Dermatologic care of the transgender patient.

Literature is limited regarding the medical and cosmetic dermatologic issues pertinent to transgender patients and the reasons why 19 transgender individuals seek care from dermatologists. Clinical management of this population has historically been limited to 20 mental health providers, endocrinologists, and select surgeons with expertise in sex reassignment surgery. The impact of hormonal 21 therapy on transgender skin has been well documented in endocrinology journals, but is underrepresented in dermatology 22 literature. Hormonal therapy leads to drastic skin alterations, impacting sebum production, hair growth, and acne, all of which may 23 become a dermatologic concern for the transgender patient. Dermatologists may also be consulted regarding issues such as 24 permanent hair removal, androgenic alopecia, or scar revision following breast reduction surgery or genital reassignment surgery. 25 The purpose of this review is to provide relevant information for use by all dermatology providers who care for transgender 26 patients or patients undergoing transition.

Epidermal consumption in benign and malignant melanocytic neoplasms.

Consumption of the epidermis associated with effacement of the rete ridge pattern has been cited as a useful criterion in the diagnosis of melanoma, but the significance of consumption in the absence of rete ridge effacement is unknown. We evaluated 701 melanocytic neoplasms for presence and 'grade' of consumption by melanocytic nests relative to diagnosis, body location, gender and age. We defined 1+ consumption as collections of melanocytes occupying greater than two thirds of the viable epidermis, with or without loss of the rete ridge pattern. Nests extending to the bottom of, within, and through the granular layer were graded 2+, 3+ and 4+, respectively. Consumption was more frequent and higher grades were found in melanomas followed by Spitz nevi compared with conventional melanocytic nevi (p < 0.001). Melanomas with higher Breslow thickness showed higher grades (p < 0.05). In conventional nevi, consumption occurred most frequently in back (13.7%), acral (11.9%) and scalp (9.8%) locations. Consumption without the requirement for rete ridge effacement occurs more frequently and at higher grades in melanoma. Higher grades correlate with higher Breslow thickness. Consumption is also common in Spitz nevi and occurs at lower grades in conventional (non-Spitz) nevi, especially on the back, the scalp and at acral sites.

CD99 expression in dermatofibrosarcoma protuberans and dermatofibroma.

BACKGROUND: Differentiating between dermatofibrosarcoma protuberans (DFSP) and hypercellular dermatofibroma (DF) can sometimes be challenging, and a panel of immunostains is often employed. Expression of conventional markers oftentimes overlaps. We evaluated CD99 expression in DFSP and DF and its utility in distinction between these 2 entities. METHODS: CD99 immunostaining was performed on 34 DFSPs and 24 hypercellular DFs. The intensity of staining was graded as "weak," "moderate," or "strong," and the proportion of positive cells was graded as follows: "scattered" when individual cells comprised <5% of the total cellularity of the lesion; "focal" with >5% but <25% of the cells; or "diffusely distributed" with staining of >25% of lesional spindle cells. RESULTS: Overall, DFSPs showed positive CD99 staining in 21 (61.76%) cases. Moderate and weak patterns of staining were the most frequent, seen in 13 (38.2%) and 7 (20.6%) cases, respectively. CD99 staining in DFSPs was predominantly scattered or patchy (4 and 11 lesions respectively) with less than 25% of cells expressing CD99. In comparison, all 24 DF cases showed strong CD99 positivity in >25% of the spindle cell component (P = 0.0003). The most striking difference related to the distribution of staining. In DFSP, tumor cells in the superficial dermis, when present, were always CD99 negative. In contrast, DF cells in the superficial dermis always demonstrated strong CD99 positivity. CONCLUSIONS: DF strongly expresses CD99 in a diffuse pattern that may serve as evidence in distinction from DFSP. As the differences in staining were most pronounced in the superficial portions of the tumor, CD99 staining may be well suited to superficial biopsy specimens, where distinction in hematoxylin and eosin sections may be most problematic.

Immunotherapy for melanoma: current status and perspectives.

Immunotherapy is an important modality in the therapy of patients with malignant melanoma. As our knowledge about this disease continues to expand, so does the immunotherapeutic armamentarium. Nevertheless, successful preclinical models do not always translate into clinically meaningful results. The authors give a comprehensive analysis of most recent advances in the immune anti-melanoma therapy, including interleukins, interferons, other cytokines, adoptive immunotherapy, biochemotherapy, as well as the use of different vaccines. We also present the fundamental concepts behind various immune enhancement strategies, passive immunotherapy, as well as the use of immune adjuvants. This review brings into discussion the results of newer and older clinical trials, as well as potential limitations and drawbacks seen with the utilization of various immune therapies in malignant melanoma. Development of novel therapeutic approaches, along with optimization of existing therapies, continues to hold a great promise in the field of melanoma therapy research. Use of anti-CTLA4 and anti-PD1 antibodies, realization of the importance of co-stimulatory signals, which translated into the use of agonist CD40 monoclonal antibodies, as well as activation of innate immunity through enhanced expression of co-stimulatory molecules on the surface of dendritic cells by TLR agonists are only a few items on the list of recent advances in the treatment of melanoma. The need to engineer better immune interactions and to boost positive feedback loops appear crucial for the future of melanoma therapy, which ultimately resides in our understanding of the complexity of immune responses in this disease.

Kallikrein expression and cathelicidin processing are independently controlled in keratinocytes by calcium, vitamin D(3), and retinoic acid.

Cathelicidin has dual functions in the skin, acting as an innate antibiotic and as an immunomodulator in diseases such as rosacea and psoriasis. The serine proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7) control enzymatic processing of cathelicidin precursor in the skin and regulate the eventual function of the final forms of these peptides. We analyzed factors that control expression of KLK5 and KLK7 in normal human epidermal keratinocytes to better understand how these may influence cathelicidin processing and function. Increased extracellular calcium-induced KLK5 and KLK7 mRNA expression and protein release in a time-dependent manner that is similar to induction of differentiation markers such as keratin 10 and involucrin. However, 1,25(OH)(2) vitamin D(3), 9-cis retinoic acid (RA), and 13-cis RA also induced the KLKs, but the timing and pattern of KLK induction for each were different and distinct from changes in differentiation markers. Increased protease activity and differential processing of cathelicidin accompanied increased KLK expression. These findings show that the expression and activity of KLK are under fine control and can be distinctly influenced by variables such as differentiation, calcium, vitamin D, and RA. Thus, these variables may further control the functions of antimicrobial peptides in the skin.

Sea urchin granuloma secondary to Strongylocentrotus purpuratus and Strongylocentrotus franciscanus.

Sea urchin injuries have been associated with a variety of cutaneous lesions, ranging from acute, transient reactions, to more chronic inflammatory conditions that result in the formation of granulomas. Although diverse species of sea urchins have been reported to produce chronic cutaneous granulomas, the two most prevalent organisms found on the US West Coast, purple and red sea urchins (Strongylocentrotus purpuratus and Strongylocentrotus franciscanus), have not yet been reported to induce persistent granulomatosis in humans. We describe one case of a 35-year-old marine biologist with chronic cutaneous lesions produced after repeated exposures. The lesions were similar to the ones produced by other urchin species, consisting of small, firm, erythematous nodules on his palms, dorsum of the hands, elbows, and knees. Increased awareness of this condition, including its association with the two prevalent organisms on the West Coast, should lead to a more rapid diagnosis for those affected. This article reviews the types of injuries, clinical cutaneoous lesions, histopathological features, and pathogenesis of the chronic inflammatory process induced by sea urchins.

Malignant melanoma in African-Americans.

Although relatively uncommon, malignant melanoma in African-Americans and other minority ethnic populations represents an aggressive disease highly associated with invasive lesions and a more advanced stage of disease at diagnosis, and consequently with a decreased survival compared with Caucasians. Data on biology of melanoma in African-Americans is very limited, which complicates the analysis of epidemiological information, as well as identification of accurate prognostic variables. This review article explores critical features of melanoma in African-Americans that distinguish it from disease seen in Caucasians, including the clinical presentation, histological patterns, prognostic indicators, and etiology. Emerging data from biologic and genetic studies will also be discussed, raising the possibility that melanoma in pigmented skin may represent molecular distinct cancers that are inherently more aggressive. Improved understanding of the unique manifestations of melanoma in African-Americans, and its underlying tumor biology, will help improve clinical detection, optimize preventative measures through public health education, and potentially lead to the development of novel targeted therapeutic approaches.