Case reports: multiple nonmelanoma skin cancers n a patient with epidermolytic hyperkeratosis on long-standing retinoid therapy

Journal of Drugs in Dermatology, May, 2008 by Deborah S. Samoff, Ritu Saint

Abstract

Epidermolytic hyperkeratosis is a rare genetic disorder of kcratinization. In childhood, patients are erythrodermic and have a compromised stratum corneum, replaced with generalized hyperkeratosis as the patients age. Treatment consists of topical emollients as well as, topical and oral retinoids. Ultraviolet (UV) light, often in combination with psoralen ultraviolet A (PUVA) is widely used as a therapeutic modality for a multitude of hyperproliferative disorders. Although not strictly indicated for epidermolytic hyperkeratosis, it has been utilized as experimental treatment, particularly in the days prior to retinoids. Psoralen ultraviolet A has also been implicated in the development of nonmelanoma skin cancers, especially, squamous cell carcinoma (SCC). Retinoids are well-known to protect against nonmelanoma skin. A patient with epidermolytic hyperkeratosis with multiple nonmelanoma skin cancers, previously treated with PUVA and long-standing oral retinoids is reported.

Introduction

Nonmelanoma skin cancers are the most common forms of human malignancy, with an estimated yearly incidence of 1 000 000 in the [US.sup.1] Ninety-five percent of these cancers are comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The etiology most frequently reported is DNA damage from ultraviolet (UV) light [exposure.sup.2-4] Interestingly, UV light is also in the dermatologist's therapeutic armamentarium. It is useful in treating a variety of dermatologic diseases especially those characterized by kcratinocyte hyperproliferation such as psoriasis in the form of ultraviolet B (UVB) light therapy, narrowband UV light therapy, and ultraviolet light A (UVA) therapy along with psoralen ultraviolet A (PUVA).' Psoralen ultraviolet A has a known association with the development of nonmelanoma skin cancer, particularly squamous cell carcinoma.(6)

Epidermolytic hyperkeratosis (EHK) is a genodermatosis that falls into the category of a proliferative disorder and is generally treated by emollients and systemic retinoids, the latter of which have been shown to prevent the development of skin [cancers.sup.7-9] Prior to the advent of systemic retinoids for this disorder, experimental therapies such as PUVA were often employed. Herein, a case of multiple nonmelanoma skin cancers in a patient with epidermolytic hyperkeratosis previously treated with PUVA and long-standing retinoids is reported.

Case

A 55-year-old Caucasian woman presented with a nonhealing, nonpruritic, crusted pink lesion on her right upper cheek for several weeks. Her past medical history was significant for epidermolytic hyperkeratosis, diagnosed at hirth when she was born with collodian skin. The condition was well-managed with topical emollients during her childhood. The hyperkeratosis worsened while in college, necessitating experimental therapy with full-body PUVA treatments twice weekly, intermittently for 4 years. Shortly thereafter, the patient was started on topical and then oral retinoids (etretinate followed by acitretin), in lieu of PUVA. In addition to various topical emollients, the patient has since been maintained on acitretin 25 mg daily for nearly 20 years and concurrently takes antihypertriglyceridemic medication with good results.

In addition, the patient had a malignant melanoma on the right thigh 22 years ago and has had upwards of 1 5 non-melanoma (BCC and SCC) skin cancers over the past 10 years, with a predominance of BCCs. While the patient has had a SCC or her left leg and a BCC on her right hand, the vast majority of her tumors have arisen on her face. Over the 3 months prior to this presentation, the patient had been treated for BCCs on her left upper cheek, chin, right lateral canthus, and mid forehead. The patient had been started on diclofenac gel on one half of the face and topical fluorouracil cream to the other half to determine which was better tolerated, just 4 weeks earlier. Aside from a sunburn that she suffered during a tropical vacation, the patient denied excessive sun exposure as a child due to the fragility of her skin. Her family history is significant for a brother who developed a malignant melanoma 2 years ago.

On physical examination, the patient has Fitzpatriek type 2 skin with brown hair and hazel eyes and generalized exfoliation with mild erythema (Figure 1). The patient has a distinct pungent body odor. There were no blisters or denuded areas. The palms and soles of the patient were hyperkeratotic and she had areas of patchy alopecia with clear evidence of broken hairs on her scalp. The patient has multiple subtle atrophic scars on her forehead, cheeks, nose, and helices of her ears. On her right cheek was a crusted, pink, indurated papule at the edge of an atrophic plaque (Figure 2). A biopsy was performed which was consistent with BCC demonstrating broad shaped buds of tumor extending from the basal layer of the epidermis in the papillary dermis along with coarse keratohyalin granules and a prominent granular layer demonstrative of epidermolytic hyperkeratosis (Figure 3). The patient underwent Mohs micrographic surgery to 2 stages (Figure 4) with subsequent repair of the defect.