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Report of Three Cases of Renal Oncocytoma in the Same French Chemical Industrial Factory

Saillant, Julie MD; Fontana, Luc PhD; Biat, Isabelle MD; Boudet, Gil; Maublant, Charlotte; Chamoux, Alain PhD

Journal of Occupational and Environmental Medicine: October 2009 - Volume 51 - Issue 10 - p 1113-1115
doi: 10.1097/JOM.0b013e3181ad49eb
Letters to the Editor
Free

Service Santé Travail Environnement; CHU Clermont-Ferrand, France (Saillant)

Institut de Médecine du travail; UFR Médecine; Univ Clermont 1; CHU Clermont-Ferrand; France (Fontana)

Service Santé Travail Environnement; CHU Clermont-Ferrand, France (Biat)

Institut de Médecine du travail; UFR Médecine; Univ Clermont 1; CHU Clermont-Ferrand; France (Boudet)

Service Santé Travail Environnement; CHU Clermont-Ferrand, France (Maublant)

Institut de Médecine du travail; UFR Médecine; Univ Clermont 1; CHU Clermont-Ferrand; France (Chamoux)

To the Editor: Renal oncocytoma is a rare benign tumor, accounting for 3% to 7% of primary renal tumors. There are no clearly established etiological factors. Three cases of renal oncocytoma detected between 2000 and 2008 in employees or subcontractors working for the same factory “F” in central France during a systematic screening campaign by ultrasonography are reported. The company specializes in vitamin and amino acid synthesis, in particular, vitamin A, vitamin E, and methionine. The factory is currently undergoing epidemiological investigations by the National Health and Work Department of the National Health Watch Institute (InVS) following nine cases of renal cell carcinoma (RCC) detected in workers between 1994 and 2002, at first by chance and later by systematic ultrasonography.1

The company began systematic screening for hepatic angiosarcoma in 1986 by yearly abdominal ultrasonography of employees exposed to monomer vinyl chloride (MVC). In 1992, the screening program was extended to workers exposed to chloracetal C5. This molecule is an intermediate chemical produced in the course of a new process for vitamin A synthesis called NAVAS (new vitamin A synthesis) first implemented in the factory in 1982. At that time, the molecule was known to be mutagenic in vitro. Since 2002, all company employees undergo ultrasound screening on a voluntary basis.

To date, 28 cases of RCC have been detected in this company; most were clear-cell and papillary RCC, but there were also three cases of oncocytoma and one angiomyolipoma. We describe the cases of oncocytoma with particular focus on the possible relation to occupational exposure.

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Observations

Observation 1

An asymptomatic mass in the left kidney was detected incidentally in 2000 in a 63-year-old woman by abdominal ultrasonography performed during medical surveillance of occupational exposure to MVC. The patient underwent extensive nephrectomy of the left kidney with aorta-renal curettage in May 2000. The anatomo pathology found a renal oncocytoma. A compensation for occupational disease was refused.

The patient had worked in the research laboratory of factory “F” from 1971 until her retirement in 2001. The products handled in the laboratory were chloroform, benzene, hexane, acetone, toluene, MVC, trichloroethylene, vitamins A and E, and amino acids including methionine and intermediate products occurring during synthesis such as chloracetal C5.

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Observation 2

A 66-year-old man had abdominal ultrasonography for consistent lumbar pain. A mass was detected in the right kidney. Right nephrectomy was performed in 2002. Pathological anatomy findings indicated a renal oncocytoma. A compensation for occupational disease was refused.

From 1991 to 2002, he was the sole agent for a civil engineering firm assigned on the factory F site and as such, he took measurements of the inside and outside of the factory buildings and was regularly present on the site (116 assignments lasting between half a day and 3 days).

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Observation 3

A 56-year-old man had a systemic yearly ultrasound examination in April 2008 that revealed a mass in the right kidney. Partial right nephrectomy was performed in 2008. Analysis of the nephrectomy specimens evidenced an oncocytoma.

From 1974 until his retirement in 2008, he had worked in the factory and successively been involved in the old process of vitamin A synthesis, the recycling of solvents, and then in the NAVAS process. Thus, he was widely exposed to a large number of solvents and chemicals such as hydroquinone, pyridine, hexane, ether, soda, MVC, and chloracetal C5 during the weighing and mixing of the products and during maintenance work.

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Discussion

Cluster or Incidental Association?

Can we really speak of a cluster of renal oncocytomas in this company rather than an incidental association because all cases were detected during systematic ultrasound screening? A 2-year screening program using ultrasonography was established in Germany in 1996 to assess its effectiveness in detecting RCCs: 9959 healthy volunteers (49% men and 51% women; mean age, 61 years; range, 40–94) underwent the examination and 79% returned for reexamination the following year. Nine RCC were detected and only one oncocytoma (incidence of 0.1 per 1000).2 In comparison, screening in factory “F,” which involved 801 employees working on the site and 600 people employed by outside companies, detected three cases of oncocytoma (incidence of 2.14 per 1000). Although the studied population is too small to carry out a proper statistical analysis, the increase in the prevalence of observed cases compared with the expected number (×20) speaks in favor of a relation with occupational activity.

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Occupational Causes of Oncocytomas

Little is known about the causal factors of oncocytomas. A few documented reports show an occurrence concomitant with exposure to chemical products.

In animals, an American study investigated the effects of ethylbenzene inhalation on the kidney of 344 Fischer rats; one oncocytoma was observed in a group of 50 male rats exposed to low doses and another case in a control group of nonexposed female rats.3

N-Nitrosomorpholine is known to induce renal oncocytomas in rats.4,5 The molecule has been classified as possibly carcinogenic in humans by the International Agency for Research on Cancer (IARC, group 2B) on the basis of studies showing evidence of its carcinogenicity in animals.6

In humans, a German study compared genetic mutations in renal tumors of workers exposed to trichloroethylene, a chloride solvent, with sporadic renal tumors of nonexposed controls. Histological investigations of 12 tumors detected in exposed workers showed nine cases (75%) of clear-cell carcinoma, two (18%) papillary carcinomas, and one (8%) oncocytoma. Of the 615 tumors investigated in control patients, 451 (73%) were diagnosed as clear-cell carcinomas, 88 (15%) as papillary carcinomas, and 18 (3%) as oncocytomas.7 Hence, there was an increased proportion of oncocytomas in workers exposed to trichloroethylene, and the proportion of oncocytoma compared with the total number of renal tumors was similar to that in our study (9%).

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What Is the Connection Between Oncocytomas and Renal Carcinomas?

Tumors in renal oncocytoma, unlike those in renal carcinoma, are benign and have no ability for metastasis. These develop from A-type intercalated cells in the collecting ducts, whereas those in clear-cell carcinoma develop from cells in proximal Henle’s loop and those in papillary carcinoma from distal Henle’s loop.8 Cytogenetically, a mosaic pattern of normal and aberrant karyotypes is observed: the most common abnormalities include loss of chromosomes 1 and Y, deletions from chromosome 14, and rearrangements involving chromosome 11q13. Genomically, therefore, oncocytomas are distinctly different from RCC of the clear-cell type, in most of which chromosome three abnormalities are observed.9,10

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Environmental Causal Factors of Renal Carcinomas

Several nonoccupational etiological factors such as smoking,11 obesity,12 certain drugs including diuretics,13,14 and certain renal diseases are known to induce renal carcinoma. The occupational factors suspected in the development of renal carcinomas are solvents, metals,15 hydrocarbons,16 and asbestos.17 But only long-term exposure to high doses of trichloroethylene has been significantly linked to renal carcinomas.18,19

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Occupational Exposure in the Observed Cases

Table 1 shows the main chemical products to which the two factory workers were exposed. The employees in factory “F” are exposed to these products by inhalation and skin contact.

TABLE 1

TABLE 1

The InVS investigation significantly linked the occupational exposure and the cluster of renal carcinomas, particularly in maintenance workers and those involved in the NAVAS manufacturing process. The InVS cited chloracetal C5 as one of the possible causes but could not establish a dose/effect relationship. The final report will be published in the course of 2009. The case had already been referred to the National Institute for Research and Safety in 2004. The Institute’s report showed that chloracetal C5 is mutagenic in vitro with a greater effect for certain strains when a system of renal activation is used. In 2005, the Institut Pasteur of Lille showed that the molecule is mutagenic in vivo.

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Conclusions

The occurrence of three cases of renal oncocytoma, a rare disease, in workers exposed to the same chemical products is suggestive of a strong causal relationship. In addition, a cluster of renal carcinomas has been observed on the same site: the existence of benign tumors of the same organ as that of the cluster is a further argument in favor of the carcinogenicity of the products studied. Current findings point toward the potential role of chloride molecules, including chloracetal C5, in tumor development, but further studies are required to determine the extent of their responsibility. The diagnosis of a renal oncocytoma, should be followed by a study of the patient’s occupational exposure to chemical products and to chlorides in particular.

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Acknowledgments

The authors thank Dr Claude Desplechain, Dr François Alcalay, French National Network for the Surveillance and Prevention of Occupational Diseases (RNV3P), and especially J.F. Jehanno and J.F. Juillard.

Julie Saillant, MD

Service Santé Travail Environnement

CHU Clermont-Ferrand, France

Luc Fontana, PhD

Institut de Médecine du travail

UFR Médecine

Univ Clermont 1

CHU Clermont-Ferrand

France

Isabelle Biat, MD

Service Santé Travail Environnement

CHU Clermont-Ferrand, France

Gil Boudet

Institut de Médecine du travail

UFR Médecine

Univ Clermont 1

CHU Clermont-Ferrand

France

Charlotte Maublant

Service Santé Travail Environnement

CHU Clermont-Ferrand, France

Alain Chamoux, PhD

Institut de Médecine du travail

UFR Médecine

Univ Clermont 1

CHU Clermont-Ferrand

France

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References

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