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 Table of Contents  
Year : 2017  |  Volume : 50  |  Issue : 3  |  Page : 110-113

Multiple Bowen's disease and epithelioid malignant peripheral nerve sheath tumor in a patient who experienced chronic arsenic poisoning

1 Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
2 Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Date of Submission13-Jun-2016
Date of Decision22-Sep-2016
Date of Acceptance28-Oct-2016
Date of Web Publication29-May-2017

Correspondence Address:
Hsu Ma
Department of Surgery, Division of Plastic and Reconstructive Surgery, Taipei Veterans General Hospital, Taipei
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/fjs.fjs_37_17

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The Southwest coastal plain of Taiwan is an endemic area of arsenic contamination. Residents who lived there before the 1970s and who used raw groundwater for drinking have a higher risk of arsenic poisoning. In 1968, Tseng et al. described Blackfoot disease as a peripheral vascular disease caused by chronic exposure to arsenic, thereby introducing the concept of arsenic-induced systemic illness in Taiwan. Multiple Bowen's disease (BD) is one of the characteristic consequences of chronic arsenic poisoning and it usually presents as cutaneous carcinoma in situ. Multiple BD can also be associated with squamous cell carcinoma and basal cell carcinoma of the skin, as well as lung, liver, gastrointestinal, and bladder cancers. We encountered a 79-year-old male from Yun-Lin, a county in Southwest Taiwan, who presented with a progressing tumor in his right anterior chest wall. In addition, numerous keratoses and scaly skin lesions were noted on his trunk and extremities, some of which were combined with erosions. The patient was diagnosed with chronic arsenic poisoning with multiple BD and the huge tumor was confirmed as an epithelioid malignant peripheral nerve sheath tumor.

Keywords: Arsenic, Bowen's disease, epithelioid malignant peripheral nerve tumor, soft-tissue sarcoma

How to cite this article:
Chen CE, Wang YC, Ma H. Multiple Bowen's disease and epithelioid malignant peripheral nerve sheath tumor in a patient who experienced chronic arsenic poisoning. Formos J Surg 2017;50:110-3

How to cite this URL:
Chen CE, Wang YC, Ma H. Multiple Bowen's disease and epithelioid malignant peripheral nerve sheath tumor in a patient who experienced chronic arsenic poisoning. Formos J Surg [serial online] 2017 [cited 2021 Jul 24];50:110-3. Available from: https://www.e-fjs.org/text.asp?2017/50/3/110/207183

  Introduction Top

Contamination with inorganic arsenic compounds has been observed along the Southwest coast of Taiwan, not only in potable groundwater but also in crops.[1] Chronic arsenic poisoning is well known to be associated with Blackfoot disease, which was first described in 1968 by Tseng et al. as distal gangrene of the lower extremities caused by peripheral vascular disease.[1] In addition, several visceral cancers, including those of the respiratory system, gastrointestinal tract, and genitourinary tract, have also been described in relation to chronic arsenic poisoning. Since John T. Bowen described the first two cases of chronic atypical epithelial proliferation in 1912,[2] Bowen's disease (BD) has been recognized as carcinoma in situ instead of precancerous dermatosis. Multiple BD is often found in patients exposed to arsenic-contaminated water. Epithelioid malignant peripheral nerve sheath tumor (EMPNST) is one of the subtypes of malignant peripheral nerve sheath tumor (MPNST), which accounts for only 3%–10% of soft-tissue sarcomas that originate from peripheral nerve cells.[3] As we found no previous reports describing an association between chronic arsenic poisoning and EMPNST, this case of arsenic intoxication accompanied by progressing EMPNST of the right anterior chest wall was very interesting.

  Case Report Top

A 79-year-old male from Yun-Lin County presented at our outpatient department with a mass in his right anterior chest wall that had grown over the previous 6 months. The patient was a retired soldier and worked as a farmer after retirement. In his personal history, he did not report any systemic disease or use of herbal remedies, but stated that one of his cousins who lived near him had died of Blackfoot disease more than 20 years ago. Tumor excision surgery of the previous right chest wall was performed twice in a local hospital in 2013 and 2014, respectively, but the patient did not pay much attention on the histopathology report and lost to follow-up. He was otherwise fit and did not undergo any chemotherapy or radiotherapy after the excision. However, recurrent tumor was noted 6 months later and progressed more rapidly compared to before.

Physical examination at our department in 2015 showed a huge, solid, rubbery, fixed tumor was observed in the right chest wall. It measured about 13 cm in diameter, had abrasions, and bled upon being touched [Figure 1]. Furthermore, numerous erythematous scaly skin plaques were found on the patient's anterior chest wall, back, right hip, both forearms, and both legs [Figure 2]. All the results on hemogram and blood biochemistry tests were within the normal ranges. Computed tomography (CT) of the chest revealed a soft-tissue mass in the right anterior chest wall, sized 45 mm × 133 mm × 83 mm, with invasion of the pectoralis major muscle and skin; accordingly, breast cancer or soft-tissue sarcoma was suspected [Figure 3]. Subsequently, the patient underwent wide excision of the main tumor and the skin lesion located superiorly to it. During surgery, we observed that the base of this huge tumor was fixed to the fascia above the pectoralis major muscle. To ensure adequate excision of the tumor, the pectoralis major muscle was partially removed. Histopathological analysis of the huge tumor revealed the presence of round to spindle-shaped cells with pleomorphic and hyperchromatic nuclei, and abundant, faintly eosinophilic cytoplasm. Some of the cells had wavy nuclei. Rapid mitosis was observed in high-power fields. The tumor cells tested positive for S100 protein and Sox10, but not for CD34 [Figure 4]. All these findings prompted a diagnosis of an EMPNST. Moreover, the skin lesion was confirmed to be BD [Figure 5]. According to environmental studies, arsenic contamination of well water and rice is characteristic of the Southwest coast (Yun-Lin, Cha-Yi, and Tainan) of Taiwan. Raw groundwater is used as drinking water and for cultivated field irrigation.[4] As multiple BD has been strongly related to arsenic poisoning, we analyzed the patient's urine and serum arsenic levels and found that both were within normal limits. We also analyzed his hair for the presence of arsenic (total hair weight: 0.214 g), and the result was 0.355 ppm (normal range: <0.2 ppm). Finally, as the excision margin was disease free, a split-thickness skin graft was harvested from the patient's scalp to reconstruct the large soft tissue and skin defects. At the 6-month outpatient follow-up, one verrucous nodule was noted to the right of the graft site. Because the patient was reluctant to undergo surgical intervention, he chose to receive conservative treatment and attend regular follow-ups at the outpatient department. At the 10-month follow-up, the size of this lesion had reduced and there was no malignant tumor recurrence or erythematous skin lesion over the graft area.
Figure 1: A huge chest wall tumor: An old scar at the medial side of the tumor (black arrow), compatible with previous history of tumor excision. The skin lesion superior to the huge tumor (yellow arrow) is one of the multiple scaly erythematous plaques

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Figure 2: Numerous hyperkeratosis skin lesions on the right hip (left) and back (right). Bowen's disease with possible malignant changes was suspected

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Figure 3: Post-IV contrast computerized tomography scan revealed a soft-tissue mass in the right anterior chest wall, sized 45 mm × 133 mm × 83 mm, with invasion into the pectoris major muscle and skin. The mass had an irregular surface and heterogeneous attenuation

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Figure 4: Malignant peripheral nerve sheath tumor composed of round to spindle-shaped cells with pleomorphic and hyperchromatic nuclei and abundant, faintly eosinophilic cytoplasm, ×100 (a); S-100 positive, ×100 (b); necrotic malignant peripheral nerve sheath tumor, ×100 (c); spindle pattern of malignant peripheral nerve sheath tumor, ×100 (d); mitotic malignant peripheral nerve sheath tumor, ×400 (e), epithelioid pattern of malignant peripheral nerve sheath tumor, ×400 (f)

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Figure 5: Bowen's disease was confirmed in the lesion superior to the epithelioid malignant peripheral nerve sheath tumor

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This study was performed according to the Code of Ethics of the World Medical Association (Declaration of Helsinki). Oral informed consent was obtained from the patient.

  Discussion Top

Arsenic-contaminated areas are found across most of Southeast Asia, including Japan, India, Malaysia, Thailand, and Taiwan.[4] In the 1970s, approximately 100,000 people residing on the Southwest coast of Taiwan developed Blackfoot disease, and the disease was more predominant in men (male:female ratio - 2.9:1).[1] Before the 1970s, people in this region drank groundwater daily and used it for crop irrigation. The arsenic level of well water in this area was approximately 0.4–0.6 ppm, while the normal upper limit was 0.10 ppm. In humans, the normal average level is 0.05 mg of arsenic per 100 mg of hair, with an acceptable range of 0.025–0.088 mg. Pubic hair is more useful for estimation of chronic arsenic intoxication because of its slower growth and lower contamination. When the concentration of arsenic in hair is higher than 0.1 mg/100 mg of hair, chronic arsenic poisoning is strongly suspected.[2]

Chronic arsenic poisoning has varying patient presentation. The latent period after environmental exposure may be as long as 25–60 years.[5] Microvascular circulation and peripheral nerve conduction are highly influenced by chronic arsenic exposure, causing Blackfoot disease, hyperpigmentation and keratosis of the skin, cardiovascular diseases, bone marrow suppression, delirium, encephalopathy, and peripheral neuropathy. Avoiding drinking groundwater is the first and most effective method of disease prevention. Unfortunately, most chelating agents used for arsenic poisoning have proven ineffective in the treatment and prevention of peripheral neuropathy. Only dimercaptosuccinic acid showed temporary positive results for the treatment of chronic arsenic exposure-induced peripheral neuropathy.[6]

Chronic arsenic intoxication causes not only skin cancers such as BD, squamous cell carcinoma (SCC), and basal cell carcinoma,[2],[7],[8] but is also associated with porocarcinoma and Merkel cell carcinoma.[9],[10] A report on 17 Chinese patients with chronic arsenic poisoning and cutaneous manifestations of BD showed that 70% of them had 2–10 lesions, and 41% of these patients had SCCs.[7] Cancers of visceral organs, including the lungs, liver, stomach, kidneys, and bladder, have also been associated with long-term arsenic intoxication, regardless of the manner of exposure (ingestion or direct contact with colemanite). The mechanism of arsenic-induced malignancy is still controversial, but chromosomal abnormality caused by inorganic arsenic and its metabolites is one possibility.[11] Moreover, Hsu et al. performed an analysis of 23 patients with BD in the Blackfoot disease-endemic area of Taiwan and found that the P53 gene (accession number U94788) was mutated in 39% of cases.[8]

The most common localization of MPNST is the trunk, followed by the extremities and head and neck. More than half of MPNST cases result from malignant changes' characteristic of neurofibromatosis type 1 (NF1), and 8%–13% of patients with NF1 develop MPNST during their lifetime. However, although CT may show no contrast enhancement in central areas of large MPNST due to necrosis, hemorrhage, or cystic degeneration, it is still difficult to accurately distinguish benign peripheral nerve sheath tumor from MPNST due to several similarities, such as irregular borders and bone erosion.[12] The most effective treatment for MPNST is extensive surgical resection of the surrounding nerves, but the optimal safe margin is still disputed. The benefits of chemotherapy and radiotherapy are limited.[3] Patients with NF1-related MPNST, larger tumors, and central localizations have higher recurrence and distal metastases rates and lower survival rates. On the other hand, early diagnosis, smaller tumor size (<5 cm), complete tumor resection with negative S-100 staining, and a lower mitotic grade are associated with a better prognosis.[3],[12]

EMPNST is a variant subtype and constitutes approximately 5%–17% of all MPNST cases.[13] It was first described by McCormack in 1954,[14] and is characterized by diffuse S-100 protein immunostaining (100%), which occurs in 50%–90% of MPNST cases. Furthermore, it is infrequently associated with NF1 (1.5%). In comparison with conventional MPNST, EMPNST mostly develops on the lower extremities and trunk.[14] Most EMPNST cases are superficial, including dermal and subcutaneous types, and have a better prognosis compared to internal EMPNST (subfascial type).[14] In a case report from Kusumoto et al., a patient with a huge EMPNST in the left axilla showed losses and gains of DNA copies on chromosomes, suggesting chromosomal instability with impairments in gene expression.[3] This finding was similar to the chromosomal abnormality and mutations noted by Evans [11] and Hsu et al.[8]

The patient described in this study was finally diagnosed with chronic arsenic poisoning with multiple BD. Moreover, he presented with a rare case of EMPNST with classical characteristics observed using CT, classic clinical symptoms, strong and diffuse S-100 staining, characteristic histopathological features, as well as no association with NF1.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Tseng WP, Chu HM, How SW, Fong JM, Lin CS, Yeh S. Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Natl Cancer Inst 1968;40:453-63.  Back to cited text no. 1
Cöl M, Cöl C, Soran A, Sayli BS, Oztürk S. Arsenic-related Bowen's disease, palmar keratosis, and skin cancer. Environ Health Perspect 1999;107:687-9.  Back to cited text no. 2
Kusumoto E, Yamaguchi S, Sugiyama M, Ota M, Tsutsumi N, Kimura Y, et al. Huge epithelioid malignant peripheral nerve sheath tumor in the left axilla: A case report. Surg Case Rep 2015;1:64.  Back to cited text no. 3
Chen CJ. Health hazards and mitigation of chronic poisoning from arsenic in drinking water: Taiwan experiences. Rev Environ Health 2014;29:13-9.  Back to cited text no. 4
Ghosh SK, Bandyopadhyay D, Bandyopadhyay SK, Debbarma K. Cutaneous malignant and premalignant conditions caused by chronic arsenicosis from contaminated ground water consumption: A profile of patients from eastern India. Skinmed 2013;11:211-6.  Back to cited text no. 5
Wax PM, Thornton CA. Recovery from severe arsenic-induced peripheral neuropathy with 2,3-dimercapto-1-propanesulphonic acid. Clin Toxicol 2000;38:777-80.  Back to cited text no. 6
Wong SS, Tan KC, Goh CL. Cutaneous manifestations of chronic arsenicism: Review of seventeen cases. J Am Acad Dermatol 1998;38(2 Pt 1):179-85.  Back to cited text no. 7
Hsu CH, Yang SA, Wang JY, Yu HS, Lin SR. Mutational spectrum of p53 gene in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan. Br J Cancer 1999;80:1080-6.  Back to cited text no. 8
Chen IS, Kuo HW, Eng HL. Porocarcinoma in a patient with chronic arsenism and multiple Bowen's disease: Case report. Dermatol Surg 2005;31(9 Pt 1):1149-51.  Back to cited text no. 9
Ohnishi Y, Murakami S, Ohtsuka H, Miyauchi S, Shinmori H, Hashimoto K. Merkel cell carcinoma and multiple Bowen's disease: Incidental association or possible relationship to inorganic arsenic exposure? J Dermatol 1997;24:310-6.  Back to cited text no. 10
Evans S. Arsenic and cancer. Br J Dermatol 1977;7 Suppl 15:13-4.  Back to cited text no. 11
Kragha KO. Malignant peripheral nerve sheath tumor: MRI and CT findings. Case Rep Radiol 2015;2015:241259.  Back to cited text no. 12
Tsuchiya D, Takamura H, Saito K, Kashiwa H, Maeda K, Yamashita H. Immunohistochemical diagnosis of a rare case of epithelioid malignant peripheral nerve sheath tumor with multiple metastases. Jpn J Ophthalmol 2004;48:565-9.  Back to cited text no. 13
McCormack LJ, Hazard JB, Dickson JA. Malignant epithelioid neurilemoma (schwannoma). Cancer 1954;7:725-8.  Back to cited text no. 14


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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