|Year : 2015 | Volume
| Issue : 3 | Page : 669
Multiple skin cancers in a single patient: Multiple pigmented Bowen's disease, giant basal cell carcinoma, squamous cell carcinoma
Ravi Saini, Nidhi Sharma, Kritika Pandey, K. J. P. S. Puri
Department of Skin and STD, Guru Nanak Dev Hospital, Amritsar, Punjab, India
|Date of Web Publication||9-Oct-2015|
7 Tara Enclave, Near Mental Hospital, Amritsar - 143 001, Punjab
Source of Support: None, Conflict of Interest: None
Basal cell carcinoma (BCC) and squamous cell carcinoma are the most common type of nonmelanoma skin cancers (NMSCs). Bowen's disease (BD), a premalignant condition, has a marginal potential (3-5%) to progress to invasive carcinoma. We report here a rarest of a rare case of multiple pigmented BD with overlying squamous cell cancer along with a giant neglected BCC on the scalp of a 76-year-old man. The occurrence of multiple BD and NMSC in a single patient compelled us to explore the following hypothesis: (1) The multiple precancerous and cancerous lesions can be due to common etiopathogenesis. Chronic ultraviolet exposure, immunosupresssion, human papillomavirus infection, dietary factors, and environmental factors including arsenic exposure were probed in to. (2) There is evolution of precancerous lesions into a different type of cancers in different time frame. (3) The new cancerous lesions are subsequent cancers that developed after neglected untreated primary cancer.
Keywords: Basal cell carcinoma, Bowen′s disease, carcinoma in situ, nonmelanoma skin cancer, squamous cell carcinoma
|How to cite this article:|
Saini R, Sharma N, Pandey K, Puri K. Multiple skin cancers in a single patient: Multiple pigmented Bowen's disease, giant basal cell carcinoma, squamous cell carcinoma. J Can Res Ther 2015;11:669
|How to cite this URL:|
Saini R, Sharma N, Pandey K, Puri K. Multiple skin cancers in a single patient: Multiple pigmented Bowen's disease, giant basal cell carcinoma, squamous cell carcinoma. J Can Res Ther [serial online] 2015 [cited 2019 Nov 12];11:669. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/669/140803
| > Introduction|| |
Bowen's disease (BD) commonly seen in Caucasians has a marginal potential (3-5%) to progress to invasive carcinoma. Sunlight and chronic arsenic (As) exposure are usually incriminated as causative factors of BD. It is usually nonpigmented, but pigmented variant of BD (pBD) has been reported.  Multiple BD is rare with incidence of 10-20% of all cases of BD.
Basal cell carcinoma (BCC) is the most common skin malignancy, but on the contrary giant BCC (GBCC) is a rare skin malignancy.
| > Case report|| |
A brown eyed 76-year-old man with skin type III and gray hair presented with a huge neglected ulcerated lesion over the scalp since 25 years. It was initially noted as an asymptomatic plaque, which gradually enlarged to present size, but patient never sought any medical advice for it. Another cauliflower like exuberant growth of 5 years duration was present on the chest. It was initially noted as asymptomatic hyperpigmented plaque, which gradually converted into a painful growth discharging pus. The patient being a farmer by occupation had a history of chronic sun exposure since adolescence. There was a significant weight loss in the past 3 years, but no history of cigarette smoking, radiotherapy or family history of any skin tumor. Systemic symptoms were unremarkable.
Cutaneous examination revealed multiple plaques on the back ranging in size from 0.5 cm × 1 cm to 2.5 cm × 3 cm, with irregular raised margins [Figure 1]. Few lesions had bluish speckled hyperpigmentation with satellite lesions. The lesion over the scalp involved frontotemporal area extending to forehead (8 cm × 15 cm). It was ulcerated in the center with floor covered with yellow, brown crusts at places and atrophy at other places. The margins were raised, well-defined and hyperpigmented with scattered papules, nodules and telangiectasias at the periphery. The cauliflower like growth (4.5 cm × 5 cm) present over chest just above the right nipple was covered with foul smelling, yellow crust [Figure 2]. On palpation, the mass was friable, tender, bled, and indurated but unattached to underlying structures. Just above this growth, a hyperpigmented plaque (2.5 cm × 3 cm) with irregular well-defined borders was present.
|Figure 2: Squamous cell carcinoma on the chest and H or E stained histopatholgical slide|
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Complete hemogram, liver function tests, renal function tests, X-ray skull, chest and spine, ultrasonography of the abdomen and computerized tomography scan of the chest and abdomen were unremarkable. Multiple skin biopsies done from the lesions on the scalp, chest, back, and the cauliflower growth were consistent with BCC [Figure 3], pBD, pBD, and squamous cell carcinoma (SCC), respectively without any evidence of human papillomavirus (HPV) DNA (by in situ hybridization method). The elemental estimation of As in drinking water, hair and fertilizer was found to be 6.3 μg.
|Figure 3: Basal cell cancer on the scalp and H or E stained histopatholgical slide|
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| > Discussion|| |
Bowen disease was first described by the American Dermatologist John T. Bowen in 1912. Exposure to ultraviolet (UV) radiation from the sun or photochemotherapy and radiotherapy is the dominant causative factor, but heavy metals (As), immunosuppression and HPV infection and pre-existing skin lesions like seborrheic keratosis have also been implicated [Table 1]. 
Bowen disease is most commonly reported in sun-exposed sites of whites and rarely occurs in patients with darker-pigmented skin; if it does, it usually affects nonsunexposed sites. 
Previous studies suggest that intermittent and childhood sunlight exposure may be important for the pathogenesis of BCC, whereas continuous lifelong sunlight exposure may be important for SCC.  On nonsun exposed areas, irradiation and HPV are the major causative factors. HPV infection into host chromosomes leads to down regulation of E6 and E7 proteins indirectly. This promotes malignant change and aids cellular transformation.  It is difficult to rule out HPV as the causative factor for BD as presence of HPV DNA is found in only 30-58% of extragenital BD lesions. 
There is an association between multiple BD and As exposure, often occurring after a time lag of 10 years. The main sources of As exposure include Fowler solution - formerly used to treat psoriasis; Gay solution - formerly used to treat asthma; homeopathic and ayurvedic medicines; contaminated well water; and certain pesticides.  Clinically, arsenical BD can be differentiated from nonarsenical BD by its multiple and recrudescent lesions, occurring mainly on sun-protected areas of skin. Our patient being farmer had exposure to various fertilizers, which may contain heavy metals like As. The elemental estimation of As in drinking water, hair and fertilizer was done, which was found to be <10 μg/L (WHO guideline value of As) and 50 μg/L (Indian standard of As). 
The pBD is rare (<2%). Traditionally, pBD has been described more frequently in dark skinned individuals with involvement of sun-protected areas, lower extremities. 
Histopathologically, pBD is characterized by increased melanin pigment in basal cells, melanocytes with hypertrophic dendritic processes and dermal melanophages. In pBD, the suggested mechanism of pigmentation is neoplastic cells may produce cytokines that induce proliferation of melanocytes and stimulate melanin synthesis. 
According to the American Joint Committee on Cancer, GBCC is defined as a tumor with a diameter larger than 5 cm.  Only 1% of all BCCs achieve this size.  By the tumor, node, metastasis classification, these tumors are characterized as T3.  In general, BCC grows at a rate of 1 mm in diameter on an average per year; when BCC exist for a long period of time, this tumor may grow to a large size and in an aggressive manner.
Neglect is regarded as the primary cause of GBCC resulting in continuous growth of the tumor over a period of 10-20 years.  It is usually reported among people with a poor socioeconomic status, physical or psychiatric disability, chronic alcoholism which impedes access to health care providers. In this case, long-standing tumors were the rule and neglect for a long time period was the main cause.
Bowen disease is a SCC in situ with potential for significant lateral spread. About 30-50% of subjects with BD may have previous or subsequent nonmelanoma skin cancers (NMSC).  Personal history of NMSC is known to be an additional risk in developing secondary primary cancer, probably for the common risk factor of UV.  Patients who are relatively young at their first BCC diagnosis, have a BCC lesion on their upper extremities and those having multiple NMSC have a higher risk of developing multiple lesions and require closer follow-up over time. 
The occurrence of multiple BD and NMSC in our patient compelled us to explore the possibilities about common etiopathogenesis in their development. After ruling out other possible causative factors, chronic sun exposure was the only possible common etiology in our case.
Other possibilities could be the evolution of precancerous lesions into a different type of cancers in different time frame, or the new cancerous lesions are subsequent cancers that developed after neglected untreated primary cancer.
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[Figure 1], [Figure 2], [Figure 3]