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The etiology of CTCL is a subject of extensive investigation. Researchers have explored links between CTCL and environmental chemical exposures, such as aromatic hydrocarbons (eg, pesticides and benzene), as well as infectious factors, including various viruses (eg, human T-lymphotropic virus [HTLV]-I and HTLV-II) and bacteria (eg, Staphylococcus aureus). There has been growing emphasis on the role of malignant inflammation in CTCL development. In this review, we synthesize studies of environmental and infectious exposures, along with research on the aryl hydrocarbon receptor and the involvement of pathogens in disease etiology, providing insight into the pathogenesis of CTCL., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Emergent tremor in Parkinson's disease (PD) can occur during sustained postures or movements that are different from action tremor. Tremor can contaminate the clinical rating of bradykinesia during finger tapping. Currently, there is no reliable way of isolating emergent tremor and measuring the cardinal motor symptoms based on voluntary movements only. In this study, we investigated whether emergent tremor during repetitive alternating finger tapping (RAFT) on a quantitative digitography (QDG) device could be reliably identified and distinguished from voluntary tapping. Ninety-six individuals with PD and forty-two healthy controls performed a thirty-second QDG-RAFT task and the Movement Disorders Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III). Visual identification of tremor during QDG-RAFT was labeled by an experienced movement disorders specialist. Two methods of identifying tremor were investigated: 1) physiologically informed temporal thresholds 2) XGBoost model using temporal and amplitude features of tapping. The XGBoost model showed high accuracy for identifying tremor (area under the precision-recall curve of 0.981) and outperformed temporal-based thresholds. Percent time duration of classifier-identified tremor showed significant correlations with MDS-UPDRS III tremor subscores (r = 0.50, p < 0.0001). There was a significant change in QDG metrics for bradykinesia, rigidity, and arrhythmicity after tremor strikes were excluded (p < 0.01). The results demonstrate that emergent tremor during QDG-RAFT has a unique digital signature and the duration of tremor correlated with the MDS-UPDRS III tremor items. When involuntary tremor strikes were excluded, the QDG metrics of bradykinesia and rigidity were significantly worse, demonstrating the importance of distinguishing tremor from voluntary movement when rating bradykinesia., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest Dr LJG has served as an investigator for and/or received research support from Helsinn Group, J&J, Mallinckrodt, Kyowa Kirin, Soligenix, Innate, Incyte, Trillium, Merck, BMS, and Stratpharma; on the speakers’ bureau for Mallinckrodt and Recordati; and on the scientific advisory board for SciTech and Celsyntec. The other authors have no disclosures.

There are no established maintenance protocols for cutaneous lymphomas. We aim to determine patient treatments and outcomes during the COVID-19 pandemic in order to uncover the most effective maintenance protocols for cutaneous lymphomas and impact of treatment interruption. Data was collected retrospectively from nine international institutions, including 149 patients. Younger patients had earlier stages of disease and were most frequently treated with skin-directed therapies including topical steroids, mechlorethamine gel, and phototherapy. Treatment interruption varied by treatment type and stage, with patients on topical therapies and earlier stages of disease being least likely to experience interruption. Treatment interruption was significantly associated with progression of disease and worse outcomes, with twice as many patients progressing who had interruption compared to those without interruption. This study may demonstrate the significance of continuous maintenance therapies, even in younger patients with early stages of disease.

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a clonal plasma cell disorder that is considered preneoplastic, asymptomatic, and only requiring observation. However, MGUS may result in cutaneous complications, which are poorly understood, causing treatment delays and patient suffering. We present 30 patients with cutaneous findings associated with MGUS, characterizing clinical presentations, isoforms, treatments, and outcomes. These included: MGUS-associated 'rashes' (pruritic eczematous rashes), reactive and mucin-depositional conditions (pyoderma gangrenosum, scleromyxedema), M-protein-related deposition disorders (POEMS syndrome, Waldenstrom macroglobulinemia), and cutaneous lymphomas. Twelve of 30 (40%) patients received multiple myeloma drugs (MMDs). Eleven (92%) patients improved, and those not receiving MMDs rarely improved, suggesting that MMDs have efficacy for cutaneous manifestations of MGUS. Therefore, trialing MMDs may be warranted for patients with MGUS not responding to other therapies. Moreover, evaluation for monoclonal gammopathy in elderly patients with intractable pruritus or other chronic skin conditions that are non-responsive to skin-directed therapies should be considered.

Competing Interests: Conflicts of interest Dr Geskin has served as an investigator for and/or received research support from Helsinn Group, J&J, Mallinckrodt, Kyowa Kirin, Soligenix, Innate, Merck, BMS, and Stratpharma; on the speakers' bureau for Helsinn Group and J&J; and on the scientific advisory board for Helsinn Group, J&J, Mallinckrodt, Sanofi, Regeneron, and Kyowa Kirin. Authors Gordon, Chen, Adeuyan, and Lapolla; Dr Trager; Authors Fahmy and Schreidah; and Dr Wetter have no conflicts of interest to declare.

Nonmelanoma skin cancers (NMSCs) are among the top five most common cancers globally. NMSC is an area with great potential for novel application of diagnostic tools including artificial intelligence (AI). In this scoping review, we aimed to describe the applications of AI in the diagnosis and treatment of NMSC. Twenty-nine publications described AI applications to dermatopathology including lesion classification and margin assessment. Twenty-five publications discussed AI use in clinical image analysis, showing that algorithms are not superior to dermatologists and may rely on unbalanced, nonrepresentative, and nontransparent training data sets. Sixteen publications described the use of AI in cutaneous surgery for NMSC including use in margin assessment during excisions and Mohs surgery, as well as predicting procedural complexity. Eleven publications discussed spectroscopy, confocal microscopy, thermography, and the AI algorithms that analyze and interpret their data. Ten publications pertained to AI applications for the discovery and use of NMSC biomarkers. Eight publications discussed the use of smartphones and AI, specifically how they enable clinicians and patients to have increased access to instant dermatologic assessments but with varying accuracies. Five publications discussed large language models and NMSC, including how they may facilitate or hinder patient education and medical decision-making. Three publications pertaining to the skin of color and AI for NMSC discussed concerns regarding limited diverse data sets for the training of convolutional neural networks. AI demonstrates tremendous potential to improve diagnosis, patient and clinician education, and management of NMSC. Despite excitement regarding AI, data sets are often not transparently reported, may include low-quality images, and may not include diverse skin types, limiting generalizability. AI may serve as a tool to increase access to dermatology services for patients in rural areas and save health care dollars. These benefits can only be achieved, however, with consideration of potential ethical costs., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cutaneous squamous cell carcinoma in-situ (SCCis) is an intraepithelial tumor with a good prognosis. Standard treatment includes both surgical and non-surgical interventions. We determined the clearance rate for SCCis and residual SCCis identified on frozen section during Mohs micrographic surgery (MMS) after treatment with topical fluorouracil 5% cream (5-FU). All MMS cases were initiated for biopsy-proven invasive squamous cell carcinoma (SCC). A retrospective chart review was conducted from January 2017-February 2024 at Columbia University Irving Medical Center (CUIMC) to identify patients with SCCis who were treated with topical 5-FU as primary therapy or adjuvant therapy (AT) for residual SCCis post-MMS for invasive SCC. 41 patients were included (80% males, 70.1 ± 11.8 years). The average follow-up time for the primary therapy group was 25.4 ± 12.8 months, and for the post-MMS AT group 22.5 ± 11.1 months. In the group treated with topical 5-FU as primary therapy (n = 28), 27 patients (96.43%, 95% confidence interval: 81.65-99.91%) achieved complete clearance. One patient had recurrence at 8 months post-treatment. Of the patients in the post-MMS adjuvant treatment group (n = 13), 12 (92.3% clearance, 95% confidence interval 63.97-99.81%) achieved complete clearance. One patient had recurrence at 8 months post-treatment. This study found that topical 5-FU cream is effective as both primary therapy for SCCis and as adjuvant therapy for residual SCCis following MMS of invasive SCC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The field of dermatology is experiencing the rapid deployment of artificial intelligence (AI), from mobile applications (apps) for skin cancer detection to large language models like ChatGPT that can answer generalist or specialist questions about skin diagnoses. With these new applications, ethical concerns have emerged. In this scoping review, we aimed to identify the applications of AI to the field of dermatology and to understand their ethical implications. We used a multifaceted search approach, searching PubMed, MEDLINE, Cochrane Library and Google Scholar for primary literature, following the PRISMA Extension for Scoping Reviews guidance. Our advanced query included terms related to dermatology, AI and ethical considerations. Our search yielded 202 papers. After initial screening, 68 studies were included. Thirty-two were related to clinical image analysis and raised ethical concerns for misdiagnosis, data security, privacy violations and replacement of dermatologist jobs. Seventeen discussed limited skin of colour representation in datasets leading to potential misdiagnosis in the general population. Nine articles about teledermatology raised ethical concerns, including the exacerbation of health disparities, lack of standardized regulations, informed consent for AI use and privacy challenges. Seven addressed inaccuracies in the responses of large language models. Seven examined attitudes toward and trust in AI, with most patients requesting supplemental assessment by a physician to ensure reliability and accountability. Benefits of AI integration into clinical practice include increased patient access, improved clinical decision-making, efficiency and many others. However, safeguards must be put in place to ensure the ethical application of AI., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

With an increase in number of patients on antithrombotic therapies, management of bleeding during dermatologic surgery is increasingly important. As described in Part 1, perioperative discontinuation of antithrombotic therapies may increase the risk of embolic events thus the risks and benefits must be weighed carefully when deciding whether to continue or suspend therapy. However, continuing oral anticoagulants may result in increased intraoperative and postoperative bleeding. Here we describe various methods to effectively achieve hemostasis which include: 1) mechanical methods to compress the vasculature 2) pharmacologic agents that induce vasoconstriction 3) physiologic agents that augment clot formation and 4) physical agents that promote platelet aggregation., (Copyright © 2024. Published by Elsevier Inc.)

Perioperative management of antithrombotic agents requires practical and medical considerations. Discontinuing antithrombotic therapies increases the risk of thrombotic adverse events including cerebrovascular accidents, myocardial infarction, pulmonary embolism, deep vein thrombosis, and retinal artery occlusion. Conversely, continuation of antithrombotic therapy during surgical procedures has associated bleeding risks. Currently, no guidelines exist regarding management of antithrombotic agents in the perioperative period for cutaneous surgeries and practice differs by surgeon. Here, we review the data on antithrombotic medications in patients undergoing cutaneous surgery including medication-specific surgical and postoperative bleeding risk if the medications are continued, and thromboembolic risk if the medications are interrupted. Specifically, we focus on vitamin K antagonist (VKA) (warfarin), direct-acting oral anticoagulants (DOAC) (rivaroxaban, apixaban, edoxaban, dabigatran), antiplatelet medications (aspirin, clopidogrel, prasugrel, ticagrelor, dipyridamole), unfractionated heparin, low molecular weight heparin (enoxaparin and dalteparin), fondaparinux, bruton tyrosine kinase inhibitors (BTKi) (ibrutinib, acalabrutinib), and dietary supplements (i.e., garlic, ginger, gingko)., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: LJG has served as an investigator for and/or received research support from Helsinn Group, J&J, Mallinckrodt, Kyowa Kirin, Soligenix, Innate, Merck, BMS, and Stratpharma; on the speakers’ bureau for Helsinn Group and J&J; and on the scientific advisory board for Helsinn Group, J&J, Mallinckrodt, Sanofi, Regeneron, and Kyowa Kirin. OA, CMM, MHT, ERG, BAL, CMS and LMF have no conflicts of interest to declare.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disorder, most often characterized by atrophic skin plaques located on female genitalia. Infrequently, LSA may present extragenitally; however, much is unknown about the temporal relationship between genital and extragenital LSA. Morphea, also known as localized scleroderma, is a rare inflammatory skin condition characterized by sclerotic plaques. Investigators debate whether LSA and morphea exist on the same spectrum of disease, with LSA representing a superficial variant of morphea involving genitalia, or if they are distinct but coincidental entities. Although researchers have described LSA and morphea occurring in different locations on the same patient, few reports describe LSA and morphea occurring in the same lesion and in the inguinal folds. Herein, we report a case of a 62-year-old woman with extragenital LSA-morphea overlap in the inguinal folds, who three months later developed genital LSA. Extragenital LSA-morphea in the same plaque, with no signs of genital lesions on initial exam, with later development of genital LSA, is especially uncommon. The temporal progression of extragenital LSA-morphea overlap to genital LSA over a three-month period is an important contribution to the literature, as the temporal relationship between extragenital and genital LSA is not previously discussed.

Background: Individual reports have described lymphoproliferative disorders (LPDs) and cutaneous lymphomas emerging after administration of the COVID-19 vaccine; however, the relationship between reactions and vaccine types has not yet been examined., Objective: Determine if there are cases of cutaneous LPDs associated with certain COVID-19 vaccines and their outcomes., Methods: We analysed PubMed, the Vaccine Adverse Events Reporting System (VAERS), and our database for instances of biopsy-proven LPDs following COVID-19 vaccines., Results: Fifty cases of biopsy-proven LPDs arising after COVID-19 vaccination were found: 37 from medical literature, 11 from VAERS and two from our institution. Geographical distribution revealed the most cases in the United States, Italy, and Greece, with single cases in Spain, Colombia, Canada, Japan, and Romania. The average age of patients was 53; with a slight male predominance (male-to-female ratio of 1.5:1). The Pfizer-BioNTech vaccine was associated with LPDs in 36/50 (72%) cases, aligning with its 70% share of the global vaccine market. Histopathology revealed CD30+ in 80% of cases. The most prevalent form of LPD was lymphomatoid papulosis (LyP, 30%). All reported cases produced favourable outcomes (either complete or near-complete remission). Therapeutic approaches ranged from observation to treatment with steroids, methotrexate, or excision., Conclusion: LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character., Competing Interests: LJG has served as an investigator for and/or received research support from Helsinn Group, J&J, Mallinckrodt, Kyowa Kirin, Soligenix, Innate, Merck, BMS, and Stratpharma; on the speakers’ bureau for Helsinn Group and J&J; and on the scientific advisory board for Helsinn Group, J&J, Mallinckrodt, Sanofi, Regeneron, and Kyowa Kirin. ERG, BDK, CMS, LMF, OA, DQ, MHT, CMM have no conflicts of interest to declare., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

No randomized trials exist to inform the peripheral surgical margins or depth of wide excision for eyelid melanoma. We performed a meta-analysis examining surgical margins and Breslow depth for eyelid melanomas. A systematic review was performed in August 2022 using PubMed, Cochrane, and Medline databases (1/1/1990 to 8/1/2022). Inclusion criteria included studies reporting surgical treatment of primary cutaneous melanomas of the eyelid with reported surgical margins. Ten articles were included. The studies were examined by surgical margin size (group 1: ≤ 0.5 cm; group 2 > 0.5 cm and ≤ 1.5 cm) and Breslow depth (group 1: ≤ 1 mm; group 2: > 1 mm). The odds ratio (OR) for local recurrence was 2.55 [95% CI 0.36-18.12], p = 0.18; regional metastasis was 0.70 [95% CI 0.00-23671.71], p = 0.48; and distant metastasis was 2.47 [95% CI 0.00-1687.43], p = 0.66. When examining by Breslow depth, the OR for local recurrence was 0.53 [95% CI 0.14-1.94], p = 0.34; regional metastasis was 0.14 [0.00-176.12], p = 0.54; and the OR for distant metastasis was 0.24 [95% CI 0.01-8.73], p = 0.46. There was a trend toward higher likelihood of recurrence and metastasis in the ≤ 0.5 cm group. Similarly, there is a trend toward higher likelihood of recurrence and metastasis with Breslow depth > 1 mm. A surgical margin of at least 0.5 cm and achievement of negative margins via permanent sections or MMS are likely needed to prevent adverse outcomes. En face sectioning may be a superior method of histological processing for eyelid melanoma., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: LJG has served as an investigator for and/or received research support from Helsinn Group, J&J, Mallinckrodt, Kyowa Kirin, Soligenix, Innate, Merck, BMS, and Stratpharma; on the speakers’ bureau for Helsinn Group and J&J; and on the scientific advisory board for Helsinn Group, J&J, Mallinckrodt, Sanofi, Regeneron, and Kyowa Kirin. OA, MHT, ERG, BAL, CMS, LMF, CC and CMM have no conflicts of interest to declare.

Individual reports described lymphoproliferative disorders (LPDs) after COVID-19 vaccination; however, the relationship between cases is unexamined. We aim to determine if there are cases of cutaneous LPDs associated with COVID-19 vaccination and their outcomes. We present a review of world literature, vaccine registries, and two unreported cases of LPDs after COVID-19 vaccination. Review of the medical literature, VAERS, and our two cases reveal predominance of Pfizer-BioNTech vaccine, younger patients, and males. All cases resulted in favorable outcomes. Approximately 84% of cases demonstrated CD30+ positivity in their skin biopsies, suggesting that an antigenic trigger may lead to a type IV adaptive immune response, with clonal expansion of CD30+ T-cells and subsequent oncogenic mutational hits eventuating in transient LPDs. LPDs after COVID-19 vaccination appear in the context of the same vaccines (proportionally to their global market shares), share clinical and pathological findings, and have indolent, self-limited character.

Introduction: Cutaneous T-cell lymphoma (CTCL) is a heterogenous group of non-Hodgkin lymphomas. Similar presentation to benign conditions, significant genetic variation, and lack of definitive biomarkers contributes to diagnostic delay. The etiology of CTCL is unknown, and environmental exposures, such as geographic, occupational, chemicals, sunlight, and insects have been investigated., Evidence Acquisition: Review of the literature for CTCL and exposures was performed in PubMed and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Extension for Scoping Reviews. This search yielded 193 total results, which were initially screened with defined inclusion and exclusion criteria. The 45 remaining articles were reviewed and classified by exposure type., Evidence Synthesis: The most frequently investigated CTCL exposure type was geographic (13/45 articles, 29%). Chemical exposures were commonly discussed (10/45 articles, 22%), along with occupational (10/45 articles, 22%). Insect exposures (6/45, 13%) and sun exposure (3/45, 7%) were also reviewed, along with articles describing multiple exposure types (3/45, 7%). Article types ranged from cases to systematic reviews and case-control studies. Evidence linking CTCL and these exposures was mixed. Limitations of this investigation include reliance on patient reporting and frequent speculation on disease association versus causality., Conclusions: This investigation synthesizes the current literature on exposures potentially implicated in the pathogenesis of CTCL, while offering guidance on patient history-taking to ensure potential exposures are captured. Awareness of these possible associations may improve understanding of disease pathogenesis and diagnosis. Moreover, these insights may help with public health decision-making and disease mitigation.

Objective: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long-term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13-30 Hz) dynamics or a wider bilateral network dysfunction., Methods: Twenty-one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist-flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN-STN beta coherence., Results: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN-STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia., Interpretation: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029-1039., (© 2023 American Neurological Association.)

Background: Assessment of motor signs in Parkinson's disease (PD) requires an in-person examination. However, 50% of people with PD do not have access to a neurologist. Wearable sensors can provide remote measures of some motor signs but require continuous monitoring for several days. A major unmet need is reliable metrics of all cardinal motor signs, including rigidity, from a simple short active task that can be performed remotely or in the clinic., Objective: Investigate whether thirty seconds of repetitive alternating finger tapping (RAFT) on a portable quantitative digitography (QDG) device, which measures amplitude and timing, produces reliable metrics of all cardinal motor signs in PD., Methods: Ninety-six individuals with PD and forty-two healthy controls performed a thirty-second QDG-RAFT task and clinical motor assessment. Eighteen individuals were followed longitudinally with repeated assessments for an average of three years and up to six years., Results: QDG-RAFT metrics showed differences between PD and controls and provided correlated metrics for total motor disability (MDS-UPDRS III) and for rigidity, bradykinesia, tremor, gait impairment, and freezing of gait (FOG). Additionally, QDG-RAFT tracked disease progression over several years off therapy and showed differences between akinetic-rigid and tremor-dominant phenotypes, as well as people with and without FOG., Conclusions: QDG is a reliable technology, which could be used in the clinic or remotely. This could improve access to care, allow complex remote disease management based on data received in real time, and accurate monitoring of disease progression over time in PD. QDG-RAFT also provides the comprehensive motor metrics needed for therapeutic trials.

The rates of melanoma and non-melanoma skin cancer (NMSC) have been increasing over the last twenty years in the United States, and this has been attributed to increased ultraviolet radiation exposure (UVR). Given these rising rates, preventative measures have become increasingly important to reduce the incidence and promote early detection of these cancers. Skin cancer prevention remains a challenging task to accomplish mainly due to the lack of reliable and sensitive methods to provide objective risk information that can educate and motivate individuals to avoid sunburn. Currently, minimal erythema dose (MED) is used as a marker of UVR. However, it is not an ideal marker because significant cancer-related molecular damage can occur after UVR exposure that cannot be detected by MED. Thus, over the recent years there has been significant interest in development of biomarkers indicative of exposure to UVR to improve early detection of cutaneous malignancies. Here, we will discuss emerging biomarkers for melanoma and NMSC that can help with risk stratification and targeted prevention and treatment., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Online reviews are the newest method for patients to evaluate their providers. However, insufficient studies focus on the role of inherent physician characteristics, such as gender and years of experience, on patient satisfaction. We analyzed both quantitative and qualitative online reviews of 350 general dermatology providers at 121 Accreditation Council for Graduate Medical Education-accredited dermatology programs across the country to determine the effect of gender and years of experience. There were 38,008 online reviews of general dermatology providers. There was no significant difference in male and female overall ratings. Ratings were overall equally positive for both genders. Female providers were more likely to have positive written comments regarding time spent with patients ( P  = 0.027). New providers received highest overall, promptness, and time spent with patient ratings ( P < 0.001). Medium experience providers received highest scores in bedside manner ( P < 0.001), accurate diagnosis ( P  = 0.018), and ability to answer questions ( P  = 0.005). Advanced providers scored the lowest across all categories. In conclusion, gender did not significantly affect ratings, although females received more positive written comments on time spent with patients. Years of experience, however, is a significant factor in patient ratings, with new or medium experience providers scoring higher than advanced providers in every category., (© 2021 The Authors.)

Abstract: Paraneoplastic granulomatous disease occurs in approximately 7.3% of patients with non-Hodgkin lymphoma, most commonly among patients with chronic lymphocytic leukemia (CLL). These lesions are often reported to appear similar to sarcoidosis in clinical presentation and under light microscopy. However, comprehensive descriptions of the cytomorphologic characteristics of these paraneoplastic granulomas are lacking, and the mechanisms involved in their formation remain ill-defined. Noninfectious dermal granulomatous reactions have also been reported in many primary immunodeficiencies, including common variable immune deficiency and ataxia-telangiectasia. We present a case of noninfectious CD8+ predominant granulomatous dermatitis with ocular involvement occurring in the setting of CLL and marked hypogammaglobulinemia. Based on the analysis of shared factors in patients with primary immunodeficiencies and CLL, we conclude that the presence of pan-humoral immunodeficiency could itself be a risk factor for developing a CD8+ lymphogranulomatous reaction. This report and associated discussion evince that CD8+ predominant granulomatous reactions, distinct from sarcoidosis, may represent a previously unappreciated segment of the paraneoplastic granulomas observed in hematologic malignancies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Sézary syndrome is an aggressive and disseminated form of cutaneous T-cell lymphoma associated with dismal prognosis in which the histone deacetylase inhibitor romidepsin has shown remarkable activity as a single agent. However, clinical responses to romidepsin are typically transient, highlighting the need for more effective therapies. In this study, we show synergistic antilymphoma effects of romidepsin in combination with mechlorethamine, an alkylating agent, in cutaneous T-cell lymphoma cell lines and primary samples with strong antitumor effects in an in vivo model of Sézary syndrome. Mechanistically, gene expression profiling points to abrogation of Jak/signal transducer and activator of transcription (STAT) signaling as an important mediator of this interaction. Consistently, the combination of mechlorethamine plus romidepsin resulted in downregulation of STAT5 phosphorylation in romidepsin-sensitive cell lines and primary Sézary syndrome samples, but not in romidepsin-resistant tumors. Moreover, in further support of Jak/STAT signaling as a modulator of romidepsin activity in cutaneous T-cell lymphoma, treatment with romidepsin in combination with Jak inhibitors resulted in markedly increased therapeutic responses. Overall, these results support a role for romidepsin plus mechlorethamine in combination in the treatment of cutaneous T-cell lymphoma and uncover a previously unrecognized role for Jak/STAT signaling in the response to romidepsin and romidepsin-based combination therapies in Sézary syndrome., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS)., Methods: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale - motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state., Results: After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS-UPDRS III score., Interpretation: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Measuring patient satisfaction of general dermatology providers is an important goal because it can lead to improved clinical outcomes. Online reviews are emerging as the newest forum for evaluating physicians in real time and provide a valuable tool for measuring patient satisfaction. We analyzed both quantitative and qualitative online reviews of general dermatology providers at 121 Accreditation Council for Graduate Medical Education‒accredited dermatology programs across the country to determine which elements are most discussed in online ratings using the online platforms Vitals, US News, WebMD, Google Reviews, and Healthgrades. There were 38,008 online reviews included from general dermatology providers at Accreditation Council for Graduate Medical Education‒accredited programs. The median average overall quantitative rating of providers was 4.35 of 5. There were more positive (77%) than negative (23%) comments. The overall ratings of general dermatology providers were favorable. The most influential factors in both positive and negative comments were patient's perceived experience and physician's bedside manner (26% and 17%, respectively). Less important factors included office space, treatment by auxiliary staff, wait time, costs, and time spent with patients. This suggests that a provider's personality, expressed compassion, empathy, and kindness may overcome other issues and create an overall positive experience., (© 2021 Published by Elsevier Inc. on behalf of the Society for Investigative Dermatology.)

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are scarring alopecias that cause significant distress and psychological morbidity. Limited studies have been performed examining the epidemiology of FFA and LPP. We performed a retrospective case cohort analysis by querying for patients with the ICD 10 code L66.1 (LPP, FFA) between 2015 and 2018 using the Clinical Data Warehouse (CDW) at NewYork-Presbyterian Hospital and Columbia Doctors. We calculated the one-year incidence of LPP/FFA between January 1, 2018 to December 31, 2018 by identifying all patients without a previously recorded ICD code for L66.1 who presented as a new hair loss patient based on chart review. A total of 170 patients were identified with a new diagnosis of LPP or FFA in 2018 among 1,187,583 patients. The standardized incidence per 100,000 was 12.75 for LPP and FFA combined, 7.35 for LPP alone, and 5.41 for FFA alone. The incidence peaked in the 51 to 60 age range (3.36). The incidence was highest in non-Hispanic White patients (17.27), White patients of unknown ethnicity (26.26), and non-Hispanic Asian patients (17.27). In New York City, LPP and FFA are uncommon diseases that are most common in middle-aged females and non-Hispanic White patients.

Breast cancer is a highly heterogeneous disease, encompassing many subtypes that have distinct origins, behaviors, and prognoses. Although traditionally seen as a genetic disease, breast cancer is now also known to involve epigenetic abnormalities. Epigenetic regulators, such as DNA methyltransferases and histone-modifying enzymes, play essential roles in gene regulation and cancer development. Dysregulation of epigenetic regulator activity has been causally linked with breast cancer pathogenesis. Hairless (HR) encodes a 130-kDa transcription factor that is essential for development and tissue homeostasis. Its role in transcription regulation is partly mediated by its interaction with multiple nuclear receptors, including thyroid hormone receptor, retinoic acid receptor-related orphan receptors, and vitamin D receptor. HR has been studied primarily in epidermal development and homeostasis. Hr-mutant mice are highly susceptible to ultraviolet- or carcinogen-induced skin tumors. Besides its putative tumor suppressor function in skin, loss of HR function has also been implicated in increased leukemia susceptibility and promotes the growth of melanoma and brain cancer cells. HR has also been demonstrated to function as a histone H3 lysine 9 demethylase. Recent genomics studies have identified HR mutations in a variety of human cancers, including breast cancer. The anticancer function and mechanism of action by HR in mammary tissue remains to be investigated. Here, we review the emerging role of HR, its histone demethylase activity and histone methylation in breast cancer development, and potential for epigenetic therapy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

The presence of actinic keratoses (AKs) increases a patient's risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.

Actinic cheilitis is a premalignant condition that can progress to squamous cell carcinoma with a higher propensity for metastasis than cutaneous squamous cell carcinoma. Optimal treatment for actinic cheilitis has not been established, and evidence-based estimates of clinical cure in the dermatology literature are limited. Here, we review and synthesize outcome data published for patients with actinic cheilitis after treatment with various modalities. A systematic review was conducted in MEDLINE, Embase and the Cochrane library for English, French and German-language studies and references of included articles from inception to 20 January 2020. Studies were included if they reported on at least six patients with biopsy-proven actinic cheilitis. After quality appraisal, results of studies with the strongest methodology criteria were synthesized. 18 studies of 411 patients (published 1985 to 2016) were included. The majority of the studies were case series. Carbon dioxide laser ablation and vermilionectomy were associated with the most favourable outcomes with fewest recurrences. Chemical peel and photodynamic therapy were associated with higher recurrence. Adverse effects generally resolved in the weeks following treatment and cosmetic outcomes were favourable overall. In conclusion, there is a lack of high-quality comparative studies evaluating different treatment options for actinic cheilitis. The included publications used various outcome measures; however, the majority reported on the recently defined core outcome sets. These results suggest that both carbon dioxide laser ablation and vermilionectomy are effective treatments for actinic cheilitis. Prospective head-to-head studies are needed to compare these treatment modalities and to assess patient preferences., (© 2020 European Academy of Dermatology and Venereology.)

Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) images of early-stage melanomas. We tested whether automated digital (TIL) analysis (ADTA) improved accuracy of prediction of disease specific survival (DSS) based on current pathology standards. ADTA was applied to a training cohort (n = 80) and a cutoff value was defined based on a Receiver Operating Curve. ADTA was then applied to a validation cohort (n = 145) and the previously determined cutoff value was used to stratify high and low risk patients, as demonstrated by Kaplan-Meier analysis (p ≤ 0.001). Multivariable Cox proportional hazards analysis was performed using ADTA, depth, and ulceration as co-variables and showed that ADTA contributed to DSS prediction (HR: 4.18, CI 1.51-11.58, p = 0.006). ADTA provides an effective and attainable assessment of TILs and should be further evaluated in larger studies for inclusion in staging algorithms.

Background: Patients with cancer who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to develop severe illness and die compared with those without cancer. The impact of immune checkpoint inhibition (ICI) on the severity of COVID-19 illness is unknown. The aim of this study was to investigate whether ICI confers an additional risk for severe COVID-19 in patients with cancer., Methods: We analyzed data from 110 patients with laboratory-confirmed SARS-CoV-2 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe and Australia. The primary objective was to describe the clinical course and to identify factors associated with hospital and intensive care (ICU) admission and mortality., Findings: Thirty-five (32%) patients were admitted to hospital and 18 (16%) died. All patients who died had advanced cancer, and only four were admitted to ICU. COVID-19 was the primary cause of death in 8 (7%) patients. Factors independently associated with an increased risk for hospital admission were ECOG ≥2 (OR 39.25, 95% CI 4.17 to 369.2, p=0.0013), treatment with combination ICI (OR 5.68, 95% CI 1.58 to 20.36, p=0.0273) and presence of COVID-19 symptoms (OR 5.30, 95% CI 1.57 to 17.89, p=0.0073). Seventy-six (73%) patients interrupted ICI due to SARS-CoV-2 infection, 43 (57%) of whom had resumed at data cut-off., Interpretation: COVID-19-related mortality in the ICI-treated population does not appear to be higher than previously published mortality rates for patients with cancer. Inpatient mortality of patients with cancer treated with ICI was high in comparison with previously reported rates for hospitalized patients with cancer and was due to COVID-19 in almost half of the cases. We identified factors associated with adverse outcomes in ICI-treated patients with COVID-19., Competing Interests: Competing interests: MiM: consultant/advisor for Bristol Myers Squibb, MSD, Novartis, Roche, Pierre Fabre. AANR: fellowship funding from Alamos Gold Inc. JMG: project focused consultant/advisor for Merck/Pfizer, MSD, Amgen, Novartis, Bristol Myers Squibb and Pierre Fabre; travel support from Ultrasun, L’Oreal, MSD, Bristol Myers Squibb and Pierre Fabre outside of the submitted work. TPM: fellowship funding from Alamos Gold Inc. SDS: consultant/advisor for Janssens, Novartis and Sanofi. AMM: consultant/advisor to Bristol Myers Squibb, MSD, Novartis, Roche, Pierre Fabre and QBiotics. MSC: consultant/advisor for Bristol Myers Squibb, MSD, Amgen, Novartis, Pierre Fabre, Roche, Sanofi, Merck, Ideaya, Regeneron, Nektar, Eisai; honoraria from Bristol Myers Squibb, MSD, Novartis. CB: consultant/advisor for Amgen, Bristol Myers Squibb, MSD, Novartis Pharma AG, Regeneron Pharmaceuticals Inc, Roche Pharma, Sanofi Aventis. LiZ: consultant/advisor for Bristol Myers Squibb, Novartis, Pierre Fabre, Sunpharma, Sanofi, MSD; research funding from Novartis; travel support from Bristol Myers Squibb, Pierre Fabre, Sanofi, Amgen, Novartis, Sunpharma. DS: consultant/advisor for Roche/Genentech, Novartis, Bristol Myers Squibb, MSD, Merck Serono, Amgen, Immunocore, Incyte, 4SC, Pierre Fabre, Mologen and Sanofi/Regeneron; honoraria from Roche/Genentech, Novartis, MSD, Bristol Myers Squibb, Merck Serono, Amgen, Immunocore, Incyte, 4SC, Pierre Fabre, Sysmex, Grünenthal Group, Agenus, Array BioPharma, AstraZeneca, LEO Pharma, Pfizer, Philogen, Regeneron and Mologen; travel/accommodation expenses from Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Serono, Amgen and Merck; speakers bureau for Novartis, Bristol Myers Squibb, MSD, Amgen, Incyte, Pierre Fabre and Roche; research funding from Novartis and Bristol Myers Squibb; steering committee membership for Novartis, MSD and Bristol Myers Squibb. AH: consultant/advisor for Amgen, Bristol Myers Squibb, MSD/Merck, Pfizer, NeraCare, Novartis, Philogen, Pierre Fabre, Roche and Regeneron/Sanofi-Genzyme. RD: intermittent, project focused consulting and/or advisory relationships with Novartis, MSD, Bristol-Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaxiVAX SA and touchIME outside the submitted work. JH: consultant/advisor for AIMM, AchillesTx, Bristol Myers Squibb, BioNTech, GSK, Immunocore, Merck Serono, MSD, Neogene Tx, Novartis, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, Vaximm; research grants from Amgen, Bristol Myers Squibb, MSD, BioNTech, Novartis. CUB: consultant/advisor for Bristol Myers Squibb, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre, Third Rock Ventures; research funding from Bristol Myers Squibb, Novartis, NanoString; stock ownership: Uniti Cars; co-founder: Immagene BV. CR: consultant/advisor for Bristol Myers Squibb, MSD, Roche, Novartis, CureVac, Sanofi, Pierre Fabre. RJS: consultant/advisor for Asana Biosciences, Astrazeneca, Bristol Myers Squibb, Eisai, Iovnace, Pfizer, Merck, Novartis, Replimune; research funding: Amgen, Merck. PAA: consultant/advisory for Bristol Myers Squibb, Roche/Genentech, MSD, Novartis, Array, Merck Serono, Pierre Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron; research funding from Bristol Myers Squibb, Roche/Genentech, Array and travel support from MSD. FSH: consultancy/advisory for Bristol Myers Squibb, Merck, EMD Serono, Novartis, Surface, Compass Therapeutics, Apricity, Aduro, Sanofi, Pionyr, 7 Hills Pharma, Torque, Rheos, Kairos, Bicara, Psioxus Therapeutics, Pieris Pharmaceutical, Zumutor, Corner Therapeutics, Idera, Takeda, Genentech/Roche, Bioentre, Gossamer. KPMS: consulting/advisory for Bristol Myers Squibb, MSD, Abbvie, Pierre Fabre, Novartis; honoraria received from Novartis, Roche, MSD (all paid to institution). KLR: consultant/advisor for Teladoc. OER: consultant/advisor for Merck, Celgene, Five Prime, GSK, Bayer, Roche/Genentech, Puretech, Imvax, Sobi; research support from Merck; speaker for activities supported by educational grants from Bristol Myers Squibb and Merck; patent “Methods of using pembrolizumab and trebananib” pending. PCL: consultant/advisor for Bristol Myers Squibb, MSD, Pierre Fabre, Novartis, Amgen and Roche; travel support from Bristol Myers Squibb and MSD; research support from Bristol Myers Squibb. MaM: consultant advisor for Bristol Myers Squibb, MSD, Novartis, Roche, PierreFabre. GVL: consultant/advisor for Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Highlight Therapeutics SL, MSD, Novartis Pharma AG, QBiotics Group Limited, Regeneron Pharmaceuticals Inc, SkylineDX BV, all declarations of interest are outside of the submitted work. AR, IPS, CT, CAT, JMG, MHT, SN, LZ, PB, AE, NP, MGV, JB, SR, TC, JL, AV, MOB, ME, LP, PQ, CP, WHM, RDC and SL have no conflict of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Reliable and accurate measures of rigidity have remained elusive in remote assessments of Parkinson's disease (PD). This has severely limited the utility of telemedicine in the care and treatment of people with PD. It has also had a large negative impact on the scope of available outcomes, and on the costs, of multicenter clinical trials in PD. The goal of this study was to determine if quantitative measures from an engineered keyboard were sensitive and related to clinical measures of rigidity., Methods: Sixteen participants with idiopathic PD, off antiparkinsonian medications, and eleven age-matched control participants performed a 30 second repetitive alternating finger tapping task on an engineered keyboard and were assessed with the Unified Parkinson's Disease Rating Scale - motor (UPDRS-III)., Results: The speed of the key release was significantly slower in the PD compared to control cohorts (p < 0.0001). In the PD cohort key release speed correlated with the lateralized upper extremity UPDRS III rigidity score (r = - 0.58, p < 0.0001), but not with the lateralized upper extremity tremor score (r = - 0.14, p = 0.43)., Conclusions: This validated measure of rigidity complements our previous validation of temporal metrics of the repetitive alternating finger tapping task with the UPDRS III, bradykinesia and with the ability to quantify tremor, arrhythmicity and freezing episodes, and suggests that 30 seconds of alternating finger tapping on a portable engineered keyboard could transform the treatment of PD with telemedicine and the precision of multicenter clinical trials., (Copyright © 2020. Published by Elsevier Ltd.)

The signal transducer and activator of transcription 6 (STAT6) is a critical up-stream mediator of interleukin-13 (IL-13) and IL-4 signaling and is constitutively activated in malignant lymphocytes from Sezary syndrome (SS) and mycosis fungoides (MF), the most common subtypes of cutaneous T-cell lymphomas. By combining genome-wide expression profiling with pharmacological STAT6 inhibition, we have identified the genes regulated by STAT6 in MF/SS tumors. We found that STAT6 regulates several common pathways in MF/SS malignant lymphocytes that are associated with control of cell-cycle progression and genomic stability as well as production of Th2 cytokines. Using ex vivo skin explants from cutaneous MF tumors as well as Sezary cells derived from the blood of SS patients, we demonstrated that inhibition of STAT6 activation downregulates cytokine production and induces cell-cycle arrest in MF/SS malignant lymphocytes, inhibiting their proliferation but not their survival. Furthermore, we show that STAT6 promotes the protumoral M2-like phenotype of tumor-associated macrophages in the tumor microenvironment of advanced stage MF by upregulating the expression of genes associated with immunosuppression, chemotaxis, and tumor matrix remodeling. Thus, we show STAT6 to be a major factor in the pathogenesis and progression of MF/SS, promoting proliferation and invasion of the malignant lymphocytes while inducing a progressive depression of the antitumor immune response. Together, our results provide new insights into disease pathogenesis and offer new prospective targets for therapeutic intervention., (© 2020 by The American Society of Hematology.)

The high mobility group AT-hook 2 (HMGA2) gene encodes a transcription factor that is expressed during embryonic development but down-regulated in adult tissues. Its re-expression in adult tissues is often associated with tumorigenesis. In this study, we found that HMGA2 is highly expressed in human cutaneous squamous cell carcinoma (SCC) cell lines and primary SCC tumors, but not in adjacent normal skin. In non-ultraviolet (UV)-irradiated mouse skin, baseline Hmga2 expression was detected in the epidermis but not in hair follicles. Following chronic UV exposure, we found activation of Hmga2 in hair follicles. UV-induced mouse skin SCC tumors displayed a ubiquitous increase in Hmga2 expression compared to non-tumor-bearing adjacent skin. In human SCC cells, decreased HMGA2 expression was linked with reduced cell proliferation following depletion of FOXM1 and TRIP13, two UV master regulator genes. Taken together, these findings highlight an important biomarker function of HMGA2 expression in UV-induced skin tumorigenesis and cell proliferation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Currently, there is no sensitive molecular test for identifying transformation-prone actinic keratoses (AKs) and aggressive squamous cell carcinoma (SCC) subtypes. Biomarker-based molecular testing represents a promising tool for risk stratifying these lesions. We evaluated the utility of a panel of ultraviolet (UV) radiation-biomarker genes in distinguishing between benign and transformation-prone AKs and SCCs. The expression of the UV-biomarker genes in 31 SCC and normal skin (NS) pairs and 10 AK/NS pairs was quantified using the NanoString nCounter system. Biomarker testing models were built using logistic regression models with leave-one-out cross validation in the training set. The best model to classify AKs versus SCCs (area under curve (AUC) 0.814, precision score 0.833, recall 0.714) was constructed using a top-ranked set of 13 UV-biomarker genes. Another model based on a 15-gene panel was developed to differentiate histologically concerning from less concerning SCCs (AUC 1, precision score 1, recall 0.714). Finally, 12 of the UV-biomarker genes were differentially expressed between AKs and SCCs, while 10 genes were uniquely expressed in the more concerning SCCs. UV-biomarker gene subsets demonstrate dynamic utility as molecular tools to classify and risk stratify AK and SCC lesions, which will complement histopathologic diagnosis to guide treatment of high-risk patients., (© 2020 Federation of American Societies for Experimental Biology.)

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Response to talimogene laherparepvec (T-Vec) is difficult to assess as pigmented macrophages that have ingested melanoma cells ('melanophages') persist after injection, mimicking melanoma. We used quantitative immunofluorescence (qIF) to (1) distinguish melanophages from melanoma in biopsies from two patients treated with T-Vec and (2) evaluate the tumor microenvironment pretreatment and posttreatment. Tissues were stained with 4',6-diamidino-2-phenylindole, cluster of differentiation (CD) 3, CD8, CD68, human leukocyte antigen-DR isotype (HLA-DR), and SRY-Box Transcription Factor 10 (SOX10), and multispectral images were analyzed. Post-T-Vec samples showed melanophages with cytoplasmic costaining of CD68, SOX10, and HLA-DR, without nuclear SOX10 expression. qIF revealed a dense immune infiltrate of CD3, CD8, and CD68 cells in post-T-Vec samples. Melanophages from tumors post-T-Vec stain the nuclear melanoma marker SOX10 in their cytoplasms as compared to melanoma cells that stain nuclear SOX10. This novel finding highlights the phagocytosis of melanoma cell components by macrophages after treatment with T-Vec. qIF may assist pathologists in determining whether lesions treated with immunotherapy contain residual viable melanoma.