Arsenical Keratosis with Unusual Lung Involvement

Dear Editor,

Arsenic keratosis is characterized by guttate skin hyperpigmentation and hypopigmentation, and multiple punctate corn-like yellowish hyperkeratotic papules and plaques predominantly involving the palms and soles resulting from ingestion of arsenic above the safe limit (50 μg/L) for a period of minimum 6 months and lesions may progress to Squamous cell carcinoma and Basal cell carcinoma and other internal organ malignancies like lung, bladder, kidney, and GIT.[1,2] Inorganic arsenic has been classified as a class 1 human carcinogen with contaminated groundwater, medications, occupation, and tobacco consumption to be the sources of exposure.[3] Diagnosis is through clinical examination, estimation of blood, urine, hair and nail arsenic levels, and histopathology.

A 65-year-old male shopkeeper from West Bengal presented with multiple yellowish hyperkeratotic lesions over both palms and trunk and multiple hyperpigmented and hypopigmented lesions over the trunk of 3 months duration. There was no history of similar lesions in the family or immediate neighborhood, relevant drug intake, or substance abuse. On direct questioning, the source of drinking water was from bore well. There was associated significant weight loss (>10% in the past 6 months) in the absence of any other known cause.

On examination, there was the presence of multiple well-defined non-tender, thick hyperkeratotic yellow to brown plaques with circumferential hyperpigmentation and conical projections arising over the indurated base, of size ranging from 0.5 × 0.5 cm to 2 × 2 cm present over bilateral palms, right supraclavicular area (2 × 2 cm), and suprasternal area [Figure 1a and 1b and 2a]. Well-circumscribed hypopigmented macules and hyperpigmented plaques of variable sizes, with smooth surface, were scattered over the torso [Figure 2a]. Systemic evaluation of the respiratory system revealed decreased air entry over the right side of lung. All other examination were within normal limits.

Figure 1.

(a and b) Thick hyperkeratotic yellow to brown plaques with hard conical projections arising from indurated base with a circumferential rim of hyperpigmentation, ranging from 0.5 × 0.5 cm to 2 × 2 cm. (c) Multiple close-set yellow-white hard projections arising over the crateriform base. The height of conical projection is less than the base

Figure 2.

(a) Multiple, whitish, hard conical projections overlying erythematous indurated tender base of size around 4 × 3 cm. Another lesion present over the suprasternal area. (blue arrow and red circle, respectively. Well-circumscribed hypopigmented macules (black arrow) and hyperpigmented plaques (orange circle) of variable sizes with smooth surface scattered over the torso. (b) Arborizing vessels over the periphery of the lesion, blue-grey ovoid nests, globules, bluish veil, features s/o BCC. (c) Basaloid cells in nest with peripheral palisading and retraction clefting with areas of pigmentation (arsenic-induced) (H & E, 40x)

Dermoscopic findings of hyperkeratotic plaques showed multiple closely set yellow-white hard projections arising over the crateriform base with circumferential erythema and few areas of hemorrhage. There were visible adherent whitish scales and hyperpigmentation at the periphery reflecting a collarette, as well as on the surface of lesions [Figure 1c]. Histopathological examination of the same revealed thick alternate hyperkeratosis and parakeratosis with dysplastic lower epidermis. Hyperchromatic dysplastic cells were haphazardly arranged, with loss of polarity, few necrotic keratinocytes and intact basement membrane [Figure 3a and b]. Dermoscopy of the trunk lesion showed arborizing vessels over the periphery of the lesion, blue grey ovoid nests, globules, bluish veil, and erosions, which were features suggestive of BCC. Histopathology of the lesion with similar morphology revealed basaloid cells in the nest with peripheral palisading and retraction clefting with areas of pigmentation (arsenical induced) [Figure 2b and 2c, respectively].

Figure 3.

(a and b) Thick alternate hyperkeratosis and parakeratosis with dysplastic lower epidermis. Hyperchromatic dysplastic cells haphazardly arranged with loss of polarity, few necrotic keratinocytes with intact basement membrane. (white arrow and circle)

Routine blood investigations were within normal limits, with increased urinary arsenic levels (64.90 μg/L (n < 35)).

Chest X-ray (PA view) showed well-defined oval radio opacity in the right middle zone overlying the hilar region forming an acute angle over the right lung field. On further evaluation, Contrast-Enhanced Computed Tomography (CECT) scan of the chest revealed a large well-defined thick-walled heterogeneously enhancing hypodense lesion with spiculated margins representing right upper and middle lobe anterior segment lung malignancy with lymphangitic spread, with encasement of a superior branch of the right pulmonary artery (Stage: T4N0Mx) [Figure 4a-c].

Figure 4.

(a) Chest X-ray PA view showing well-defined oval radio opacity in right middle zone overlying the hilar region forming an acute angle over right lung field. (4b and 4c) CECT chest showing a large well-defined thick-walled heterogeneously enhancing hypodense lesion with spiculated margins. Right upper and middle lobe anterior segment lung malignancy with lymphangitic spread, encasement of superior branch of right pulmonary artery

On the basis of typical clinical features, and histological and radiological correlation, the diagnosis was made of arsenical keratosis with Basal cell carcinoma with mass lesion in the right upper and middle lobe, probably mesothelioma.

The patient was initiated on cap acitretin 25 mg once daily, broad-spectrum sunscreen SPF 50, and topical application of imiquimod 5% on alternate days over the basal cell carcinoma lesion. The patient was referred to a cancer institute for further workup and management of lung malignancy. Arsenicosis as defined by WHO is a chronic health condition resulting from the ingestion of arsenic above the safe limit (50 μg/L) for a minimum duration of 6 months. Arsenic occurs in two oxidative states: trivalent arsenite (more toxic form) and pentavalent arsenate. The sources of arsenic exposure are contaminated groundwater (most common as seen in our patient), occupation, medications, fowlers solution, tobacco, and food products. Arsenic tends to concentrate in the ectodermal tissue including skin, hair and nail, leading to cutaneous lesions presenting as one of the most common adverse effects of chronic arsenic exposure in a dose-dependent manner. Arsenic keratosis presents as raindrop hypopigmentation over diffuse hyperpigmentation with multiple hyperkeratotic punctate and solitary lesions, mucosal pigmentation, and Mees lines over nails. The most common arsenic-induced skin cancers are Bowen’s disease (carcinoma in situ), basal cell carcinoma, and squamous cell carcinoma, usually occurring over sun protected areas. Apart from skin, other sites related to arsenic-induced malignancy are lung (mesothelioma (as seen in our case) and small cell carcinoma), liver, kidney, GIT, and peritoneal involvement.[3,4] Possible modes of action in arsenic-induced carcinogenesis are chromosomal abnormality, oxidative stress, and biotransformation process via genetic and epigenetic effects.[5] Diagnosis is usually made clinically with estimation of serum, urine (recent exposure), and hair (chronic exposure) arsenic levels and histopathological examination to look for malignant transformation. In our case, the level of urinary arsenic levels was well above the normal levels. We were unable to do the hair and nail arsenic level estimation due to COVID circumstances as it was difficult for the patient to follow-up and get it done. The treatment of arsenic keratosis should be tailored to the patient’s need, severity of disease, and comorbidities. Various treatment options are available, including oral retinoids, topical keratolytic agents, curettage, cryotherapy, atopical 5-FU and imiquimod, and surgical excision.[6] Our patient had classical clinical features of arsenical keratosis of chronic arsenic exposure. The concentration of arsenic was well above the normal level in urine. The temporal relationship between the evolution of clinical lesions and respiratory involvement supports arsenicosis-induced lung malignancy. Therefore, extensive workup of patients with chronic arsenic exposure is of utmost importance to rule out visceral involvement in any form, and cutaneous lesions are a reflection of internal milieu. Our case highlights the typical environmental toxicity of arsenic leading to premalignant and malignant dermatosis.

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