Mixed histiocytic neoplasms: A multicentre series revealing diverse somatic mutations and responses to targeted therapy.

Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy.

Oral minoxidil for late alopecia in cancer survivors.

PURPOSE: Late alopecia, defined as incomplete hair regrowth > 6 months following cytotoxic chemotherapy or > 6 months from initiation of endocrine therapy, negatively impacts quality of life and may affect dose intensity of adjuvant therapy. This study investigates the effect of oral minoxidil in women with chemotherapy and/or endocrine therapy-induced late alopecia. METHODS: The rate of clinical response was assessed by standardized photography and quantitated with trichoscopy. RESULTS: Two hundred and sixteen patients (mean age 57.8 ± 13.7) were included. The most common cancer diagnosis was breast, in 170 patients (79.1%). Alopecia developed after chemotherapy in 31 (14.4%) patients, endocrine monotherapy in 65 (30.1%) patients, and chemotherapy followed by endocrine therapy in 120 (55.6%) patients. In 119 patients, standardized photography assessments were used to determine clinical change in alopecia after a median of 105 (IQR = 70) days on oral minoxidil and revealed improvement in 88 (74%) patients. Forty-two patients received quantitative trichoscopic assessments at baseline and at follow-up after a median of 91 (IQR = 126) days on oral minoxidil. Patients had clinically and statistically significant increases in frontal hair shaft density (from 124.2 hairs/cm2 at initial to 153.2 hairs/cm2 at follow-up assessment, p = 0.008) and occipital shaft density (from 100.3 hairs/cm2 at initial to 123.5 hairs/cm2 at follow-up assessment. p = 0.004). No patients discontinued oral minoxidil due to adverse events. CONCLUSIONS: Overall, oral minoxidil was well tolerated by patients and may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy by increasing hair shaft and follicle density.

Mucocutaneous toxicities from MEK inhibitors: a scoping review of the literature.

BACKGROUND: MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. PURPOSE: To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. METHODS: We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. RESULTS: Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. CONCLUSION: Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy.

Position statement of the EADV Artificial Intelligence (AI) Task Force on AI-assisted smartphone apps and web-based services for skin disease.

BACKGROUND: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer. OBJECTIVE: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI-assisted smartphone applications (apps) and web-based services for skin diseases with emphasis on skin cancer detection. METHODS: An initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance. RESULTS: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non-medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web-based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users. CONCLUSIONS: The utilisation of AI-assisted smartphone apps and web-based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Outcomes after interruption of targeted therapy in patients with histiocytic neoplasms.

Little is known about outcomes following interruption of targeted therapy in adult patients with histiocytic neoplasms. This is an IRB-approved study of patients with histiocytic neoplasms whose BRAF and MEK inhibitors were interrupted after achieving complete or partial response by 18-fluorodeoxyglucose positron emission tomography (FDG-PET). 17/22 (77%) of patients experienced disease relapse following treatment interruption. Achieving a complete response prior to interruption, having a mutation other than BRAFV600E, and receiving MEK inhibition only were each associated with a statistically significant improvement in relapse-free survival. Relapse is common following treatment interruption however some patients may be suitable for limited-duration treatment.

Use of Asynchronous Interprofessional e-Consults in Cancer Patients During the COVID-19 Pandemic: Current and Future Role.

The COVID-19 pandemic created a unique challenge to health care systems, requiring rapid implementation of telemedicine services to provide continued care to patients while preserving personal protective equipment and decreasing the risk of disease transmission. Herein, we describe how our institution, an urban cancer center, utilized provider-to-provider telemedicine consultations (interprofessional e-consults) to provide subspecialty access to care to vulnerable patients in the epicenter of a global pandemic.

Digital skin imaging applications, part II: a comprehensive survey of post-acquisition image utilization features and technology standards.

BACKGROUND: Despite the increasing ubiquity and accessibility of teledermatology applications, few studies have comprehensively surveyed their features and technical standards. Importantly, features implemented after the point of capture are often intended to augment image utilization, while technical standards affect interoperability with existing healthcare systems. We aim to comprehensively survey image utilization features and technical characteristics found within publicly discoverable digital skin imaging applications. MATERIALS AND METHODS: Applications were identified and categorized as described in Part I. Included applications were then further assessed by three independent reviewers for post-imaging content, tools, and functionality. Publicly available information was used to determine the presence or absence of relevant technology standards and/or data characteristics. RESULTS: A total of 20 post-image acquisition features were identified across three general categories: (1) metadata attachment, (2) functional tools (i.e., those that utilized images or in-app content to perform a user-directed function), and (3) image processing. Over 80% of all applications implemented metadata features, with nearly half having metadata features only. Individual feature occurred and feature richness varied significantly by primary audience (p < 0.0001) and function (p < 0.0001). On average, each application included under three features. Less than half of all applications requested consent for user-uploaded photos and fewer than 10% provided clear data use and privacy policies. CONCLUSION: Post-imaging functionality in skin imaging applications varies significantly by primary audience and intended function, though nearly all applications implemented metadata labeling. Technical standards are often not implemented or reported consistently. Gaps in the provision of clear consent, data privacy, and data use policies should be urgently addressed.

Digital skin imaging applications, part I: Assessment of image acquisition technique features.

BACKGROUND: The rapid adoption of digital skin imaging applications has increased the utilization of smartphone-acquired images in dermatology. While this has enormous potential for scaling the assessment of concerning skin lesions, the insufficient quality of many consumer/patient-taken images can undermine clinical accuracy and potentially harm patients due to lack of diagnostic interpretability. We aim to characterize the current state of digital skin imaging applications and comprehensively assess how image acquisition features address image quality. MATERIALS AND METHODS: Publicly discoverable mobile, web, and desktop-based skin imaging applications, identified through keyword searches in mobile app stores, Google Search queries, previous teledermatology studies, and expert recommendations were independently assessed by three reviewers. Applications were categorized by primary audience (consumer-facing, nonhospital-based practice, or enterprise/health system), function (education, store-and-forward teledermatology, live-interactive teledermatology, electronic medical record adjunct/clinical imaging storage, or clinical triage), in-app connection to a healthcare provider (yes or no), and user type (patient, provider, or both). RESULTS: Just over half (57%) of 191 included skin imaging applications had at least one of 14 image acquisition technique features. Those that were consumer-facing, intended for educational use, and designed for both patient and physician users had significantly greater feature richness (p < 0.05). The most common feature was the inclusion of text-based imaging tips, followed by the requirement to submit multiple images and body area matching. CONCLUSION: Very few skin imaging applications included more than one image acquisition technique feature. Feature richness varied significantly by audience, function, and user categories. Users of digital dermatology tools should consider which applications have standardized features that improve image quality.

Suggested methodology for longitudinal evaluation of nevi based on clinical images.

BACKGROUND: Melanoma screening includes the assessment of changes in melanocytic lesions using images. However, previous studies of normal nevus temporal changes showed variable results and the optimal method for evaluating these changes remains unclear. Our aim was to evaluate the reproducibility of (a) nevus count done at a single time point (method I) versus two time points (method II); and (b) manual and automated nevus diameter measurements. MATERIALS AND METHODS: In a first experiment, participants used either a single time point or a two time point annotation method to evaluate the total number and size of nevi on the back of an atypical mole syndrome patient. A Monte Carlo simulation was used to calculate the variance observed. In a second experiment, manual measurements of nevi on 2D images were compared to an automated measurement on 3D images. Percent difference in the paired manual and automated measurements was calculated. RESULTS: Mean nevus count was 137 in method I and 115.5 in method II. The standard deviation was greater in method I (38.80) than in method II (4.65) (p = 0.0025). Manual diameter measurements had intraclass correlation coefficient of 0.88. The observed mean percent difference between manual and automated diameter measurements was 1.5%. Lightly pigmented and laterally located nevi had a higher percent difference. CONCLUSIONS: Comparison of nevi from two different time points is more consistent than nevus count performed separately at each time point. In addition, except for selected cases, automated measurements of nevus diameter on 3D images can be used as a time-saving reproducible substitute for manual measurement on 2D images.

Interactive Multimedia Reporting Technical Considerations: HIMSS-SIIM Collaborative White Paper.

Despite technological advances in the analysis of digital images for medical consultations, many health information systems lack the ability to correlate textual descriptions of image findings linked to the actual images. Images and reports often reside in separate silos in the medical record throughout the process of image viewing, report authoring, and report consumption. Forward-thinking centers and early adopters have created interactive reports with multimedia elements and embedded hyperlinks in reports that connect the narrative text with the related source images and measurements. Most of these solutions rely on proprietary single-vendor systems for viewing and reporting in the absence of any encompassing industry standards to facilitate interoperability with the electronic health record (EHR) and other systems. International standards have enabled the digitization of image acquisition, storage, viewing, and structured reporting. These provide the foundation to discuss enhanced reporting. Lessons learned in the digital transformation of radiology and pathology can serve as a basis for interactive multimedia reporting (IMR) across image-centric medical specialties. This paper describes the standard-based infrastructure and communications to fulfill recently defined clinical requirements through a consensus from an international workgroup of multidisciplinary medical specialists, informaticists, and industry participants. These efforts have led toward the development of an Integrating the Healthcare Enterprise (IHE) profile that will serve as a foundation for interoperable interactive multimedia reporting.

Supporting Virtual Dermatology Consultation in the Setting of COVID-19.

While telemedicine has been utilized with more frequency over the past two decades, there remained significant barriers to its broad implementation. The COVID-19 global pandemic served as a stimulus for rapid expansion and implementation of telemedicine services across medical institutions worldwide in order to maximize patient care delivery, minimize exposure risk among healthcare providers and patients alike, and avoid overcrowding of patient care facilities. In this experience report, we highlight the teledermatology initiatives executed by the Dermatology Service at Memorial Sloan Kettering Cancer Center in New York City, with particular emphasis on image ingestion and potential for future automation and improvement.

Multispecialty Enterprise Imaging Workgroup Consensus on Interactive Multimedia Reporting Current State and Road to the Future: HIMSS-SIIM Collaborative White Paper.

Diagnostic and evidential static image, video clip, and sound multimedia are captured during routine clinical care in cardiology, dermatology, ophthalmology, pathology, physiatry, radiation oncology, radiology, endoscopic procedural specialties, and other medical disciplines. Providers typically describe the multimedia findings in contemporaneous electronic health record clinical notes or associate a textual interpretative report. Visual communication aids commonly used to connect, synthesize, and supplement multimedia and descriptive text outside medicine remain technically challenging to integrate into patient care. Such beneficial interactive elements may include hyperlinks between text, multimedia elements, alphanumeric and geometric annotations, tables, graphs, timelines, diagrams, anatomic maps, and hyperlinks to external educational references that patients or provider consumers may find valuable. This HIMSS-SIIM Enterprise Imaging Community workgroup white paper outlines the current and desired clinical future state of interactive multimedia reporting (IMR). The workgroup adopted a consensus definition of IMR as "interactive medical documentation that combines clinical images, videos, sound, imaging metadata, and/or image annotations with text, typographic emphases, tables, graphs, event timelines, anatomic maps, hyperlinks, and/or educational resources to optimize communication between medical professionals, and between medical professionals and their patients." This white paper also serves as a precursor for future efforts toward solving technical issues impeding routine interactive multimedia report creation and ingestion into electronic health records.

Eosinophilic Fasciitis Following Checkpoint Inhibitor Therapy: Four Cases and a Review of Literature.

BACKGROUND: Checkpoint inhibitor therapy is widely known to cause a number of immune-related adverse events. One rare adverse effect that is emerging is eosinophilic fasciitis, a fibrosing disorder causing inflammatory infiltration of subcutaneous fascia. It is characterized clinically by edema and subsequent induration and tightening of the skin and subcutaneous tissues. The condition is rare, yet at our institutions we have seen four cases in the past 3 years. We describe our 4 cases and review 11 other cases reported in the literature. CASE PRESENTATION: We present four cases of eosinophilic fasciitis following treatment with programmed cell death protein 1 or programmed cell death-ligand 1 blockade. All patients had extremity involvement with characteristic skin changes ranging from peripheral edema to induration, tightening, and joint limitation. The patients had varying degrees of peripheral eosinophilia. In two of our patients, the diagnosis was made by full-thickness skin biopsy showing lymphocytic infiltration of the subcutaneous fascia, with CD4+ T cells predominating in one case and CD8+ T cells in the other. In the other two cases, the diagnosis was made on the basis of characteristic imaging findings in the context of clinical features consistent with the diagnosis. All four patients were treated with glucocorticoids with varying degrees of success; immunotherapy had to be discontinued in all four. Patients with advanced melanoma who experienced this adverse effect had either a partial response or a complete response to therapy. CONCLUSION: Eosinophilic fasciitis can occur as a result of checkpoint inhibitor therapy. Although a tissue diagnosis is the gold standard, imaging studies may facilitate the diagnosis in the presence of consistent clinical features, but a degree of suspicion is key to recognizing the condition early. Therapy requires a collaborative approach by oncology, rheumatology, and dermatology; physical therapy is an important adjunct in treatment. For advanced melanoma, it may be a good prognostic indicator. IMPLICATIONS FOR PRACTICE: It is important for clinicians to recognize that eosinophilic fasciitis is a potential immune-related adverse event (irAE) as a consequence of immune checkpoint inhibitor therapy. The presentation is quite stereotypical; the diagnosis can be made by imaging in the absence of a full-thickness skin biopsy. Early intervention is important to limit morbidity. This irAE may be a good prognostic sign among patients with melanoma.

NPM1 and FLT3-TKD mutations are enriched in patients with leukemia cutis.

Leukemia cutis (LC) is a dermatologic manifestation of leukemia. Its clinical implications for the patient and the biological mechanism behind the manifestation of LC are unknown. The oncology community is increasingly utilizing mutations to classify a number of malignancies to prognosticate outcomes and to choose targeted therapies. A single-center, retrospective analysis of dermatopathology cases with a diagnosis of leukemia cutis was performed. Patients with genetic testing using the Columbia Combined Cancer Panel (a targeted sequencing protocol of 467 genes) or Genoptix (targeted sequencing protocol of 44 genes) were identified. The frequency of the presence of genetic mutations in LC patients was compared to AML patients from the COSMIC (Catalogue of Somatic Mutations in Cancer) database. Twenty nine cases were confirmed to have leukemia cutis, 22 of which had acute myeloid leukemia (AML). Genetic testing was available in 11 patients. Twelve different mutations were observed with particular enrichment for NPM1 and FLT3-TKD. Our original hypothesis was that patients with LC would display a distinct mutation profile. Ultimately, the distribution of mutations observed in our cohort of LC patients largely reflects the mutational profile seen in AML patients in general.

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.

Use of "natural" oils for moisturization: Review of olive, coconut, and sunflower seed oil.

Despite the availability of effective medications for the management of atopic dermatitis and xerosis, patients may use nonconventional therapies such as topical oils. Patients choose these treatments because of the perceived lower risk of natural products and the fear of potential adverse effects of topical steroids. We review the use of topical olive, coconut, and sunflower seed oil in the treatment of atopic dermatitis and xerosis with a focus on children Currently available evidence suggests that olive oil may exacerbate xerosis and atopic dermatitis. Further studies are needed to make definitive recommendations regarding the use of coconut and sunflower seed oil.