Dirk M. Elston

Tumors composed of malignant epithelial and melanocytic populations: a case series and review of the literature

Over the last 30 years, there have been approximately 49 case reports of tumors composed of both malignant epithelial and malignant melanocytic populations. Herein, we present four additional cases of combined tumors that consist of two phenotypically distinct but intermingled populations of malignant cells. Each tumor was composed of an invasive melanoma closely associated with either a basal cell carcinoma or a squamous cell carcinoma. We review all previous case reports in the English literature and attempt to clarify the terminology and summarize what is currently known about these unique tumors.

Skin biopsy: Biopsy issues in specific diseases

Misdiagnosis may result from biopsy site selection, technique, or choice of transport media. Important potential sources of error include false-negative direct immunofluorescence results based on poor site selection, uninformative biopsy specimens based on both site selection and technique, and spurious interpretations of pigmented lesions and nonmelanoma skin cancer based on biopsy technique. Part I of this 2-part continuing medical education article addresses common pitfalls involving site selection and biopsy technique in the diagnosis of bullous diseases, vasculitis, panniculitis, connective tissue diseases, drug eruptions, graft-versus-host disease, staphylococcal scalded skin syndrome, hair disorders, and neoplastic disorders. Understanding these potential pitfalls can result in improved diagnostic yield and patient outcomes.

Advances in immunotherapy for melanoma management

ABSTRACT Melanoma remains a leading cause of death among young adults. Evidence that melanoma tumor cells are highly immunogenic and a better understanding of T-cell immune checkpoints have changed the therapeutic approach to advanced melanoma. Instead of targeting the tumor directly, immunotherapy targets and activates the immune response using checkpoint inhibitors, monoclonal antibodies, vaccines, and adoptive T cell therapy. This review focuses on the immune signaling and biological mechanisms of action of recent immune-based melanoma therapies as well as their clinical benefits.

Nuclear and cytoplasmic features in the diagnosis of banal nevi, Spitz nevi, and melanoma

BACKGROUND Many authors have described cytologic features in a variety of melanocytic lesions but, to our knowledge, a statistical analysis of sensitivity, specificity, and overall accuracy of these features alone or in combination has not been performed. OBJECTIVE We sought to determine the diagnostic value of nuclear and cytoplasmic characteristics in the diagnosis of melanocytic lesions via multivariate statistical analysis. METHODS This is a retrospective observational study conducted on 300 melanocytic lesions. We evaluated a series of distinctive features; subsequently a multivariate model was used to determine sensitivity and specificity. RESULTS Major features that favor a diagnosis of melanoma include: pleomorphism with enlarged nuclei, mitotic figures, notching/corrugation of the nuclear envelope, and peppered moth nucleus. Features with intermediate value include: solid hyperchromasia, vesicular nucleus with single round nucleolus, and nuclear/cytoplasmic ratio greater than 4:1. LIMITATIONS Limitations of this study include its retrospective nature, and the reliance on the original diagnostic classification of each neoplasm. CONCLUSION Our data suggest that some nuclear alterations have greater value in the diagnosis of benign and malignant melanocytic lesions.

Two cases of anti-programmed cell death 1-associated bullous pemphigoid-like disease and eruptive keratoacanthomas featuring combined histopathology

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Interventional treatments for Hailey-Hailey disease.

Hailey-Hailey disease or familial benign chronic pemphigus is a rare blistering dermatosis that is characterized by recurrent erythematous plaques with a predilection for the skin folds. For extensive Hailey-Hailey disease that is recalcitrant to conventional therapy, laser ablation, photodynamic therapy, electron beam radiotherapy, botulinum toxin type A, dermabrasion, glycopyrrolate, and afamelanotide have been reported as useful treatments, but comparative trials are lacking. This review discusses the various treatment modalities for Hailey-Hailey disease and a summary of the evidence for the most recommended treatments.

Central centrifugal cicatricial alopecia

Central centrifugal cicatricial alopecia is a common cause of progressive permanent apical alopecia. This unique form of alopecia includes entities previously know as “hot comb alopecia,” “follicular degeneration syndrome,” “pseudopelade” in African Americans and “central elliptical pseudopelade” in Caucasians. The etiology appears to be multifactorial and the condition occurs in all races.

When worlds collide: Th17 and Treg cells in cancer and autoimmunity

The balance between Th17 cells and regulatory T cells (Tregs) has emerged as a prominent factor in regulating autoimmunity and cancer. Th17 cells are vital for host defense against pathogens but have also been implicated in causing autoimmune disorders and cancer, though their role in carcinogenesis is less well understood. Tregs are required for self-tolerance and defense against autoimmunity and often correlate with cancer progression. This review addresses the importance of a functional homeostasis between these two subsets in health and the consequences of its disruption when these forces collide in disease. Importantly, we discuss the ability of Th17 cells to mediate cancer regression in immunotherapy, including adoptive transfer and checkpoint blockade therapy, and the therapeutic possibilities of purposefully offsetting the Th17/Treg balance to treat patients with cancer as well as those with autoimmune diseases.

Gene expression of sphingolipid metabolism pathways is altered in hidradenitis suppurativa

Background Hidradenitis suppurativa (HS) is a debilitating skin disease characterized by painful recurrent nodules and abscesses caused by chronic inflammation. Early events in the development of HS are believed to occur in the folliculopilosebaceous unit; however, the signaling pathways behind this mechanism are unknown. Sphingolipids, such as ceramide, are essential components of the skin and appendages and have important structural and signaling roles. Objective We sought to explore whether the gene expression of enzymes involved in sphingolipid metabolic pathways is altered in HS. Methods A microarray data set including 30 samples was used to compare the expression of sphingolipid‐related enzymes in inflammatory skin lesions from HS patients (n = 17) with the expression in clinically healthy skin tissue (n = 13). Differential expression of sphingolipid metabolism–related genes was analyzed using Gene Expression Omnibus 2R. Results HS lesional skin samples have significantly decreased expression of enzymes generating ceramide and sphingomyelin, increased expression of enzymes catabolizing ceramide to sphingosine, and increased expression of enzymes converting ceramide to galactosylceramide and gangliosides. Limitations Limitations of this study include assessing the expression of sphingolipid‐related enzymes without assessing the levels of the related sphingolipids. Conclusion Our study suggests that sphingolipid metabolism is altered in HS lesional skin compared with normal skin.

Skin biopsy: Identifying and overcoming errors in the skin biopsy pathway

The skin biopsy pathway involves numerous communication requirements, technical events, human handoffs, and cognitive decisions. Every step in the process has an error rate >0. To deliver the highest quality care, dermatologists obtaining skin biopsy specimens should implement systems in their office to minimize errors. This includes the prevention of wrong-site surgery, which in most instances involves accurate communication of the correct biopsy location to the performing surgeon. Part II of this continuing medical education article presents techniques for assessing and planning improvement to the skin biopsy pathway in your office, and provides a simple online quality improvement activity that allows Board-certified dermatologists the opportunity to potentially improve aspects of the skin biopsy process in their own practices, and in the process obtain Maintenance of Certification credit.