Clinicopathologic, misdiagnosis, and survival differences between clinically amelanotic melanomas and pigmented melanomas.

BACKGROUND: Amelanotic malignant melanoma (AMM) is challenging to diagnose. Clinical risk factors for AMM are not well defined. OBJECTIVE: To investigate clinicopathologic, misdiagnosis, and survival differences between patients with AMM and those with pigmented malignant melanoma (PMM). METHODS: A cross-sectional retrospective medical record review at a tertiary academic medical center. RESULTS: A total of 933 patients with melanoma with known presenting tumor color were identified (342 with AMM vs 591 with PMM). AMM was associated with older age, history of nonmelanoma skin cancer, and red hair, whereas AMM was inversely associated with a family history of melanoma, more than 50 nevi, and a history of dysplastic nevi. Compared with PMM, AMM was more likely to be located on the head and/or neck, had more aggressive pathologic features (greater Breslow depth and/or mitoses, ulceration, nodular subtype), and was less likely to be associated with a precursor nevus or regression. Finally, patients with AMM were more likely to be misdiagnosed than were patients with PMM (25% vs 12% clinically and 12% vs 7% pathologically), and they had poorer melanoma-specific survival (5-year overall survival rate, 0.77 [95% confidence interval, 0.72-0.82] vs 0.84 [95% confidence interval, 0.80-0.87]). LIMITATIONS: Retrospective study design, single-institutional study. CONCLUSION: Greater clinician awareness, lower biopsy thresholds, and increased patient education may be useful to enhance AMM detection in patients with certain characteristics.

Clinicopathologic features correlated with paradoxical outcomes in stage IIC versus IIIA melanoma patients.

Under current AJCC staging criteria, stage IIC patients paradoxically have worse outcomes than IIIA patients despite the lack of nodal metastatic disease. This study sought to identify additional clinicopathologic characteristics correlated with worse patient outcomes. Retrospective chart review of stage IIC and IIIA melanoma patients were evaluated between 1995 and 2011 with clinical follow-up through 2015. Records were reviewed for demographics, clinical characteristics, and tumor pathology. Fisher's exact test and Wilcoxon's rank-sum test were used to assess group differences. Clinicopathologic features were evaluated relative to overall survival (OS), time to distant metastases, and local/regional recurrence. Overall, 128 patients were included (45 stage IIC and 83 stage IIIA) with a median follow-up time of 5.7 years. Compared with stage IIIA patients, stage IIC patients were older, and their melanomas were more likely to be nodular, amelanotic, thicker, have higher mitotic rate, tumor lymphocytic infiltrate, no radial growth phase, and less likely to have associated precursor lesions. Stage IIC patients had shorter OS and time to distant metastases; multivariate regression revealed that older age (>55 years) and mitotic rate (>5 mitoses/mm) were independent predictors of OS. Melanomas in stage IIC disease may be biologically distinct from those that are seen in stage IIIA. While sentinel node biopsies remain the standard-of-care, these results suggest that clinicians may want to assess the clinicopathologic characteristics described above to aggressively counsel, screen for distant disease, and consider adjuvant therapy, in particular for older patients and higher mitotic rates in thicker primary tumors, regardless of nodal status.

Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis.

Alopecia areata (AA) is a common, inflammatory, nonscarring type of hair loss. Significant variations in the clinical presentation of AA have been observed, ranging from small, well-circumscribed patches of hair loss to a complete absence of body and scalp hair. Patients affected by AA encompass all age groups, sexes, and ethnicities, and may experience frustration with the unpredictable nature of their disease for which there is currently no definitive treatment. The cause of AA remains incompletely understood, though it is believed to result-at least in part-from a loss of immune privilege in the hair follicle, autoimmune-mediated hair follicle destruction, and the upregulation of inflammatory pathways. Patients with AA frequently experience marked impairment in psychological well-being, self-esteem, and may be more likely to suffer from psychiatric comorbidities. Part one of this two-part continuing medical education series describes the epidemiology, clinical evaluation, prognosis, and recent advancements in the understanding of the pathogenesis of AA.

Alopecia areata: An appraisal of new treatment approaches and overview of current therapies.

Many therapies are available for the treatment of alopecia areata, including topical, systemic, and injectable modalities. However, these treatment methods produce variable clinical outcomes and there are no currently available treatments that induce and sustain remission. When making management decisions, clinicians must first stratify patients into pediatric versus adult populations. Disease severity should then be determined (limited vs extensive) before deciding the final course of therapy. The second article in this continuing medical education series describes the evidence supporting new treatment methods, among them Janus kinase inhibitors. We evaluate the evidence concerning the efficacy, side effects, and durability of these medications. An overview of conventional therapy is also provided with new insights gleaned from recent studies. Finally, future promising therapeutic options that have not yet been fully evaluated will also be presented.

An Overview of the Biology of Platelet-Rich Plasma and Microneedling as Potential Treatments for Alopecia Areata.

Platelet-rich plasma and microneedling have been investigated recently as potential therapeutic options for the treatment of hair disorders. Evidence from laboratory studies indicates that these treatments enhance growth factor production that in turn facilitates hair follicle development and cycling. Several small studies and case reports have presented encouraging findings regarding the use of these treatments for alopecia areata. Future investigations will be needed to validate these therapeutic techniques for patients with alopecia areata and further refine which subtypes of the disease these methods are best indicated for.

An Overview of the Biology of Platelet-Rich Plasma and Microneedling as Potential Treatments for Alopecia Areata.

Platelet-rich plasma and microneedling have been investigated recently as potential therapeutic options for the treatment of hair disorders. Evidence from laboratory studies indicates that these treatments enhance growth factor production that in turn facilitates hair follicle development and cycling. Several small studies and case reports have presented encouraging findings regarding the use of these treatments for alopecia areata. Future investigations will be needed to validate these therapeutic techniques for patients with alopecia areata and further refine which subtypes of the disease these methods are best indicated for.

Novel Treatment Using Low-Dose Naltrexone for Lichen Planopilaris.

Lichen planopilaris (LPP) is a variant of lichen planus that affects the scalp causing scarring hair loss. Patients also frequently experience symptoms of scalp itch, pain, and burning. To date, there are no long-term remittive nor curative therapies available. Low-dose naltrexone has anti-inflammatory properties and has recently been described in the context of treating autoimmune conditions. This retrospective medical record review describes four LPP patients treated with low-dose (3 milligrams per day) naltrexone. This medication provided benefit in these four patients including reduction in symptoms of pruritus, clinical evidence of inflammation of the scalp, and disease progression. All patients tolerated naltrexone without adverse effects. This is the first case series demonstrating the beneficial effects of low-dose naltrexone for patients with LPP. This medication was well-tolerated by the patients and is cost-effective.

J Drugs Dermatol. 2017;16(11):1140-1142.

An incomplete picture: challenges of partial biopsies in large diameter atypical melanocytic lesions.

Large diameter atypical pigmented lesions (LDAPL) can be challenging to diagnose accurately using partial biopsies because of pathologic heterogeneity, while at the same time large excisions of these lesions confer significant morbidity to patients. Consequently, clinicians are often challenged by the management of these lesions. In this case, we describe an elderly patient with a history of multiple basal cell carcinomas, prior melanomas, and a family history of melanoma who presented with an irregularly pigmented brown and dark brown patch on his upper back. This lesion was evaluated with multiple partial incisional biopsies from the most atypical appearing areas of the lesion identified on dermoscopy, each showing mild and moderate atypical melanocytes. However, the patch continued to change clinically and eventually the patient underwent a 5mm wide local excision, which revealed severely atypical melanocytic proliferation with areas consistent with melanoma in situ. This case highlights the need for clinicians to lower their threshold for excisional biopsy of LDAPL in high-risk patients.

An Update on Kaposi's Sarcoma: Epidemiology, Pathogenesis and Treatment.

Kaposi's sarcoma is an angioproliferative neoplasm which has undergone considerable epidemiologic change since the original description by Moritz Kaposi in the late 1800s. This opportunistic neoplasm gained widespread notoriety within the US during the height of the AIDS epidemic, where it was frequently found co-occurring with opportunistic infections. With the advent of modern antiretroviral therapies, as well as an increasing number of individuals on immunosuppression for autoimmune disease or organ transplantation, the landscape of the immunocompromised individual has changed. It is now important for clinicians to be mindful of Kaposi's sarcoma manifesting in a growing variety of clinical contexts.

Regulation of bone and cartilage by adenosine signaling.

There is growing recognition that bone serves important endocrine and immunologic functions that are compromised in several disease states. While many factors are known to affect bone metabolism, recent attention has focused on investigating the role of purinergic signaling in bone formation and regulation. Adenosine is a purine nucleoside produced intracellularly and extracellularly in response to stimuli such as hypoxia and inflammation, which then interacts with P1 receptors. Numerous studies have suggested that these receptors play a pivotal role in osteoblast, osteoclast, and chondrocyte differentiation and function. This review discusses the various ways by which adenosine signaling contributes to bone and cartilage homeostasis, while incorporating potential therapeutic applications of these signaling pathways.