Polydactylous subungual squamous cell carcinoma caused by chemical contact.

SUMMARY: Polydactylous squamous cell carcinoma (SCC) is rare and has been associated with human papillomavirus (HPV). Our recent case was HPV negative and provides greater evidence for chemical irritants being an alternative cause of subungual SCC. Our patient had spent a number of years with her hands in direct contact with undiluted cleaning chemicals including one containing ethanolamine. Ethanolamine has been shown to have carcinogen sensitizing role. Although HPV has a strong association with subungual SCCs, the accumulation and concentration of noxious substances around and under the nails must also be considered as a potential cause.

CASE REPORT

A 50-year-old, right-hand-dominant woman was referred to the plastic surgery department for a biopsy of a subungual lesion on her left little finger which had been present for 12 months. She had been unsuccessfully treated with topical antifungal ointment, and the lesion had increased in size and become more painful. Examination revealed a hyperkeratotic nail bed lesion under the distorted nail plate, a swollen tender finger, and dorsal scalloping of the distal phalanx on x-ray. Histology diagnosed well-differentiated squamous cell carcinoma (SCC). The patient underwent amputation at the distal interphalangeal joint with complete clearance of the tumor.

Over the following 24 months, the patient represented twice with lesions in the right ring and middle finger and the right thumb (Figs. 1 and 2). Each time initial biopsies showed only hyperkeratosis but following further growth each of these lesions was subsequently diagnosed as SCC. Human papillomavirus (HPV) testing on the specimens was negative. The lesions were all treated with amputation at the distal interphalangeal joint and the patient remains under close surveillance.

Fig. 1.

Persistent fleshy hyperkeratotic lesion of right thumb nail bed just before excision. Histology confirmed SCC.

Fig. 2.

Scalloping of distal phalanx of right thumb associated with overlying SCC.

The patient’s medical and occupational history was reviewed. Past medical history was insignificant, and a general examination showed no other skin lesions. She had had no discernible exposure to high levels of radiation, arsenic, or other compounds associated with the development of subungual SCC. She had never experienced cutaneous or genital warts and regular PAP smears had been normal.

During her working life, she had undertaken a series of cleaning jobs, but for the last 6 years she had been working as a service operator for a long-distance train company. Her duties predominantly involved intensive cleaning of the carriages, cabins, toilets, and kitchens. The cleaning chemicals were used in large amounts (4–5 L/d) and often undiluted (contrary to recommendations). Disposable gloves were worn; however, the fluids used would often run down inside her gloves and soak her hands. She described difficulty in ridding herself of the chemicals on the skin despite thorough hand washing at the end of the day. She regularly developed rashes and peeling skin on her forearms after direct skin contact with those chemicals.

The most commonly used cleaning agent contained the active ingredients limonene and ethanolamine at concentrations up to 10% wt/wt. Material hazard information was obtained for these chemicals; ethanolamine appeared the most likely to perform a carcinogen sensitizing role. It is documented to produce skin irritation, and its cutaneous safe exposure limit is usually restricted to 3 ppm in a normal working day.[1,2] Used undiluted, its concentration could be up to 100,000 ppm.

DISCUSSION

Subungual SCC is rare, with only about 150 cases reported in the literature. Multiple subungual SCCs in a single patient are even rarer, and less than 20 cases have previously been reported.[3-11] However, it is thought to be underrecognized, and is often diagnosed late, due to varied clinical features that mimic common conditions such as onychomycosis, paronychia, and verruca.[3,12-14] Previously little was known about its etiology, and only arsenic exposure and radiation exposure were reported.[15,16]

In recent years, attention has focused on the association between subungual SCC and HPV infection.[4,5,7,17-20] Several studies have shown evidence of HPV infection in 60–80% of patients with subungual SCC.[4,17,18] In the case reported here, HPV was not detected in any of the tumors tested. In fact, the histological appearance was morphologically quite different from a subungual SCC excised from a different patient who was HPV positive. This correlates with reports that HPV-associated subungual SCC does not show benign features before becoming malignant.[7]

A careful detailed history showed that her only likely causative agent in developing separate subungual SCCs in 4 digits was from occupational exposure to carcinogen. The patient’s hands had daily exposure to concentrated cleaning fluids in large amounts for 6 years, which would have accumulated on her skin and around and under her fingernails. Some of these chemicals are listed as skin irritants that may cause defatting, and at least one of the cleaning agents used most often was strongly alkaline, at pH 11 (Materials Safety Data Sheet).

The other occupational exposure that the patient had was to burnt residue from the galley kitchen ovens. The residue would form a suspension in the cleaning fluid, regularly running down her arms into the gloves and accumulating around her fingers. It is well recognized that chemicals and debris can accumulate and concentrate under the nail plate and in the paronychial folds.[21]

It was postulated that, in the absence of any of the known associated factors, this patient’s subungual SCCs may have arisen due to one or more occupational causes. The cleaning agents themselves may have had a direct carcinogenic effect, either alone or in combination, although none have a recognized carcinogenic role, if used as directed.[1,2] Ethanolamine is a known skin irritant and the patient had a history of unprotected, high concentration exposure to this chemical. Her paronychial dermatitis might have provided better access for carcinogenic effects of other chemicals. The chronic skin and subungual irritation would have lead to repeated tissue repair and regeneration cycles, a situation thought to predispose to reduced DNA repair and hence carcinomatous transformation.[7] Burnt residue collecting under the nails would have acted as a further irritant and may also have been directly carcinogenic.[7,22,23]

Interestingly, the first reported case of subungual SCC, in 1850, was of a lesion in a laundress who worked with her hands immersed in water and Prussian Blue—a commonly used whitening agent.[21] Another report describes polydactylous subungual SCC that developed in the hands of a wastewater worker.[10] He also worked with his hands immersed in water, potentially containing a combination of chemicals. The case of a lathe worker exposed to metalworking fluids again suggests occupational exposure as a potential etiology.[11] Unlike our case, none of these cases was documented HPV negative. Our case provides further evidence that chronic skin maceration in combination with irritants or carcinogens collecting and concentrating around the nail apparatus may be responsible for the development of some polydactylous subungual SCCs.

ACKNOWLEDGMENTS

The authors would like to thank Dr. Phillippa Van Essen for help with editing and manuscript preparation.

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