Tumour regression predicts better response to interferon therapy in melanoma patients: a retrospective single centre study.

We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan-Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1-T4) of the primary tumour. Regression was significantly positively related to PFS ( P  = 0.0018, HR = 0.352) and OS ( P  = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P  = 0.0001, HR = 2.629; OS: P  = 0.0003, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.

Evaluation of Calcium Electroporation for the Treatment of Cutaneous Metastases: A Double Blinded Randomised Controlled Phase II Trial.

Calcium electroporation (Ca-EP) is a new anticancer treatment providing similar features to electrochemotherapy (ECT). The aim of our study is to compare the efficacy of Ca-EP with bleomycin-based ECT. This double-blinded randomized controlled phase II study was conducted at the Medical University of Szeged, Hungary. During this once only treatment up to ten measurable cutaneous metastases per patient were separately block randomized for intratumoral delivery of either calcium or bleomycin, which was followed by reversible electroporation. Tumour response was evaluated clinically and histologically six months after treatment. (ClinicalTrials.gov: NCT03628417, closed). Seven patients with 44 metastases (34 from malignant melanoma, 10 from breast cancer) were included in the study. Eleven metastases were taken for biopsies, and 33 metastases were randomised and treated once. The objective response rates were 33% (6/18) for Ca-EP and 53% (8/15) for bleomycin-based ECT, with 22% (4/18) and 40% (6/15) complete response rates, respectively. The CR was confirmed histologically in both arms. Serious adverse events were not registered. Ulceration and hyperpigmentation, both CTCA criteria grade I side effects, were observed more frequently after bleomycin-based ECT than for Ca-EP. Ca-EP was non-inferior to ECT, therefore, it should be considered as a feasible, effective and safe treatment option.

Nuclear Factor κB Activation in a Type V Pityriasis Rubra Pilaris Patient Harboring Multiple CARD14 Variants.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous skin disorder, which is phenotypically related to psoriasis. Some familial PRP cases show autosomal dominant inheritance due to CARD14 mutations leading to increased nuclear factor κB (NFκB) activation. Moreover, CARD14 polymorphisms have also been implicated in sporadic PRP. A Hungarian PRP patient with childhood onset disease showing worsening of the symptoms in adulthood with poor therapeutic response underwent genetic screening for the CARD14 gene, revealing four genetic variants (rs117918077, rs2066964, rs28674001, and rs11652075). To confirm that the identified genetic variants would result in altered NFκB activity in the patient, functional studies were carried out. Immunofluorescent staining of the NFκB p65 subunit and NFκB-luciferase reporter assay demonstrated significantly increased NFκB activity in skin samples and keratinocytes from the PRP patient compared to healthy samples. Characterization of the cytokine profile of the keratinocytes and peripheral blood mononuclear cells demonstrated that the higher NFκB activation in PRP cells induces enhanced responses to inflammatory stimuli. These higher inflammatory reactions could not be explained solely by the observed CARD14 or other inflammation-related gene variants (determined by whole exome sequencing). Thus our study indicates the importance of investigations on other genetic factors related to PRP and their further functional characterization to bring us closer to the understanding of cellular and molecular background of disease pathogenesis.

Melanoma and melanocytic nevi in decorative tattoos: three case reports.

BACKGROUND: In response to the demands of style and fashion, the number of decorative tattoos has been increasing worldwide. This has been paralleled by a rising incidence of melanocytic proliferations, including melanoma. The coincidence of various dermatological diseases and skin tumors with tattoos has been documented with some frequency, but reports of melanoma associated with tattoos are exceedingly rare. To date, only 13 cases have been documented in the English language literature. The possibility of an association between melanocytic proliferations and tattoos remains an area for further study. OBSERVATIONS: This report presents two cases of melanocytic nevi and one of melanoma occurring in association with a decorative tattoos. CONCLUSIONS: At present, the pathogenesis of melanoma developing in a tattoo is unknown. Mere coincidence cannot be ruled out. However, trauma, ultraviolet light exposure, a photoallergic effect, or an inflammatory reaction may promote malignant transformation. Clinicians and histopathologists should be aware of the clinical and pathological features if they are to make a correct diagnosis.

Neglected Basal cell carcinomas in the 21st century.

Although tumors on the surface of the skin are considered to be easily recognizable, neglected advanced skin neoplasms are encountered even in the 21st century. There can be numerous causes of the delay in the diagnosis: fear of the diagnosis and the treatment, becoming accustomed to a slowly growing tumor, old age, a low social milieu, and an inadequate hygienic culture are among the factors leading some people not to seek medical advice. The treatment of such advanced neoplasms is usually challenging. The therapy of neglected cases demands an individual multidisciplinary approach and teamwork. Basal cell carcinoma (BCC), the most common cutaneous tumor, usually develops in the elderly, grows slowly, and has an extremely low metastatic potential; these factors are suggesting that BCCs might well be the "ideal candidates" for neglected tumors. Five neglected advanced cases of BCC were diagnosed in our dermatological institute between 2000 and 2009. The clinical characteristics and treatment modalities of these neoplasms are discussed, together with the possible causes of the neglect.

Collagen XVII/BP180 protein expression in squamous cell carcinoma of the skin detected with novel monoclonal antibodies in archived tissues using tissue microarrays and digital microscopy.

Collagen XVII/BP180, a hemidesmosomal adhesion protein, is lost during normal keratinocyte maturation; however, it may be reexpressed upon malignant transformation. In this work, highly sensitive monoclonal antibodies 6D1 and 9G2 were produced, characterized, and used for the detection of collagen XVII in a tissue microarray series of archived samples of nonmelanocytic epithelial neoplasias, including 5 verruca vulgaris, 14 seborrheic keratosis, 38 actinic keratosis, 38 basal cell carcinoma (BCC), 15 basosquamous carcinoma, 58 squamous cell carcinoma (SCC), and 9 normal skin. Digital microscopy and a new tissue microarray software linking image and patient data allowed easy and validated evaluation and quality archiving of stained samples. In normal skin and benign epidermal lesions, collagen XVII protein was restricted to basal keratinocytes. However, possibly as a sign of undifferentiated/transformed state, it was widely expressed in SCC showing elevated levels around invasive tumor fronts with some staining in tumor adjacent stroma, endothelium, and histiocytes. Collagen XVII immunostaining of atypical keratinocytes in most actinic/solar keratosis supports the view of their malignancy and common origin with SCC. Squamous component of basosquamous carcinoma showed moderate reaction, whereas islets of BCC were mainly negative reflecting the diverse genotype and phenotype, and pathogenesis of SCC and BCC. These results suggest that collagen XVII neoexpression may be associated with early atypia/malignant transformation of keratinocytes. Further investigations are under way to analyze the potential of these antibodies for tracing progression and metastatic potential of skin tumors.

Congenital syringocystadenoma papilliferum.

We present a boy with a congenital, ulcerated nodule on the scalp. At birth, the lesion was considered to be the result of a traumatic injury, but a biopsy at the age of 6 months pointed to a diagnosis of syringocystadenoma papilliferum. We draw attention to the difficulty of identifying head lesions in young children from clinical signs alone.

Necrolytic migratory erythema.

BACKGROUND: Necrolytic migratory erythema is considered to be a paraneoplastic dermatosis. The classical symptoms are associated with alpha-cell pancreatic islet cell tumor or 'glucagonoma'. Generally, extracutaneous hallmarks of this disease include weight loss, diabetes, anaemia and diarrhoea. OBSERVATION: We report a case of a 39-year-old woman with a 3-year history of recalcitrant psoriasiform eruption, who had no other associated symptoms on routine examination. Histologic examinations suggested necrolytic migratory erythema. Abdominal computer tomography was performed, which revealed a tumor in the tail of the pancreas. After distal resection of the pancreas her skin symptoms resolved in a few days time. Histology was consistent with glucagonoma. She is clinically well and symptomless and no signs of metastasis after 4 years. CONCLUSIONS: It is infrequent to have only necrolytic migratory erythema, hyperglucagonaemia and islet-cell tumor but no other extracutaneous symptoms in glucagonoma syndrome. To our knowledge, ours is the second such case reported in the literature. Skin symptoms are important, often they are the clue to the diagnosis of glucagonoma syndrome.

Experimental bullous pemphigoid generated in mice with an antigenic epitope of the human hemidesmosomal protein BP230.

Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease that targets the hemidesmosomal proteins BP230 and BP180. To investigate the pathogenic role of anti-BP230 antibodies, rabbit polyclonal antibodies were generated against an antigenic sequence of the human BP230 antigen (BPAG 1, 2479-2499), which shows 67% homology in the human and the mouse BP230. Purified IgG from the rabbit anti-serum was transferred subcutaneously into the dorsal skin of neonatal isogeneic CBA/Ca (CBA) mice in a dose of 5 mg (n=7) or 1.2 mg IgG/50 microl (n=16). After 24 h, 1 of the mice injected with 5 mg IgG exhibited blisters, but the dorsal skin of all 7 of them was erythematous, and gentle friction produced a fine persistent wrinkling of the epidermis in 4 mice. The mice injected with 1.2 mg IgG developed less severe symptoms. Immunohistological examinations revealed linear rabbit IgG and mouse C3 depositions along the basement membrane of the perilesional skin and subepidermal blister formation. An intradermal inflammatory reaction (granulocyte infiltration) was also detected. None of these symptoms was seen in mice injected with IgG from a control rabbit anti-serum. These findings demonstrate that antibodies against BP230 can elicit the clinical and immunopathological features of BP in neonatal mice, suggesting that anti-BP230 antibodies may possibly play a pathogenic role in this disease.