Mauro Salvatore Alessandro Alaibac

Histopathological characteristics of subsequent melanomas in patients with multiple primary melanomas

Backgroundu2002 Multiple primary melanomas (MPM) occur in up to 20% of melanoma patients, and subsequent tumours seem to have a favourable histopathological pattern.

Pemphigus foliaceus evolving into pemphigus vulgaris: a probable example of ‘intermolecular epitope spreading’ confirmed by enzyme-linked immunosorbent assay study

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Multiple paradoxical adverse events in a patient affected with ankylosing spondylitis treated with TNF blockers.

ejd.2010.1235 Auteur(s) : Alessandro LO NIGRO1 alessandro.lonigro@sanita.padova.it, Roberta RAMONDA1, Mauro ALAIBAC2, Valentina MODESTI1, Leonardo PUNZI1 1 Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy 2 Dermatology Unit, Department of Medical and Surgical Sciences, University of Padova, Italy TNF blockers represent a milestone in the treatment of inflammatory joint diseases, including ankylosing spondylitis (AS). Some [...]

PIBI(D)S: clinical and molecular characterization of a new case

The term PIBI(D)S has been used to indicate a rare recessively inherited genetic disorder characterized by photosensitivity, mild non‐congenital ichthyosis, brittle sulphur‐deficient hair with trichoschisis (trichothiodystrophy), impaired intelligence, occasionally decreased fertility and short stature. To the best of our knowledge, about 20 cases have been reported in the literature. Here we report the characterization of the hair, brain, ultraviolet sensitivity and DNA excision repair defects of a new patient affected by PIBI(D)S. The diagnosis of PIBI(D)S syndrome was made in our patient on the basis of the clinical features and then confirmed by hair microscopy and biochemical analysis. Our patient has increased muscular tone, alteration of the deep tendon reflexes and psychomotor retardation, all consistent with hypomyelination of the brain showed by magnetic resonance imaging and computed tomography. A deficiency of DNA repair capacity was demonstrated in our patient. Furthermore, complementation analysis by cell fusion assigned our patient to xeroderma pigmentosum group D. The nucleotide excision repair defect of the other reported patients with PIBI(D)S falls generally into the same group as xeroderma pigmentosum group D and carry a mutation on the same repair gene (XPD). The relationship between these molecular characteristics and the clinical spectrum of PIBI(D)S is discussed.

In situ expression of the CTLA-4 receptor in T-cell-mediated inflammatory and neoplastic skin diseases.

CTLA-4 is a surface glycoprotein which was originally identified in a cDNA library derived from activated T cells [1]. The natural ligands for CTLA-4 are B7-1 (CD80) and B7-2 (CD86) membrane receptors which were originally identified as natural ligands for CD28 [2]. CTLA-4 and CD28 are clustered in the same chromosomal location and share significant amino acid homology as well as their ligands (B7-1 and B7-2) [3]. The interaction of the B7 molecules (on antigen-presenting cells) with their ligands CD28 and CTLA-4 (on T cells) has been shown to play an important role in delivering positive as well as negative signals to the T cells. Binding of CD28 to its receptors leads to productive T-cell activation by augmentation of several T-cell functions, notably proliferation, cytokine production, adhesion, and cytotoxicity [4, 5]. Several in vitro and in vivo studies and the availability of CTLA-4-deficient mice have contributed to the current understanding of CTLA-4 function. With a few exceptions, all of the results are compatible with a negative regulatory role of CTLA-4 in T-cell activation, which is in clear contrast with the stimulatory function of CD28 in Tcell activation [6]. There are data available concerning the expression of B7 and CD28 in skin tissues [7], but the expression of CTLA-4 has not yet been fully investigated in T-cell-mediated skin diseases. In the study reported here, we examined the expression of CTLA-4 in a large series of human pathological skin conditions (Table 1). All tissue samples had been obtained for diagnostic purposes. Detection of CTLA-4 was performed on frozen sections from reactive and neoplastic skin conditions using an anti-CTLA-4 monoclonal antibody (mAb) (clone BNI3; Immunotech, USA). The BNI3 anti-CTLA-4 mAb has been extensively characterized previously. Briefly, BNI3 is a murine IgG2a obtained by immunization of Balb/c mice with a fusion protein of the extracellular domain of human CTLA-4 and constant regions of the human IgG heavy chain [8]. Most of the samples were also stained with the XIVD3 antiCTLA-4 mAb. Clone XIVD3 is a murine IgG2a obtained by immunization of Balb/C mice with Sf9 insect cells transformed with human CTLA-4 cDNA as previously described [9]. Air-dried acetone-fixed frozen sections were incubated overnight with the anti-CTLA-4 mAbs and, after washing, processed with a standard alkaline phosphatase antialkaline phosphatase (APAAP) technique. The antigen was visualized using fast red as substrate. Sections were counterstained for 5 min with Mayer’s haematoxylin. Negative controls were performed by omitting the primary mAb on samples or by replacing the primary antibody by irrelevant mAbs of identical isotype. Sections from a group of selected samples were double-stained for CTLA-4 and for M. Alaibac · A. Belloni Fortina · A. Poletti · P. Vandenberghe · F. Marino · M. Tarantello · A. Peserico

Basal cell carcinoma: 10-year experience with electrochemotherapy

AbstractBackgroundElectrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking.MethodsIn this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016.ResultsDisease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39–61%). Primary presentation (pxa0=xa00.004), tumor sizexa0<3xa0cm (pxa0<xa00.001), well-defined borders (pxa0=xa00.021), absence of tumor ulceration (pxa0=xa00.001), non-aggressive BCC histology (pxa0=xa00.046) and agexa0≤69xa0years were associated with higher complete response rate. In patients with local BCC, the clearance rate was 72.5 and 85% after one or two ECT cycles, respectively. In the laBCC group, 32 patients (78%) achieved an objective response. Five-year recurrence rate for local and laBCC was 20 and 38%, respectively (pxa0≤xa00.001).ConclusionsOne or two ECT cycles with bleomycin may be a valuable palliative treatment in well-selected patients with multiple BCCs and favorable tumor features. Validation of predictive factors will be imperative to match patients with optimal ECT treatment modalities. Management of laBCC with ECT warrants further investigation.n Trial registration ISRCTN14633165 Registered 24 March 2017 (retrospectively registered)

Anetoderma in cutaneous marginal-zone B-cell lymphoma

Anetoderma is a rare condition, consisting of well‐circumscribed areas of slack skin, in which dermal elastic fibres are destroyed or deficient. We present the case of a 45‐year‐old man with a 25‐year history of deep nodules and plaques gradually progressing to areas of anetoderma. Histological examination found an infiltrate composed of neoplastic cells with lymphoplasmocytoid morphology. The cells were positive for CD20, CD38 and CD138, and there was a monoclonal kappa light chain gene rearrangement of plasma cells. A diagnosis of cutaneous marginal‐zone B‐cell lymphoma was made. The pathogenesis of anetoderma remains unknown, but it is possible that cytokines or other soluble factors produced by the infiltrating lymphocytes have a role in this process.

Atrophic pityriasis versicolor occurring in a patient with Sjögren's syndrome.

Pityriasis versicolor is one of the most frequent epidermal mycotic infections in the world, but its atrophic variant is rarely described. The aetiology of the atrophy is still unknown, and two main hypotheses have been formulated, one suggesting a correlation with long-term use of topical steroids and the other a delayed type hypersensitivity to epicutaneous antigens derived from components of the fungus. Atrophic pityriasis versicolor is a benign disease, but needs to be distinguished from other more severe skin diseases manifesting with cutaneous atrophy. The diagnosis can be easily confirmed by direct microscopic observation of the scales soaked in 15% potassium hydroxide, which reveals the typical ‘spaghetti and meatball’ appearance, or by a skin biopsy in doubtful cases. Here, we describe a case of extensive atrophic pityriasis versicolor occurring in a woman affected by Sjögrens syndrome which completely resolved after topical antifungal treatment.

Localised pseudoepitheliomatous hyperplasia: unusual cutaneous reaction pattern to tattoo.

Dear Editors, Tattoing has been practiced for centuries in many cultures, and has become increasingly popular in Western countries since the 1970s, with a parallel increase in adverse reactions. It is well established that tattooes may be associated not only with different skin diseases, like transient acute inflammatory reactions at the site of needling, but also with serious medical complications such as allergic contact dermatitis, contact urticaria, photodermatitis and other dermatoses like psoriasis, Systemic Lupus Erythematosus (SLE), sarcoidosis, lichen planus or localisation of skin cancer in the area of the tattoo. The reason for this occurrence has not been fully elucidated, but a locus minoris resistentiae or the isomorphism of Koebner has been hypothesised. Herein, we describe a case of a 26-year-old woman who presented to our clinic for an itchy overgrowing reaction at the tattoo site on the posterior side of her right leg. The tattoo had been placed about 6 months prior to spotting the lesion and contained purple, green and blue-black pigment. Cutaneous examination showed a verrucous plaque limited to the purple area of the tattoo, where the patient had applied different topical antibiotic and corticosteroid ointments, without any benefit (Figure 1). Cultural examinations of the lesion were done to exclude an infective pathogenesis and showed negative results. A diagnosis of tattoo granuloma was considered and a cutaneous biopsy was performed. Microscopically, it has: hyperkeratosis, parakeratosis and striking pseudoepitheliomatous hyperplasia (PEH) (Figure 2), with marked perivascular and periadnexial mononuclear inflammatory infiltrate in the dermis and superficial epidermis, composed primarily of lymphocytes and histiocytes (Figure 3A–C). Dermal blackish pigment was also noted (Figure 4A, B). All these findings were consistent with the diagnosis of PEH at the tattoo site. The patient was treated with monthly intralesional triamcinolone injections and she is currently in follow-up. Although inflammatory reactions to tattoos are uncommon, more and more cases are being documented as tattooing becomes increasingly popular in today’s society. Different cutaneous delayed reaction patterns have been described, usually secondary to red pigment injection – the most common are allergic and lichenoid reactions, but granulomatous, pseudolymphomatous and morpheiform reactions can also occur (1,2) The development of cutaneous cancer has been rarely described in the area of a tattoo, but it could be coincidental (3–5). Figure 1 Clinical picture of hyperplastic epidermal reaction localised only to the red pigmented area.

Relapse of pemphigus vulgaris after topical application of ingenol mebutate

Ingenol mebutate is a recently approved topical agent for the treatment of actinic keratosis. Its most common adverse effects are transient local skin reactions. We report a 63‐year‐old white man who presented with a red–brownish crusted plaque involving the dorsum of his nose and an eroded area on his lower lip, which appeared soon after topical application of ingenol mebutate gel. Clinical, histological and immunopathological features were consistent with a diagnosis of pemphigus vulgaris (PV). To our knowledge, this is the first report of relapse of PV after topical application of ingenol mebutate gel. The temporal relationship between the application of the drug and the outbreak of PV supports the involvement of this agent in triggering the disease. It is plausible that ingenol mebutate may have induced the disease by its action on the production of proinflammatory cytokines.