Euphemia W. Mu

Anatomy and Physiology of the Skin

The human skin is organized into three primary layers: epidermis, dermis, and the subcutaneous fat residing directly beneath them. Most germane to melanoma is the melanocyte, a specialized pigment-producing cell which transfers melanin from cellular cytoplasm to keratinocytes. This pigment is responsible for both skin color and protection from ultraviolet radiation (UVR). Exposure to particular wavelengths of UVR may result in DNA damage through a variety of mechanisms, which, in turn, predisposes to cutaneous malignancies such as melanoma. The development, invasion, and spread of melanoma are largely dependent on the interaction of melanocytes and their surrounding microenvironment. Melanocytes promote their own growth and survival by secreting growth factors. Keratinocytes are the main regulators of melanocytes, while surrounding fibroblasts become associated with melanocytes and promote their proliferation. Integrin proteins in the microenvironment mediate cytoskeleton adhesion to the extracellular matrix, which contributes to melanocyte migration and invasion. Melanoma tumors tend to invade lymphatic vessels and involve regional lymph nodes early in their course. Metastasizing through blood vessels may also be possible, but is less common and leads to an overall worse prognosis. Therefore, there is a great emphasis placed upon the early detection and removal of involved lymph nodes in melanoma management. Melanocytic nevi, nonmalignant nests of melanocytes, are classified as either dysplastic or common. Nevi that appear clinically suspicious for malignancy based on certain criteria are called atypical nevi, while those which bear histopathological resemblance to melanoma are termed dysplastic nevi. Whether dysplastic or common nevi carry greater proportionate risk for malignancy is uncertain.

Alternative Systemic Treatments for Vitiligo: A Review

Vitiligo is a common, acquired disorder of skin pigmentation that can significantly impact quality of life. It often represents a therapeutic challenge, which has resulted in interest in alternative treatments such as herbal and vitamin supplements. In this review, we provide an overview of the most commonly studied complementary agents, describe proposed mechanisms of action, identify potential adverse effects, and discuss the primary evidence supporting their use. Our discussion focuses on l-phenylalanine, Polypodium leucotomos, khellin, Ginkgo biloba, and vitamins and minerals, including vitamins B12, C, and E, folic acid, and zinc used as monotherapy or in combination with other treatments for the management of vitiligo.

Use of Digitally Stained Multimodal Confocal Mosaic Images to Screen for Nonmelanoma Skin Cancer.

Importance Confocal microscopy has the potential to provide rapid bedside pathologic analysis, but clinical adoption has been limited in part by the need for physician retraining to interpret grayscale images. Digitally stained confocal mosaics (DSCMs) mimic the colors of routine histologic specimens and may increase adaptability of this technology. Objective To evaluate the accuracy and precision of 3 physicians using DSCMs before and after training to detect basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in Mohs micrographic surgery fresh-tissue specimens. Design This retrospective study used 133 DSCMs from 64 Mohs tissue excisions, which included clear margins, residual BCC, or residual SCC. Discarded tissue from Mohs surgical excisions from the dermatologic surgery units at Memorial Sloan Kettering Cancer Center and Oregon Health & Science University were collected for confocal imaging from 2006 to 2011. Final data analysis and interpretation took place between 2014 and 2016. Two Mohs surgeons and a Mohs fellow, who were blinded to the correlating gold standard frozen section diagnoses, independently reviewed the DSCMs for residual nonmelanoma skin cancer (NMSC) before and after a brief training session (about 5 minutes). The 2 assessments were separated by a 6-month washout period. Main Outcomes and Measures Diagnostic accuracy was characterized by sensitivity and specificity of detecting NMSC using DSCMs vs standard frozen histopathologic specimens. The diagnostic precision was calculated based on interobserver agreement and κ scores. Paired 2-sample t tests were used for comparative means analyses before and after training. Results The average respective sensitivities and specificities of detecting NMSC were 90% (95% CI, 89%-91%) and 79% (95% CI, 52%-100%) before training and 99% (95% CI, 99%-99%) (P = .001) and 93% (95% CI, 90%-96%) (P = .18) after training; for BCC, they were 83% (95% CI, 59%-100%) and 92% (95% CI, 81%-100%) before training and 98% (95% CI, 98%-98%) (P = .18) and 97% (95% CI, 95%-100%) (P = .15) after training; for SCC, they were 73% (95% CI, 65%-81%) and 89% (95% CI, 72%-100%) before training and 100% (P = .004) and 98% (95% CI, 95%-100%) (P = .21) after training. The pretraining interobserver agreement was 72% (κ = 0.58), and the posttraining interobserver agreement was 98% (κ = 0.97) (P = .04). Conclusions and Relevance Diagnostic use of DSCMs shows promising correlation to frozen histologic analysis, but image quality was affected by variations in image contrast and mosaic-stitching artifact. With training, physicians were able to read DSCMs with significantly improved accuracy and precision to detect NMSC.

Dermoscopic features of a solitary fibrofolliculoma on the left cheek

CLINICAL PRESENTATION A 72-year-old woman with no skin cancer history requested a total body skin examination at her initial visit. A 4-mm dome-shaped flesh-colored papule was noted on her left cheek (Fig 1). Reportedly, the lesion was present for several years without change. She denied any associated symptoms or precipitating trauma. No other concerning skin lesions were noted. She denied a personal or family history of Birt-Hogg-Dub e syndrome or any associated stigmata.

Infertility and Teratogenicity after Paternal Exposure to Systemic Dermatologic Medications: A Systematic Review

Background: This systematic review assesses effects of paternal exposure to dermatologic medications by using the former US Food and Drug Administration (FDA) pregnancy categories as a benchmark. Objective: To assess whether systemic dermatologic medications can cause infertility and teratogenicity when taken by men. Methods: Categories D and X dermatologic medications were identified; a systematic review of the literature and reviews of the FDA Adverse Events Reporting System and prescribing information were performed to identify the effects of these medications on male fertility and teratogenicity. A secondary search was performed to assess for other systemic dermatologic medications causing teratogenicity or infertility following paternal exposure. Results: A total of 13 medications met the inclusion criteria. Of 1,032 studies identified, 19 were included after a systematic review of the literature. Studies evaluating medication effects with paternal exposure were identified for 10 of the 13 evaluated medications, and evidence of a negative effect was identified for 6 medications. Limitations: We did not encounter any studies for 3 medications that met the inclusion criteria. Information submitted to the FDA Adverse Events Reporting System may not reflect the incidence of side effects. Conclusions: Many former pregnancy category D and X systemic dermatologic medications also have effects on male fertility. More research and better‐quality studies are required in this area, particularly studies assessing potential teratogenicity.

55-year-old man with ulcers in inguinal fold and intergluteal cleft found to have systemic Langerhans cell histiocytosis

LCH: Langerhans cell histiocytosis INTRODUCTION This article describes the case of a patient with cutaneous ulcers who was found to have systemic Langerhans cell histiocytosis (LCH). This article includes the clinical, histology, and electron microscopy images, in addition to a description of the presentation, workup, and management of this rare disease in this patients, with a review of the literature.

An immunosuppressed man with an isolated necrotic plaque on the chest

A 54-year-old man on systemic immunosuppressive therapy for 1 month after a liver transplant for hepatitis C virus presented with a 5-day history of a solitary plaque on the chest. Physical examination found an indurated, violaceous 53 3-cm tender plaque studded with pustules. Over the following days, the plaque became more purulent and developed a central erosion with necrosis (Fig 1). Punch biopsy found a nodular and diffuse dermal mixed cell infiltrate with multinucleated histiocytes and neutrophils (Fig 2, A). Fungal organisms with nonseptated hyphae and right angle branching were identified by Gomori methenamine silver stain (Fig 2, B).

Line scanning, stage scanning confocal microscope (LSSSCM)

For rapid pathological assessment of large surgical tissue excisions with cellular resolution, we present a line scanning, stage scanning confocal microscope (LSSSCM). LSSSCM uses no scanning mirrors. Laser light is focused with a single cylindrical lens to a line of diffraction-limited width directly into the (Z) sample focal plane, which is parallel to and near the flattened specimen surface. Semi-confocal optical sections are derived from the linear array distribution (Y) and a single mechanical drive that moves the sample parallel to the focal plane and perpendicular to the focused line (X). LSSSCM demonstrates cellular resolution in the conditions of high nuclear density within micronodular basal cell carcinoma.

Comparison of Childhood Vitiligo Presenting with or without Associated Halo Nevi

Previous studies have characterized differences in vitiligo associated with halo nevi, but the features of vitiligo presenting with halo nevus in children have yet to be fully described.