Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND:  Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE:  To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS:  A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS:  The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION:  The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12):54-60.   doi:10.36849/JDD.7691.

Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE: To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS: A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS: The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION: The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12): doi:10.36849/JDD.7691e.

Photodynamic Therapy with 5-aminolevulinic Acid 10% Gel and Red Light for the Treatment of Actinic Keratosis, Nonmelanoma Skin Cancers, and Acne: Current Evidence and Best Practices.

Photodynamic therapy (PDT) can be an effective treatment for actinic keratosis (AK) as well as selected non-melanoma skin cancers (NMSCs), such as Bowen's disease and superficial basal cell carcinoma. PDT has also demonstrated effectiveness in the management of acne vulgaris. Results from controlled clinical trials have shown the safety and efficacy of PDT for these conditions with the use of different photosensitizers and a wide range of light sources. PDT has been employed effectively as monotherapy and in combination with other topicals and alternate light or laser energy therapies. This article provides expert practical guidance for the use of the newest 5-aminolevulinic acid (ALA) product (ALA 10% gel) plus red light as monotherapy for AKs, NMSC, and acne. Here, information from clinical guidelines and a summary of supporting evidence is provided for each cutaneous condition. The authors also provide detailed guidance for employing ALA 10% gel, a photosensitizer precursor, for each of these applications.

Isolated Nail Dystrophy: An Unlikely Presentation of Metastatic Renal Cell Carcinoma.

Metastasis of any malignancy to the nail unit is uncommon, and only a handful of cases of subungual renal cell carcinoma (RCC) metastasis have been reported. We describe a case of isolated nail dystrophy that proved to be the presenting symptom of a previously undetected RCC. In a patient presenting with a subungual lesion, tumor metastasis to the nail unit should be included in the clinical differential diagnosis in both oncology patients and previously cancer-free individuals, as a subungual metastasis may be the first indication of a clinically silent visceral malignancy.

Treatment of Actinic Purpura.

Mature skin is prone to bruising, resulting in a condition known as actinic purpura, characterized by unsightly ecchymosis and purple patches. Similar to other skin conditions, the incidence of actinic purpura increases with advancing age and occurs with equal frequency among men and women. The unsightly appearance of actinic purpura may be a source of emotional distress among the elderly. A new product has been formulated specifically for the treatment of actinic purpura. This product contains retinol, α-hydroxy acids, arnica oil, ceramides, niacinamide, and phytonadione, which effectively treat actinic purpura by improving local circulation, thickening the skin, and repairing the skin barrier. The objective of this paper is to review the beneficial properties of these ingredients and their respective roles in the treatment of actinic purpura.

Understanding the Role of Photolyases: Photoprotection and Beyond.

The limitations of photoprotection modalities have been the inability to arrest the progression of photodamage. Chemoprevention strategies involving a sunscreen has been incomplete because of the need to induce sustained repair of mutations and slow carcinogenesis. Photolyases, or photoreactivation enzymes, serve the role of repairing mutations and damage to DNA induced by ultraviolet (UV) radiation and therefore influence the initiation phases of carcinogenesis. As these enzymes are absent in humans, exogenous forms have been manufactured and are now utilized in topical agents to supplement and augment the innate repair mechanisms that are mostly inefficient. J Drugs Dermatol. 2017;16(5 Suppl):61-66.

Expert Consensus on Cosmetic Outcomes After Treatment of Actinic Keratosis.

Dermatologists treat actinic keratosis (AK) primarily because these lesions have the potential to progress to invasive squamous cell carcinoma. Patients, on the other hand, generally seek treatment to remove the lesions and achieve an improved appearance of their skin following treatment. In selecting a treatment option for AK, dermatologists should consider post-treatment cosmesis, because cosmetic outcomes differ across AK treatments. To obtain expert opinion on the cosmetic sequelae related to chronically photodamaged skin and the treatment of AK, an expert panel meeting among dermatologists was conducted in February 2016. These experts reviewed current treatment options for photodamage, including AK, and discussed the relative merits of the various cosmetic assessments commonly used by investigators and patients in both clinical trial and dermatology practice settings. A main goal of the expert panel meeting was to propose assessment tools that could be specifically designed to characterize cosmesis results after treatment of AK. The panel agreed that existing tools for measurement of cosmetic outcomes following treatment of photodamage could also be used to evaluate cosmesis after treatment of AK. Digital photography is probably the best method used for this, with validation by other technologies. Better measurement tools specifically for assessing cosmesis after AK treatment are needed. Once they are developed and validated, regulatory agencies should be educated about the importance of including cosmetic outcomes as a component of product labeling.

J Drugs Dermatol. 2017;16(3):260-265.

Chronic Wound Healing: A Review of Current Management and Treatments.

Wound healing is a complex, highly regulated process that is critical in maintaining the barrier function of skin. With numerous disease processes, the cascade of events involved in wound healing can be affected, resulting in chronic, non-healing wounds that subject the patient to significant discomfort and distress while draining the medical system of an enormous amount of resources. The healing of a superficial wound requires many factors to work in concert, and wound dressings and treatments have evolved considerably to address possible barriers to wound healing, ranging from infection to hypoxia. Even optimally, wound tissue never reaches its pre-injured strength and multiple aberrant healing states can result in chronic non-healing wounds. This article will review wound healing physiology and discuss current approaches for treating a wound.

Staged Excision for Lentigo Maligna and Lentigo Maligna Melanoma: Analysis of Surgical Margins and Long-term Recurrence in 68 Cases from a Single Practice.

INTRODUCTION: Lentigo maligna is a form of in situ melanoma that occurs commonly on sun-exposed skin of middle-aged to elderly adults. Margin-control surgery offers the highest cure rate for lentigo maligna/lentigo maligna melanoma. MATERIALS AND METHODS: Charts from the authors' private office from the 20-year period from January 1986 to December 2005 were reviewed to identify patients with histologically confirmed lentigo maligna or lentigo maligna melanoma treated by staged excision. RESULTS: Sixty-eight patients (39 men, 29 women; mean age at diagnosis 67.4±10.2 years, range 48-87 years) with 68 tumors were treated in the authors' office for lentigo maligna (58) or lentigo maligna melanoma (10) between January 1986 and December 2005. After excision, patients were followed clinically for a minimum of three years. The mean follow-up duration was 138 months (median 139 months; range 37-330 months). The overall margin for tumor clearance was 7.0±0.55mm with a recurrence rate of 5.9 percent. LIMITATIONS: The limitations of this study include the retrospective nature of the authors' review, and data collected from a single, private practice setting. CONCLUSION: The authors' findings support staged excision as an effective method of treating lentigo maligna and lentigo maligna melanoma, offering a high cure rate while maximally preserving normal tissue.

High-dose Rate Electronic Brachytherapy: A Nonsurgical Treatment Alternative for Nonmelanoma Skin Cancer.

The authors summarized data from a group of physicians with experience using high-dose rate electronic brachytherapy for the treatment of nonmelanoma skin cancer. The data have been published or presented in abstract format at national dermatology and radiation oncology meetings. The data included 1,822 treated lesions from 2009 to 2014 in patients ranging in age from 52 to 104 years. Most lesions were basal cell carcinoma (57%) or squamous cell carcinoma (38%) less than 2cm in size (97%). Median follow-up at the various centers ranged from 4 to 16 months, and results yielded an extremely low recurrence rate of less than one percent. Results show that within the confines of this follow up period, electronic brachytherapy is an effective, convenient, nonsurgical treatment option for patients with nonmelanoma skin cancer with few recurrences and excellent cosmetic results.

Phototherapy-induced Purpuric Eruption in a Neonate.

Phototherapy is commonly utilized in the treatment of neonatal jaundice. The authors observed a rare cutaneous complication of visible blue light phototherapy in a neonate with hyperbilirubinemia. A three-day-old neonate was evaluated for a purpuric rash after initiation of phototherapy for treatment of hyperbilirubinemia. Cutaneous examination revealed purpuric, nonblanching, well-demarcated lesions on the chest, abdomen, arms, and chin with sparing at shielded sites. The history, physical examination, and laboratory results support the diagnosis of purpuric phototherapy-induced eruption. The authors present a case report of this uncommon cutaneous eruption in a transfused neonate undergoing phototherapy for treatment of hemolytic disease of the newborn.

Role of oral Polypodium leucotomos extract in dermatologic diseases: a review of the literature.

Polypodium leucotomos extract (PLE), derived from the tropical fern of Polypodiaceae family, has properties ranging from immunomodulatory and antioxidative to photoprotective. It is these multiple mechanisms of action, in combination with a favorable side effect profile, which makes PLE a promising adjunctive treatment for several dermatologic disorders. Studies are summarized on the use and potential applications of PLE in the treatment or management of photodermatoses, vitiligo, melasma, psoriasis, atopic dermatitis, and more recently, in minimizing infections in high-performance athletes. More data, however, with larger sample sizes are needed to confirm these benefits.

Current issues in the management of actinic keratosis.

Actinic keratoses are common sun-induced skin lesions that should be treated to prevent the development of nonmelanoma skin cancer. Although cryotherapy is commonly used to treat individual lesions, it fails to address the actinically damaged field of neighboring sun-damaged skin, which is more effectively treated by field therapies to clear both visible and subclinical lesions. Most topical treatments require prolonged use and cause an inflammatory response that limits tolerability and adherence. Education is essential to teach patients about the chronic nature of actinic keratosis, the risk of nonmelanoma skin cancer, and the importance of correct use of topical medications. The addition of nonphysician clinicians to dermatologic practices provides a valuable source of education, treatment, and follow-up care to the management of actinic keratosis.

Mechanisms of action of topical 5-fluorouracil: review and implications for the treatment of dermatological disorders.

Topical 5-fluorouracil has proved to be a useful therapy since its discovery nearly 50 years ago for the treatment of a range of cancers (e.g. skin, colorectal, breast) and dermatological conditions (e.g. cancerous and precancerous conditions such as actinic keratosis, benign tumors, nail psoriasis, mycosis fungoides, and porokeratoses). As a result of the enduring utility in these conditions, the mechanism of action of 5-fluorouracil has been studied extensively in vivo and in vitro. This review provides an overview of the history and general mechanism of action of 5-fluorouracil and discusses the dermatological implications of the drug, including systemic absorption, selectivity for abnormal skin, targeted delivery, and skin-specific molecular effects. Considerations of 5-fluorouracil treatment in specific dermatological settings are also discussed, as well as recent findings of a role for 5-fluorouracil in the treatment of photoaging.

Advances in topical delivery systems in acne: new solutions to address concentration dependent irritation and dryness.

Formulation development is key to the successful treatment of acne. There has been significant progress over the past few years, but not all developments can be universally applied. An effective topical formulation must provide chemical stability and enhanced penetration of active ingredients at optimal concentrations for efficacy and safety; be cosmetically acceptable; and not add side effects of its own. Both retinoids and fixed combinations containing benzoyl peroxide are commonly used to treat acne, but both have the potential to cause troublesome dose-dependent irritation and dryness. Excipients such as surfactants and alcohol have added to the problem. Two products have recently been introduced where a combination of micronization skills and well-chosen excipients has minimized irritation and dryness without compromising efficacy. Results from two major studies are discussed in this article.

The role of immunohistochemistry in discriminating primary from secondary extramammary Paget disease.

BACKGROUND: Extramammary Paget disease (EMPD) is categorized into 2 groups: primary EMPD or EMPD secondary to underlying malignancy. Primary EMPD has a better prognosis, and the ability to distinguish between the 2 subsets has clinical relevance. Recent studies have suggested that immunostains, including cytokeratin (CK) 7, CK20, and BRST-2, distinguish between the 2 groups. We analyzed a large series of EMPD with an expanded immunohistochemical panel to assess its value in distinguishing primary from secondary disease. DESIGN: Formalin-fixed, paraffin-embedded sections of 98 EMPD specimens from 61 patients (45 primary and 16 secondary) were immunostained with CK7, CK20, HER-2/neu, BRST-2, CDX2, androgen receptor (AR), and cyclin D1. The study included 44 women and 17 men (median age: 73 years). Median follow-up time was 47 months. RESULTS: All EMPD specimens were vibrantly positive for CK7. The frequency of positivity for all EMPD samples was CK20 (28%), BRST-2 (40%), HER-2/neu (64%), CDX2 (10%), AR (16%), and cyclin D1 (76%). For primary EMPD, the frequency of positivity was CK20 (22%), BRST-2 (48%), HER-2/neu (65%), CDX2 (2%), AR (21%), and cyclin D1 (84%). For secondary EMPD, the frequency of positivity was CK20 (50%), BRST-2 (25%), HER-2/neu (60%), CDX2 (33%), AR (0%), and cyclin D1 (53%). Notably, all 6 of 7 cases of EMPD secondary to an anorectal adenocarcinoma tested were HER-2/neu negative and 5 of those 6 cases (80%) were CDX2 positive. CONCLUSIONS: The role of CK7, CK20, and BRST-2 in distinguishing primary and secondary EMPD is limited because CK20 and BRST-2 were positive in large subsets of both groups. An expanded immunohistochemical panel, including HER-2/neu and CDX2, may be useful in discriminating primary EMPD from EMPD secondary to anorectal adenocarcinoma but fails to distinguish primary EMPD from EMPD secondary to urothelial or prostatic malignancy. The consistent overexpression of HER-2/neu in primary EMPD suggests a role for trastuzumab therapy in patients with recurrent disease.

The unintended effects of a boxed warning.

OBJECTIVE: To demonstrate a real-life correlation that after the US Food and Drug Administration introduced a boxed warning concerning malignancies to the labeling for topical calcineurin inhibitors, reluctance to use topical calcineurin inhibitors has led to their substitution with other therapies that have their own risks. PARTICIPANTS: An anonymous survey of attendees of the 2007 Fall Clinical Dermatology conference in Las Vegas, Nevada, from October 17-19, 2007. More than 95 percent of attendees were dermatologists; a small number of mid-level practitioners attended as well. Of nearly 700 attendees, the first 504 who agreed to complete the survey were included. RESULTS: More than 40 percent of dermatologists surveyed claimed that more than 20 percent of their atopic dermatitis patients are not adequately controlled since the introduction of the boxed warning. Forty-eight percent claim that more than 20 percent of those patients were adequately controlled with topical calcineurin inhibitors as part of their regimens. Eighty percent of dermatologists surveyed agree that more than 10 precent of those patients were adequately controlled with topical calcineurin inhibitors in their regimens. CONCLUSION: While caution is usually prudent, the introduction of a boxed warning in the case of topical calcineurin inhibitors has led to the use of treatments that often have greater risks than the topical calcineurin inhibitors that they replaced.