Genital porokeratosis

ARTICLE

Auteur(s) : L. LAINO¹, S. PALA D. INNOCENZI¹, G. ACCAPPATICCIO¹, M.A.M. VAN STEENSEL²

¹ Department of Dermatology, University of Rome “La Sapienza”, Rome, Italy 
² Department of Dermatology, University Hospital Maastricht, the Netherlands

Article accepted on 19/1/2004

Porokeratosis of Mibelli (PM) is defined as a rare disorder of epidermal keratinisation characterized by centrifugally spreading patches surrounded by narrow horny ridges and with central atrophy. The lesions are craterlike. It has been suggested that the disease results from the expansion of an abnormal clonal population of keratinocytes [1-3]. Histological examination shows a highly characteristic abnormality: columns of parakeratotic cells extending through the entire thickness of the stratum corneum, or “cornoid lamella” [4]. The existence of other, clinically distinct, types of porokeratotis is commonly accepted. For PM, classically occurring in middle-aged males and on skin that is not exposed to sunlight, immunosuppression is a well-documented association. Occurrence in the genital area has been described on a number of occasions [5-12] and it is rarely observed in Negroid people. It seems to be more common in Italians [13]. 
Here we report on a negroid man with proven porokeratosis and immune abnormalities. The case shows that although porokeratosis is not per se indicative of immunosuppression, its presence may serve as a warning sign and should prompt immunological evaluation. A genital localization of suspect lesions in persons not belonging to one of the classical at-risk groups should prompt suspicion of the diagnosis.

Case report

A 36-year-old Negroid man, born in Italy from non-consanguineous parents, presented to our department with a 3-year-history of multiple, raised, annular and well defined skin lesions on the scrotum. These varied from 5 to 15 mm in diameter (Figs. 1a, b) and showed a raised hyperkeratotic border with a central depressed area lacking hair follicles. An incisional biopsy from the edge of one of the lesions showed hyperkeratotic and acanthotic epidermis. A column of parakeratotic cells surrounded by orthohyperkeratosis (Fig. 2) was visible in the centre of the lesion. This finding of a typical cornoid lamella confirmed the clinical suspicion of porokeratosis. Routine laboratory investigations showed a decreased number of T-helper lymphocytes in blood, and a decreased CD4+/CD8+ ratio (Table I). Further immunological evaluation failed to show other abnormalities. Screening for HIV-1 and HIV-2 (ELISA) infection was negative. The patient was in good health; in particular, there were no signs of infections associated with immunosuppression. There was no history of exposure to carcinogens in the workplace.

There was no family history of similar skin lesions and the patient did not use any type of systemic or topical medications. Based on the presence of cornoid lamellae in the biopsy specimen, immune disturbance and a negative family history, a diagnosis of genital porokeratosis was made.

Discussion

Porokeratosis is a rare disorder of epidermal keratinisation, clinically characterized by centrifugally enlarging hyperkeratotic plaques, associated with the histopathological hallmark of cornoid lamellae [13]. Several other types of porokeratosis that are thought to be clinically distinct have been described. Considering the identical histology of all postulated subtypes, we feel that the porokeratoses may be a more homogeneous group than is commonly thought. All types that are currently distinguished on clinical grounds may share the same molecular background. Xia et al. have identified two loci so far, one located near the Darier disease gene SERCA2 on chromosome 12p and one on chromosome 15q25 [14, 15]. The particular event triggering the clinical appearance of the disorder may be determined by the nature of the mutation, genetic background, or the presence of mosaicism. The nature and availability of the triggering event will also differ between patients. In disseminated superficial actinic porokeratosis (DSAP), for instance, occurring in sun-exposed areas, the trigger appears to be UV-exposure [16]. UV exposure can cause p53 mutations by inducing thymidine dimers [17], which may contribute to the disease phenotype. Incidentally, this may be an explanation for the observed rarity of porokeratosis in blacks or in the genital region. In both cases, exposure of keratinocytes to UV radiation will be relatively low. In so-called porokeratosis Mibelli, immune suppression or an ethnically determined genetic background effect may allow the abnormal clone to expand [2]. Mosaicism can also explain why porokeratosis sometimes occurs only locally and in a linear distribution. If the abnormal clone arises in the skin during embryogenesis it may spread along the lines of Blaschko, later in life giving rise to a porokeratotic eccrine ostial dermal duct nevus (PEODDN) or linear porokeratosis. Linear forms of the various clinical presentations of porokeratosis should occur. Indeed, there is a report of a case of linear porokeratosis Mibelli [18]. In such cases, the distribution of the disorder is determined by the extent of mosaicism. Mixed types of porokeratosis should also occur as type 2 segmental manifestations. Indeed, there are reports of a linear porokeratosis superimposed on DSAP, interpreted as a type 2 segmental event. In these cases, the patients were probably heterozygous for mutations in the DSAP gene [19,20]. Loss of the wild type allele for instance due to somatic recombination [21] later in life resulted in the development of a linear porokeratosis superimposed on the generalised disorder. These cases lend further support to the notion that all types of porokeratosis share the same molecular background. Hence, the clinical subtypes are useful as pointers to possible underlying causes but do not indicate fundamentally different genetic backgrounds.
Loss of heterozygosity may be a frequent event in porokeratosis as the presence of microsatellite instability and chromosomal instability have been demonstrated in porokeratosis [22-25]. This observation may also explain the cancer-proneness of the lesion. Interestingly, microsatellite instability affects a number of genes that contain repeat tracts such as β-catenin and PTEN [26-31]. Both genes are involved in epithelial tumorigenesis and may contribute to malignant transformation of porokeratoses. All considered the use of different terms to denote the clinical appearance of porokeratosis does in our view not contribute significantly to the diagnostic process and may lead to confusion and semantic discussion. We suggest that the disorder henceforth be referred to as “porokeratosis” only.
In conclusion, we describe a black man suffering from genital porokeratosis in the context of sub-clinical immunosuppression of unknown cause. Although the relationship between porokeratosis and immunosuppression is not absolute, immunological evaluation should be considered in negroid people presenting with suspicious lesions because triggering by UV radiation is unlikely. Histological examination of the lesions should be performed in order to confirm the diagnosis since porokeratosis predisposes to the development of squamous cell carcinoma. Careful follow-up or local therapy, for instance with immunomodulators, seems to be warranted. n

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