Dermo Beta Brachytherapy with 188Re in extramammary Paget's disease.

AIM: Extramammary Paget's disease (EMPD) is a rare neoplastic pathology involving the vulva, scrotum, and perianal areas, and it is characterized by a slow and insidious course. EMPD may also be associated with internal malignancy, and its clinical presentation features long-standing pruritic lesions, eczema-like, refractory to any therapy. The pathogenesis is unclear, and univocal standardization of treatment is yet to be determined. As regard to the patients who suffer from it, women are more often affected than men. The therapeutic approach depends on the extent of involvement; wide surgical excision is the first choice among treatments, but other forms of therapy, alone or in combination, include imiquimod 5%, photodynamic therapy, Mohs surgery as well as external beam radiotherapy and Brachytherapy. In the present paper a new therapeutic alternative is proposed: Dermo-Beta-Brachytherapy (DBBT) with 188Re. METHODS: Five patients with EMPD, one secondary and four primary cases, have been treated by Brachytherapy with DBBT. This therapy has been successfully used for non-melanocytic skin tumors and basically consists in the topical application of a specially designed, tailor-made mould containing a radioactive beta-emitting isotope, rhenium-188. RESULTS: The patients healed completely, after one session in one case and after two sessions in four cases, with 34 months mean follow-up. CONCLUSION: Brachyterapy could represent a new alternative therapy, instead than invasive treatments as surgery and conventional radiotherapy, capable to treat EMPD independently of its extension, with aesthetic and functional satisfactory results.

Visceral leishmaniasis revealed by a squamous cell carcinoma in an HIV-1 infected patient.

We present a case of visceral leishmaniasis confirmed after the histological investigation of an ulcerate lesion of the scalp in an HIV-1-infected patient receiving highly active antiretroviral therapy (HAART). Histological examination of the skin lesion revealed a squamous cell carcinoma superinfected by amastigotes of Leishmania infantum from the bloodstream. Because HIV-1-infected individuals can harbour parasitic infections in normal and neoplastic tissue, it is necessary to examine carefully any skin lesions, particularly those with uncommon aspects or a worsening course, to exclude superinfections by unsuspected pathogens.

Lichen sclerosus and the risk of malignant progression: a case series of 159 patients.

AIM AND METHODS: We analyzed 159 stored specimens of Lichen Sclerosus (LS) collected in the period 1999-2011 from 159 patients, in order to evaluate the histological patterns, clinical outcomes and possible associations with malignancies. The histopathologic analysis revealed 145 cases (males and females) with LS alone, 7 in whom penile LS was associated with spinocellular carcinoma (SCC), and 7 in whom LS was associated with a pseudocarcinomatous-hyperplasia (PCH). Extragenital LS was found in 20% (17/85) of the males and 78% (58/74) of the females. In the cases of SCC, immunohistochemical analyses was performed. RESULTS AND CONCLUSION: The results showed very low positivity to p16INK4A and Ki-67; biomolecular PCR was positive in only two cases, and in both cases the non-oncogenic genotype HPV 100 was detected. No important additional risk factors for malignancies were found (e.g., hormones, infections, other autoimmune diseases).

Association of p53 Arg72Pro polymorphism and beta-catenin accumulation in mycosis fungoides.

BACKGROUND: Aberrant activation of beta-catenin contributes to the onset of a variety of tumours. There are many tumours that display beta-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type beta-catenin has been associated with mutational inactivation of the p53 tumour suppressor. OBJECTIVES: To investigate the potential role of p53 and its homologue p63 in beta-catenin deregulation and to correlate this with disease outcome. METHODS: We analysed a panel of 24 samples of mycosis fungoides (MF), the most frequent manifestation of cutaneous T-cell lymphoma (CTCL), for beta-catenin, p53 and p63 protein expression by immunohistochemistry. Based on the immunostaining results for beta-catenin protein, 11 positive cases were selected for laser microdissection, genomic DNA isolation and subsequent mutation analysis of beta-catenin exon 3 and p53 exons 4-8. RESULTS: Our findings revealed overexpression of beta-catenin, p53 and p63 in 46%, 38% and 17% of cases, respectively. The number of p53-positive cases of MF was significantly higher (P < 0.05) in the beta-catenin-positive group (73%). Sequence analysis demonstrated that wild-type beta-catenin accumulation in MF is not associated with mutational inactivation of the p53 gene and, more importantly, our data provide evidence that a common polymorphic form of p53 (Arg72Pro) is significantly associated with beta-catenin overexpression (P < 0.05). No significant differences in the three genotypes were observed between the CTCL cases and the control group, demonstrating that Arg72Pro polymorphism of the p53 gene is not associated with the risk of developing cutaneous lymphomas (P > 0.05). CONCLUSIONS: We found an association of beta-catenin and p53 overexpression without detection of structural alteration in the genes, suggesting that p53 mutation is not an important mechanism for beta-catenin activation in primary CTCL. Additionally, we speculate that the p53 codon 72 polymorphism may influence negative feedback control involving beta-catenin and p53.

Early but not lasting improvement of recalcitrant subcorneal pustular dermatosis (Sneddon-Wilkinson disease) after infliximab therapy: relationships with variations in cytokine levels in suction blister fluids.

Subcorneal pustular dermatosis (SCPD) is an uncommon disorder, characterized by a chronic relapsing vesiculopustular eruption, mainly involving the trunk and intertriginous areas, and usually seen in women > 40 years old. Various therapies have been reported to be effective in treating SCPD, such as dapsone, systemic glucocorticoids, acitretin, etretinate, infliximab and phototherapy. We report a case of a 54-year-old woman affected by SCPD who after failure of different therapies showed a dramatic but only temporary improvement of her disease during a cycle of therapy with infliximab. In addition, an array of cytokines was simultaneously measured in suction blister fluids obtained from involved or uninvolved skin at various time intervals during the first 12 weeks of observation.

HPV5b variant in a neoplastic lesion of an Italian patient affected by epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) can be defined as a genetic disorder that determines a lifelong infection of the skin by human Papillomaviruses (HPV). The benign lesions contain different HPVs; whereas in the tumors HPV types 5, 8, and, much less frequently, types 14, 17, 20 and 47 can be detected. Variants of HPV5 have been recognized on the basis of the genetic heterogeneity of the E6 open reading frame. We report a typical case of EV in which the presence and expression of the HPV type 5 were clearly detectable. Direct sequence analysis demonstrated a perfect homology with the sequence of the HPV5b variant. This variant was first isolated in a Japanese patient and thereafter in a Polish one. Its presence in the Italian patient indicates that the same variant can be detected in different geographic areas and therefore that some cellular genes may exert a selection pressure so strong as to induce the emergence of this stable HPV5b infectious variant.

Papuloverrucous colloid milium: an occupational variant.

We report a case of adult colloid milium in a 47-year-old mechanic with a long history of professional contact with lubricating oils and of sun exposure. In addition to the typical translucent papules seen on the forehead, there were warty papules on the backs of both hands with unusual histological and ultrastructural features: marked hyperplasia of the epidermis with orthokeratotic hyperkeratosis and papillary deposits of colloid material that were contiguous with the basal layer of the epidermis. The hand lesions caused by occupational exposure to mineral oils and solar radiation represent an occupational variant of adult colloid milium.

Isolated granulocytic sarcoma of the skin in an elderly patient: good response to treatment with local radiotherapy and low-dose methotrexate.

Granulocytic sarcoma of the skin is frequently associated with haematological diseases and is rarely isolated. The disease generally develops into acute systemic myeloid leukaemia and is associated with a poor prognosis. We report an elderly patient presenting isolated granulocytic sarcoma of the skin who showed a very good response to treatment with local radiotherapy and low-dose methotrexate.

Primary cutaneous plasmacytoma: report of a case with review of the literature.

Primary cutaneous plasmacytoma (PCP) is a rare cutaneous B-cell lymphoma. We report a new case of PCP and review data published in the literature. A 55-year-old man presented with 2 erythematous plaques on the upper trunk, showing histologic and immunohistochemical features of PCP. Staging investigations excluded extracutaneous manifestations of the disease. The patient was treated with melphalan and prednisone associated with local radiotherapy. Twenty-four months after the first presentation he is alive and well. Only 29 cases of PCP have been reported in the last 50 years. The main prognostic factor seems to be the clinical presentation (solitary vs multiple lesions). Solitary lesions of PCP may be treated conservatively by surgical excision or local radiotherapy.

[Plantar fibromatosis: ultrasonography results]. / La fibromatosi plantare: risultati ecografici.

INTRODUCTION: Plantar fibromatosis, or Ledderhose's disease, is a fibrous proliferation arising within the plantar fascia end exhibiting typical clinical nodular features. The lesion appears as a firm single thickening or a nodule, occasionally painful, localized to the medial portion of the sole of the foot. This unusual condition has not been extensively studied with US and very little has been written about it. MATERIAL AND METHODS: In 1998-99, six patients with plantar fibromatosis were submitted to US with 13 MHz linear array and 20 MHz mechanical annular array probes. All patients were examined in prone recumbency with the probe positioned on the sole of the foot. Only some of them were subsequently submitted to surgery. RESULTS: Plantar fibromatosis exhibited an almost pathognomonic pattern and US proved to be a quick, noninvasive and cost-effective technique to confirm clinical diagnosis. The nodule is typically single and isoechoic, with maximum diameter of about 1 cm, inhomogeneous internal structure and few thin hyperechoic septa. The nodular fibrous proliferation adheres with the major axis along the plantar fascia; it exhibits clear-cut margins and US beam transmission is good. No calcifications or fluid collections are seen within the nodule. Color and power Doppler show no flow inside. CONCLUSIONS: US is an adequate tool for the study of plantar fibromatosis.

Widespread microsatellite instability in sebaceous tumours of patients with the Muir-Torre syndrome.

Muir-Torre syndrome (MTS) is an autosomal dominant disorder characterized by the presence of at least one sebaceous gland tumour and a minimum of one visceral malignant tumour. Recently, microsatellite instability (MSI) has been detected in the tumours of patients with MTS and germline mutations of the hMSH2 and hMLH1 mismatch repair genes have been detected in some patients with this syndrome. To determine if the tumours of patients with MTS have widespread genomic instability and whether loss of heterozygosity (LOH) in the chromosomal regions containing hMSH2 and hMLH1 is detectable, MSI and LOH were examined at 10 dinucleotide repeats on chromosomes 2p, 3p, 5q, 9p, 17p and 18q. Data were obtained from six sebaceous gland tumours and two adenocarcinomas of the colon from three patients of two Muir-Torre families. MSI was detected at more than half of the loci tested in all sebaceous tumours examined. In addition, there was LOH at D2S119 in one sebaceoma and one sebaceous carcinoma from one patient. The colon carcinomas from two patients showed MSI at five of the 10 loci analysed. These results show that widespread MSI is a feature of tumours in patients with MTS. In addition, the finding of LOH at D2S119, a marker located in the vicinity of hMSH2, in sebaceous tumours of one patient indicates that this gene may have a pathogenetic role in this patient.