Melanoma clinicopathological groups characterized and compared with dermoscopy and reflectance confocal microscopy.

BACKGROUND: Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described. OBJECTIVE: Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation. METHODS: Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression. RESULTS: Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern + regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network + regression structures, and nonevident follicles + heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis. LIMITATIONS: Small SK-like lesions sample, single RCM analyses (no reproduction of outcome). CONCLUSION: RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features.

An Update and Review of Clinical Outcomes Using Immunohistochemical Stains in Mohs Micrographic Surgery for Melanoma.

BACKGROUND: Mohs micrographic surgery (MMS) provides optimal margin control through complete peripheral and deep margin assessment. The treatment of melanoma using MMS has historically been limited by difficulty in interpreting melanocytes using frozen sections. Immunohistochemical (IHC) staining, a technique whereby chromogen-tagged antibodies are used to detect antigens of interest, has revolutionized the surgical treatment of melanoma. OBJECTIVES: This article provides an update and literature review of current IHC stains used in MMS for melanoma, their sensitivities and specificities, and clinical outcomes. MATERIALS AND METHODS: A PubMed search was performed using keywords including "immunohistochemistry," "staining," and "Mohs surgery." Articles related to the use of IHC staining for the treatment of melanoma with MMS were included. RESULTS: Six IHC stains met the criteria for the review including melanoma antigen recognized by T cells (MART-1), SRY-related HMG-box (SOX10), microphthalmia-associated transcription factor, HMB-45, MEL-5, S-100, and preferentially expressed antigen in melanoma. CONCLUSION: The adaptation of IHC methods to frozen sections has enabled MMS to become a preferred treatment option for melanoma in special-site areas. Future studies are needed to standardize IHC techniques and to define best practices when using frozen section in the treatment of melanoma.

Pathologic Upstaging of Cutaneous Melanoma After Mohs Micrographic Surgery.

BACKGROUND: Mohs micrographic surgery (MMS) is used for melanoma in situ (MIS) and thin invasive melanomas, particularly on the head and neck, during which a debulk section is typically prepared. Tumor upstaging occurs if the debulking specimen meets criteria for an increased tumor (T) stage per the American Joint Committee on Cancer 8th edition compared with the initial biopsy. Upstaging can alter survival and recurrence outcomes, resulting in increased patient morbidity and mortality. OBJECTIVE: To determine the rate of cutaneous melanoma upstaging during MMS. MATERIALS AND METHODS: A multicenter study was performed. Information from electronic medical records from 3 dermatologic surgeons performing MMS for cutaneous melanoma were logged from January 1, 2017 to December 31, 2021. Deidentified information regarding patient demographics and tumor characteristics was recorded. RESULTS: Three-hundred and ten cases of cutaneous melanoma treated with MMS were identified. 2.3% of cases were upstaged, ranging from T1a to T3a. No significant risk factors for upstaging were identified. CONCLUSION: Our data demonstrate a lower rate of cutaneous melanoma upstaging during MMS than the current literature. Differences may be accounted for because of differing patient populations, cutaneous melanoma detection at an earlier clinical stage, and evolving melanoma histologic criteria.

Photodynamic Skincare: A Prospective Single-Center Study.

BACKGROUND: Peer-reviewed, clinical studies measuring the efficacy and usability of skin care products enhance their integrity and may guide experts in the field in providing recommendations. A single-blind, prospective clinical study was designed to assess the subject satisfaction, clinical benefit, and safety of three photodynamic topical formulations referred to as MMSRepose (MMSRep), MMSRevive (MMSRev), and MMSBalance (MMSB).  Methods: Thirteen male and female patients (mean age 49 +/- 17.8 years) applied one of the three topical serums twice daily over a period of 12 weeks. Subjects returned for photography, and blinded investigator evaluation of rhytides (fine lines) and dyspigmentation were measured on a 6- and 4-point scale, respectively. Patient-perceived efficacy of multiple clinical outcomes was measured on a 5-point scale.  Results: 100% of subjects reported at least a 1-grade improvement in global aesthetic at the conclusion of the study. Investigator assessment revealed an overall 53.3% decrease in rhytides, correlating to a mean point reduction from 1.65 +/- 0.77 to 0.77 +/- 0.53 (P<0.001) from baseline to week 12. Investigator assessment of dyspigmentation revealed a 62.7% decrease, correlating to a mean point reduction of 1.85 +/- 0.68 from week 1 to 0.69 +/- 0.48 at week 12 (P<0.001). CONCLUSION: Photodynamic serums demonstrate clinical efficacy in skin rejuvenation and high user satisfaction. There were no serious adverse events. This study is limited by the inability to randomize to placebo due to the small sample size, as subject retention was heavily impacted by the SARS-CoV-2 pandemic. Future studies may be indicated to undergo comparison with a larger cohort.  J Drugs Dermatol. 2024;23(5):332-337. doi:10.36849/JDD.7167.

Permanent section margin concordance after Mohs micrographic surgery with immunohistochemistry for invasive melanoma and melanoma in situ: A retrospective dual-center analysis.

BACKGROUND: Mohs micrographic surgery (MMS) for melanoma practices vary among dermatologic surgeons. The implementation of immunohistochemical staining in MMS for melanoma mitigates challenges associated with slide interpretation; however, the reliability of melanoma antigen recognized by T cells 1 (MART-1), the preferred immunostain for melanoma, has yet to be compared with permanent section pathology. OBJECTIVE: To assess concordance rates of MART-1 frozen sections and permanent section pathologic interpretation of melanoma treated with MMS. METHODS: A dual-center retrospective analysis was conducted to collect concordance and demographic data. Chi-square tests were performed for group comparisons of categorical variables. RESULTS: Of the 379 permanent sections sent, 367 were concordant with frozen section pathology for an overall concordance rate of 96.8%. Cases were stratified into indeterminately concordant and indisputably concordant. Twenty-two (6%) of cases were indeterminately concordant, whereas 345 (94.0%) of cases were indisputably concordant. LIMITATIONS: The concordance rate is derived from a comparison of adjacent tissue margins, an inevitable consequence of utilizing 2 techniques. CONCLUSION: To the author's knowledge, this study represents the largest investigation examining concordance rates of MART-1 frozen sections in Mohs for melanoma. High concordance disputes the ongoing need for additional permanent margins when using MART-1 in routine cases.

BINANA 2: Characterizing Receptor/Ligand Interactions in Python and JavaScript.

BINding ANAlyzer (BINANA) is an algorithm for identifying and characterizing receptor/ligand interactions and other factors that contribute to binding. We recently updated BINANA to make the algorithm more accessible to a broader audience. We have also ported the Python3 codebase to JavaScript, thus enabling BINANA analysis in the web browser. As proof of principle, we created a web-browser application so students and chemical-biology researchers can quickly visualize receptor/ligand complexes and their unique binding interactions.

Increasingly severe cyanobacterial blooms and deep water hypoxia coincide with warming water temperatures in reservoirs.

Cyanobacterial blooms are expected to intensify and become more widespread with climate change and sustained nutrient pollution, subsequently increasing threats to lentic ecosystems, water quality, and human health. However, little is known about their rates of change because long-term monitoring data are rare, except for some well-studied individual lakes, which typically are large and broadly dispersed geographically. Using monitoring data spanning 1987-2018 for 20 temperate reservoirs located in the USA, we found that cyanobacteria cell densities mostly posed low-to-moderate human health risks until 2003-2005, after which cell densities rapidly increased. Increases were greatest in reservoirs with extensive agriculture in their watersheds, but even those with mostly forested watersheds experienced increases. Since 2009, cell densities posing high human health risks have become frequent with 75% of yearly observations exceeding 100,000 cells ml-1 , including 53% of observations from reservoirs with mostly forested watersheds. These increases coincided with progressively earlier and longer summer warming of surface waters, evidence of earlier onset of stratification, lengthening durations of deep-water hypoxia, and warming deep waters in non-stratifying reservoirs. Among years, higher cell densities in stratifying reservoirs were associated with greater summer precipitation, warmer June surface water temperatures, and higher total Kjeldahl nitrogen concentrations. These trends are evidence that expected increases in cyanobacterial blooms already are occurring as changing climate conditions in some regions increasingly favor their proliferation. Consequently, their negative effects on ecosystems, human health, and socioeconomic wellbeing could increase and expand if warming trends and nutrient pollution continue.

Comparison of satellite reflectance algorithms for estimating turbidity and cyanobacterial concentrations in productive freshwaters using hyperspectral aircraft imagery and dense coincident surface observations.

We analyzed 37 satellite reflectance algorithms and 321 variants for five satellites for estimating turbidity in a freshwater inland lake in Ohio using coincident real hyperspectral aircraft imagery converted to relative reflectance and dense coincident surface observations. This study is part of an effort to develop simple proxies for turbidity and algal blooms and to evaluate their performance and portability between satellite imagers for regional operational turbidity and algal bloom monitoring. Turbidity algorithms were then applied to synthetic satellite images and compared to in situ measurements of turbidity, chlorophyll-a (Chl-a), total suspended solids (TSS) and phycocyanin as an indicator of cyanobacterial/blue green algal (BGA) abundance. Several turbidity algorithms worked well with real Compact Airborne Spectrographic Imager (CASI) and synthetic WorldView-2, Sentinel-2 and Sentinel-3/MERIS/OLCI imagery. A simple red band algorithm for MODIS imagery and a new fluorescence line height algorithm for Landsat-8 imagery had limited performance with regard to turbidity estimation. Blue-Green Algae/Phycocyanin (BGA/PC) and Chl-a algorithms were the most widely applicable algorithms for turbidity estimation because strong co-variance of turbidity, TSS, Chl-a, and BGA made them mutual proxies in this experiment.

Case report: Regression of in-transit metastases of cutaneous squamous cell carcinoma with combination pembrolizumab and topical diphencyprone.

While typically low-risk, cutaneous squamous cell carcinoma (cSCC) can infrequently progress to metastatic disease with in-transit lesions, localized to the dermis or subcutaneous tissue between the primary tumor and draining regional lymph nodes. These lesions are associated with poor prognostic values, including decreased survival rates and increased risk of recurrence. We present the case of a 75-year-old male with cSCC and in-transit metastases on his scalp treated with the immune checkpoint inhibitor (ICI) pembrolizumab in conjunction with diphencyprone (DPCP), a topical hapten that induces a delayed-type hypersensitivity reaction in the skin. The patient was enrolled in a clinical trial (NCT05481658) that involved the twice-weekly application of DPCP 0.04% ointment to four of the in-transit metastases on his frontal scalp, concurrent with pembrolizumab 300 mg administered every three weeks. Following effective sensitization and a twelve-week treatment course, complete clearance of all lesions, DPCP-treated and non-DPCP treated, was achieved, with no adverse events. The immunologic profiles of the post-treatment biopsies were analyzed by TaqMan Low Density Array quantitative real-time polymerase chain reaction to measure immune marker gene expression. Relative to the non-DPCP-treated lesion, the DPCP-treated lesion demonstrated increased pro-inflammatory genetic markers and T-cell activation. This case represents the first reported instance of in-transit metastases of cSCC successfully treated with DPCP and an ICI. It highlights the potential safety and efficacy of DPCP with systemic immunotherapy for the management of in-transit metastases of cSCC in patients for whom surgery and radiation may be contraindicated.

The skinny on skin: The role of skin-aware professionals in skin cancer surveillance.

BACKGROUND: Licensed nonmedical, skin-aware professionals (e.g., hairdressers, massage therapists, etc.) have the potential to identify skin cancer, but baseline knowledge may not be sufficient to accomplish this goal. Following educational intervention, self-efficacy is one of the best surrogate metrics for behavior change. Curricula that increase knowledge and confidence levels can improve screening behaviors, but few have been tested for efficacy in this population AIMS: We assessed whether an online curriculum could reliably improve skin screening knowledge, attitudes, and behaviors of nonmedical professionals PATIENTS/METHODS: Skin-aware professionals were recruited through the Oregon Health Authority and IMPACT Melanoma TM. Participants completed a pre-survey, online training module, post-survey, and one-year follow-up survey. We evaluated participants' indicated levels of concern for suspicious and nonsuspicious lesions relative to "gold standard" physician ratings. We also assessed confidence and self-reported behavior change regarding talking to clients about skin cancer and recommending they see a provider to evaluate suspicious lesions RESULTS: The pre-survey was completed by 9872 skin-aware professionals; 5434 completed the post-survey, and 162 completed the one-year follow-up survey. Participants showed a significant improvement in ability to indicate the correct level of concern for all lesion types in concordance with "gold standard" physician ratings (p < 0.001). Participants reported increased comfort levels in discussing health-related topics with their clients posttraining CONCLUSIONS: Our training module effectively increased skin-aware professionals' knowledge, confidence, and concern for malignant lesions. Skin-aware professionals may serve as a valuable extension of the skin self-exam, but additional studies are needed to evaluate the impact of these curricula long-term, including potential downstream consequences.

Eosinophilic Annular Erythema Responding to Doxycycline.

Eosinophilic annular erythema (EAE) is a rare skin disease characterized by relapsing and remitting pruritic, annular erythematous plaques and tissue eosinophilia. A 39-year-old male presented with a mildly pruritic, relapsing, and remitting urticarial rash. A biopsy revealed superficial and deep perivascular dermatitis with numerous eosinophils and some neutrophils, with an absence of flame figures. Based on clinical and histopathologic findings, the patient was given a diagnosis of eosinophilic annular erythema. Treatment was initiated with doxycycline 100 mg twice daily. The patient reported substantial improvement at three months and sustained clearance at one year, remaining on doxycycline well tolerated throughout. To our knowledge, no cases of EAE improving with doxycycline have been reported in the literature and, thus, our findings highlight a potential new therapy to consider in a patient with EAE.

Dasatinib-Associated Acneiform Eruption Successfully Treated With Sarecycline in a Patient With Chronic Myeloid Leukemia.

Dasatinib is a second-generation tyrosine inhibitor that is used for the treatment of patients with chronic myeloid leukemia (CML). It can cause a myriad of skin toxicities, including pruritis, pigmentary abnormalities of hair and skin, and maculopapular rashes. Rarely, it can be associated with acneiform eruptions, which are typically treated with doxycycline. However, doxycycline may not be an ideal therapy, especially for long-term use, due to the risk of gut flora disruption, antimicrobial resistance, and side effects. We present a case of a CML patient who developed an acneiform eruption associated with dasatinib and was successfully treated with sarecycline, a narrow-spectrum tetracycline. Given its targeted spectrum of activity, sarecycline has a lower risk of antimicrobial resistance and an improved safety profile compared to first- and second-generation tetracyclines such as doxycycline. As acneiform drug eruptions can have a significant impact on a patient's quality of life, effective management by dermatologists is paramount. Sarecycline may be a suitable treatment with a favorable safety profile, making it an appropriate choice for patients, especially those who require long-term therapy.

The benefit of early-stage diagnosis: A registry-based survey evaluating the quality of life in patients with melanoma.

Background: The morbidity associated with advanced stage melanoma is an important consideration in the dialog surrounding early detection and overdiagnosis. Few studies have stratified melanoma patient quality of life (QoL) by stage at diagnosis. Objective: We sought to investigate if melanoma stage is independently associated with changes in QoL within a large, community-based melanoma registry. Secondarily, we investigated whether demographic factors such as age, geographic location or level of education are associated with changes in QoL in the same population. Methods: 1108 melanoma patients were surveyed over a three-month period using the QoL in Adult Cancer Survivors Survey, consisting of 47 items on a 7-point frequency scale. Data were analysed using both descriptive statistical models and adjusted multivariate logistic regression. Results: There were 677 respondents generating a 61% response rate. Overall, higher stage at diagnosis correlated with the largest decreases in QoL as it pertained to both general (p = 0.001) and Cancer-Specific stressors (p < 0.001). Education level (p = 0.020), age (p < 0.001), rural area code designation (p = 0.020) and family history of melanoma (p = 0.017) were also independently associated with changes in QoL. Conclusion: Earlier stage at melanoma diagnosis is associated with better QoL and thus represents a crucial intervention in patient care. Given our findings and the growing body of evidence surrounding morbidity in late-stage melanoma, it is essential that QoL be included in assessing the benefits of early detection.

Outcomes and Follow-Up Data From Two Skin Cancer Screening Events.

This study investigated the outcomes and follow-up behaviors of participants from two free skin cancer screening events in the United States. This survey, with 296 participants and a 31% response rate, gathered information on participant demographics, personal history of skin cancer, knowledge of skin screening practices, and follow-up behaviors. There was a high follow-up rate of 92.3% among individuals recommended for further dermatological consultation, but a low (22%) concordance rate between the preliminary diagnoses from the screening and patient-recalled diagnoses. Additionally, about one-sixth of participants identified limited access to care as a motivation for participating in the screening. The study emphasizes the need to improve awareness about the limitations of free screenings, enhance participant education, and ensure equitable access to skin cancer screening. Future research should focus on factors influencing follow-up behaviors and the development of targeted interventions to increase awareness and access to skin cancer screening.

Dermatologic Manifestations of Neurofibromatosis Type 1 and Emerging Treatments.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that increases one's risk for both benign and malignant tumors. NF1 affects every organ in the body, but the most distinctive symptoms that are often the most bothersome to patients are the cutaneous manifestations, which can be unsightly, cause pain or pruritus, and have limited therapeutic options. In an effort to increase awareness of lesser-known dermatologic associations and to promote multidisciplinary care, we conducted a narrative review to shed light on dermatologic associations of NF1 as well as emerging treatment options. Topics covered include cutaneous neurofibromas, plexiform neurofibromas, diffuse neurofibromas, distinct nodular lesions, malignant peripheral nerve sheath tumors, glomus tumors, juvenile xanthogranulomas, skin cancer, and cutaneous T-cell lymphoma.

Unique protein signatures evolve during the course of a delayed-type hypersensitivity reaction in human skin.

Diphencyprone (DPCP) is a hapten that causes a delayed-type hypersensitivity reaction when applied topically. It has clinical uses in the treatment of various conditions such as melanoma metastases, warts, and alopecia areata, but the mechanisms are currently not well understood in humans. To further characterize the immunologic effects of DPCP, the authors performed a proteomic analysis of normal skin of eight healthy volunteers following a single application of DPCP and compared them with placebo-treated skin from the same volunteers. A total of 96 proteins were examined using the Olink immuno-oncology panel at 3 days (peak response), 14 days (partially resolved response), and 120 days (completely resolved response). Our analysis revealed significant upregulation of markers of immune cell activation (interleukin [IL] 8), vascular and tissue remodeling (matrix metallopeptidase 12 [MMP12], nitric oxide synthase 3 [NOS3]), antineoplastic markers (granzyme B [GZMB]), and the Th1 axis (interferon gamma [IFNG], chemokine (C-X-C motif) ligand [CXCL] 9, CXCL10, CXCL11) at days 3 and 14 compared with placebo (p < 0.05). In addition, several negative regulators of immune function such as programmed cell death 1 (PD1), programmed cell death ligand 1 (PDL1) (p < 0.001), and lymphocyte activation gene 3 (LAG3) (p < 0.05) were significantly upregulated at days 3 and 14. This induction of negative regulators may explain the seemingly paradoxical therapeutic benefits of DPCP in autoimmune conditions such as alopecia areata. The current analysis also indicated IL-4 upregulation only at day 3, followed by IL-12 upregulation only at day 14, suggesting a transient Th2 response followed by Th1 polarization. Overall, these data suggest a complex and evolving immunological delayed-type hypersensitivity response to a single application of DPCP over time. Future proteomic studies of samples from patients with melanoma metastases, warts, and alopecia areata treated long term with DPCP are needed to further evaluate its pharmacologic mechanisms.

Hidden in plain sight: Considerations for an ulcer of the scalp.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare inflammatory skin condition characterized by painful, irregularly shaped skin ulcers mainly affecting the lower extremities. PG rarely affects the head and neck, making the diagnosis of this condition even more challenging. A high index of suspicion is paramount in the diagnosis of PG, especially after surgical procedures. METHODS: We describe a clinical case of a patient with initially undiagnosed PG of the scalp who underwent surgical excision and full thickness skin graft with subsequent graft necrosis as initial clue for the diagnosis. RESULTS: Twenty months after initial presentation, this patient healed with a multimodal medical approach of immunosuppressive therapy and wound care. CONCLUSION: Prompt recognition of PG by physicians assessing any surgical wounds is vital in reducing misdiagnosis and improving patient outcomes.