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A preliminary clinical experience suggested tazarotene, a new acetylenic retinoid, as an effective alternative topical treatment of basal cell carcinomas (BCC). The mechanisms of action of this synthetic retinoid, however, have not been yet clarified. In this work we assessed the in vivo effects of daily application of tazarotene for 24 wk, on 30 small superficial and nodular BCC, and the in vitro effects of tazarotene on immortalized basal and squamous tumor epidermal cells. Cellular proliferation, apoptosis and changes in expression of retinol and retinoic acid receptors (RAR), p53, bcl-2, and bax were studied by immunohistochemistry, western blotting and PCR. Overall, 76.7% of treated tumors showed50% regression. Complete healing was observed in 46.7% of all treated BCC, without recurrences at 2-y observation. Regression was associated with reduced proliferation and increased apoptosis, demonstrated by Ki-67- and TdT-mediated dUTP-biotin nick-end labelling-positive nuclear staining, and with enhanced RAR-beta and bax expression, with RAR-alpha and -gamma expression unchanged. In vitro, tazarotene induced a concentration-dependent increase of RAR-beta and bax associated with a greater rate of apoptosis and growth inhibition in basaloid tumor cells compared with squamous tumor cells. Our studies provide convincing evidence that tazarotene induces BCC regression possibly by synergistic RAR-beta-dependent anti-proliferative and pro-apoptotic pathways.

MCAM/MUC18 is a cell adhesion molecule associated with higher incidence of relapse in melanoma. The purpose of our study was to evaluate its role as a promising disease biomarker of progression through sequential molecular MCAM/MUC18 RT-PCR assay on serial blood samples collected during the clinical follow-up of 175 melanoma patients in different American Joint Committee on Cancer (AJCC) stages. MCAM/MUC18 molecular detection, found at least once in 22 out of the 175 patients, was significantly associated with poor prognosis and death (p < 0.001), regardless of the AJCC stages. Positive expression, either if primarily present or later acquired, was associated with melanoma progression, whereas patients primarily negative or with subsequent loss gained clinical remission or stable disease, even if in advanced stages (p < 0.005). Six AJCC advanced stages always MCAM/MUC18 negative are in complete remission or with a stable disease (p < 0.007). Semiquantitative immunohistochemical MCAM/MUC18 staining on corresponding primary melanomas was related to peripheral molecular expression. Correlations between circulating molecular and tissutal immunohistochemical detection, primary tumour thickness, AJCC stages and clinical outcome were statistically evaluated using Student's t test, ANOVA, Spearman's rank correlation test, Pearson χ (2)-test and McNemar's test. In our investigation, MCAM/MUC18 expression behaves as a "molecular warning of progression" even in early AJCC patients otherwise in disease-free conditions. Achievement of this molecule predicted the emergence of a clinically apparent status, whereas absence or persistent loss was related to a stable disease or to a disease-free status. If confirmed in larger case series, MCAM/MUC18 molecular expression could predict good or poor clinical outcome, possibly becoming a promising prognostic factor.

Pyoderma vegetans (PV) is a chronic, vegetating pustular disorder characterized clinically by erythematous vesiculopustular vegetating cutaneous plaques. Marked epidermal hyperplasia, intraepidermal and subepidermal neutrophilic microabscesses and a dermal inflammatory infiltrate are the prominent histopathological findings. We describe a patient with PV associated with ulcerative colitis and mammary Paget's disease. Pustular eruptions associated with ulcerative colitis are reviewed.

T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell-derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis.

Elena Campione1, Chiara Centonze2, Laura Diluvio1, Augusto Orlandi3, Cesidio Cipriani4, Alessandro Di Stefani3, Emilio Piccione2, Sergio Chimenti1 and Luca Bianchi1 Departments of 1Dermatology, 2Gynaecology and 3Anatomic Pathology, University of Rome, Tor Vergata, Viale Oxford, 81, IT-00133 Rome, and 4Department of Nuclear Medicine, S. Eugenio Hospital, Rome, Italy. E-mail: campioneelena@hotmail.com Accepted Nov 7, 2011; Epub ahead of print Jun 21, 2012

Basal cell carcinoma is the most common non-melanoma skin cancer, and its incidence continues to raise. Although surgery can be considered the mainstay of therapy, new current pharmacological options are available and focus on tumor eradication, maximizing cosmetic results, and functional capacity. Several studies have recently reported on safety and efficacy of topical ingenol mebutate gel, a derivative of the plant Euphorbia Peplus, used to treat actinic keratosis and superficial basal cell carcinoma. In our knowledge, we report for the first time the dermoscopic evaluation of outcome and monitoring of superficial pigmented and non-pigmented basal cell carcinomas in four patients treated by this novel non-ablative agent. Ingenol mebutate gel therapy has showed to be effective and without important side-effects for pigmented and non-pigmented superficial basal cell carcinomas. We emphasize the usefulness of dermoscopy in supporting the clinical diagnosis and excluding the presence of tumor residue or recurrence. In a future scenario, we hope it will be soon possible to follow-up the lesions, after treatment, avoiding post-control biopsy punch.

Actinic keratoses (AKs) are intraepidermal tumours, which result from the proliferation of transformed neoplastic keratinocytes. They are typically induced by chronic exposure to ultraviolet radiation, and can often develop into squamous cell carcinoma (SCC). Six patients, who presented with AKs located on the head, face and chest, were treated with the immune response modifier, imiquimod, as a 5% cream five times per week for up to 8 weeks. The majority of patients experienced mild to moderate side-effects, consisting of erythema, itching and burning. Topical application of imiquimod for 4-8 weeks resulted in complete clearance in all patients. No new or recurrent lesions were observed during a 6-8 month follow-up period.

The efficacy of tazarotene 0.1% gel in a 30-year-old woman with type I lamellar ichthyosis is reported. The drug was applied to 15% of the total body surface area as follows: once daily for 2 weeks, three times a week for further 2 weeks, followed by a once weekly maintenance application. During the first week of treatment there was partial improvement obtained and in the next 14 days further reduction of scaling within the tazarotene-treated areas was observed. After 4 months of maintenance application, there was a marked overall improvement in the treated areas. Side-effects consisted only of mild pruritus, slight burning and irritation. In essence, the therapeutic benefit obtained was comparable with that of systemic retinoids but without the adverse systemic side-effects. As noted in other reports, tazarotene 0.1% gel seems to be a valuable and safe therapeutic option for this severe genodermatosis.

Lamellar Ichthyosis (LI) is a form of congenital ichthyosis that is caused by mutations in the TGM1 gene that encodes for the transglutaminase 1 (TG1) enzyme. Functional inactivation of TG1 could be due to mutations, deletion or insertions. In this study, we have screened 16 patients affected by LI and found six new mutations: two transition/transversion (R37G, V112A), two nonsense mutations and two putative splice site both leading to a premature stop codon. The mutations are localized in exons 2 (N-terminal domain), 5, 11 (central catalytic domain), and none is located in the two beta-barrel C-terminal domains. In conclusion, this study expands the current knowledge on TGM1 mutation spectrum, increasing the characterization of mutations would provide more accurate prenatal genetic counselling for parents at-risk individuals.

KID syndrome (MIM 148210) is an ectodermal dysplasia characterized by the occurrence of localized erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. KID syndrome is inherited as an autosomic dominant disease, due to mutations in the gene encoding gap junction protein GJB2 (connexin 26, Cx26). Cx26 is a component of gap junction channels in the epidermis and in the stria vascularis of the cochlea. These channels play a role in the coordinated exchange of molecules and ions occurring in a wide spectrum of cellular activities. In this paper we describe two patients with Cx26 mutations cause cell death by the alteration of protein trafficking, membrane localization and probably interfering with intracellular ion concentrations. We discuss the pathogenesis of both the hearing and skin phenotypes.

Summary Background Multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) was originally reported to reveal melanoma-associated mRNAs (MAMs) in melanoma cells but not in the peripheral blood of healthy individuals. Objectives To evaluate the expression of MAMs in the peripheral blood of melanoma patients at different American Joint Committee on Cancer (AJCC) stages, and to correlate their presence with early and/or advanced stages of the disease. Materials and methods One hundred blood samples of melanoma patients (AJCC I–IV) were analysed using multimarker RT-PCR to assess the co-expression of Tyr-OH, MART-1, MAGE-3, MUC-18/MCAM and p97. Patients were stratified into two disease categories: early and advanced stages. The former includes in situ and melanoma stages AJCC I–II, the latter AJCC III–IV. χ2 and Fisher’s exact tests were used to statistically evaluate the association between each MAM and disease categories. The recognized significant associations were subsequently resubmitted to univariate logistic regression. Furthermore, sensitivity and specificity were established. Results At least one MAM could be detected in 24% of our series. Tyr-OH was the most common marker (14%), followed by MUC-18 (12%), MART-1 (5%), MAGE-3 (4%) and p97 (3%). No significant association among Tyr-OH, MART-1, MAGE-3, p97 and disease stages were evidenced. Only MUC-18 was statistically associated (P

Background Animal-type melanoma (ATM) is a rare variant of the tumor showing diffuse, heavily pigmented neoplastic cells in the dermis. Despite the high mean thickness of the lesions, reports seem to indicate a less aggressive behavior and a better survival rate for ATM compared with conventional melanoma, but the underlying pathways related to this favorable outcome are still unknown. Observations Five women and 2 men aged 20 to 92 years presented with pigmented skin nodules (n = 5) or plaques (n = 2), varying in size from 1.0 to 4.5 cm. Findings from microscopic examination showed monotypic-appearing melanocytes with abundant intracytoplasmic melanin in a nodular or fascicular arrangement (mean Breslow thickness, 4.97 mm). Immunohistochemical analysis of ATM cells demonstrated the typical positive staining for S-100, vimentin, HMB-45, and melan-A. The investigation of the π isoform of glutathione S-transferase, a family of enzymes involved in tumor progression, revealed that nuclear expression is reduced in ATMs compared with control melanomas, whereas results from cytoplasmic staining did not vary. One patient died of cardiac failure without evidence of disease progression; the remaining patients are disease-free at 3 (n = 4) and 5 years (n = 3). Conclusions Our findings confirm that ATM is a variant of melanoma with distinctive clinical and histological features. Low nuclear expression of glutathione S-transferase π expression is a characteristic of ATM and could add new insight to better understand the unusual biological behavior of this rare neoplasm.

Imiquimod is a 240.3-Da synthetic imidazoquinolinamine (C14H16N4), developed in 1983 and approved in 1997 by the US Food and Drug Administration for the topical treatment of external genital and perianal warts and, more recently, also for actinic keratosis and superficial basal cell carcinomas. We report five cases of patients affected by basal cell carcinomas localized in seborrhoeic areas of the face, successfully treated with topical imiquimod and characterized by the occurrence of eruptive epidermoid cysts at the end-point of therapy. The dermatoscopic evaluation disclosed the presence in all lesions of a common feature characterized by a hyperkeratotic yellow-withish area, resembling 'popcorn', excluding dermoscopic basal cell carcinoma features. Furthermore, histological proof confirmed the diagnosis of epidermoid cysts. As reported in the literature and as observed in our clinical experience, the occurrence of epidermoid cysts, after the topical treatment of basal cell carcinomas with imiquimod, may represent a local immune reaction that is drug-related and is a typical remission pattern in particular anatomical areas. We also emphasized the usefulness of dermoscopy in supporting the clinical diagnosis of epidermoid cysts, excluding the presence of tumoural residue or recurrence. In the future, it will be possible to follow-up the lesions after treatment avoiding the post-control biopsy punch.

The cases are reported of two women patients presenting asymptomatic solitary lesions: one in the anterior tibial region of the right leg, the other on the right arm. The first patient's lesion was 3 cm in diameter and had appeared 2 years earlier as a translucent oval atrophic patch with a definite border. The second patient presented a whitish area with a lilac ring, 2.5 cm in diameter, which had appeared nearly a year earlier. Both patients had no other similar cutaneous lesions, and their family histories for cutaneous disease were negative. The lesions underwent punch biopsy, and the histopathological findings confirmed the diagnosis of morphea. Laboratory investigations showed no abnormalities. Imiquimod 5% cream was prescribed for 5 consecutive days a week for 16 weeks. Clinical and dermoscopic assessment of the lesions was performed before treatment, during follow-up and at treatment end point. No local or systemic side effects were observed during treatment. Following treatment, both patients achieved complete clinical remission of the lesions, with a definitive improvement in the lesions' initial disfiguring features.

Keratoacanthoma (KA), a cutaneous neoplasm histologically resembling squamous cell carcinoma, is characterized by rapid growth and common spontaneous regression. The regression depends on an individual's immune response. We are reporting a case of a 53-year-old man who presented with an ulcerated tumor, which had arisen as a nodular lesion 9 months earlier. This was localized on the the left thumb. The patient had undergone a kidney transplant after severe glomerulonephritis. Following the operation, he was treated with systemic immunosuppressive drugs and developed multiple nonmelanoma skin cancers. The histology examination of biopsy specimens was consistent with keratoacanthoma and showed low-density chronic inflammatory cells. Our patient refused surgical excision, so we prescribed imiquimod 5 percent cream once daily for 5 days a week. After 6 weeks of treatment the lesion had regressed completely, yielding an excellent cosmetic result. Continued resolution was documented 3 years after treatment. The patient had no signs of graft rejection related to the imiquimod treatment. © 2008 Dermatology Online Journal.

Sir, Atopic dermatitis (AD) is associated with genetic and environmental factors, defects in the cutaneous barrier, bacterial and viral skin infections and immunological changes (1). AD influences the quality of life of both the patient and his or her family (2). Topical steroids are the gold standard treatment for AD, but their use is limited by potential adverse effects, including impairment of the function Langerhans’ cells, cutaneous atrophy, telangiectasias and acne. Nonsteroidal immunomodulant drugs, such as calcineurin inhibitors, tacrolimus and pimecrolimus, do not have these side-effects. Pimecrolimus is indicated in both the shortand long-term treatment of AD (3) and can be applied to areas such as the face and neck. Cyclosporin A (CsA) is another calcineurin inhibitor that blocks the activation of T lymphocytes with transcriptional block of the interleukin (IL)-2, IL-4, tumour necrosis factor (TNF)-α and interferon (IFN)-γ cytokine genes. CsA is used in adults and in children with severe AD refractory to topical treatments (4). AD may be associated with hepatitis; in fact, atopic patients have presented an inadequate Th-1 response and impaired function of natural killer (NK) cells, promoting chronic liver infections such as hepatitis B (5). Treatment with CsA has a therapeutic effect both on hepatitis B and hepatitis C as it inhibits viral replication (6). We report here a patient with severe AD and chronic hepatitis B who was treated successfully with combined treatment of low-dose of CsA (100 mg/daily) and local pimecrolimus.

Background Autosomal dominant gain of function mutations in caspase recruitment domain family member 14 (CARD14) were found to cause plaque psoriasis in two families and severe generalized pustular psoriasis as a monogenic form of childhood (CARD14-mediated pustular psoriasis, CAMPS) [1]. CARD14 mutations have also been implicated in plaque-type psoriasis and pityriasis rubra pilaris [2]. Objectives Describing a family with an unusual clinical phenotype characterized by some members with childhood-onset erytrodermic psoriasis first localized and then diffuse over all the skin surface; in some family members is also reported psoriatic arthritis. Methods We assessed for the first time the family in december 2013, because of their skin lesions and family recurrence for erytrodermic psoriasis associated to arthritis in some cases. There are three pairs of twins, five of them presenting psoriasis and two of them presenting psoriatic arthritis. The children presented poor clinical response to topic and systemic therapy with antihistamine, steroid, retinoids, cyclosporine and etanercept. The whole pedigree is depicted in the figure with the grey symbols indicating the affected members and an asterisk pointing out members for whom we got a biological sample (Figure). After exclusion of the most common genes associated to autoinflammatory diseases (IL36RN, IL1RN, MVK, TNFRSF1A, NLRP3, NLRP12, MEFV, IL1RN, NOD2, PSMB8, PSTPIP1, LPIN2). Successively, we approached the new gene search by subjecting to Whole Exome Sequencing (WES) analysis five members of the family, namely those indicated by an arrow. Samples were processed in outsourcing and raw data were transferred to our lab for the bio-informatic analysis. Results Among variants shared by the four affected individuals and not present in the unaffected subject, a missense mutation of the CARD14 gene resulted worth of further investigation. In particular, it was the case of an exon4 heterozygous nucleotide change, c.446T>G, leading to the missense amino acid substitution p.L149R. The presence of this variant was validated by Sanger sequencing not only in the affected members undergone WES, but also assessed in all the rest of the available family members. This allowed us to confirm the expected segregation of the CARD14 mutation with the disease phenotype. Conclusions CARD14 gain of function mutations can give rise to unusual clinical phenotype like diffuse erytrodermic psoriasis and psoriatic arthritis. WES appears to be a powerful, suitable and proper approach to identify new SAID genes, thus also disclosing new molecular pathogenic mechanisms. References Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF, Joyce CE, et al. PSORS2 is due to mutations in CARD14. American journal of human genetics. 2012; 90(5):784–95. Epub 2012/04/24. Fuchs-Telem D, Sarig O, van Steensel MA, Isakov O, Israeli S, Nousbeck J, et al. Familial pityriasis rubra pilaris is caused by mutations in CARD14. American journal of human genetics.n 2012; 91(1):163–70. Epub 2012/06/19. Disclosure of Interest None declared

Summary Background Basal cell carcinoma (BCC) is the most common cancer in humans. Medical treatment modalities offer cost reductions and clinical advantages in selected cases such as low-risk areas, surgically inaccessible sites, patients with multiple neoplasms, and older, infirm or anticoagulated subjects. Tazarotene has been proposed for the treatment of BCC; however, data on its efficacy are lacking. Objectives To investigate the efficacy of tazarotene in a large series of BCCs, better to define the clinical advantages and the mechanisms of action in vivo. Methods Tazarotene 0·1% gel was applied daily for 24 weeks to 154 small superficial and nodular BBCs. Clinicopathological changes were followed during the therapy by dermoscopic and histological examination. Proliferation, retinoic acid receptors and apoptosis were investigated by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling on biopsies. Results At 24 weeks of therapy, 70·8% of the BCCs showed > 50% clinical and dermoscopic regression, and 30·5% healed without recurrences after 3 years of follow-up. At 12 weeks, biopsies showed that regression was associated with reduced proliferation and increased apoptosis of basaliomatous cells. Most unresponsive tumours displayed a keratotic differentiation. Conclusions Tazarotene was effective in the majority of superficial and nodular undifferentiated BCCs treated, possibly by antiproliferative and proapoptotic actions in vivo. Keratotic BCCs were the major type among the unresponsive tumours, and were characterized by overexpression of p53 and cellular retinol binding protein-1 in comparison with undifferentiated tumours. Topical tazarotene represents an alternative medical choice for selected cases of BCC.

Immunosuppressive medications such as corticosteroids and cyclosporin are the most commonly employed therapies in pyoderma gangrenosum. We describe a patient with multiple ulcers of pyoderma gangrenosum on the lower extremities in whom immunosuppressive therapy caused serious side effects and had to be discontinued but who was subsequently treated successfully with high dose intravenous immunoglobulin (IVIG).IVIG was given intravenously at a dose of 400 mg/kg per day for 5 consecutive days. After 1 week there was an arrest in the progression of the ulcers and a marked reduction in pain. Two weeks later clinical improvement of the ulcers was observed. Subsequently, IVIG was given at a dose of 1 g/kg per day for 2 consecutive days.The treatment induced a dramatic clinical improvement of one ulcer and healing of the others. Side effects were minimal and well tolerated, and consisted of chills and a slight fever, which resolved with the administration of acetaminophen.We feel that IVIG can be used in patients with pyoderma gangrenosum in whom conventional therapies are ineffective or produce serious side effects.

Background Pediatric erythroderma is a severe cutaneous disorder, which may pose diagnostic and therapeutic challenges. Psoriasis, ichthyoses, atopy, seborrhoeic dermatitis, pityriasis rubra pilaris, infections, metabolic diseases, drugs reaction, may cause erythroderma. The therapy should be tailored on each aetiology, if possible. The biochemical and metabolic imbalance should be corrected, and particular attention should be paid to the psychosocial behavior often related to this disfiguring disease. Case presentation Two 3 year-old Caucasian twins have been suffering from an unmanageable erythroderma since the age of 8 months. The diagnosis of psoriasis, already remarkably expressed in the father’s family in three cases of fraternal twins, could be enforced for several points. Major histocompatibility complex, class I, Cw*06 was detected in both twins; we found no transglutaminase-1, no corneodesmosin, nor any Interleukin-36 receptor antagonist gene mutations. We performed a cutaneous histology, positive immunostaining for Lympho-epithelial Kazal-type-related inhibitor, dermoscopy and reflectance confocal microscopy. The twins had previously received systemic steroids, short cycles of low-dosage ciclosporine, followed by etanercept at the dosage of 0,8 mg/kg, without reliable results. Cyclosporine was then reconsidered at a dosage of 5 mg/kg/day with close blood monitoring. After three months of treatment, consistent clearing and significant improvement of their social and psychological behaviour were achieved. After over one year of continuous therapy with cyclosporine, the twins have still maintained the result obtained. Conclusion Pediatric erythroderma may pose a great challenge as a potentially life-threatening condition causing extreme distress in children, parents and pediatricians. In young patients it is mandatory to establish correct clinical and instrumental procedures, possibly supplemented by genetic analyses such as those we required, in order to determine an effective and safe therapy in terms of cost-benefit and put patients and family in the best condition to perform common daily activities.

Nail psoriasis occurs in 7% to 40% of children, with a similar pattern of clinical presentation to that of adults. In 0.6% to 2.3% of the patients nail changes appear as the only sign of the disease, preceding other skin and articular involvement. No pediatric clinical trials are available yet, but considering the successful use of tazarotene for nail dystrophy therapy in adults, we chose this drug to treat a child.

Effective systemic treatments for severe acne vulgaris, such as oral antibiotics, oral isotretinoin and anti-andro-gens, are often associated with undesirable side-effects or are limited to a selected patient population. Furthermore, some patients with severe acne fail to respond to these therapies (1).Etanercept, a dimeric fusion protein linking part of the human p75 tumour necrosis factor (TNF) receptor extracellular domain with the Fc region of IgG

Background Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis characterized by painful cutaneous ulcerations and often associated with systemic inflammatory and neoplastic diseases. Here we report the first case of pyoderma gangrenosum in a patient with refractory celiac disease. Case presentation A 52-year-old woman with a previously diagnosed refractory celiac disease resistant to steroids and immunosuppressive drugs presented to our hospital for a rapidly growing, painful inflammatory skin lesion of the left leg. Physical examination revealed a painful lesion with focal ulceration, necrosis and pus discharge with active inflammatory borders at the external part of the left leg. Histological evaluation of a skin biopsy and analysis of inflammatory cytokines and matrix-degrading proteases in lesional skin samples confirmed the clinical suspicion of pyoderma gangrenosum. Treatment with oral prednisone was rapidly followed by a complete healing of the skin lesion but no improvement of symptoms/signs of malabsorption. Conclusion Treatment of the patient with systemic steroids healed the skin lesion without improving the underlying refractory celiac disease. This observation raises the possibility that refractory celiac disease and pyoderma gangrenosum may be immunologically different.

Sir, Naevus spilus (NS), also named speckled lentiginous naevus, is a congenital or more frequently acquired naevus clinically characterized by small hyperpigmented speckles overlying a tan macular background. The combination of NS with other melanocytic lesions, such as Spitz naevus (1, 2), blue naevus (3 – 7) or melanoma (9 – 17), has been observed occasionally. In the present study we report an unusual association of NS and ink spot lentigo as an example of a clinical simulator of melanoma.

carried out 3 months after the second ECT, and the excised mass, including a narrow rim of healthy tissue margin and a small triangle of adherent skin, sparing the inner layer, the oral mucosa and the floor of the orbit. Reconstruction was easily achieved with a rotation flap. Pathological examination of the specimen showed necrotic tissue without residual melanoma. One year after the last ECT treatment, the patient was disease-free, as determined by CT and PET-CT scans, with a good functional and esthetic result. Conclusion: ECT represents a safe and effective therapeutic approach that is associated with clear benefits in terms of quality of life (minimal discomfort, mild post-treatment pain and short hospital stay) and may, in the neoadjuvant setting as reported here, offer the option of more conservative surgery and an improved cosmetic effect with complete local tumor control.

Epidermolytic PalmoPlantar keratoderma (EPPK) Vörner-type is an autosomal dominantly inherited skin disease, characterized by severe thickening of the palms and soles, caused by mutations in the keratin K9 (KRT9) gene. To date, a number of KRT9 mutations have been detected, most of which affect the highly conserved 1A region of the central alpha-helical domain, important for keratin heterodimerization. The most common mutation is the substitution of the arginine in position 163 with a tryptophan (R163W), which has been reported in North American, European, and Japanese populations. In a small number of cases, EPPK is associated with knuckle pad keratosis, but no correlation between this additional phenotype and a specific mutation has been found. Moreover, K9 is not normally expressed in knuckle skin, raising the question of the pathogenic mechanism leading to this additional phenotype. Here we show that in a family affected by EPPK and knuckle pad keratosis, carrying the R163W substitution, wild type (wt) and mutated K9 are strongly expressed in knuckle pads. These results suggest that the knuckle pad phenotype is due to ectopical expression of K9.

BACKGROUND Cerebral cavernous malformations (CCM) comprise enlarged capillary cavities in the central nervous system, with possible retinal or cutaneous vascular malformations. This condition is associated with CCM1, CCM2, and CCM3 gene mutations. OBJECTIVE Cutaneous clinical, histological and cerebral MRI findings, including CCM1, CCM2, and CCM3 gene sequencing, of two unrelated, neurological symptom-free patients who consulted for late-onset of deep multiple cutaneous angiomatoid lesions, are described. RESULTS The diagnosis of multiple cutaneous angiomatosis was confirmed and related to CCM as detected by MRI in both cases. Analysis of our patients showed normal nucleotide sequences of the genes proposed. CONCLUSIONS A progressive late-onset of multiple, deep cutaneous venous malformations may indicate the need to investigate a potential coexistence of CCM by MRI. Early diagnosis and prompt treatment is required in these patients. The absence of CCM1, CCM2, and CCM3 mutations might indicate that different genes could be involved in the pathogenesis of these late-onset patients. Careful questioning about family history of CCM is important; our first patient's daughter had a history of cerebral cavernoma.