Paola Savoia

Wide local excision vs. Mohs Tübingen technique in the treatment of dermatofibrosarcoma protuberans: a two‐centre retrospective study and literature review

Dermatofibrosarcoma protuberans (DFSP) is a rare, low‐grade mesenchymal skin tumour, characterized by slow infiltrative growth and common local recurrence, with infrequent distant metastases.

An unusual cutaneous infection caused by Mycobacterium marinum

Introduction. Mycobacterium marinum is a non-tubercular mycobacterium residing in fresh or salt water (in tropical or temperate areas); it is a fish and human pathogen, and in immunocompromised patients can cause severe cutaneous and subcutaneous infections. Case presentation. A 46-year-old white man who underwent immunosuppressive therapy was admitted to our department in May 2016 for skin lesions previously diagnosed as ‘unusual erysipelas’. We rejected the hypothesis of erysipelas, due to the clinical features, and our diagnostic hypotheses were oriented towards sporotrichosis, atypical mycobacteriosis, cutaneous tuberculosis and cutaneous sarcoidosis. Histological examination performed after a skin biopsy was compatible with a diagnosis of sporotrichosis. However, PCR performed on fresh tissue demonstrated the presence of M. marinum. Conclusion. The case reported is interesting for the unusual clinical localization and modality of infection. The patient became infected by contact with contaminated remains or in the sea, in a geographical area not endemic for M. marinum. The previous state of immunosuppression favoured infection; however, the presence of M. marinum in this area suggests a possible tropicalization of the water of the Mediterranean Sea. To our knowledge, this case is the only one reported in the literature with this modality of infection and in that geographical area.

Ipilimumab (Anti-Ctla-4 Mab) in the treatment of metastatic melanoma: effectiveness and toxicity management

ABSTRACT In the last years the onset of new therapies changed the management of malignant melanoma. Anti CTLA-4 antibody ipilimumab was the first drug to achieve a significant improvement in survival of advanced stage melanoma. This new therapeutic agent is characterized by a number of side effects that are totally different from those of traditional chemotherapy, mainly caused by the immune system activation. The purpose of this paper is to underline the central role of ipilimumab in the treatment of metastatic melanoma and to characterize related adverse events in terms of incidence, duration and severity of presentation. The early recognition of these side effects is crucial in order to ensure an appropriate management of the toxicities, thus reducing the long term clinical sequelae and the inappropriate treatment discontinuation.

Anti-oxidative effects of 17 β-estradiol and genistein in human skin fibroblasts and keratinocytes

BACKGROUND Estrogens and phytoestrogens can hinder the aging process through mechanisms related to estrogen receptors (ERs), guanine nucleotide-binding protein-coupled receptor (GPER30), mitochondria function and nitric oxide (NO) release. Up to date, however, the above issues are a matter of debate. OBJECTIVE To examine the effects elicited by 17 β-estradiol and genistein against peroxidation in human keratinocytes/fibroblasts and evaluate the role played by ERs, GPER30, mitochondria and NO. METHODS Human fibroblasts/keratinocytes, either subjected to peroxidation or not, were exposed to 17 β-estradiol/genistein in the absence or presence of the NO synthase (NOS) inhibitor, the ERs and GPER30 blockers, fulvestrant and G15, the phosphatidyl-inositol-3-kinase (PI3K-Akt), the p38 mitogen-activated protein (MAP) kinase and the extracellular signal-regulated kinases (ERK) 1/2 inhibitors. Specific kits were used for cell viability, NO, ROS and glutathione (GSH) detection and mitochondrial membrane potential measurement. Western Blot analysis was performed for kinases expression/activation detection. RESULTS In physiological and peroxidative conditions, 17 β-estradiol/genistein respectively increased and reduced NO release by fibroblasts/keratinocytes. Moreover, both agents prevented the ROS release and the fall of cell viability and mitochondrial membrane potential, while increasing GSH levels and the proliferation rate. Fulvestrant and G15 counteracted all above responses. Also, the NOS, and the kinases blockers reduced the protection exerted by 17 β-estradiol/genistein on cell viability/mitochondria function. The involvement of PI3K-Akt and p38-MAPK was confirmed by Western blot. CONCLUSION 17 β-estradiol/genistein protected fibroblasts/keratinocytes against peroxidation by modulating oxidant/antioxidant system and mitochondria membrane potential, through mechanisms related to ERs and GPER30 and kinases activation.

Pili torti, bleiche und elastische Haut sowie eine schwere neurologische Beeinträchtigung

Ein 7 Monate altes, männliches hellhäutiges Baby wurde zur Untersuchung einer angeborenen Haardysplasie vorstellig. Das hellbraune Haar war stumpf, brüchig, dick, und kraus. Das Baby hatte außerdem blasse und elastische Haut mit überschüssiger Nackenhaut, pausbäckige Wangen, eine abnormale Schädelform und war psychomotorisch stark eingeschränkt (Abbildung 1). Im Alter von 10 Tagen war der Pili torti, bleiche und elastische Haut sowie eine schwere neurologische Beeinträchtigung Pili torti, pale and elastic skin, and severe neurological impairment Diagnosequiz

A female newborn with papulovesicular lesions

A female newborn of Pakistani origin presented at birth with papulovesicular lesions with a surrounding erythematous base on the trunk and all four limbs. The baby was born at term after an uneventful pregnancy and vaginal delivery. She had a weight of 3,400 grams and an APGAR score of 9 at the 1 st and 5 th minute. Her parents were not blood-related. The mother was 26 years of age, healthy and without a history of abortion; her three-year-old fi rstborn female was in good health. A female newborn with papulovesicular lesions Case for Diagnosis

Sensitivity to asbestos is increased in patients with mesothelioma and pathogenic germline variants in BAP1 or other DNA repair genes

Pathogenic germline variants in the BAP1 tumor suppressor gene can cause a cancer syndrome called BAP1 tumor predisposition syndrome (BAP1‐TPDS), which is characterized by predisposition to mesothelioma, melanoma, renal cell carcinoma, basal cell carcinoma, and other tumors. Other genes that may predispose to mesothelioma are CDKN2A and DNA repair genes. Asbestos exposure has often been reported in patients with malignant pleural mesothelioma (MPM) and germline variants in BAP1, but this exposure has never been quantified. We aimed to search for germline variants in BAP1 among 25 new Italian probands with suspected BAP1‐TPDS, summarize the prevalence of these variants in 39 Italian patients with familial MPM and other tumors recruited over a 5‐year period, and compare cumulative asbestos exposure in 14 patients with MPM and pathogenic germline variants in BAP1, CDKN2A, or DNA repair genes with that of 67 patients without germline variants in 94 cancer‐predisposing genes.

Aberrant expression of aquaporin-3 in hereditary papulotranslucent acrokeratoderma and aquagenic palmoplantar keratoderma

Aquagenic keratoderma (AK) is an uncommon dermatosis characterized by transient eruptions of translucent palmarplantar papules and plaques, triggered by contact with sweat or water [1]. Sporadic cases occur often in young women, frequently associated with intake of COX-2 inhibitors [1]. However, several autosomal dominant or recessive hereditary cases have been described; about one third of which are associated with germline mutations of the CFTR gene (cystic fibrosis transmembrane conductance regulator), both in healthy carriers and cystic fibrosis (CF) patients, while others remain without clear aetiology [2-4]. AK may clinically resemble hereditary papulotranslucent acrokeratoderma (HPA), an extremely infrequent autosomal dominant keratoderma of which the genetic basis remains unknown; it is characterized by permanent, palmarplantar whitish papules and plaques, worsening after water contact [5, 6]. We report clinicopathological, genetic, and immunohistochemistry findings of six new cases of sporadic and familial AK and one new case of HPA, diagnosed at our institution. The clinical and genetic characteristics are summarised in table S1. All patients, except Patient 7, had a history of transitory, recurrent, palmar-plantar symmetric lesions which occurred during sweating or bathing, or as a permanent feature in humid conditions. Patients reported a transient burning sensation, itching, and/or a reduction in tactile sensitivity that disappeared with drying. Patient 7 presented with permanent, bilateral, macerated acral papules-plaques, which appeared in childhood and progressively increased in number. Lesions systematically worsened upon short periods of contact with water. In all cases, the short exposure to water at room temperature (water immersion test [WIT]) generated a prompt appearance of hyperkeratotic, whitish, macerated palmar-plantar papules and plaques. These lesions vanished within one hour in all subjects except for Patient 7 who manifested with the pre-existing lesions (figure 1A-C). Patient 1 and 7 reported similar lesions in other family members, who also had a positive WIT test. Clinical features led to diagnosis of AK in Patients 1, 2, 3, 4, 5 and 6; in Patient 4, diagnosis was histologically confirmed by marked acanthosis and orthokeratotic hyperkeratosis, associated with dermal sclerosis and dilatation of intraepidermal eccrine ducts (figure 1D, E). For Patient 7, there were clinical findings and features within the family suggesting a rare case of HPA; histology showed typical features with hyperkeratosis, hypergranulosis, and acanthosis of the epidermis, without alterations of eccrine ducts (figure 1F, G). It is well known that AK may be a clue to CF carrier status in healthy subjects, while CFTR gene mutations have never been tested previously in HPA cases. We performed a search for the 67 more common mutations of the CFTR gene in all KA and HPA patients, with the exception of Patient 6. Patient 1 resulted as compound heterozygote for the 5T A C

Pili torti, pale and elastic skin, and severe neurological impairment

A 7-month-old male Caucasian infant was presented for evaluation of congenital hair dysplasia with light-brown, opaque, fragile, thick, kinky hair. He also showed pale and elastic skin with redundant nuchal skin, pudgy cheeks, craniofacial abnormalities, and severe psychomotor impairment (Figure 1). At 10 days of life, he was hospitalized due to poor weight gain and hyporeactivity. One month later, he developed anemia (Hb 6.4 g/dL), a urinary tract infection, and gastroesophageal reflux. From the age of four months, he started having focal seizures with intermittent eye deviation, hand and finger myoclonus, as well as hypertonia and dyskinesia of the shoulder girdle; EEG showed a left temporal-occipital focus.

Complete response to anti-PD-1 nivolumab in massive skin metastasis from melanoma: efficacy and tolerability in an elderly patient.

The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma. The 30–40% of treated patients experience an objective tumour regression, with a significantly prolonged survival and an improved quality of life. Here, we report a case of a 75-year-old Caucasian woman affected by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced multiple relapses after surgery and repeated electrochemotherapy treatments. A poor response was observed after systemic therapy with ipilimumab, whereas a marked reduction in the lesion size was obtained during the treatment with nivolumab, with an objectively complete response after 6 months. Therapy was well tolerated, without immune-related side effects. During treatment, LDH levels decreased up to the standard values. Our experience confirms the good efficacy and the safety of anti-PD-1 nivolumab for the treatment of relapsed or refractory massive skin lesions, also in elderly patients.