Porokeratosis and malignancy: Incidental or causal association?

Porokeratosis is a unique genodermatosis inherited by an autosomal dominant trait.[1] It is characterized by hyperkeratotic lesions with atrophic center and raised wall-like border, which histologically show the classical cornoid lamella. The five distinct clinical types of porokeratosis include the classical Mibelli, disseminated superficial actinic porokeratosis (DSAP), porokeratosis palmaris et plantaris disseminata (PPPD), linear, and punctate types. Rarely pruritic and ptychotropic variants have also been described.

A mutant clone of epidermal cells is thought to be the cause for cornoid lamella, predisposing affected patients to malignancy.[2] The exact risk of cutaneous malignancy developing in porokeratosis is unknown. Radiation therapy could be a precipitating factor for development of malignancy.[1] Other important trigger factors for the development of malignancy in porokeratosis include ultraviolet radiation, electron beam therapy, and immunosuppression associated with malignancies such as lymphoma, HIV infection, or due to immune-modulatory drugs used for autoimmune diseases or following organ transplantation.[3] Development of squamous or basal cell carcinomas has been reported in all forms of porokeratosis.[4] Chromosomal instability and reduced immune surveillance with overexpression of p53 are hypothesized to play a role in the development of cutaneous malignancies within porokeratosis[45] and throughout epidermis in Bowenoid lesions.[6] Gene expression profiles reveal an upregulation of mRNAs of hyperproliferative keratins, calcium-binding proteins, connexin 26 and 30 and involucrin in the cornoid lamellae, as in psoriasis.[7]

In a 30-year study by Sasson et al. to know the frequency of malignancy in porokeratosis, 7.5% (21/281 patients) developed malignancy. Increased risk of malignancy was observed in linear, large, and long-standing cases. Squamous cell carcinoma developing in linear and giant types of porokeratosis, has been reported.[78] Metastasis although rare, has occurred in a giant lesion along with hypercalcemia.[7]

There are reports of epithelioma[9] and basal cell carcinoma[10] arising from porokeratosis of Mibelli, DSAP, as well as in PPPD, and linear porokeratosis possibly from the mutant clone of cells. Chromosomal instability of cultured fibroblasts from patients with porokeratosis of Mibelli is thought to have a causal role for the associated malignancy.[11]

Premalignant lesions such as Bowen's disease,[12] cutaneous horns,[1314] and dysplasia at the base of cutaneous horn[1516] may arise from porokeratosis, which may progress to malignancy. Porokeratosis is now considered a premalignant condition, with certain groups of patients at greatest risk for malignant transformation.[3]

In view of the overexpression of p53 gene(whichhas a wide spectrum of mutations) in porokeratosis, it is possible that malignant transformation is likely in long-standing lesions with prolonged sun exposure irrespective of the type of porokeratosis. Hence a close follow up of lesions is mandatory. Although there is only one report of malignant melanoma arising from porokeratosis[17] so far, in view of the malignant potential of porokeratosis in general, the present report of malignant melanoma in DSAP could be more than an incidental association and hence may be significant.