Multiple synchronous primary malignancies induced by benzene exposure: a case report
© Wang et al; licensee BioMed Central Ltd. 2009
Received: 29 September 2008
Accepted: 16 April 2009
Published: 16 April 2009
Chronic exposure to high concentrations of benzene is usually associated with the development of haematological diseases. However, solid tumors induced by benzene exposure are less frequent.
We present an unusual case of triple synchronous primary malignancies most likely induced by occupational benzene exposure in a male patient. This spray painter was diagnosed as chronic aplastic anemia in his 21 years old after exposing to high concentration of benzene for three years. Then he was treated with glucocorticoid for four years. 40 years later, this patient developed three synchronous primary neoplasms with three different histologies including a basaloid squamous cell carcinoma of the esophagus, primary hepatocellular carcinoma, and well-differentiated squamous cell carcinoma of the gum.
This case reminds us that the occurrence of solid tumors should be monitored in workers with occupational history linked with a high concentration exposure to benzene, though it's rarely happened.
Chronic exposure to high concentrations of benzene in humans is usually associated with the development and progression of leukaemia and other haematological diseases [1–3]. Less frequently, solid tumors induced by benzene exposure may occur.
We present a rare case of triple synchronous primary malignancies with chronic aplastic anemia induced by strongly related occupational benzene exposure in a male patient. This patient had three primary neoplasms with three different histologies including a basaloid squamous cell carcinoma of the esophagus, primary hepatocellular carcinoma, and well-differentiated squamous cell carcinoma of the gum. These neoplasms simultaneously occurred 40 years after benzene exposure.
A 61-year old male patient was admitted to our hospital in May 2007 with a solid mass in the right-inferior gum for almost a year and progressive enlargement in latest two weeks. He had no respiratory or gastrointestinal complaints, and he denied any weight loss. In this spray painter, chronic aplastic anemia was diagnosed when he was 21 years old, after a previous three-year exposure to high concentration of benzene. Consequently, he was treated with glucocorticoid for four years. After that this patient lived together with his brother in Hangzhou, and he only did some houseworks. He had never smoked nor been exposed to smoking environment. 40 years later, three synchronous primary neoplasms including a basaloid squamous cell carcinoma of the esophagus, primary hepatocellular carcinoma and well-differentiated squamous cell carcinoma of the gum were diagnosed in this patient.
This is a case report of a patient diagnosed with three synchronous primary tumors and who had previous occupational benzene exposure for 3 years (1964–1966) and an acute benzene poisoning.
Multiple primary malignant neoplasms (MPMN) in a single patient are not frequent. The majority of MPMN occurring in multiple organs are metachronous, while the synchronous tumors, which are defined that two or more primary tumors are diagnosed within 6 months of the first primary tumor, are less frequent. Our case had three such synchronous primary neoplasms. Regarding the aetiology of multiple primary malignancies, several factors have been incriminated: genetic, hormonal (e.g. sex steroids), environmental, iatrogenic (e.g. chemotherapy, radiation therapy, hormonal and immunosuppressive medications) and immunologic factors (the loss of immunity). In this case, the benzene exposure history was considered as the most possible causative factor for his MPMN.
Benzene and its metabolites are highly clastogenic. Chronic exposure to high concentrations of benzene in humans is associated with hematotoxicities, including pancytopenia, aplastic anemia, myelodysplasia, and acute myeloid leukemia [5–7]. The hematotoxicity of benzene is related to the amount and duration of exposure. At high levels of exposure (air concentration > 100 ppm), the incidence of aplastic anemia is approximately 1/100 individuals exposed; at lower levels of exposure (10–20 ppm), this drops abruptly to approximately 1/10,000. Although the exact benzene exposure level for this patient could not be determined, some earlier studies of benzene exposure provided useful information [5, 6]. In a NCI-CAPM study, Dosemeci et al provided that the expose level for "spray painter" at a Shanghai bicycle factory during 1965–1969 was 331 mg/m3 or 104.1 ppm. The author also implicated that some engineering changes took place over the years, resulting in lower exposure levels. Thus, exposure for spray painters before 1965 should be the same as, or more likely, higher than those recorded during 1965–1969. Wong also pointed out the actual level might be higher than that in the NCI-CAPM study. According to these studies, we can estimate that the benzene exposure level for this patient would be much higher at that time. It seemed almost certain that his benzene exposure history played a key role in the occurring of aplastic anemia.
The relationship between benzene exposure and solid tumor is not known well. According to a previous study in 12 cities in China, a small increase was observed in total cancer mortality among benzene-exposed compared with unexposed workers (relative risk [RR] = 1.2). Statistically significant excess was noted for lung cancer (RR = 1.4), but less than leukemia (RR = 2.3). Some studies showed that there was no indication of increased incidences of solid tumors for chronic benzene exposed workers or children [10–12]. However, animal experimental results showed that several solid tumors occured in the Zymbal gland, oral and nasal cavities, liver, and mammary gland of Sprague-Dawley rats following chronic, high-dose administration of benzene, which was thought to be caused by activation of toxic metabolites that can interact with DNA, and form covalent adducts.
Treatment for aplastic anemia is another possible cause of multiple tumors. Long-term administration of androgenic steroids for aplastic anemia was reported in some cases correlating to multiple neoplasms[14, 15]. Our patient had never taken androgen but glucocorticoid to treat the aplastic anemia. To our knowledge, there was no case reported that glucocorticoid treatment for aplastic anemia resulted in the occurrence of MPMN.
This is a rare case manifesting a combination of three synchronous primary malignant neoplasms and chronic aplastic anemia most likely induced by occupational benzene exposure. It reminds us that the occurrence of solid tumors should be monitored in workers with occupational history linked with a high concentration exposure to benzene, though it's rarely happened.
Written informed consent was obtained from the patient's brother (legal guardian) for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Aksoy M, Ozeris S, Sabuncu H, Inanici Y, Yanardağ R: Exposure to benzene in Turkey between 1983 and 1985: a haematological study on 231 workers. Br J Ind Med 1987, 44: 785–787.PubMed CentralPubMedGoogle Scholar
- Yardley-Jones A, Anderson D, Parke DV: The toxicity of benzene and its metabolism and molecular pathology in human risk assessment. Br J Ind Med 1991, 48: 437–444.PubMed CentralPubMedGoogle Scholar
- Baak YM, Ahn BY, Chang HS, Kim JH, Kim KA, Lim Y: Aplastic anemia in a petrochemical factory worker. Environ Health Perspect 1999, 107: 851–853. 10.2307/3454585PubMed CentralPubMedView ArticleGoogle Scholar
- Holecková B, Piesová E, Sivikova K, Dianovskỳ J: Chromosomal aberrations in humans induced by benzene. Ann Agric Environ Med 2004, 11: 175–179.PubMedGoogle Scholar
- Dosemeci M, Li GL, Hayes RB, Yin SN, Linet M, Chow WH, Wang YZ, Jiang ZL, Dai TR, Zhang WU: Cohort study among workers exposed to benzene in China: II. Exposure assessment. Am J Ind Med 1994, 26: 401–411. 10.1002/ajim.4700260313PubMedView ArticleGoogle Scholar
- Wong O: Investigations of benzene exposure, benzene poisoning, and malignancies in China. Regul Toxicol Pharmacol 2002, 35: 126–135. 10.1006/rtph.2001.1520PubMedView ArticleGoogle Scholar
- Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Leaverton PE, Shapiro S, Young NS: The epidemiology of aplastic anemia in Thailand. Blood 2006, 107: 1299–1307. 10.1182/blood-2005-01-0161PubMed CentralPubMedView ArticleGoogle Scholar
- Smith MT: Overview of benzene-induced aplastic anemia. Eur J Haematol Suppl 1996, 60: 107–110.PubMedGoogle Scholar
- Yin SN, Hayes RB, Linet MS, Li GL, Dosemeci M, Travis LB: An expanded cohort study of cancer among benzene-exposed workers in China. Benzene Study Group. Environ Health Perspect 1996,104(Suppl 6):1339–1341. 10.2307/3433187PubMed CentralPubMedView ArticleGoogle Scholar
- Harrison RM, Leung PL, Somervaille L, Smith R, Gilman E: Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations. Occup Environ Med 1999, 56: 774–780. 10.1136/oem.56.11.774PubMed CentralPubMedView ArticleGoogle Scholar
- Paxton MB, Chinchilli VM, Brett SM, Rodricks JV: Leukemia risk associated with benzene exposure in the pliofilm cohort: I. Mortality update and exposure distribution. Risk Anal 1994, 14: 147–154. 10.1111/j.1539-6924.1994.tb00039.xPubMedView ArticleGoogle Scholar
- Paxton MB: Leukemia risk associated with benzene exposure in the Pliofilm cohort. Environ Health Perspect 1996,104(Suppl 6):1431–1436. 10.2307/3433199PubMed CentralPubMedView ArticleGoogle Scholar
- Reddy MV, Blackburn GR, Schreiner CA, Mehlman MA, Mackerer CR: 32P analysis of DNA adducts in tissues of benzene-treated rats. Environ Health Perspect 1989, 82: 253–257. 10.2307/3430783PubMed CentralPubMedGoogle Scholar
- Nakao A, Sakagami K, Nakata Y, Komazawa K, Amimoto T, Nakashima K, Isozaki H, Takakura N, Tanaka N: Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis. J Gastroenterol 2000, 35: 557–562. 10.1007/s005350070081PubMedView ArticleGoogle Scholar
- Sale GE, Lerner KG: Multiple tumors after androgen therapy. Arch Pathol Lab Med 1977, 101: 600–603.PubMedGoogle Scholar
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