A case of acquired tufted angioma in adulthood

Tufted angioma is a rare vascular tumor whose name derives from its histopathological appearance, characterized by tufts of capillaries within the dermis. Its etiology and pathogenesis are uncertain. Tufted an\uc2\uadgioma typically occurs during infancy or early childhood and displays various clinical patterns. It may present as a subtle stain-like area that later thickens as a large plaque, infiltrated or dusky blue-purple lesion, or as an exophytic, firm, violaceous, cutaneous nodule. Medical treatment is not necessary for tufted angioma, given its benign nature and slow progression. Only clinical follow-up is therefore recommended

Cutaneous T-cell lymphomas CD8+

Recently the expression ofcytotoxic CD8+ immunophenotype in several cutaneous T-cell lymphomas entities was identified. Around 5% of mycosis fungoides (MF) may express a CD8+, CD45RA+, TIA-1+, CD5-(intraepitelial-pagetoid variant) or a CD8+, CD45RO+, CD5+, TIA-1 (dermal, band-like lichenoid variant) immunophenotype and usually present large erythemato-squamous, hycthyosiform plaques in the gluteal area or arms, showing a very indolent course as classical MF. Annular or erythemato-squamous psoriasiform lesions in the abdominal area or arms, with an hypochromic evolution and an indolent course, was characteristic of MF in children and adolescent. In the group of CD30+ lymphoproliferative disorders CD8+ lymphomatoid papulosis cases were associated witb a PLEVA type clinical presentation, with papulo-necrotic or papulo-haemorragic blistering skin lesions and strong epidermotropism. Cases of CD30+, CD8+ cutaneous anaplastic large cell lymphoma were also observed with frequent systemic involvement and fatal outcome in 50% of our cases. Subcutaneous panniculitis-like T-cell lymphoma in the classical cytotoxic (CD45RO+, TIA-1+) alpha-beta (BF-1+) variant showed an intermediate prognosis characterized by cutaneous relapses and possible haemophagocytic syndrome. Aggressive epidermotropic cytotoxic CD8+ T-cell lymphoma (AeCxCD8+L) showed multiple hyperkeratotic or ulcerated nodules and plaques, with a typical CD8+, TIA-1, CD45RA+, CD5-/+, CD2+/-phenotype and a very aggressive fatal course. Cases of pleomorphic small-medium or medium-large lymphoma with an aggressive course (4 cases) or with a benign evolutions may be also CD8+, interestingly three of these aggressive cases were CD8- at presentation and positive in subsequent biopsies. Finally, very rare cases of NK/T nasal type extranodal lymphomas or cases of hydroa vacciniforme-like T ce1l lymphoma showing a very aggressive course may express CD8+, but in association with EBV strong positivity. Cytomorphology, immunohistochemistry and genomics must be used for the diagnosis and in the future they should be useful to better classify CD8+ CTCLs variants

Granulomatous mycosis fungoides: the role of tissue macrophages

Four cases of granulomatous mycosis fungoides (GMF) were analyzed by histological, immunohistochemical and molecular methods. Patients were adult males 18 to 40 years old presenting several plaques and nodules. Complete haematological staging was negative at presentation. The patient was treated by polychemotherapy and radiotherapy. Two patients developed systemic CD30+ lymphoma or disseminated pleomorphic T-cell lymphoma and died of disease. Skin biopsies showed a dermal infiltrate formed by isolated multinucleated giant cells or sarcoid-like granulomas surrounded by atypical lymphocytes, forming rosette-like features and showing focal epidermotropism. Tumor cells were CD2+, CD3+, CD4+, CD5-, CD7-, CD45RO+, IL-17-. Multinucleated giant cells were interleukin (IL)-17+, interferon (IFN)-gamma+ and tumour necrosis factor (TNF)-alpha+, CD68-KP-l+ and CD163+. Interestingly, neoplastic cells rosetting around and located into the multinucleated giant cells, as the epidermotropic lymphocytes, lost the CD5 marker and were proliferating (Ki-67+), while macrophages were hyperplastic forming a nourse-like features. Molecular analysis revealed a T cell clone in all cases and in one case genotypic studies by microarrays CGH showed a loss of 5q33.1, only containing IL-17 beta and PCYOX1L genes. Recently, genetic alterations with reciprocal translocation t(3;9)(q12;p24) and trisomy of chromosome 8 have been reported in two cases of GSS, which may indicate predisposition to granuloma formation. In our case one of the 2 genes deleted is IL17B, involved in the regulation of IL-17 expression. Immunohistochemical stains showed that tumor lymphocytes do not express IL-17, but a strong expression of IL-17 was detected in the multinuc1eated giant celIs. IL-17 has been reported in cutaneous T-cell lymphomas as a cytokine that represents an early event in the development of the inflammatory reaction within the tumour microenvironment, a process that may influence tumour phenotype and growth. Conclusion: Four cases of granulomatous CTCL was analyzed showing characteristic histopathologic, immunohistochemical and molecular features, the loss of IL-17-beta could be considered to play a key role in granuloma formation and tumor microenvironment reaction

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course

Characteristics associated with significantly worse quality of life in mycosis fungoides/Sezary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study

Background Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. Aim To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. Methods Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. Results The study population consisted of 237 patients [60 center dot 3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (beta = 8 center dot 61; P = 0 center dot 003) and alopecia (beta = 9 center dot 71, P = 0 center dot 02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2 center dot 14, 95% confidence interval (CI) 1 center dot 19-3 center dot 89] and emotions (OR 1 center dot 88, 95% CI 1 center dot 09-3 center dot 27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. Conclusions HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients.Peer reviewe

European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part II

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

An ulcer on the foot: a quiz.

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