chemotherapy. In May 2003, a progression of the disease was documented. Involvement of spinal cord and large subcutaneous neoplastic infiltration coexisted. The patient died in June 2003. In the period 1974‑1981, the patient had intermittently worked as an insulator at a sodium carbonate factory for a total of about 3 years. Moreover, in the period 1977‑1986, he was intermittently employed in various sugar refineries for a total of nearly 3 years. Case 2 A 56‑year‑old man, the brother of the Case 1, was admitted to a hospital in northern Italy in March 2006. A thoracic computed tomography (CT) showed two nodules adjacent 122
to pleura in the right lung. One year previously the patient had been treated with oral anticoagulants for pulmonary thromboembolism. At the right videothoracoscopy, multiple neoplastic pleural nodules were visible, associated with hyaline pleural plaques. At the histological examination, malignant mesothelioma, epithelial type, was diagnosed. Despite chemotherapy with cysplatin and alimta, thoracic CT showed severe progression of the neoplasia. In March 2007, the patient was treated with mediastinal radiotherapy for a mediastinal syndrome. He died in April 2007.
Claudio Bianchi, Tommaso Bianchi Center for the Study of Environmental Cancer, Italian League against Cancer, Monfalcone, Italy For correspondence: Dr. Claudio Bianchi, Center for the Study of Environmental Cancer, Italian League against Cancer, Hospital of Monfalcone, 34074 Monfalcone, Italy. E‑mail: legatumori1@ interfree.it
The patient had worked as an insulator for some 20 years (1967‑1986). His work took place in thermoelectric plants and chemical industries in Italy as well as in foreign countries (Algeria, Libya, Saudi Arabia). The two patients were born in central Italy. Their parents came from a town of Sicily; some degree of blood relationship existed between the parents, they being second cousins.
DISCUSSION Both the aforementioned patients had severe exposure to asbestos, having worked as insulators. The exposure was different in duration (about 6 years in the case 1 and 20 years in the case 2). Latency periods also differed markedly, being unexpectedly short in the case 1 (26 years) and longer in the case 2 (38 years). In the case 2, the pulmonary thomboembolism presented by the patient in 2005 may be considered as the first manifestation of the tumor, given the low frequency of thromboembolism in the general population and the high incidence in mesotheliomas.[7]
Access this article online Website: www.ijoem.com DOI: 10.4103/0019-5278.130865 Quick Response Code:
Indian Journal of Occupational and Environmental Medicine - December 2013 - Volume 17 - Issue 2
Bianchi and Bianchi: Mesothelioma in two brothers
The high incidence of malignant mesothelioma among insulators has been documented by many investigations.[8‑12] There is no doubt that the two cases have to be considered as induced by asbestos. Nevertheless, the fact that only a relatively low percentage of people exposed to asbestos develop mesothelioma indicates that cofactors play a role in the genesis of asbestos‑related mesothelioma.[13,14] Mesotheliomas arising in blood‑related people suggest a genetic predisposition to develop this rare malignancy. It is difficult to form an idea about the frequency of such an occurrence. In a large majority of the familial mesotheliomas reported in the literature, there is no reference to a denominator. In two studies conducted in Italy a denominator is reported, with different findings. In a series of 610 pleural mesotheliomas examined in the Trieste‑Monfalcone area, Italy, the percentage of familial cases with blood relationship reached the value of 3.8%.[1] A percentage somewhat lower, 22 cases in a series of 1,954 pleural mesotheliomas, was observed by examining the data collected by three Italian Mesothelioma Registries.[2] Recently, de Klerk et al., have investigated the familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia. [5] More than 11,000 people have been followed. The researchers observed 369 family groups with at least one mesothelioma case and 25 cases of mesothelioma among relatives in the same families. The risk ratio for blood relatives was 1.9 (CI 1.3-2.9). After the authors, these findings suggest an important, but not large, genetic component in mesothelioma. In a study regarding 1,403 people hired at the shipyards of Monfalcone in the period 1950‑59, 35 cases of mesothelioma were observed.[15] Of the 33 men with pleural mesothelioma in this group, four had a blood relative with the same tumor.
REFERENCES 1.
2.
3. 4.
5.
6.
7. 8. 9.
10.
11.
12.
13. 14. 15.
Bianchi C, Brollo A, Ramani L, Bianchi T, Giarelli L. Familial mesothelioma of the pleura. A report of 40 cases. Ind Health 2004;42:235‑9. Ascoli V, Cavone D, Merler E, Barbieri PG, Romeo L, Nardi F, et al. Mesothelioma in blood related subjects: Report of 11 clusters among 1954 Italy cases and review of the literature. Am J Ind Med 2007;50:357‑69. Bianchi C, Nemo A, Bianchi T. Familial mesothelioma: A puzzling issue. Eur J Oncol 2008;13:181‑6. Kalogeraki AM, Tamiolakis DJ, Lagoudaki ED, Papadakis MN, Papadakis GZ, Agelaki SI, et al. Familial mesothelioma in first degree relatives. Diagn Cytopathol 2013;41:654‑7. de Klerk N, Alfonso H, Olsen N, Reid A, Sleith J, Palmer L, et al. Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia. Int J Cancer 2013;132:1423‑8. IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. A review of Human carcinogens: Metals, arsenic, dusts, and fibres. Lyon, WHO, IARC 2012;100C: 293 Nguyen D, Lee SJ, Libby E, Verschraegen C. Rate of thromboembolic events in mesothelioma. Ann Thorac Surg 2008;8:1032‑8. Elmes PC, Simpson MJ. Insulation workers in Belfast. A further study of mortality due to asbestos exposure (1940‑75). Br J Ind Med 1977;34:174‑80. Selikoff IJ, Seidman H. Asbestos‑associated deaths among insulation workers in the United States and Canada, 1967‑1987. Ann N Y Acad Sci 1991;643:1‑14. Järvholm B, Sandén A. Lung cancer and mesothelioma in the pleura and peritoneum among Swedish insulation workers. Occup Environ Med 1998;55:766‑70. Ulvestad B, Kjaerheim K, Martinsen JI, Mowe J, Andersen A. Cancer incidence among members of Norwegian Trade Union of Insulation Workers. J Occup Environ Med 2004;46:84‑9. Cocco P, Dosemeci M. Peritoneal cancer and occupational exposure to asbestos: Results from the application of a job‑exposure matrix. Am J Ind Med 1999;35:9‑14. Bianchi C, Bianchi T. Malignant mesothelioma: Global incidence and relationship with asbestos. Ind Health 2007;45:379‑87. Bianchi C, Bianchi T. Susceptibility and resistance in the genesis of asbestos‑related mesothelioma. Indian J Occup Environ Med 2008;12:57‑60. Bianchi C, Bianchi T. Mesothelioma among shipyard workers in Monfalcone, Italy. Indian J Occup Environ Med 2012;16:119‑23.
CONCLUSIONS On the whole, the aforementioned data show that the occurrence of more mesothelioma cases among blood‑related persons is not rare. Such occurrence may indicate a genetic predisposition to develop mesothelioma, even if asbestos exposure remains the principal cause.
Cite this article as: Bianchi C, Bianchi T. Pleural mesothelioma in a couple of brothers. Indian J Occup Environ Med 2013;17:122-3. Source of Support: Nil, Conflict of Interest: One of the authors (CB) has been asked to provide scientific information in criminal or civil court cases relates to asbestos diseases; he served as an expert for the court or for the plaintiff.
Indian Journal of Occupational and Environmental Medicine - December 2013 - Volume 17 - Issue 3
123
Copyright of Indian Journal of Occupational & Environmental Medicine is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Pleural mesothelioma in a couple of brothers Abstract Malignant mesotheliomas of the pleura, epithelial type, were observed in two brothers. Both the patients had histories of severe exposure to asbestos, having worked as insulators. The latency periods in the two cases were 26 and 38 years, respectively. Available literature data suggest that mesothelioma occurrence among blood‑related people is favored by a genetic predisposition. Key words: Asbestos, cofactors, familial mesothelioma, insulators
INTRODUCTION A number of reports have been devoted to familial mesothelioma.[1‑5] The meaning of such an occurrence remains controversial. The recent International Agency for Research on Cancer (IARC) monograph on asbestos suggests that familial mesothelioma is a rather rare event.[6] However, various data are at odds with such view. We describe a couple of brothers with pleural mesothelioma. Both the patients had histories of severe occupational exposure to asbestos.
CASE REPORT Case 1 A 45‑year‑old man was admitted to a hospital in central Italy in August 2000 for right pleural effusion. Three‑months later, a diagnosis of malignant mesothelioma, epithelial type, was made on the basis of multiple pleural biopsies obtained at right thoracotomy. Hyaline pleural plaques were also visible. Partial right pleurectomy was performed on December 2000. In the following years, the patient was treated by chemotherapy. In May 2003, a progression of the disease was documented. Involvement of spinal cord and large subcutaneous neoplastic infiltration coexisted. The patient died in June 2003. In the period 1974‑1981, the patient had intermittently worked as an insulator at a sodium carbonate factory for a total of about 3 years. Moreover, in the period 1977‑1986, he was intermittently employed in various sugar refineries for a total of nearly 3 years. Case 2 A 56‑year‑old man, the brother of the Case 1, was admitted to a hospital in northern Italy in March 2006. A thoracic computed tomography (CT) showed two nodules adjacent 122
to pleura in the right lung. One year previously the patient had been treated with oral anticoagulants for pulmonary thromboembolism. At the right videothoracoscopy, multiple neoplastic pleural nodules were visible, associated with hyaline pleural plaques. At the histological examination, malignant mesothelioma, epithelial type, was diagnosed. Despite chemotherapy with cysplatin and alimta, thoracic CT showed severe progression of the neoplasia. In March 2007, the patient was treated with mediastinal radiotherapy for a mediastinal syndrome. He died in April 2007.
Claudio Bianchi, Tommaso Bianchi Center for the Study of Environmental Cancer, Italian League against Cancer, Monfalcone, Italy For correspondence: Dr. Claudio Bianchi, Center for the Study of Environmental Cancer, Italian League against Cancer, Hospital of Monfalcone, 34074 Monfalcone, Italy. E‑mail: legatumori1@ interfree.it
The patient had worked as an insulator for some 20 years (1967‑1986). His work took place in thermoelectric plants and chemical industries in Italy as well as in foreign countries (Algeria, Libya, Saudi Arabia). The two patients were born in central Italy. Their parents came from a town of Sicily; some degree of blood relationship existed between the parents, they being second cousins.
DISCUSSION Both the aforementioned patients had severe exposure to asbestos, having worked as insulators. The exposure was different in duration (about 6 years in the case 1 and 20 years in the case 2). Latency periods also differed markedly, being unexpectedly short in the case 1 (26 years) and longer in the case 2 (38 years). In the case 2, the pulmonary thomboembolism presented by the patient in 2005 may be considered as the first manifestation of the tumor, given the low frequency of thromboembolism in the general population and the high incidence in mesotheliomas.[7]
Access this article online Website: www.ijoem.com DOI: 10.4103/0019-5278.130865 Quick Response Code:
Indian Journal of Occupational and Environmental Medicine - December 2013 - Volume 17 - Issue 2
Bianchi and Bianchi: Mesothelioma in two brothers
The high incidence of malignant mesothelioma among insulators has been documented by many investigations.[8‑12] There is no doubt that the two cases have to be considered as induced by asbestos. Nevertheless, the fact that only a relatively low percentage of people exposed to asbestos develop mesothelioma indicates that cofactors play a role in the genesis of asbestos‑related mesothelioma.[13,14] Mesotheliomas arising in blood‑related people suggest a genetic predisposition to develop this rare malignancy. It is difficult to form an idea about the frequency of such an occurrence. In a large majority of the familial mesotheliomas reported in the literature, there is no reference to a denominator. In two studies conducted in Italy a denominator is reported, with different findings. In a series of 610 pleural mesotheliomas examined in the Trieste‑Monfalcone area, Italy, the percentage of familial cases with blood relationship reached the value of 3.8%.[1] A percentage somewhat lower, 22 cases in a series of 1,954 pleural mesotheliomas, was observed by examining the data collected by three Italian Mesothelioma Registries.[2] Recently, de Klerk et al., have investigated the familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia. [5] More than 11,000 people have been followed. The researchers observed 369 family groups with at least one mesothelioma case and 25 cases of mesothelioma among relatives in the same families. The risk ratio for blood relatives was 1.9 (CI 1.3-2.9). After the authors, these findings suggest an important, but not large, genetic component in mesothelioma. In a study regarding 1,403 people hired at the shipyards of Monfalcone in the period 1950‑59, 35 cases of mesothelioma were observed.[15] Of the 33 men with pleural mesothelioma in this group, four had a blood relative with the same tumor.
REFERENCES 1.
2.
3. 4.
5.
6.
7. 8. 9.
10.
11.
12.
13. 14. 15.
Bianchi C, Brollo A, Ramani L, Bianchi T, Giarelli L. Familial mesothelioma of the pleura. A report of 40 cases. Ind Health 2004;42:235‑9. Ascoli V, Cavone D, Merler E, Barbieri PG, Romeo L, Nardi F, et al. Mesothelioma in blood related subjects: Report of 11 clusters among 1954 Italy cases and review of the literature. Am J Ind Med 2007;50:357‑69. Bianchi C, Nemo A, Bianchi T. Familial mesothelioma: A puzzling issue. Eur J Oncol 2008;13:181‑6. Kalogeraki AM, Tamiolakis DJ, Lagoudaki ED, Papadakis MN, Papadakis GZ, Agelaki SI, et al. Familial mesothelioma in first degree relatives. Diagn Cytopathol 2013;41:654‑7. de Klerk N, Alfonso H, Olsen N, Reid A, Sleith J, Palmer L, et al. Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom, Western Australia. Int J Cancer 2013;132:1423‑8. IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. A review of Human carcinogens: Metals, arsenic, dusts, and fibres. Lyon, WHO, IARC 2012;100C: 293 Nguyen D, Lee SJ, Libby E, Verschraegen C. Rate of thromboembolic events in mesothelioma. Ann Thorac Surg 2008;8:1032‑8. Elmes PC, Simpson MJ. Insulation workers in Belfast. A further study of mortality due to asbestos exposure (1940‑75). Br J Ind Med 1977;34:174‑80. Selikoff IJ, Seidman H. Asbestos‑associated deaths among insulation workers in the United States and Canada, 1967‑1987. Ann N Y Acad Sci 1991;643:1‑14. Järvholm B, Sandén A. Lung cancer and mesothelioma in the pleura and peritoneum among Swedish insulation workers. Occup Environ Med 1998;55:766‑70. Ulvestad B, Kjaerheim K, Martinsen JI, Mowe J, Andersen A. Cancer incidence among members of Norwegian Trade Union of Insulation Workers. J Occup Environ Med 2004;46:84‑9. Cocco P, Dosemeci M. Peritoneal cancer and occupational exposure to asbestos: Results from the application of a job‑exposure matrix. Am J Ind Med 1999;35:9‑14. Bianchi C, Bianchi T. Malignant mesothelioma: Global incidence and relationship with asbestos. Ind Health 2007;45:379‑87. Bianchi C, Bianchi T. Susceptibility and resistance in the genesis of asbestos‑related mesothelioma. Indian J Occup Environ Med 2008;12:57‑60. Bianchi C, Bianchi T. Mesothelioma among shipyard workers in Monfalcone, Italy. Indian J Occup Environ Med 2012;16:119‑23.
CONCLUSIONS On the whole, the aforementioned data show that the occurrence of more mesothelioma cases among blood‑related persons is not rare. Such occurrence may indicate a genetic predisposition to develop mesothelioma, even if asbestos exposure remains the principal cause.
Cite this article as: Bianchi C, Bianchi T. Pleural mesothelioma in a couple of brothers. Indian J Occup Environ Med 2013;17:122-3. Source of Support: Nil, Conflict of Interest: One of the authors (CB) has been asked to provide scientific information in criminal or civil court cases relates to asbestos diseases; he served as an expert for the court or for the plaintiff.
Indian Journal of Occupational and Environmental Medicine - December 2013 - Volume 17 - Issue 3
123
Copyright of Indian Journal of Occupational & Environmental Medicine is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
