Zsófia Hatvani

Genotype analysis in Hungarian patients with multiple primary melanoma.

Multiple primary melanoma patients (MPMps) have better prognosis and are more prone to genetic predisposition than single melanoma patients. We aimed to compare genetic background (CDKN2A, CDK4, MITF, MC1R) of 43 Hungarian MPMps with their clinicopathological data. We observed a higher rate of synchronous first and second melanoma (MM) (49%) and a higher frequency of non‐melanoma tumor co‐occurrence (42%) than reported previously. CDKN2A mutation frequency was 4.7% (E69G, R99P). We identified a new human MC1R variant (D117G) and reported MC1R variant distributions in Hungarian MMs for the first time. The rare R163Q was exceptionally common among Hungarian MPMps, a variant otherwise frequent in Asia, but not in Europe. MC1R ‘R’ carriers showed histopathological signs of a more progressive disease than ‘r’ carriers did; however, tumor‐infiltrating lymphocytes (TILs) in their second melanomas occurred significantly more frequently. Calculating 5‐year overall survival, ‘R’ carriers showed more unfavourable prognosis (87%) than ‘r’ carriers did (95%).

Stage distribution of malignant melanomas in a Hungarian centre

INTRODUCTION Survival of patients with malignant melanoma primarily depends on tumor stage. Hungarian National Cancer Registry does not specify tumors according to TNM stages. AIM The authors aimed to survey the stage distribution of melanomas at the Department of Dermatology, Dermatooncology and Venerology, Semmelweis University. METHOD 1160 patients (558 males and 602 females, aged 60.5±16 and 57±17 years, respectively) diagnosed with cutaneous melanoma between 2004-2009 were included. RESULTS In comparison with international studies, the case distribution was favorable in stages IA and IV, i.e. the proportion of early melanomas was relatively high (IA: 43.8%), while the incidence in stage IV was low (0.4%). In stages IB-IIA the incidence was significantly lower, while in IIC, IIIA, IIIB it was higher as compared to published data from Western-Europe, Australia and the United States. CONCLUSIONS The study underlines the necessity of prevention and awareness campaigns that may result in increase of early diagnosis of melanomas.

Confirmation of the role of a KRT5 mutation and successful management of skin lesions in a patient with Galli-Galli disease

Galli–Galli disease (GGD) is a rare autosomal dominant genodermatosis, which is considered an acantholytic variant of Dowling–Degos disease (DDD). It is characterized by reticular, lentigo-like hyperpigmentation on the groins, axillae and large folds, occurring between puberty and early adulthood. Histology shows increased pigmentation of the basal layer, acanthosis with moderate to severe acantholysis, and finger-like rete ridges that result in antler-like patterns of epidermal downgrowths. Despite the presence of acantholysis, skin fragility has not been observed. There is no curative treatment for GGD, but symptoms may be managed by topical corticosteroids, topical and systemic retinoids, intense pulsed light or ablative laser therapy. The aforementioned clinical presentation corresponds to the DDD1 (OMIM 179850) variant caused by KRT5 mutations. Several mutations have been identified in the first exon of KRT5, all of which lead to premature termination codons (PTC), both in sporadic and familial cases. Most cases were reported from Germany, in which c.418dupA was described as the most common mutation in patients with acantholytic DDD. Further mutations were described in Spanish, Arabic, Asian-American, Chinese and Indian patients. In some cases, acantholysis was not observed, and it has also been reported that acantholysis may not necessarily be present at all times or at all anatomical sites. In many cases, both from Europe and Asia, an association between DDD/ GGD and a KRT5 mutation could not be detected. Recently, novel mutations in the POGLUT1 and POFUT1 genes of the Notch signalling pathway have also been identified as causative of DDD in German and Chinese familial and sporadic cases. A 74-year-old Hungarian man presented with a 30year history of a slowly progressing skin condition. Physical examination revealed poikiloderma and widespread pigmented lesions on the patient’s neck and trunk, and on the flexor surfaces of the extremities with small hypopigmented papules, and hyperpigmented macules, which occasionally became inflamed, forming psoriasiform papules over the reticular pattern (Fig. 1a). The patient’s father, grandfather and two brothers had the same ‘ocelot-like’ skin. Histopathology revealed increased pigmentation of the basal layer, finger-like rete ridges in the suprapapillary epidermis, and presence of acantholysis (Fig. 1c,d). A diagnosis of GGD was suggested. Both the inflamed skin condition and pigmentation improved significantly after the introduction of acitretin 25 mg daily (Fig. 1b), which was later reduced to 25 mg alternate daily. When the therapy was temporarily discontinued, the lesions suddenly worsened. Following ethics approval and informed consent, genetic analysis was performed. A heterozygous duplication of the base 418 of KRT5 was found, which causes a frameshift mutation resulting in a PTC in codon 179 (c.418dupA; p.Ile140AsnfsX39; Fig. 1e). This is the first Hungarian case of GGD with a clear genetic background. The KRT5 mutation c.418dupA (p.Ile140AsnfsX39) has been previously identified by Hanneken et al. as being the most common mutation Correspondence: Dr Norbert M. Wikonk al, Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, 41 M aria Street, 1085 Budapest, Hungary E-mail: wikonkal.norbert@med.semmelweis-univ.hu

Epidemiological and molecular genetic examination in epidermolysis bullosa

Semmelweis Egyetem, Általános Orvostudományi Kar, Bôr-, Nemikórtani és Bôronkológiai Klinika, Budapest, Magyarország, Zuglói Egészségügyi Szolgálat, Gyermek Bôrgyógyászat Szakrendelés, Budapest, Magyarország, Men for Care Egészségügyi Központ, Százhalombatta, Magyarország, Egyesített Szent István és Szent László Kórház és Rendelôintézet Bôrgyógyászati Szakambulancia és Lymphoedema Rehabilitációs Osztály, Budapest, Magyarország, Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands