Summary Melanoma is comprised of biologically distinct subtypes. The defining clinical, histomorphologic and molecular features are not fully established. This study sought to validate the association between genetic and histomorphologic features previously described, determine their reproducibility, and association with important clinical variables. Detailed clinical and histomorphologic features of 365 primary cutaneous melanomas were assessed by 11 pathologists and correlated with mutation status of BRAF and NRAS. There was substantial agreement in the quantitative assessment of histomorphologic features showing similar or better interobserver reproducibility than the established WHO classification scheme. We confirmed that melanomas with BRAF mutations showed characteristic morphologic features (p<0.0001) and metastasized more frequently to regional lymph nodes (p=0.046). Importantly, melanomas without mutations were a heterogeneous group, with a subset having very similar features clinical and morphological features than those with BRAF mutation raising the possibility that they are biologically related. Our study confirms an association between histomorphologic features, mutation status and pattern of metastasis, providing criteria for a refined melanoma classification aimed at defining biologically homogeneous disease subgroups.

| GETTING TO GRIPS WITH PSORIASISThe stage set to unfold before us the fascinating pathophysiology of psoriasis is ever changing. Some of the actors have added intriguing insight to our understanding of this complex inflammatory disorder.Formerly, psoriasis had been regarded as a skin disease that is based primarily on disturbances of epidermal homeostasis.1,2 In fact, even in more recent times there are some absolutely serious "pockets of resistance" providing experimental evidence that a primary epithelial abnormality alone can initiate psoriasis-like hyperproliferative inflammatory skin changes, at least in animal models. 3,4 Alas, as this is a viewpoint article, we dare to phrase the "heretic" notion that tampering with almost any component of the cutaneous environment, be it epithelium, vasculature or immune functions, can ultimately result in so-called psoriasiform inflammation. 5 The predominant current scenario, however, which is substantiated quickly by even a cursory survey of the literature, is this: psoriasis is a systemic inflammatory disorder, has an immunogenetic basis and is centred around tightly intertwined interactions of the innate and the adaptive immune system. 6-11More than 18 000 publications pertaining to the pathogenesis of

Neutrophilic epitheliotropism is a new sensitive and specific histopathological clue for NUD, a histopathological reaction pattern within the spectrum of neutrophilic dermatoses that needs to be differentiated from conventional urticaria.

A reliable, fast, and non-invasive determination of melanoma thickness in vivo is highly desirable for clinical dermatology as it may facilitate the identification of surgical melanoma margins, determine if a sentinel node biopsy should be performed or not, and reduce the number of surgical interventions for patients. In this work, optical coherence tomography (OCT) and high frequency ultrasound (HFUS) are evaluated for quantitative in vivo preoperative assessment of the skin infiltration depth of melanocytic tissue. Both methods allow non-invasive imaging of skin at similar axial resolution. Comparison with the Breslow lesion thickness obtained from histopathology revealed that OCT is slightly more precise in terms of thickness determination while HFUS has better contrast. The latter does not require image post-processing, as necessary for the OCT images. The findings of our pilot study suggest that non-invasive OCT and HFUS are able to determine the infiltration depth of lesions like melanocytic nevi or melanomas preoperatively and in vivo with a precision comparable to invasive histopathology measurements on skin biopsies. In future, to further strengthen our findings a statistically significant study comprising a larger amount of data is required which will be conducted in an extended clinical study in the next step. Comparison of optical coherence tomography and high frequency ultrasound B-Scans and a H&E stained histology of a melanocytic nevus.