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Corynebacterium ulcerans is mainly known for its ability to cause animal infections. Some strains of C. ulcerans produce diphtheria toxin, which can cause life-threatening cardiopathies and neuropathies in humans. Human cutaneous C. ulcerans infection is a very rare disease that mimics classical cutaneous diphtheria. We present a very rare case of a C. ulcerans skin infection caused by a non-diphtheria toxin-producing strain of C. ulcerans that resolved after 3weeks of therapy with amoxicillin-clavulanate. A pet cat was the probable source of infection. The presence of C. ulcerans in the mouth of the cat was confirmed by 16S rRNA gene analysis and the API Coryne system. In cases of human infection with potentially toxigenic corynebacteria, it is important to determine the species and examine the isolate for diphtheria toxin production. If toxigenicity is present, diphtheria antitoxin should be administered immediately. Carriers and potential infectious sources of C. ulcerans include not only domestic livestock but also pet animals. For the primary prevention of disease caused by diphtheria toxin-producing corynebacteria, vaccination with diphtheria toxoid is recommended

Item does not contain fulltext, Spindle cell hemangioma (SCH) is a distinct vascular soft-tissue lesion characterized by cavernous blood vessels and a spindle cell component mainly occurring in the distal extremities of young adults. The majority of cases harbor heterozygous mutations in IDH1/2 sporadically or rarely in association with Maffucci syndrome. However, based on mosaicism and accordingly a low percentage of lesional cells harboring a mutant allele, detection can be challenging. We tested 19 sporadic SCHs by Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), conventional next generation sequencing (NGS), and NGS using a single molecule molecular inversion probes (smMIP)-based library preparation to compare their diagnostic value. Out of 10 cases tested by Sanger sequencing and 2 analyzed using MLPA, 4 and 1, respectively, revealed a mutation in IDH1 (p.R132C). The 7 remaining negative cases and additional 6 cases were investigated using smMIP/NGS, showing hot spot mutations in IDH1 (p.R132C) (8 cases) and IDH2 (3 cases; twice p.R172S and once p.R172G, respectively). One case was negative. Owing to insufficient DNA quality and insufficient coverage, 2 cases were excluded. In total, in 16 out of 17 cases successfully tested, an IDH1/2 mutation was found. Given that IDH1/2 mutations were absent in 161 other vascular lesions tested by smMIP/NGS, the mutation can be considered as highly specific for SCH.

Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like pericytes. Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF(WT/V600E); 33.3% (1 of 3 samples) of BRAF(WT/V600E)-MPCs were multifocal/infiltrative/recurrent. Patient-MPC and primary MPC cells harbored BRAF(WT/V600E), were clonal and expressed pericytic-differentiation biomarkers crucial for its microenvironment. BRAF(WT/V600E)-positive thyroid MPC primary cells triggered in vitro (8.8-fold increase) and in vivo (3.6-fold increase) angiogenesis. Anti-BRAF(V600E) therapy with vemurafenib disrupted angiogenic and metabolic properties (~3-fold decrease) with down-regulation (~2.2-fold decrease) of some extracellular-matrix (ECM) factors and ECM-associated long non-coding RNA (LincRNA) expression, with no effects in BRAF(WT)-pericytes. Vemurafenib also inhibited (~3-fold decrease) cell viability in vitro and in BRAF(WT/V600E)-positive thyroid MPC patient-derived xenograft (PDX) mice (n = 5 mice per group). We established the first BRAF(WT/V600E)-dependent thyroid MPC cell culture. Our findings identify BRAF(WT/V600E) as a novel genetic aberration in MPC pathogenesis and MPC-associated biomarkers and imply that anti-BRAF(V600E) agents may be useful adjuvant therapy in BRAF(WT/V600E)-MPC patients. Patients with BRAF(WT/V600E)-MPC should be closely followed because of the risk for multifocality/recurrence.

01 juli 2012, Item does not contain fulltext, A detailed analysis of the results of the international annual International Committee for Dermatopathology-Union Europeene des Medecins Specialistes dermatopathology examination was undertaken to identify clues for further improvement. The analysis covered 5 consecutive years (2006-2010) and involved a total of 860 questions (591 common questions and 269 uncommon questions) and 181 participants. It focused on the overall performance of the participants, the performance per part of the examination (theoretical or practical), the performance per format of question (multiple choice or open), the performance per dermatopathological topic, and the performance per professional background (dermatologist or pathologist). The overall performance of the participants was high (on average 75% correct answers in 2006 and 85% correct answers in the subsequent years). In the theoretical part of the examination, the topics of vascular diseases and lichenoid dermatoses scored better than the average of all topics, and the topics of cutaneous lymphoproliferative diseases and melanocytic disorders scored worse. In the first practical part (interpretation of images), dermatologists outperformed pathologists, especially on providing a diagnosis (open question format) of clinical images. In the second practical part (microscopical examination), the topics of vascular diseases, granulomatous diseases, including necrobiotic and degenerative and metabolic diseases scored better than the average of all topics, and the topic of infectious diseases scored worse. The results of this detailed analysis provide an excellent feedback to the examination committee that will be used to consider the adjustment of parts and/or topics of the examination that showed a deviant performance by the participants. In addition, it is recommended to give more attention to the postgraduate education of certain dermatopathological topics, including cutaneous lymphoproliferative diseases, melanocytic disorders, and

Corynebacterium ulcerans is mainly known for its ability to cause animal infections. Some strains of C. ulcerans produce diphtheria toxin, which can cause life-threatening cardiopathies and neuropathies in humans. Human cutaneous C. ulcerans infection is a very rare disease that mimics classical cutaneous diphtheria. We present a very rare case of a C. ulcerans skin infection caused by a non-diphtheria toxin-producing strain of C. ulcerans that resolved after 3 weeks of therapy with amoxicillin-clavulanate. A pet cat was the probable source of infection. The presence of C. ulcerans in the mouth of the cat was confirmed by 16S rRNA gene analysis and the API Coryne system. In cases of human infection with potentially toxigenic corynebacteria, it is important to determine the species and examine the isolate for diphtheria toxin production. If toxigenicity is present, diphtheria antitoxin should be administered immediately. Carriers and potential infectious sources of C. ulcerans include not only domestic livestock but also pet animals. For the primary prevention of disease caused by diphtheria toxin-producing corynebacteria, vaccination with diphtheria toxoid is recommended.

Item does not contain fulltext, Cutaneous myoepithelial tumors form a clinicopathological spectrum ranging from mixed tumor to myoepithelioma and myoepithelial carcinoma. Recently, EWSR1 rearrangement has been described in a subset of soft tissue myoepithelial tumors, whereas the cutaneous counterparts showed this aberration in a minority of cases. This raises the question whether cutaneous myoepithelial tumors have comparable genetic alterations. We examined 18 cases of cutaneous myoepithelial tumors arising in 7 female and 11 male patients (age range, 34-86 years; mean, 58 years). Eight mixed tumors occurred at the head, and one at the scrotum. Six myoepitheliomas arose at the extremities, and one case each at the back and head. One myoepithelial carcinoma occurred at the cheek. The tumor size ranged from 0.3 to 1.7 cm (mean, 1.0 cm). All mixed tumors and three myoepitheliomas were limited to the dermis. Four myoepitheliomas and the myoepithelial carcinoma involved the subcutis. Mixed tumors and myoepitheliomas were composed of myoepithelial cells with a variable cytomorphology, architecture and stromal background. Ductal structures were seen by definition in mixed tumors. The myoepithelial carcinoma represented an infiltrative dermal neoplasm consisting of atypical spindle cells. Immunohistochemically, all cases tested were positive for EMA and calponin, whereas S100, CK, ASMA and GFAP were expressed in 90%, 80%, 78% and 50% of the cases tested, respectively. By fluorescent in situ hybridization analysis, 7 out of 16 cases (44%) exhibited EWSR1 rearrangement. Four of them were mixed tumors, two were myoepitheliomas and one was a myoepithelial carcinoma, confirming that these lesions represent a spectrum of dermal myoepithelial tumors. Follow-up information, available for five patients (including the patient with a myoepithelial carcinoma), revealed no evidence of disease in all cases (range, 6-72 months). Our study provides a genetic relationship of myoepithelial tumors of the skin with their c

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. OBJECTIVE: To examine whether EV is associated with cutaneous MCPyV infection. METHODS: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. RESULTS: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. CONCLUSIONS: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.

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The histogenesis of primary cutaneous marginal zone B-cell lymphoma (PCMZL) has not yet been clarified. Plasmacytoid dendritic cells (PDC) play a crucial role in the initiation of immune responses and activation of T-cells and B-cells. We analyzed the presence of PDC by immunohistochemistry in various forms of primary cutaneous B-cell lymphomas and in B-cell pseudolymphomas. Clusters of CD123 PDC were observed in all PCMZL (23 of 23 cases; 100%) and in two-thirds of cutaneous B-cell pseudolymphomas (14 of 22; 64%), but only in a minority of primary cutaneous follicle center lymphoma (4 of 31; 13%) and not in primary cutaneous diffuse large B-cell lymphoma, leg type. CD123+ PDC clusters were found in close proximity to monoclonal plasma cells and T-cells and were already present at high numbers in early lesions and initial recurrences of PCMZL. In conclusion, the detection of larger clusters of PDC in PCMZL provides a useful adjunctive diagnostic marker and suggests a pathogenetically relevant role of these cells in PCMZL. Furthermore, the occurrence of PDC could explain the high number of T-cells typically found in PCMZL. We propose considering PCMZL as a unique and potentially antigen-driven neoplasm with PDC, T-cells, and B-cells as the constitutive tumor components. Copyright © 2009 by Lippincott Williams & Wilkins.

We describe 11 poroid neoplasms with sebaceous differentiation, including a metaplastic (sarcomatoid) carcinoma arising in association with an apocrine poroma. Six lesions had the silhouette of a classical poroma, 3 of poroid hidradenoma and 1 of dermal duct tumor. In all cases, sebaceous differentiation was identified as clustered or solitary, mature sebocytes occurring mainly at the periphery of intradermal cellular aggregations, accompanied by sebaceous ducts. In one poroma, clusters of sebocytes were seen within intradermal aggregates and intraepidermally. In 1 of the 3 poroid hidradenomas, the eosinophilic cuticle lining the cyst was crenulated in foci associated with sebocytes. In none of the cases were there signs of follicular differentiation. One poroma, in addition to sebaceous differentiation, showed decapitation secretion in some ductular structures. The single carcinoma was an ulcerated oval to spindle cell neoplasm surrounded laterally by the residuum of a poroma containing groups of sebocytes. The epithelial islands of the poroma were prominently keratinized and blended gradually with the pleomorphic cells of the metaplastic carcinoma that immunohistochemically stained focally for cytokeratins and simultaneously showed strong vimentin expression. Our study supports previous findings that sebaceous differentiation can be identified not only in classical poroma but also in the related lesions known as dermal duct tumor and poroid hidradenoma. Occurrence of metaplastic carcinoma in association with apocrine poroma is a rare event which indicates the existence of a malignant counterpart of the latter entity, which can be descriptively referred to as "sarcomatoid apocrine porocarcinoma."

To study the validity and feasibility of transferring images of cutaneous biopsy specimens via e-mail to remote physicians active in dermatopathology for teleconsultation.