Ellen Flosadóttir1,4 and Bolli Bjarnason2–4

Departments of 1Odontology and 2Dermatology, University of Iceland, Vatnsmýrarvegur 16, 101 Reykjavík, Iceland, 3Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden and 4Utlitslaekning ehf, Kópavogur, Iceland. E-mail: ellenflosa@hotmail.com

Accepted August 27, 2007.

Sir,

We describe here the case of a man aged 65-years at our first examination with non-epidermolytic epidermal naevus of a soft, papillomatous type covering large areas of the left side of his body and scalp. He reported bilateral hearing loss and earlier frequent mastoiditis. He was of short stature and had had dyspnoea since childhood affecting his sporting activities, reduced touch sensation on the soles of his feet and reduced vibration sensitivity of his toes. His upper teeth were extracted at a young age. He had had amblyopia of the left eye since childhood and an attack of paralysis of that eye. At the age of 22 years, an asymptomatic gross haematuria was discovered caused by a large bladder papilloma at the opening of the left ureter. Lost to follow-up, he presented 2 years later with intermittent gross haematuria and a cancer at the same site. The cancer was confirmed by our review of the pathological report to be of a transitional cell type. The patient had no familial history of epidermal naevi.

The term “epidermal naevus syndrome” has, in the past, been used to refer to the association between epidermal naevi and abnormalities in other organ systems (1). Several distinct birth defects have been lumped together under this designation (2). All epidermal naevus syndromes are mosaic phenotypes (2). Because of the understanding of the concepts of genetic mosaicism, that there are potentially many different epidermal naevus syndromes, or syndromes of which an epidermal naevus is a cutaneous feature, it has been argued that the term “epidermal naevus syndrome” to describe a disease entity should be abandoned (3, 4). Thus far, at least 7 different epidermal naevus syndromes have been identified; viz., naevus sebaceous syndrome, Proteus syndrome, CHILD syndrome, naevus comedonicus syndrome, Becker naevus syndrome, phakomatosis pigmentokeratotica (5, 6); and the last one was first described by Schauder et al. (7) and later termed “angora hair naevus syndrome” (1).

All these patients warrant detailed physical examination at the time of development of the naevus and close follow-up thereafter (8). Surprisingly many have shown systemic malignancies of various origins at a young age (9). We present all reported cases of epidermal naevi we could find with non-cutaneous malignancies by searching Medline (Table I). It is interesting that cancers in the genitourinary tract comprise approximately one-third of all cases reported.

Fibroblast growth factors (FGFs) play a vital role in embryonic development, and mutations of FGFs have been associated with developmental defects in various organ systems (6). It has been suggested that a large proportion of epidermal naevi are caused by a mosaicism of activating FGF receptor 3 (FGFR3) mutations in the human epidermis secondary to a post-zygotic mutation in early embryonic development (10). Interestingly, FGFR3 mutations are also frequent events in papillary urothelial carcinoma (11, 12). The correlation of epidermal neavus and urothelial carcinoma is thought to be non-stochastic and it has been suggested that patients with epidermal naevi and bladder cancer feature a mosaicism of activating FGFR3 mutations (10).

There are many abnormalities of the genitourinary tract that may be associated with the epidermal naevus syndromes, including horseshoe kidney, cystic kidneys, double collecting system, nephroblastomatosis, uretero-pelvic junction obstruction, vitamin D resistant rickets, hypospadias, testicular and paratesticular tumours, and cryptorchidism (13). Transitional cell cancer of the bladder is very rare in young people (14, 15). As 3 cases (16–18) of that cancer and epidermal naevi have already been reported, this fourth case makes coincidental association unlikely. The cancer in our case was removed in 1955, but the association between the cancer and the naevus was not noted until many decades later. As this type of cancer appears to be uniformly of a low grade and non-invasive (19) it is possible that some cases have not been reported in the literature.

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