Programmed cell death 1 protein and programmed death-ligand 1 inhibitors in the treatment of nonmelanoma skin cancer: A systematic review.

BACKGROUND: Immunotherapy using programmed cell death 1 protein (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors has been increasingly reported in a variety of nonmelanoma skin cancers (NMSCs). OBJECTIVE: To analyze the evidence of PD-1 and PD-L1 inhibitors in the treatment of NMSC. METHODS: A primary literature search was conducted with the PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases through October 28, 2018, to include studies on the use of PD-1 or PD-L1 inhibitors in patients for NMSC. Two reviewers independently performed study selection, data extraction, and critical appraisal. RESULTS: This systematic review included 51 articles. The most robust evidence was in the treatment of Merkel cell carcinoma and cutaneous squamous cell carcinomas, as supported by phase 1 and 2 clinical trials. Treatment of basal cell carcinoma, cutaneous sarcoma, sebaceous carcinoma, and malignant peripheral nerve sheath tumor also showed benefit with PD-1/PD-L1 inhibitors, but data are limited. There does not appear to be efficacy for PD-1/PD-L1 inhibitors in cutaneous lymphomas. LIMITATIONS: More investigation is needed to determine the efficacy, tumor responsiveness, and the safety profile of PD-1 and PD-L1 inhibitors in NMSC. CONCLUSION: PD-1 and PD-L1 inhibitors exhibit treatment efficacy in a variety of NMSCs.

Hyperspectral imaging in automated digital dermoscopy screening for melanoma.

OBJECTIVES: Early melanoma detection decreases morbidity and mortality. Early detection classically involves dermoscopy to identify suspicious lesions for which biopsy is indicated. Biopsy and histological examination then diagnose benign nevi, atypical nevi, or cancerous growths. With current methods, a considerable number of unnecessary biopsies are performed as only 11% of all biopsied, suspicious lesions are actually melanomas. Thus, there is a need for more advanced noninvasive diagnostics to guide the decision of whether or not to biopsy. Artificial intelligence can generate screening algorithms that transform a set of imaging biomarkers into a risk score that can be used to classify a lesion as a melanoma or a nevus by comparing the score to a classification threshold. Melanoma imaging biomarkers have been shown to be spectrally dependent in Red, Green, Blue (RGB) color channels, and hyperspectral imaging may further enhance diagnostic power. The purpose of this study was to use the same melanoma imaging biomarkers previously described, but over a wider range of wavelengths to determine if, in combination with machine learning algorithms, this could result in enhanced melanoma detection. METHODS: We used the melanoma advanced imaging dermatoscope (mAID) to image pigmented lesions assessed by dermatologists as requiring a biopsy. The mAID is a 21-wavelength imaging device in the 350-950 nm range. We then generated imaging biomarkers from these hyperspectral dermoscopy images, and, with the help of artificial intelligence algorithms, generated a melanoma Q-score for each lesion (0 = nevus, 1 = melanoma). The Q-score was then compared to the histopathologic diagnosis. RESULTS: The overall sensitivity and specificity of hyperspectral dermoscopy in detecting melanoma when evaluated in a set of lesions selected by dermatologists as requiring biopsy was 100% and 36%, respectively. CONCLUSION: With widespread application, and if validated in larger clinical trials, this non-invasive methodology could decrease unnecessary biopsies and potentially increase life-saving early detection events. Lasers Surg. Med. 51:214-222, 2019. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Splash Safety During Dermatologic Procedures Among US Dermatology Residents.

BACKGROUND: Dermatologists are at potential risk of acquiring infections from contamination of the mucous membranes by blood and body fluids. However, there are little data on splash safety during procedural dermatology. OBJECTIVE: To determine dermatology resident perceptions about splash risk during dermatologic procedures and to quantify the rate of protective equipment use. METHODS: An anonymous on-line survey was sent to 108 United States ACGME-approved dermatology residency programs assessing frequency of facial protection during dermatologic procedures, personal history of splash injury, and, if applicable, reasons for not always wearing facial protection. RESULTS: A total of 153 dermatology residents responded. Rates of facial protection varied by procedure, with the highest rates during surgery and the lowest during local anesthetic injection. Over 54% of respondents reported suffering facial splash while not wearing facial protection during a procedure. In contrast, 88.9% of respondents correctly answered that there is a small risk of acquiring infection from mucosal splash. Residency program recommendations for facial protection seem to vary by procedure. CONCLUSION: The authors' results demonstrate that although facial splash is a common injury, facial protection rates and protective recommendations vary significantly by procedure. These data support the recommendation for enhanced facial protection guidelines during procedural dermatology.

Melanoma arising in an ovarian cystic teratoma: a systematic review of presentation, treatment, and outcomes.

PURPOSE: To assess the clinical presentation, treatment modalities, and outcome of primary melanomas arising in ovarian cystic teratomas (OCT). METHODS: A systematic review on PubMed/MEDLINE was performed on June 5, 2017, to gather data on patients with primary melanomas arising in OCTs. No systematic reviews were identified. Consequently, only case reports and case series of individuals were analyzed. A total of 37 articles met our inclusion criteria, totaling 41 unique patients. RESULTS: The average age of diagnosis was 51.5 years. In total, 24% of patients were found to have metastatic disease. In total, 56.7% of patients eventually died of their disease, with an average time from diagnosis to death of 9.3 months. Disease recurrence was common, occurring in 65% of patients. The mainstay of treatment was surgical in 100% of the cases. Adjuvant chemotherapy, immunotherapy, and radiation were also used with varying degrees of efficacy. CONCLUSIONS: Malignant melanoma arising in OCT is a rare disease with poor prognosis. The current mainstay treatment is surgical. Potential benefits of targeted therapy, immunotherapy, and chemotherapy remain to be determined. A limitation of this study is that these melanomas have only been published in case reports.

The Impact of Melanoma Imaging Biomarker Cues on Detection Sensitivity and Specificity in Melanoma versus Clinically Atypical Nevi.

Incorporation of dermoscopy and artificial intelligence (AI) is improving healthcare professionals' ability to diagnose melanoma earlier, but these algorithms often suffer from a "black box" issue, where decision-making processes are not transparent, limiting their utility for training healthcare providers. To address this, an automated approach for generating melanoma imaging biomarker cues (IBCs), which mimics the screening cues used by expert dermoscopists, was developed. This study created a one-minute learning environment where dermatologists adopted a sensory cue integration algorithm to combine a single IBC with a risk score built on many IBCs, then immediately tested their performance in differentiating melanoma from benign nevi. Ten participants evaluated 78 dermoscopic images, comprised of 39 melanomas and 39 nevi, first without IBCs and then with IBCs. Participants classified each image as melanoma or nevus in both experimental conditions, enabling direct comparative analysis through paired data. With IBCs, average sensitivity improved significantly from 73.69% to 81.57% (p = 0.0051), and the average specificity improved from 60.50% to 67.25% (p = 0.059) for the diagnosis of melanoma. The index of discriminability (d') increased significantly by 0.47 (p = 0.002). Therefore, the incorporation of IBCs can significantly improve physicians' sensitivity in melanoma diagnosis. While more research is needed to validate this approach across other healthcare providers, its use may positively impact melanoma screening practices.

Medical students educate teens about skin cancer: what have we learned?

Skin cancer is a serious societal problem, and public awareness outreach, including to youth, is crucial. Medical students have joined forces to educate adolescents about skin cancer with significant impacts; even one 50-min interactive outreach session led to sustained changes in knowledge and behavior in a cohort of 1,200 adolescents surveyed. Medical students can act as a tremendous asset to health awareness public outreach efforts: enthusiastic volunteerism keeps education cost-effective, results in exponential spread of information, reinforces knowledge and communication skills of future physicians, and can result in tangible, life-saving benefits such as early detection of melanoma.

Non-invasive optical biopsy by multiphoton microscopy identifies the live morphology of common melanocytic nevi.

Multiphoton microscopy (MPM) is a promising non-invasive imaging tool for discriminating benign nevi from melanoma. In this study, we establish a MPM morphologic catalogue of common nevi, information that will be critical in devising strategies to distinguish them from nevi that are evolving to melanoma that may present with more subtle signs of malignancy. Thirty common melanocytic nevi were imaged in vivo using MPM. Quantitative parameters that can distinguish between different types of nevi were developed and confirmed by examining the histology of eleven of the imaged nevi. MPM features of nevi examined included cytologic morphology of melanocytes in the epidermis and dermis, the size and distribution of nevomelanocytes both within and around nests, the size of rete ridges, and the presence of immune cells in the dermis. Distinguishing features include cytological morphology, the size of nevomelanocytes, the size of nevomelanocyte nests, and the distribution of nevomelanocytes. Notably, these distinguishing characteristics were not easily appreciated in fixed tissues, highlighting essential differences in the morphology of live skin. Taken together, this work provides a morphologic compendium of normal nevi, information that will be critical in future studies directed at identifying melanocytic nevi that are evolving to melanoma.

A recalcitrant case of toxic epidermal necrolysis.

We describe a case that was initially diagnosed and treated as toxic epidermal necrolysis (TEN) by an outside hospital. After failure to improve on high-dose steroids and intravenous (IV) immunoglobulin, the patient was transferred to our hospital where he was subsequently diagnosed with a disseminated herpes simplex virus (HSV) infection. The patient recovered after 21 days of antiviral therapy. We review key physical examination findings that will help the clinician diagnose a viral etiology in the setting of an acute blistering eruption with mucosal involvement.

Nuclear morphometry and molecular biomarkers of actinic keratosis, sun-damaged, and nonexposed skin.

Computer-assisted image analysis is useful for quantifying the histologic and molecular changes of sun-induced squamous cell carcinoma progression. We used the CAS 200 image analysis system to measure nuclear morphometric parameters, p53 expression, and proliferation markers in actinic keratosis (AK), sun-exposed, and normal skin in 51 patients. Nuclear morphometry revealed significant increases in nuclear absorbance, irregularity of nuclear shape, and nuclear size in AK compared with normal and sun-damaged skin. These parameters showed significantly greater variability in AK nuclei. Argyrophyllic nucleolar organizer area and number were also significantly greater in AK compared with sun-damaged skin and normal skin. Ki67 and p53 expressions were both increased in sun-damaged skin relative to normal and greater still in AK. These data are evidence that sun damage induces proliferation and p53 abnormalities before the appearance of nuclear abnormalities and their associated DNA instability. Following these changes during a skin cancer chemopreventative trial can then help assess the efficacy of the agent and help determine where in the progression of neoplastic changes it exerts its biological effects.

Analysis of heterogeneity of atypia within melanocytic nevi.

BACKGROUND: Incisional biopsy of clinically atypical nevi continues to be a common practice. Questions can arise as to the adequacy of these partial biopsies. OBJECTIVE: To determine whether incisional (partial) biopsy specimens may be considered representative of the entire lesion, atypical nevi submitted to our dermatopathology laboratory were examined for the presence or absence of heterogeneity of atypia within the individual nevi. DESIGN: The study included 250 histologically atypical nevi that were selected consecutively from pigmented lesions that were submitted to our dermatopathology laboratory by community and academic dermatologists for histopathologic analysis. Also, 23 moderately to severely atypical and 25 severely atypical nevi from consecutive submissions were added for statistical reasons. Lesions with both clear and involved margins were used. Lesions were considered homogeneous if the atypia involved the entire lesion or heterogeneous if either the atypia was focal or if different degrees of atypia occurred within the same lesion. Atypia was defined by the usual parameters of architectural and cytologic atypia and host response. Also, the degree of atypia in relationship to heterogeneity and to patient age was determined. SETTING: The Dermatopathology Laboratory, University of California, Irvine. MAIN OUTCOME MEASURES: Outcome measures included the percentage of nevi exhibiting heterogeneity of atypia, heterogeneity of atypia in relation to patient age, degree of atypia in relation to patient age, and degree of atypia in relation to the presence of heterogeneity of atypia. RESULTS: Of the 298 nevi examined, 107 (35.9%) were heterogeneous in atypia and 191 (64.1%) were homogeneous in atypia. There was no significant difference in age between patients with heterogeneous lesions and those with homogeneous lesions. There was a statistically significant correlation between the degree of atypia and patient age. The average age of patients with a lesser degree of atypia was 36.9 years, while the average age of patients with a greater degree of atypia was 44.8 years (P<.005). There was no significant correlation between degree of atypia and heterogeneity of atypia (correlation coefficient, 0.1). CONCLUSIONS: A clinically significant proportion of atypical nevi exhibited heterogeneity of atypia. Also, there was a significant relationship between the degree of atypia and increasing age (P<.005). Therefore, if a clinically atypical nevus warrants a biopsy, these results give additional support for complete excisional biopsy (which can include shave or punch) to assure adequate histopathologic sampling of the lesion.

Chemoprevention of nonmelanoma skin cancer: experience with a polyphenol from green tea.

Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed.

Screening and early detection of skin cancer.

Skin cancer is the most common type of cancer in the United States. US incidence of malignant melanoma is increasing faster than any other type of cancer. To minimize increasing morbidity and mortality rates, it is imperative that appropriate screening and early detection of skin cancer become more widespread. All physicians who see patients clinically have the potential for detecting skin cancers. The scope of skin cancer as a health-care problem is discussed. Evidence for the effectiveness and necessity of skin cancer screening and early detection is presented. Costs of screening and detection are discussed in relation to impact on treatment costs and overall costs of skin cancer burden. Current methods and recommendations for skin cancer screening and detection are reviewed, especially with regard to individuals and populations that may require more specialized or intensive screening and follow-up. Newer approaches involving instrument-assisted screening and detection of skin cancer are under intense development, and these exciting emerging technologies are reviewed.