Teaching point. Case 1 2/3/18. Challenging Cases. Examples of challenging cases?

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Challenging Cases Examples of challenging cases? 1. Challenge in diagnosis 2. Challenge in monitoring an off label treatment 3. Challenge where clinical diagnosis does not match the pathology diagnosis 4. Challenge in long term management Case 1 Recurrent or persistent nevi are often melanoma stimulators In my opinion there are two types: Nevi that have been been traumatized Nevi that have been biopsied and demonstrate residual pigment 1

Common locations of nevi that have been been traumatized include: Is RCM useful in the diagnosis of traumatized nevi Yes! Upper back Trunk Upper thigh of women from shaving (Dr. Kittler commented on this at AAD 2017) Am J Dermatopathol. 2007 Apr;29(2):134-6. Melanocytic nevi with nonsurgical trauma: a histopathologic study. Selim MA 1, Vollmer RT, Herman CM, Pham TT, Turner JW..that benign melanocytic nevi (BMN) may display atypical histologic characteristics when traumatized.. The second type of recurrent or persistent nevi are nevi that have been biopsied and demonstrate residual pigment Pagetoid spread of melanocytes was limited to the site of trauma in 20% of cases and was identified away from areas of trauma in 8% of cases. Melanocytic atypia was seen in three cases. 2

2/3/18 Recurrent Melanocytic Nevi and Melanomas in Dermoscopy Results of a Multicenter Study of the International Dermoscopy Society ONLINE FIRST Andreas Blum, MDJAMA Dermatol. Published online November 13, 2013. jamadermatol.2013.6908 Design, Setting, and Participants Retrospective observational study of 15 pigmented lesion clinics from 12 countries; 98 recurrent nevi (61.3%) and 62 recurrent melanomas (38.8%) were collected from January to December 2011. The role of the cannabanoids and dermatology Characteristic Dermoscopic Pattern of Recurrent Nevi and Recurrent Melanomas Recurrent Nevi Recurrent Melanoma 1. 30 yo (younger pts) 2. Pigment confined to scar 1. 63 yo 2. Pigment traverses the scar s edge 3. H&N 4. Time to recurrence 25 months 5. Growth pattern chaotic 6. Non-contiguous pigment 3. 4. 5. 6. Torso Time to recurrence 8 months Growth pattern centrifugal Contiguous pigment What are the Cannabinoids? They are compounds(chemical structures) that produce the effects experienced from ingesting cannabis. 3

2/3/18 What is Cannabis? Role of Cannabis? Cannabis is a genus of flowering plant in the family Cannabaceae. Three species may be recognized. The History of Cannabis It has long been used for hemp fibre, for hemp oils, for medicinal purposes, and as a recreational drug. Categories of Cannabinoids? Yangshao hemp cord-marked amphora, 4800 BC, Shaanxi : Hemp fiber from the Cannabis sativa plant Chinese hemp fiber paper, used for wrapping not writing, excavated from the Han Tomb of Wu Di (140-87 Emperor Fu Hsi Source: jaars.org (accessed May 25, 2010) "The Chinese Emperor Fu Hsi (ca. 2900 BC), whom the Chinese credit with bringing civilization to China, seems to have made reference to Ma, the Chinese word for Cannabis, noting that Cannabis was very popular medicine that possessed both yin and yang." There are four types of cannabinoids recognized by the National Institutes of Health: Phytocannabinoids Endocannabinoids: Synthetic cannabinoids Purified natural occurring extracts 4

2/3/18 In the late 1990 scientific research revealed receptors in our brains for cannabinoids. These receptors were named cannaboid 1 receptors or CB1. Shortly thereafter researchers demonstrated another set of receptors mainly situated in the periphery (spleen, tonsiller, and immune cells) These receptors were named cannaboid 2 receptors or CB2. The role of cannabinoids as anticancer agents Cannabinoids block tumor progression by targeting several hallmarks of cancer 1.They impair uncontrolled cancer cell growth by inducing cancer cell death by apoptosis and by inhibiting cancer cell proliferation 2. They hamper tumour angiogenesis by downregulating the vascular endothelial (VEGF) pathway in cancer cells CB2 receptors are primarily located on immune cells and tissues When activated, affect inflammatory and immunosuppressive activity Control release of cytokines and cell migration 3. They hinder metastasis by inhibiting cancer cell adhesion and migration/invasiveness through the modulation of matrix metalloproteinase 2 (MMP2) tissue inhibitor of matrix metalloproteinase 1 (TIMP1), inhibitor of DNA binding 1(D1) and perhaps other targets. 5

The role of cannabinoids in dermatology The endocannabinoid system is known to control the proliferation, differentiation, survival, and immune competence of the integumentary organ system. Targeting and manipulating endocannabinoid balance with the intent to normalize unwanted skin cell growth and skin inflammation might be beneficial for a variety of human skin conditions July 2017 The cannabanoids have a promising role in the treatment of itch. They may also have anti-inflammatory properties useful for the treatment of both allergic contact dermatitis and atopic dermatitis. Endocannabinoids, synthetic cannabinoids, and phytocannabinoids have also been shown to have antitumor effects on keratinocyte carcinoma and melanoma both in vitro and in vivo. CB1 and CB2 receptor activation in mouse melanoma and melanoma cell lines decreased the proliferation, angiogenesis, and metastasis of melanoma through inhibition of the prosurvival protein Akt and hypophosphorylation of the prb. Dermatoscopic-specific facial features for melanoma 1. Slate gray to blue-gray dots/granules 2. Gray follicular openings 3. Angulated lines/ rhomboidal structures 4. Circle within a circle 5. Irregular gray/brown pigmentation between follicles 6. Dark structureless areas obscuring the follicular openings 7. Crystalline structures (Shiny white structures) (Polarized light) 8. Blue white veil Melanoma specific features: Slate gray to blue-gray dots/granules Brown-gray pigmented follicular openings Angulated lines/rhomboidal structures Circle within a circle Irregular perifollicular hyperpigmentation Dark structureless areas obscuring the follicular openings Chrysalis structures (Polarized light) Blue white veil Facial Patterns Melanoma specific features Yes Melanoma LPLK BCC Pigmented AK 6

Facial Patterns Melanoma specific features Is there a fine scale to the surface? No Are there only diffuse coarse gray Melanoma dots/granules or gray LPLK dots/granules following an annular distribution without other features. Pigmented AK..or are there focal gray dots/granules as well as other structures or features suggestive of a solar lentigo or a seborrheic keratosis. No 7