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Porokeratoses represent a group of uncommon, acquired or hereditary dermatoses, due to a keratinization disorder whose origin is still unclear; they could be due to the expansion of a clone of abnormal epidermal keratinocytes. Several clinical forms exist, of which the most common is disseminated superficial actinic porokeratosis; other forms include Mibelli, disseminated superficial, linear, palmoplantaris punctata and palmaris, plantaris et disseminata. These may coexist in the same patient or in different members of the same family. Porokeratoses manifest clinically with annular or linear, well-circumscribed keratotic plaques and share a common histological hallmark, the cornoid lamella, a vertical stack of parakeratotic corneocytes within the horny layer resting on a shallow depression of the underlying epidermis. Porokeratoses may be seen in the setting of various immunodeficiencies, namely in organ-transplant recipients, in whom the course of the disease may parallel the degree of immunosuppression. The overall prognosis of porokeratoses is favourable but is shadowed by the possibility of malignant transformation of the lesions (usually into squamous cell carcinoma); this happens in less than 10% of cases but may prove fatal. Although several surgical or medical (local or systemic) treatments have been tried, none of them has shown consistent and long-term efficacy.

Background: Porcine skin is increasingly being employed as a model of human skin in various research fields, including pharmacology, toxicology and immunology, with particular interest in percutaneous permeation and organ transplantation. Porcine skin shows several anatomical and physiological similarities, but also some differences, with human skin, but few in depth comparative studies are so far available., Objectives: To study the immunohistochemical properties of normal porcine skin in comparison with human skin., Materials and Methods: We performed a histological and immunohistochemical study on frozen and formalin-fixed, paraffin-embedded skin biopsies from domestic swine and normal human skin, using a panel of 93 monoclonal or polyclonal antibodies recognizing various human and porcine skin cell types or structures., Results: We found that several antibodies used to detect normal human skin cells showed equivalent immunoreactivity on normal porcine skin. However, some antibodies commonly used to detect human skin antigens remained unreactive on porcine skin., Conclusions: Our findings highlight the main immunohistochemical properties of porcine skin in comparison with those of human skin and provide a morphological and immunohistochemical basis useful to researchers using porcine skin.

Data on post-graft cutaneous cryptococcosis (CC) are rare. The objective was to delineate the epidemiological, clinical, diagnostic, therapeutic features of CC in organ transplant recipients. We compared cases from a cohort of 3,670 transplanted adults with cases from a regional cryptococcosis registry including 122 patients. Four CC were diagnosed in the transplanted cohort (1‰) corresponding in the regional registry to 33% of the 12 cases of cryptococcosis after transplantation, while among the 110 non-grafted patients, only five cryptococcosis were cutaneous (4%). CC appeared as a single (3 patients) ulcer or nodule over 1cm in size in an uncovered body zone, on average 13 months post-graft. 3 patients had concomitant opportunistic infections or a recent increase in their immunosuppression. All CC after transplantation were localized exclusively to the skin, raising the question of the mode of contamination (through the skin or the lungs). Evidence of dissemination is difficult because of the poor sensitivity of diagnostic tests. Fluconazole was the treatment of choice in association with immunosuppressive treatment tapering.

Background: Ichthyosis Follicularis, Atrichia and Photophobia (IFAP) syndrome is a rare genodermatosis due to mutations of the MBTPS2 gene. To date fewer than 40 cases have been described in the literature., Objectives: To present the first case of IFAP diagnosed in Poland due to a novel mutation of MBTPS2, and to review the relevant literature on this rare genodermatosis., Materials & Methods: A 16-year-old male presented with typical clinical features of IFAP, along with psoriasiform skin plaques, nail dystrophy, facial dysmorphy, mental retardation, severe skeletal abnormalities and chorea-like movements. DNA analysis was performed in the patient and his clinically unaffected mother, maternal grandmother and sisters., Results: A novel missense mutation p.Cys334Tyr (c.1001G>A) was found in exon 8 of the MBTPS2 gene. This mutation was also found in his clinically unaffected mother and maternal grandmother, but not his healthy sisters., Conclusions: This patient with IFAP, the first described from Poland, is original by virtue of its extensive skeletal, cutaneous and neurologic manifestations and the novel missense mutation of the MBPTS2 gene. The identification of a novel mutation further expands the known MBPTS2 molecular repertoire and the spectrum of associated clinical findings.

Basal cell carcinoma (BCC) is the commonest cancer in humans. Predisposing factors reflect common genetic variations and environmental influences in most cases. However, an underlying Mendelian disorder should be suspected in a specific subset of patients, namely those with multiple, early onset lesions. Some specific conditions, including Gorlin, Bazex-Dupré-Christol and Rombo syndromes, and Xeroderma Pigmentosum, show BCC as a prominent feature. In addition, BCC may represent a relatively common, although less specific, finding in many other genodermatoses. These include disorders of DNA replication/repair functions (Bloom, Werner, Rothmund-Thomson and Muir-Torre syndromes), genodermatoses affecting the folliculo-sebaceus unit (Brooke-Spiegler, Schöpf-Schulz-Passarge and Cowden syndromes), immune response (cartilage-hair hypoplasia and epidermodysplasia verruciformis) and melanin biosynthesis (oculocutaneous albinism and Hermansky-Pudlak syndrome), and some epidermal nevus syndromes. Further conditions occasionally associated with BCCs exist, but the significance of the association remains to be proven.

BRAF is a gene of the RAF family of kinases, frequently mutated in benign and malignant melanocytic tumors (nevi and melanomas). Organ transplant recipients are at high risk for developing various tumors, including melanocytic ones. We studied a group of 129 melanocytic tumors including various subtypes of nevi (n: 114) and melanomas (n: 15) excised from transplant (n: 63) and control (non-immunosuppressed) patients (n: 66) as to BRAF mutation status. Mutation research was performed after extraction of DNA from archival material (paraffin-embedded tissue specimens) by sequence analysis. BRAFV600E accounted for the most prevalent mutation found (94%). Melanocytic tumors from transplant patients had a lower frequency of BRAF mutations than control lesions (45.4% vs 63.5%, p<.05). The explanation for this difference is currently unknown. The possibility exists that in transplant patients, factors linked to immunosuppression (most likely immunosuppressive drugs) induce additional mutations, or activate alternative signaling pathways, which compensates for the lower rate of activating BRAF mutations in tumors developing in these patients.

Skin is a non-classical target for estrogens. Despite evidence showing that estrogen receptors (ER) are expressed in skin, there are still extensive gaps in our understanding of how estrogens exert their action in non-reproductive tissues. Estrogen-related receptor gamma (ERRgamma), an orphan member of the nuclear receptor superfamily, shows a strong sequence homology with estrogen receptor alpha but it does not bind estradiol. Here, for the first time, we demonstrate the expression of ERRgamma in adult human skin. ERRgamma mRNA was detected in the keratinocytes and fibroblasts of 8 female donor skins using RT-PCR. The presence of the protein was confirmed using immunohistochemistry on 11 adult human skins and Western Blotting on monolayer-cultures of fibroblasts and keratinocytes from respectively 4 and 2 donors. This study shows that ERRgamma is expressed in human skin and could intervene in a potentially new estrogen signaling pathway in the skin.

A Japanese newborn male with an unremarkable family history presented at birth with verrucous papules on the left side of the trunk and limbs, distributed along Blaschko's lines. Histological examination showed mild acantholytic dyskeratosis, consistent with Darier's disease; however, search for mutations of the SERCA gene, performed on DNA extracted from cells from involved and uninvolved skin and peripheral blood proved negative. The absence of detectable SERCA mutations did not allow confirmation of the diagnosis of (segmental) Darier's disease, and a tentative diagnosis of congenital acantholytic dyskeratotic epidermal nevus was considered. The relationship between the two conditions is briefly discussed.

Granular cell basal cell carcinoma (GBCC) is a very rare variant of BCC, of which ten cases have been reported in the literature. We describe here a new case of GBCC studied immunohistochemically. The tumor developed on the face of a 71-year old man and showed typical features of GBCC, i.e. a tumor reminiscent of nodular BCC consisting of cells with a granular eosinophilic cytoplasm. Immunohistochemically, tumor cells expressed cytoplasmic reactivity for keratins, CD68 and CD15 antigens, bcl-2 oncoprotein and nuclear reactivity for the p63 protein. Based on a review of the literature, the salient features of GBCC are discussed.

The experience obtained from the human hand allografts (HHA) performed to date suggests that the skin is a priviledged target of allograft rejection in this setting. The aim of this study was to establish a pathological score for assessing the severity of HHA rejection. The pathological slides of 89 skin biopsies obtained from the allografted limbs of six HHA recipients from day 0 to 5 years post-graft were retrospectively examined. According to the severity of the pathological changes observed, the following grades of rejection are proposed: 0: no rejection, I: mild rejection, II: moderate rejection, III: severe rejection, IV: very severe rejection. This grading system can be used as a basis for monitoring allograft rejection and for assessing the effects of the immunosuppressive treatment aiming at reversing HHA rejection; it can also be used for monitoring rejection of other skin-containing CTA.

The role of cytotoxicity in the defense mechanisms or pathogenesis of human cutaneous leishmaniasis is not yet well known. In the present work we assessed the presence of NK, CD8+ and CD45RO+ T cells, as well as the expression of a molecule associated with cytotoxic properties (TIA-1) in the lesions of cutaneous leishmaniasis. CD8+ T cells, NK and activated T cells were found within the dermal cell infiltrate. We found a heterogeneous but usually strong expression of TIA-1, a marker of cytotoxic granules of T and NK cells, in human cutaneous leishmaniasis lesions. These data suggest that cytotoxic activity occurs in situ in American cutaneous leishmaniasis and that both NK cells and activated CD8+ T cells are involved in this reaction.

The skin is the largest organ of the body, accounting for about 15% of the total body weight in adult humans. It exerts multiple vital protective functions against environmental aggressions, rendered possible thanks to an elaborate structure, associating various tissues of ectodermal and mesodermal origin, arranged in three layers, including (from top to bottom) the epidermis (and its appendages), the dermis and the hypodermis. This article reviews the main data concerning the anatomy, histology and immunohistochemistry of normal human skin.

Ultraviolet B light is responsible for the development of skin cancer through inhibition of cellular immune responses in the skin. Here, we addressed the question of the mechanisms involved in UVB-induced immune suppression. We used a model of antigen-specific skin inflammation, the contact hypersensitivity (CHS) reaction to DNFB, which is mediated by CD8+ effector T cells and down-regulated by CD4+ T cells. We show that UVB have opposite effects on CD4+ and CD8+ T cells. UVB irradiation reduced the number of activated CD8+ T cells in the lymphoid organs and impaired their functional activity. This resulted in deficient infiltration of IFN-gamma producing CD8+ T cells at challenged site and consequently in the inability to develop an antigen-specific CHS reaction. This effect is mediated by CD4+ suppressor cells, since in the absence of CD4+ T cells (MHC class II-KO mice and CD4+ T cell-depleted mice), UVB have no immunosuppressive effects. Indeed, UVB-irradiated CD4+ T cell-deficient mice have a normal frequency of IFN-gamma-producing hapten-specific CD8+ T cells in the lymphoid organs and develop a normal CHS reaction to DNFB. Thus, in the absence of CD4+ T cells, UVB do not alter the priming of MHC class I-restricted CD8+ effector T cells. Collectively, these data show that UVB-induced immune suppression is secondary to preferential activation of CD4+ suppressor T cells and not to deficient priming and expansion of the effector CD8+ T cell population. This may have important implications for the prevention of UV-induced skin cancers.

A 28-year-old mentally retarded, institutionalised woman was referred to us for evaluation of multiple plantar warts and ingrown nails of both great toes. The patient was born to unrelated parents of North African origin and had one brother and three half-brothers, all of whom were healthy. Physical examination revealed short stature, slight obesity, facial abnormalities (Fig. 1), short and broad thumbs and big toes (Figs. 2 and 3). A keloid was found on the right forearm, that had developed after surgical correction of a fracture (Fig. 4). Ill-defined hyperpigmented macules were observed on the trunk. The patient also presented pruritic eczematous lesions of the limbs and the back that had been present for some years and were recurrent despite treatment with emollients and local steroids. Androgenetic-type alopecia of moderate severity was seen on the vertex of the scalp. Past medical history included polydactylism of the feet and clinodactyly of the thumbs (both corrected surgically), respiratory tract infections, Wolf-Parkinson-White syndrome and refractive errors necessitating glasses.

Ossification rarely occurs within melanocytic naevi. As far as we know, mummification (presence of shadow cells) has never been described within these lesions. We report herein the case of a benign naevus associating ossification and mummification; this case suggests that, similarly to pilomatricomas, osteoma formation within melanocytic naevi may develop as a result of mummification.

Keratin 15 (K15) was recently shown to be a specific marker of stem cells of the hair-follicle bulge. We studied the reactivity of an antibody to the CD8 antigen (C8/144B), recognizing K15, on 66 cutaneous tumors with known or alleged pilar differentiation, in order to assess its usefulness in the diagnosis of this group of tumors. 2/2 basal cell nevi, 5/8 trichoepitheliomas and 1/3 trichofolliculomas showed substantial reactivity. Much weaker reactivity was observed in cases of trichilemmal tumors (trichilemmomas and trichilemmal cysts); by contrast, all cases of pilomatricomas, basal cell carcinomas and epidermoid cysts were completely unreactive. These results are in keeping with the admitted differentiation of the tumors studied, and suggest further that basal cell carcinomas do not differentiate towards hair bulge cells. From a practical point of view, immunostaining for K15 seems to be an additional useful adjunct for the differential diagnosis between basal cell carcinoma and trichoepithelioma.

Contact dermatitis (CD) is an altered state of skin reactivity induced by exposure to an external agent. "Eczema" and "dermatitis" are often used synonymously to denote a polymorphic pattern of inflammation of the skin characterized, at least in its acute phase, by erythema, vesiculation and pruritus. Substances that induce CD after single or multiple exposures may be irritant or allergic in nature. The clinical presentation may vary depending on the identity of the triggering agent and the reactivity of the subject, but in all cases the lesions are primarily confined to the site of contact. According to the mechanism of elicitation, the following types of contact reactions may be distinguished: (1) allergic contact dermatitis (ACD); (2) irritant contact dermatitis (ICD); (3) phototoxic and photoallergic contact dermatitis, and (4) immediate type contact reactions. The present review will focus on allergic contact dermatitis. ACD is the clinical presentation of contact sensitivity in humans. The pathophysiology of the contact sensitivity reaction has been reviewed in a preceding issue of this journal [1].

Peripherin is a neuronal intermediate filament reportedly expressed in neuroendocrine skin carcinomas and some melanocytic tumors. In order to assess the diagnostic usefulness of antibodies to peripherin in dermatopathology, we studied its expression in 68 skin tumors mostly of neural origin, and compared this expression with that of neurofilaments, a well-established neuronal marker. Antibodies to peripherin and neurofilaments both labeled dermal neurons present in normal skin and within the tumors. Specific labeling of tumor cells for peripherin was seen in only 2/5 neuroendocrine skin carcinomas, 3/18 benign nevi and 7/19 melanomas; even in these cases the percentage of tumor cells did not exceed 20%. We conclude that antibodies to peripherin may be used for the demonstration of cutaneous neurons in normal and diseased skin; however their diagnostic usefulness appears limited, less than that of antibodies to neurofilaments.