Case 3-2 -

Porokeratosis of Mibelli Philip E. LeBoit, M.D. Depts. of Pathology and Dermatology University of California, San Francisco

Clinical history: A 69 year old man had a 1.5 x 1.1 cm. eroded plaque with a pearly border on the right buttock. Case 3-2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Porokeratosis of Mibelli Histopathologic features in these sections include: Elongated rete ridges or roughly equal lengths A patchy lymphocytic infiltrate in the papillary dermis A slightly papillated and hyperkeratotic surface Thin suprapapillary plates Lamellar hyperkeratosis Cornoid lamellae at each end of the lesion featuring: Slanted columns of parakeratosis Subjacent keratinocytes with perinuclear vacuoles and dyskeratotic cells Porokeratosis, like keratoacanthoma and angiokeratoma is not a single entity but a family of entities. All of the forms of porokeratosis have in common the formation of cornoid lamellae. Cornoid lamellation is an abnormal form of keratinization. While it is sometimes oversimplified as just a column of parakeratosis, scrutiny of the keratinocytes that underly the tier of parakeratotic cells show that they are abnormal. The keratinocytes beneath the cornoid lamella often have brightly eosinophilic, keratinized cytoplasm, perinuclear vacuoles or both. The recognition of these findings gives much greater specificity to the diagnosis. The presence of a cornoid lamella at the edges of the lesions of most types of porokeratosis imparts a border that is sometimes described as having a threadlike scale. The major clinical forms of porokeratosis are: Porokeratosis of Mibelli Disseminated superficial actinic porokeratosis Porokeratosis palmaris et plantaris disseminata Inheritance of all of them is possible with an autosomal dominant pattern. The occurrence of several forms of porokeratosis in the same patient suggests that they are related. Porokeratosis of Mibelli results in larger and in fewer lesions than do the other forms. Some lesions of 10 cm. have been observed. Linear porokeratosis and reticulated porokeratosis seem to be variants, as may a rare condition called eccrine ostial and dermal duct nevus. The keratotic rims around lesions often have a furrow next to them, and are more substantial than are those in other forms of porokeratosis. Disseminated superficial actinic porokeratosis typically has its onset in early adult life, affecting sun exposed skin, with a thin, raised border. The lesions are typically mistaken for those of solar keratoses clinically. They can be itchy, in particular in the summer. Porokeratosis palmaris et plantaris disseminata begins in the second or third decade with hyperkeratotic papules on the palms and soles, spreading to other parts of the body, but usually sparing the face and scalp. Its lesions tend to be small, and have thready borders like those of disseminated superficial actinic porokeratosis. It has been noted for some time that the lesions of porokeratosis can give rise to squamous cell carcinoma. This is most notable with the Mibelli variant, in which squamous cell carcinoma with fatal metastasis has been observed. When the pathologist is told that the clinician suspects porokeratosis, they can look for a cornoid lamella on the presumption that the clinician took a biopsy from the edge of the lesion. If one is not present, they can obtain levels. If the specimen is a punch, there is a change that the cornoid lamella can be lost in facing the block. An incisional biopsy, oriented longitudinally is perfect in this setting, but may be impractical. Shave biopsies are often done for disseminated superficial actinic porokeratosis, and usually are adequate. Much more problematic is the case in which the clinician did not think about this diagnosis, and punches the center of the lesion. In the case of porokeratosis of Mibelli, one can see changes interpretable only as psoriasiform dermatitis, or sometimes as an atrophic interface dermatitis. In the case of disseminated superficial actinic porokeratosis, the centers are often atrophic, and vacuolar change is frequently present. Coupled with clinical data suggesting lesions in sun exposed skin, this can lead to a diagnosis of lupus erythematosus. The keratinocytes in the area bounded by the cornoid lamella may represent an altered clone of cells predisposed to give rise to carcinomas. There is over-expression of the tumor suppressor gene, p53 and of Rb in the nuclei of the basal layer, independent of Ki-67 expression in some cases, suggesting that there is alteration of these tumor suppressor genes. However, genetic abnormalities in p53 have not been detected. References: Chang SE, Lim Y, Lee H, Choi J, Sung K. Expression of p53, pRb, p16 and proliferating cell nuclear antigen in squamous cell carcinomas arising on a giant porokeratosis. Br J Dermatol. 1999 Sep;141(3):575-6. Wu LQ, Yang YF, Zheng D, Deng H, Pan Q, Zhao TL, Cai F, Feng Y, Long ZG, Dai HP, Tang BS, Yang YJ, Deng HX, Xia K, Xia JH. Confirmation and refinement of a genetic locus for disseminated superficial actinic porokeratosis (DSAP1) at 12q23.2-24.1. Br J Dermatol. 2004 May;150(5):999-1004. Silver SG, Crawford RI. Fatal squamous cell carcinoma arising from transplant-associated porokeratosis. J Am Acad Dermatol. 2003 Nov;49(5):931-3. Hivnor C, Williams N, Singh F, VanVoorhees A, Dzubow L, Baldwin D, Seykora J. Gene expression profiling of porokeratosis demonstrates similarities with psoriasis. J Cutan Pathol. 2004 Nov;31(10):657-64. Arranz-Salas I, Sanz-Trelles A, Ojeda DB. p53 alterations in porokeratosis. J Cutan Pathol. 2003 Aug;30(7):455-8. Magee JW, McCalmont TH, LeBoit PE. Overexpression of p53 tumor suppressor protein in porokeratosis. Arch Dermatol. 1994 Feb;130(2):187-90.