Pleural mesothelioma in a couple of brothers.

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.

INTRODUCTION

A number of reports have been devoted to familial mesothelioma.[12345] 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 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.

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]

The high incidence of malignant mesothelioma among insulators has been documented by many investigations.[89101112] 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.[1314] 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.

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.