Arsenic and skin cancer – Case report with chemoprevention

Uwe Wollina

Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, 01067 Dresden, Germany

Corresponding author: Prof. Dr. med. Uwe Wollina, E-mail:
Submission: 30.09.2015 , Acceptance: 17.11.2015
DOI: 10.7241/ourd.20162.46
How to cite this article: Wollina U. Arsenic and skin cancer – Case report with chemoprevention. Our Dermatol Online. 2016;7(2):172-175.


Introduction: Arsenic is a potentially hazardous metalloid that can cause skin cancer. We want to demonstrate a case of chronic arsenicosis and the potential of chemoprevention with retinoids.

Case Report: This is a case report of a 72-year-old male patient who was exposed to arsenics by dust and direct skin contact over 3 years in a chemical plant in the late fourties. He developed multiple arsenic keratosis clincialll resembling actinic keratoses, Bowen’s disease and palmar minute keratoses. To prevent a transformation into invasive cancer and to lower the burden of precancerous and in situ cancer lesions, he was treated orally with acitretin 20 mg/day. During 9 months of chemopreventive retinoid therapy a partial response of pre-existent skin lesions was noted. Treatment was well tolerated. During follow-up of 5 years no invasive malignancy developed.

Conclusions: Intense exposure to arsenics during a relatively short period of 3 years bears a life-long health hazard with the delayed development of multiple in situ carcinomas and precancerous lesions. Chemoprevention with retinoids can induce a partial response.

Key words:Arsenics; Metalloids; Occupational hazards; Multiple Bowen’s disease; Minute keratoses; Arsenic keratoses


Arsenic is an ubiquitous metalloid which poses health risks for humans. Typical non-occupational and occupational sources of exposure are summarized in Table 1. Chronic exposure possess an increased risk for lung and bladder cancer [1,2].

Table 1: Exposure to arsenic

Arsenic is a primary carcinogen in the skin following ingestion or topical exposure. Chronically exposed patients develop mainly precancerous arsenic keratosis, but in situ carcinoma (Bowen’s disease and actinic keratosis) and invasive basal or squamous cell carcinoma have also been observed (Table 2) [3].

Table 2: Cutaneous manifestations of arsenic exposure

There is a number of occupational studies demonstrating a high risk of lung cancer related to arsenic exposure by inhalation. There is less data available on the possible association of occupational arsenic exposure with nonmelanoma skin cancer (NMSC). Recent studies suggest arsenic exposure increases the risk of NMSC as a cofactor to smoking and sunlight exposure [4,5].

The pathways by which arsenic is inducing skin malignancies are yet only poorly understood. In cell culture and animal models cytotoxity leading to increased but disturbed repair activities have been observed. A number of proinflammatory cytokines are released by cells exposed to arsenic including tumor growth factor-alfa. In animals no skin cancer was induced by arsenic. Arsenic is capable to induce post-translational histone modifications that may induce global transcriptional repression including tumor suppressor genes [6,7].


A 72-year old Caucasian man presented with multiple keratoses and pits on his palms for years ago. The patient had no history of a familial occurrence of such cutaneous signs. He was not under immunosuppression nor had he received an organ transplant. His Fitzpatrick skin type was III. He reported that the lesions developed over four decades. His own medical history was unremarkable.

A thorough clinical examination and a skin biopsy were performed. On his palms small pits were found (Fig. 1). Nails, hair, teeth and oral mucous membrane had no pathologic symptoms. We observed more than 100 hypertrophic keratoses and Bowen’s disease randomly distributed over the whole body except his face (Fig. 2). These lesions in conjunction with the pathological report suggest a chronic arsenic intoxication. On request it became clear that he became exposed to arsenics (arsenites and arsenates – dust and direct skin contact) during an occupation in a chemical plant for several years as war prisoner in the 1940ies (1945-1948). After his war prison years he was neither an outdoor worker nor a smoker.

Figure 1: Palmar hyperkeratosis with minute pits.
Figure 2: Multiple keratosis (Bowen’s disease) on trunk (and extremities).

First dermatological consultation was recorded in 1988.

During follow-up over 5 years, several lesions have been removed over time under the suspicion of an early invasive squamous cell carcinoma what could be excluded by histopathology.

There was no development of internal cancer such as lung or bladder cancer.

He had neither a peripheral neuropathy nor cardiac arrhythmias. Laboratory test for plasma arsenic concentration of 24h-arsenic excretion were not performed since the exposure was decades ago. The diagnosis of chronic arsenicosis was made by medical history, clinical examination and histopathology of selected lesions. Histologically Bowen lesions and hypertrophic keratoses with atypical epidermal keratinocytes were observed.

He was given oral acitretin 20 mg per day as a chemopreventive measure for 9 months. The treatment was well tolerated under strict laboratory control. A partial regression of lesions was seen but not complete remission was achieved (Figs. 3a and b). On the other hand, no progression to invasive skin cancer has been observed.

Figure 3: (a) Actinic hyperkeratosis before chemoprevention with acitretin, (b) Partial remission after 9 months of oral acitretin therapy.


Chronic arsenic exposure poses a health risk for the whole life [810]. Skin lesions like palmar pits, multiple keratoses and multiple Bowen’s lesions on sunprotected skin are biomarkers for chronic arsenic exposure [11]. The development of precancerous lesions and in situ skin cancer is well known in the medical literature (Table 2) [3,10,12]. Invasive skin cancer such as basal cell carcinoma or squamous cell carcinoma has rarely been observed. Epidemiologic studies suggest that sunlight exposure and smoking are major factors which may become aggravated by chronic arsenic exposure [1,2]. Although skin carcinogenesis by arsenic is not completely understood, aberrant proliferation, release of proinflammatory cytokines, oxygen radical production, disturbed local immune response including impairment of p53 tumor suppressor function, and aggravation of UVB and UVA procarcinogenic effects have been detected [13].

Arsenite inhibits transcription of signaling kinase genes and downstream DNA repair genes DDB2 and RAD23B. Arsenite can displace zinc from the zinc fingers in proteins involved in DNA repair. These effects likely contribute to decreased nucleotide excision repair [14].

In our case no cofactors of arsenic toxicity (smoking or outdoor work) were evident. Drinking water is not a significant factor of chronic arsenic exposure in the region. So the only factor that could be established was a three year unprotected exposure to arsenics in a French chemical plant after World War II. It is remarkable that a relatively short but intense exposure to arsenics can cause ongoing health hazards. Patients with chronic arsenicosis need a lifelong follow-up since invasive cancer can develop with a delay of decades.

Chemoprevention of arsenic skin cancer has not really been established. In a phase I trial curcumin was applied in doses of 1 to 12 g per day. No toxicities were observed and a mild cancer protective activity was noted [15]. Other phytochemicals are under investigation [16]. A prospective trial has been initiated in Bangladesh with a 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 µg daily) for the prevention of nonmelanoma skin cancer [17]. The future will show if the promises can be fullfilled.

Long term treatment with retinoids, in particular isotretinoin and acitretin, has shown activity in NMSC [18,19]. Here we could demonstrate a partial remission of hypertrophic arsenic keratoses. If the treatment prevented lung and bladder cancer in our patient would be a matter of speculation only. Nevertheless, oral retinoid chemoprevention can be a measure in high risk patients after chronic arsenic exposure.

Key messages

  • Chronic arsenicosis is a life-long disease with the potential of skin, lung and bladder cancer development.
  • Symptomatology occurs after a delay of several years or even decades.
  • Chemoprevention by oral retinoids is a measure for high-risk patients.
  • A lifelong follow-up is recommended.



The examination of the patient was conducted according to the Declaration of Helsinki principles.


1. Christoforidou EP, Riza E, Kales SN, Hadjistavrou K, Stoltidi M, Kastania AN, Bladder cancer and arsenic through drinking water: a systematic review of epidemiologic evidenceJ Environ Sci Health A Tox Hazard Subst Environ Eng 2013; 48: 1764-75.

2. Xie H, Huang S, Martin S, Wise JP, SrArsenic is cytotoxic and genotoxic to primary human lung cellsMutat Res Genet Toxicol Environ Mutagen 2014; 760: 33-41.

3. Lansdown AB, Metal ions affecting the skin and eyesMet Ions Life Sci 2011; 8: 187-246.

4. Surdu S, Fitzgerald EF, Bloom MS, Boscoe FP, Carpenter DO, Haase RF, Occupational exposure to arsenic and risk of nonmelanoma skin cancer in a multinational European studyInt J Cancer 2013; 133: 2182-91.

5. Chen Y, Graziano JH, Parvez F, Hussain I, Momotaj H, van Geen A, Modification of risk of arsenic-induced skin lesions by sunlight exposure, smoking, and occupational exposures in BangladeshEpidemiology 2006; 17: 459-67.

6. Cohen SM, Arnold LL, Beck BD, Lewis AS, Eldan M, Evaluation of the carcinogenicity of inorganic arsenicCrit Rev Toxicol 2013; 43: 711-52.

7. Chervona Y, Arita A, Costa M, Carcinogenic metals and the epigenome: understanding the effect of nickel, arsenic, and chromiumMetallomics 2012; 4: 619-27.

8. Gentry PR, Clewell HJ, 3rdGreene TB, Franzen AC, Yager JW, The impact of recent advances in research on arsenic cancer risk assessmentRegul Toxicol Pharmacol 2014; 69: 91-104.

9. Pimparkar BD, Bhave A, Arsenicosis: review of recent advancesJ Assoc Physicians India 2010; 58: 617-24.629

10. Hall AH, Chronic arsenic poisoningToxicol Lett 2002; 128: 69-72.

11. Chen CJ, Hsu LI, Wang CH, Shih WL, Hsu YH, Tseng MP, Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in TaiwanToxicol Appl Pharmacol 2005; 206: 198-206.

12. Wong SS, Tan KC, Goh CL, Cutaneous manifestations of chronic arsenicism: review of seventeen casesJ Am Acad Dermatol 1998; 38: 179-85.

13. Yu HS, Liao WT, Chai CY, Arsenic carcinogenesis in the skinJ Biomed Sci 2006; 13: 657-66.

14. Muenyi CS, Ljungman M, States JC, Arsenic disruption of DNA damage responses-potential role in carcinogenesis and chemotherapyBiomolecules 2015; 5: 2184-93.

15. Cheng AL, Hsu CH, Lin JK, Hsu MM, Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesionsAnticancer Res 2001; 21: 2895-900.

16. Singh M, Suman S, Shukla Y, New enlightenment of skin cancer chemoprevention through phytochemicals: In vitro and in vivo studies and the underlying mechanismsBiomed Res Int 2014; 2014: 243452.

17. Argos M, Rahman M, Parvez F, Dignam J, Islam T, Quasem I, Baseline comorbidities in a skin cancer prevention trial in BangladeshEur J Clin Invest 2013; 43: 579-88.

18. Peck GL, Long-term retinoid therapy is needed for maintenance of cancer chemopreventive effectDermatologica 1987; 175: Suppl 1138-44.

19. Bettoli V, Zauli S, Virgili A, Retinoids in the chemoprevention of non-melanoma skin cancers: why, when and howJ Dermatolog Treat 2013; 24: 235-7.

20. Yahya H, Mohammed A, Bowen’s disease: report of a case in a Nigerian manWest Afr J Med 2005; 24: 350-1.

21. Lee L, Bebb G, A case of Bowen’s disease and small-cell lung carcinoma: long-term consequences of chronic arsenic exposure in Chinese traditional medicineEnviron Health Perspect 2005; 113: 207-10.

22. Koc E, Arca E, Dincer D, Acikcoz G, Turan Y, Demiriz M, A case of scrotal superficial basal cell carcinoma caused by chronic arsenic exposureG Ital Dermatol Venereol 2014; 149: 157-9.

23. Elmariah SB, Anolik R, Walters RF, Rosenman K, Pomeranz MK, Sanchez MR, Invasive squamous-cell carcinoma and arsenical keratosesDermatol Online J 2008; 14: 24.

24. Mitropoulos P, Norman R, Occupational nonsolar risk factors of squamous cell carcinoma of the skin: a population-based case-controlled studyDermatol Online J 2005; 11: 5.


Source of Support: Nil,

Conflict of Interest: None declared.

Comments are closed.