From bedside to genetic analysis: New insights into pathophysiology of melanoma, basal cell carcinoma, and other cancers.

OBJECTIVE: Patients with myotonic muscular dystrophy (MMD) were observed to have numerous basal cell carcinoma (BCC) and abnormal dysplastic nevi (DN) on non-sun exposed skin. Simultaneously a large study published in the Journal of American Medical Association (JAMA) illustrated that patients with MMD have "overall" an increased risk for cancer development. Based on these findings, this author in 2010 postulated that dysregulation of RNA binding proteins (RBP), responsible for clinical manifestations of MMD, is also responsible for the development of BCC and melanoma. METHODS: To report new research elucidating the etiology of melanoma, BCC, MMD-induced cancers, and potentially other environmentally induced malignancies. RESULTS: Dysregulation of RBP induces aberrant mRNA splicing; recent data indicates that abnormal mRNA splicing not just plays a key role in the pathogenesis of melanoma but is a hallmark of essentially all human malignancies. CONCLUSION: The author's hypothesis is that ultraviolet (UV) radiation induces DNA damage in intronic regions of a variety of genes. Furthermore, these UV-induced abnormal DNA dimers, repeats and mutations interfere with normal mRNA splicing thus producing abnormal proteins. These abnormal proteins in turn activate oncogenic pathways such as hedgehog, MAP kinase, and WNT.

Skin ultrasonography and magnetic resonance; new clinical applications and instrumentation.

BACKGROUND: Technological advances in skin ultrasonography and magnetic resonance are discussed. METHODS: Literature review. RESULTS: 40 publications cited. CONCLUSION: This article illustrates crucial contributions made by the Editors, the Editorial Board and this Journal to these fields.

Proposed guidelines for appropriate utilization of superficial radiation therapy in management of skin cancers. Zemtsov-Cognetta criteria.

OBJECTIVE: To develop appropriate use criteria (AUC) for the treatment of basal cell and squamous cell carcinoma by superficial radiation therapy (SRT) technique. MATERIAL AND METHODS: Delphi-type discussion of the experts. RESULTS: Presented in Figure 1. CONCLUSION: These AUCs are in compliance both with the position statement of the American Academy of Dermatology (AAD) and the ASTRO Clinical Practice Guideline on this subject. It is further recommended that SRT will be only performed by either a dermatologist who is board certified in Mohs surgery (MDS) and who had adequate SRT training or by radiation oncologists. Hopefully, this publication will stimulate further discussion on this topic.

Lichenoid Reaction Pattern with Pseudoepitheliomatous Hyperplasia - A Rare Tattoo Reaction: A Case Report and Review of the Literature.

Pseudoepitheliomatous hyperplasia is a benign histologic reaction pattern that in rare cases can occur shortly after a tattooing procedure. We describe a case of pseudoepitheliomatous hyperplasia in two tattoos on the same patient 1 year after filling with the same batch of red ink.

Porphyria cutanea tarda presenting as scleroderma.

Sclerodermatous skin changes were observed in a patient with porphyria cutanea tarda (PCT) who initially was diagnosed as having progressive systemic sclerosis (PSS). In extremely rare circumstances, patients with PCT initially are misdiagnosed as having generalized morphea, or PSS, because they lack the typical skin findings of PCT, such as blisters, skin fragility, scarring on the dorsal aspects of the hands, and facial hypertrichosis. However, even in cases of PCT that clinically mimic and are misdiagnosed as PSS, the sclerodermatous skin changes primarily occur in v-shaped areas of the neck. Our patient had sclerodactyly with fingertip ulcerations as well as the classic facial features and skin tightness of PSS. Upon initiation of therapeutic phlebotomy, fingertip ulcerations and sclerodactyly resolved, and there was a notable improvement of sclerodermatous skin changes of the face and forearms.

Association between basal, squamous cell carcinomas, dysplastic nevi and myotonic muscular dystrophy indicates an important role of RNA-binding proteins in development of human skin cancer.

Myotonic muscular dystrophy (MMD) is caused by an abnormal function of RNA-binding proteins (RBP) resulting in DNA spliceopathy. A case of a patient, with MMD multiple basal and squamous cell carcinomas and dysplastic nevi, is described. The association between MMD and non-melanoma skin cancer has been reported before; however, this association was described before the genetic defect of myotonic dystrophy has been fully elucidated. The author proposes a genetic mechanism on how abnormal function of RBP can result or contribute to the development of human skin cancer and propose an explanation for this association between MMD and cutaneous carcinogenesis.

Topically applied growth factors change skin cytoplasmic creatine kinase activity and distribution and produce abnormal keratinocyte differentiation in murine skin.

BACKGROUND/PURPOSE: The skin has a functional and active phosphocreatine (PCR)/creatine kinase (CPK) system that regenerates adenosine triphosphate energy reserves during periods of ischemia. The objective of this study was to evaluate how topically applied growth factors affect CPK activity and distribution, and what histological changes growth factors induce in murine skin. METHODS: Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and suramin (growth factor inhibitor) were applied to murine skin for nine days before mice were sacrificed and CPK level and distributions were measured. RESULTS: TGF-alpha considerably increased CPK activity. Both EGF and TGF-alpha induced a CPK MM to CPK BB transition and histologically induced abnormal differentiation of keratinocytes. CONCLUSION: The skin PCR/CPK system is affected by growth factors. Furthermore, this system appears to play an important role, both in the normal physiology of skin and pathophysiological conditions such as psoriasis and carcinogenesis.

Skin phosphocreatine.

BACKGROUND/PURPOSE: The skin has the unique ability to survive ischemia associated with skin grafts, flaps and hair transplantation procedures. Spectroscopic data later confirmed by chromatography, immunohistochemistry and molecular biology techniques identified the presence of large quantities of phosphocreatine in human skin. Phosphocreatine molecules regenerate ATP cellular reserves during ischemia. This reaction is mediated by creatine phosphokinase enzymes that were also isolated and studied in normal and diseased skin. METHODS: Literature search revealed important contributions by US, Swiss, German, French, Scandinavian and Japanese investigators in the development and understanding of this research field. RESULTS: Serum creatine phosphokinase levels are elevated in burn victims and patients with toxic epidermal necrolysis. Phosphocreatine concentration and creatine phosphokinase activity are elevated in psoriatic skin and in non-melanoma malignancies in comparison with normal skin. Furthermore, skin phosphocreatine and creatine phosphokinase enzymes are localized almost exclusively within the epidermis and in hair follicles. Finally, phosphocreatine and creatine phosphokinase enzymes help to protect skin from UV damage. CONCLUSIONS: Clearly, this research area is only starting to be appreciated by the scientific community. Topical and systemic phosphocreatine administration appears to reverse photodamage and improve wound healing. Spectroscopic monitoring of phosphocreatine and related phosphometabolites can be potentially used to monitor disease activity and respond to therapy in psoriasis, leg ulcers, skin malignancies and other skin conditions.