Folliculotropic mycosis fungoides.

Accepted by the WHO and EORTC as a variant of classic mycosis fungoides, folliculotropic (syn.: follicular or pilotropic) mycosis fungoides (FMF) is characterized by a broad clinical and histological spectrum with numerous differential diagnoses. Recent studies have shown that FMF can be divided into two prognostically different subgroups, both marked by histological as well as clinical differences.

Activation of the mitogen-activated protein kinase pathway in malignant melanoma can occur independently of the BRAF T1799A mutation.

BRAF exon 15 mutations have been identified in a large proportion of malignant melanomas, melanoma metastases and melanocytic nevi. Mutated BRAF is one of the potential activators of the mitogen-activated protein kinase (MAPK) signaling pathway by phosphorylating ERK (extracellular signal-regulated kinase). We therefore analyzed the correlation of BRAF V600E and ERK-activation in 20 malignant melanomas and 21 subsequently evolved, paired metastases of the same donor by BRAF exon 15 DNA sequencing and phospho-specific immunohistochemistry for ERK.

Prevalence of Merkel cell polyomavirus DNA in cutaneous lymphomas, pseudolymphomas, and inflammatory skin diseases.

Several groups confirmed Merkel cell polyomavirus (MCPyV) as the likely causative agent of Merkel cell carcinoma. Hematolymphoid disorders are known to be a substantial risk factor for Merkel cell carcinoma, and vice versa. The association between MCPyV and hematologic neoplasms is poorly analyzed, as well as the speculation that lymphocytes may serve as reservoir for MCPyV.

Classification of cutaneous lymphomas - an update.

This review focuses on the evolution and conceptual aspects of classifications for cutaneous lymphomas. The World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification and the WHO classification (4th edn, 2008) represent the first widely accepted classifications for lymphomas, in which the complete spectrum of primary cutaneous lymphomas is included. These classifications for primary cutaneous lymphomas define disease entities with distinct clinical, histological, immunophenotypic and genetic features.

Basic measures and systemic medical treatment of patients with toxic epidermal necrolysis.

Background: With an incidence of 1.5-1.8/1 million inhabitants per year, toxic epidermal necrolysis is a rare but life threatening disease.

Cutaneous gamma/delta T-cell lymphoma.

Only 40 cases of primary cutaneous gamma/delta T-cell lymphoma (GD-TCL) have been described. GD-TCL was included as a provisional entity in the WHO-EORTC classification of cutaneous lymphomas in 2005. GD-TCL often failed to respond to polychemotherapy and radiation therapy and have a poor prognosis with a mean survival of only 15 months.

Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors.

Background: Merkel cell polyomavirus (MCPyV) is the likely causative agent of Merkel cell carcinoma (MCC). However, the prevalence of MCPyV in non-MCC population and its possible role in the pathogenesis of other skin cancers are not known yet.

Methods: A molecular pathology study was performed in 33 MCC samples and 33 age- and sex-matched samples of sun exposed non-MCC tumors [12 seborrheic keratoses (SK), 11 basal cell carcinomas (BCC) and 10 lentigo maligna melanomas (LMM)].

Direct crosstalk between mast cell-TNF and TNFR1-expressing endothelia mediates local tissue inflammation.

Signaling through tumor necrosis factor receptor 1 (TNFR1) controls bacterial infections and the induction of inflammatory Th1 cell-mediated autoimmune diseases. By dissecting Th1 cell-mediated delayed-type hypersensitivity responses (DTHRs) into single steps, we localized a central defect to the missing TNFR1 expression by endothelial cells (ECs). Adoptive transfer and mast cell knockin experiments into Kit(W)/Kit(W-v), TNF(-/-), and TNFR1(-/-) mice showed that the signaling defect exclusively affects mast cell-EC interactions but not T cells or antigen-presenting cells.

Subcorneal pustulosis with combined lack of IgG/IgM and monoclonal gammopathy type IgA/Kappa.

Subcorneal pustulosis (Sneddon-Wilkinson disease) is a rare inflammatory neutrophilic dermatosis. While subcorneal pustulosis is often associated with an IgA gammopathy, the combined lack of IgG/IgM seen in our case is rare. An 83-year-old man with combined lack of IgG/IgM and monoclonal gammopathy type IgA/Kappa presented with subcorneal pustules.

PUVA-bath photochemotherapy and isotretinoin in sclerodermatous graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is almost always associated with skin diseases appearing either as lichenoid GVHD, sclerodermatous GVHD (sGVHD) or as eosinophilic fasciitis-like disease. The two latter frequently result in severe and deep sclerosis. Immunosuppressive therapy is of little help in sclerodermatous or eosinophilic fasciitis-like types of GVHD.

TNFR1 signaling and IFN-gamma signaling determine whether T cells induce tumor dormancy or promote multistage carcinogenesis.

Immune responses may arrest tumor growth by inducing tumor dormancy. The mechanisms leading to either tumor dormancy or promotion of multistage carcinogenesis by adaptive immunity are poorly characterized. Analyzing T antigen (Tag)-induced multistage carcinogenesis in pancreatic islets, we show that Tag-specific CD4+ T cells home selectively into the tumor microenvironment around the islets, where they either arrest or promote transition of dysplastic islets into islet carcinomas.

Lichen aureus with clonal T cells in a child possibly induced by regular consumption of an energy drink.

Lichen aureus is a rare disease of unknown origin that is classified under the group of pigmented purpuric dermatoses. Its most important differential diagnosis is both clinically and histologically mycosis fungoides, into which the disease can proceed in very rare cases. We describe an unusual multilocular lichen aureus possibly induced by the almost daily consumption of an energy drink.

Heterogeneity of T-cell clones infiltrating primary malignant melanomas.

It is established that primary malignant melanomas (pMM) can be infiltrated by T-cell populations with predominantly one T-cell clone. As pMM generally express multiple tumor-associated antigens (TAA), here we used laser-capture microdissection (LCM) to isolate different tumor-infiltrating lymphocyte (TIL) clusters in order to determine whether pMM are infiltrated only by one single clone or whether the TAA may attract various T-cell populations. As T-cell receptor (TCR) clonality is a useful tool for the demonstration of specific T-cell clones, we analyzed 56 pMM, three cutaneous melanoma metastases, and 15 pairs of pMM with a sentinel lymph node (SLN) for clonal rearrangements of the (TCR) gamma chain gene.

Circumscribed palmar or plantar hypokeratosis: two cases of a recently described entity of unknown origin.

Circumscribed palmar or plantar hypokeratosis is a new entity recently described by Perez et al in 2002. It seems to be underdiagnosed or clinically it is often misdiagnosed as Bowen's disease or porokeratosis. Obviously the number of case reports of circumscribed palmar or plantar hypokeratosis has increased since the first publication by Perez et al.

Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for a role of hypoxia-inducible factor-1 in bacterial infections.

Background: Bartonella species are the only known bacterial pathogens causing vasculoproliferative disorders in humans (bacillary angiomatosis [BA]). Cellular and bacterial pathogenetic mechanisms underlying the induction of BA are largely unknown.

Methods And Results: Activation of hypoxia-inducible factor-1 (HIF-1), the key transcription factor involved in angiogenesis, was detected in Bartonella henselae-infected host cells in vitro by immunofluorescence, Western blotting, electrophoretic mobility shift, and reporter gene assays and by immunohistochemistry in BA tissue lesions in vivo.

Follicular mycosis fungoides mimicking a cutaneous B-cell lymphoproliferative disorder.

Follicular mycosis fungoides (MF) is an uncommon histological variant of MF characterized by infiltrates of atypical lymphocytes around and within the epithelium of the hair follicles (folliculotropism). Here we report a patient with rapidly progressive follicular MF on the face, associated with concurrent typical MF lesions elsewhere. The histology was unusual, as apart from dense lymphoid infiltrates showing folliculotropism and epidermotropism, there was a prominent B-cell component with germinal centres, leading to an initial diagnosis of cutaneous B-cell lymphoma.

Laser-capture microdissection: applications in routine molecular dermatopathology.

Advances in molecular pathology with the introduction of the Southern blot technique and the polymerase chain reaction (PCR) have emerged as important tools, which are frequently used in routine dermato-histopathology. Applications for PCR-based diagnostics are particularly helpful for the determination of clonality in cutaneous lymphocytic infiltrates and for detection of infectious agents, such as herpes simplex virus (HSV), varicella zoster virus (VZV), Borrelia burgdorferi, Mycobacteria, Leishmania, and Treponema pallidum. As biopsies are always composed of different cells, the cells of interest are often only a minor population.

The T1796A mutation of the BRAF gene is absent in Spitz nevi.

Background: BRAF, a serine/threonine kinase, is a component of the retrovirus-associated sequence (RAS)-RAF-extracellular-regulated protein kinase (ERK)-MAP kinase signal transduction pathway mediating signals from RAS to ERK. The T1796A single point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage of malignant melanomas and benign melanocytic lesions such as congenital nevi, compound nevi, intradermal nevi and dysplastic nevi. The T1796A mutation has been shown to promote cell proliferation.

Mutations of the BRAF gene in benign and malignant melanocytic lesions.

A single-point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage in cultured melanoma cells and in 6 of 9 primary melanomas examined. To evaluate the impact of the T1796A BRAF mutation, we screened primary melanomas, various types of nevi and lesions where a melanoma developed in an underlying nevus. We could detect the mutation in 28 of 97 (29%) melanomas and in 39 of 187 (21%) nevi, including blue nevi (0/20) and Spitz nevi (0/69), which did not carry the mutation.

Demodex abscesses: clinical and therapeutic challenges.

A 53-year-old man had a 6-week history of confluent erythematous papules, pustules, and abscesses of the face initially limited to the right nasolabial fold. Histologic investigation revealed a perifollicular infiltrate with lymphocytes, histiocytes, and many Demodex folliculorum mites. A large number of mites were seen in skin scrapings.