Teledermoscopic triage of melanoma-suspicious skin lesions is safe: A retrospective comparative diagnostic accuracy study with multiple assessors.

BACKGROUND: The rising incidence of melanoma and the high number of benign lesions excised due to diagnostic uncertainty highlight the need for effective patient triage. This study assesses the safety and accuracy of teledermoscopic triage on a high-prevalence case set with pre-triaged, challenging, melanoma-suspicious lesions. METHODS: Five dermatologists independently reviewed 250 retrospectively extracted patient cases. Teledermoscopy assessments were simulated for panels of 1, 2, 3 and 5 assessors using two distinct consensus strategies, Caution Protocol and Majority Vote, and the sensitivity and specificity of the patient triages were calculated. RESULTS: Triage by a single teledermatologist showed a sensitivity of 92.3% and a specificity of 58.7%. Sensitivity improved with the number of assessors, particularly when using the Caution Protocol, though with a considerable drop in specificity. The Majority Vote showed a more balanced improvement in sensitivity and specificity. Safety analyses indicated that diagnostic accuracy decreased with poor image quality and increased case difficulty. DISCUSSION: Expert teledermoscopic triage of melanocytic skin lesions is highly sensitive and lowers the need for unnecessary excision procedures by half while dismissing as few as 0.4% (95% confidence interval 0-0.6%) of melanomas, even when applied to a high-prevalence pre-triaged subpopulation. Implementation of safety procedures increases accuracy. Using multiple teledermatologists increases sensitivity but at the cost of specificity unless a Majority Vote consensus strategy is applied. Future teledermoscopy guidelines should encompass safety procedures and protocols for disagreement between assessors.

Physician Level Assessment of Hirsute Women and of Their Eligibility for Laser Treatment With Deep Learning.

OBJECTIVES: Hirsutism is a widespread condition affecting 5%-15% of females. Laser treatment of hirsutism has the best long-term effect. Patients with nonpigmented or nonterminal hairs are not eligible for laser treatment, and the current patient journey needed to establish eligibility for laser hair removal is problematic in many health-care systems. METHODS: In this study, we compared the ability to assess eligibility for laser hair removal of health-care professionals and convolutional neural network (CNN)-based models. RESULTS: The CNN ensemble model, synthesized from the outputs of five individual CNN models, reached an eligibility assessment accuracy of 0.52 (95% CI: 0.42-0.60) and a κ of 0.20 (95% CI: 0.13-0.27), taking a consensus expert label as reference. For comparison, board-certified dermatologists achieved a mean accuracy of 0.48 (95% CI: 0.44-0.52) and a mean κ of 0.26 (95% CI: 0.22-0.31). Intra-rater analysis of board-certified dermatologists yielded κ in the 0.32 (95% CI: 0.24-0.40) and 0.65 (95% CI: 0.56-0.74) range. CONCLUSION: Current assessment of eligibility for laser hair removal is challenging. Developing a laser hair removal eligibility assessment tool based on deep learning that performs on a par with trained dermatologists is feasible. Such a model may potentially reduce workload, increase quality and effectiveness, and facilitate equal health-care access. However, to achieve true clinical generalizability, prospective randomized clinical intervention studies are needed.

TINF2 is a major susceptibility gene in Danish patients with multiple primary melanoma.

TINF2 encodes the TINF2 protein, which is a subunit in the shelterin complex critical for telomere regulation. Three recent studies have associated six truncating germline variants in TINF2 that have previously been associated with a cancer predisposition syndrome (CPS) caused by elongation of the telomeres. This has added TINF2 to the long telomere syndrome genes, together with other telomere maintenance genes such as ACD, POT1, TERF2IP, and TERT. We report a clinical study of 102 Danish patients with multiple primary melanoma (MPM) in which a germline truncating variant in TINF2 (p.(Arg265Ter)) was identified in four unrelated participants. The telomere lengths of three variant carriers were >90% percentile. In a routine diagnostic setting, the variant was identified in two more families, including an additional MPM patient and monozygotic twins with thyroid cancer and other cancer types. A total of 10 individuals from six independent families were confirmed carriers, all with cancer history, predominantly melanoma. Our findings suggest a major role of TINF2 in Danish patients with MPM. In addition to melanoma, other cancers in the six families include thyroid, renal, breast, and sarcoma, supporting a CPS in which melanoma, thyroid cancer, and sarcoma predominate. Further studies are needed to establish the full spectrum of associated cancer types and characterize lifetime cancer risk in carriers.

SUPPLEMENT INDIVIDUAL ARTICLE: Skincare for Cancer Patients in Scandinavia.

Preventive measures, earlier diagnosis, and markedly improved anticancer treatments have resulted in increasingly more patients living with or surviving cancer. Frequently cancer treatment-related cutaneous adverse events (cAEs) occur, which can severely impact patients' quality of life (QoL) and interfere with anticancer treatment outcomes. Currently, cAEs related to anticancer treatment may be under-appreciated to prevent or provide early and effective treatment. The Nordic European Cutaneous Oncodermatology Management (NECOM) project explored clinical insights in cAEs and focused on skincare regimens involving hygiene, moisturization, sun protection, and camouflage products. The NECOM panel discussed and reached a consensus on evidence and opinion-based best practice recommendations for oncology skincare programs to support all stakeholders in the Nordic European healthcare setting working with oncology patients throughout the entire continuum of care achieve optimal outcomes, improving patients' QoL. J Drugs Dermatol. 2021;20:12(Suppl):s4-14.

An Extensive Case of Merkel Cell Carcinoma due to Fright of COVID-19.

Merkel cell carcinoma (MCC) is a subtype of nonmelanoma skin cancer (NMSC) with increasing incidence. Clinically, MCC resembles other far less-aggressive NMSCs, and the pathogenesis is still not understood completely. Rapid diagnosis and treatment are essential to improve overall survival. We present a case report of a 74-year-old female, who had noticed a rapidly growing, oozing tumor on her right flank. She was hesitant to contact the dermatology ward where she had regular checkups as she was afraid of contracting COVID-19. This was in the beginning of the COVID-19 pandemic. At presentation, she had a large exophytic MCC on her right flank and multiple metastases. The disease was at a late stage, and palliative care was the only treatment option left. With this case, we wish to report a rather uncharacteristic location and size of an MCC tumor and suggest that fear of the pandemic and the COVID-19 lockdown has impacted dramatically on attendance of symptomatic patients.

Estimation of the diagnostic accuracy of real-time reverse transcription quantitative polymerase chain reaction for SARS-CoV-2 using re-analysis of published data.

INTRODUCTION: As the coronavirus disease 2019 (COVID-19) epidemic evolves and test strategies change, understanding the concepts of testing (gold standard and test performance measures) becomes essential. The challenge of any novel disease is that the gold standard has yet to be defined. METHODS: We reanalysed published data on real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) of severe acute respiratory syndrome coronavirus-2 to illustrate how predictive values vary with disease prevalence, sensitivity (set to values between 30% and 95%) and specificity (set to 99% or 99.98%). We used published data on chest CT and RT-qPCR to examine the potential of latent class analysis to estimate the sensitivity and specificity of RT-qPCR when no single gold standard exists. RESULTS: For the various sensitivity values, the negative predictive value of a RT-qPCR test remained above 92% until a COVID-19 prevalence of > 10%. The positive predictive value (PPV) was more variable. For a sensitivity of 95% and a specificity of 99%, the PPV was less-than 10% at a prevalence of 0.1%, increasing to about 90% at a prevalence of 10%. This improved to a PPV of 85% and almost 100%, respectively, when specificity increased to 99.98%. In a restricted latent class analysis, the sensitivity was 97.1% and the specificity was 99.9%, which is similar to figures from the Danish Health Authority. However, derived predictive values depended on model specification. CONCLUSIONS: A high risk of false-positives should be considered when extending the testing strategy, whereas false-negatives may occur during local outbreaks. This may have consequences for, e.g., containment strategies and research. A confirmatory test (e.g., demonstrating seroconversion or repeated RT-qPCR) may be warranted. FUNDING: none. TRIAL REGISTRATION: not relevant.

Eruptive Halo Naevi: A Possible Indicator of Malignant Disease in a Case Series of Post-Adolescent Patients.

Halo naevi are considered benign. They occur in children and adolescents. Eruptive multiple halo naevi are infrequently seen in adults. The first patient in this case series had previously had melanoma. Positron emission tomography-computed tomography (PET-CT) showed a papillary thyroid carcinoma. Subsequent adult patients underwent an examination programme similar to melanoma patients with unknown primary, including PET scanning. Sixteen patients were followed over a 6-year period. In total there were 2 papillary thyroid cancers, 1 neuroendocrine lung tumour, 1 patient had had lung metastases from a thin melanoma 7 years previously, 3 patients had primary cutaneous melanoma (1 had had halo naevi since excision of 2 melanomas 15 years previously) and 1 had melanoma metastasis with unknown primary. The incidence of melanoma was 955 times higher than expected (standardized incidence rate). The benefits of PET scanning must be validated in a controlled trial prior to implementation into clinical practice.

[Kerion Celsi on the vulva in a 15-year-old girl].

This is a case report of a 15-year-old girl, who developed kerion Celsi on the vulva after contact with a pet rodent. The skin was extremely painful, highly red, severely inflamed and oozing, mimicking a bacterial abscess. The patient's general condition was barely affected. PCR identified Trichophyton mentagrophytes, successfully treated with terbinafin 250 mg for 12 weeks. The majority of incidents in 11 published cases were caused by T. mentagrophytes, sensitive to terbinafin. Knowledge of this rare inflammatory dermatophytosis may cause the surgeon to abstain from surgery and to "keep calm and kerion".

Targeted therapy for malignant melanoma.

Treatment of advanced melanoma has undergone a paradigm shift over the last 10-15 years. The frustrating results of studies on medical treatment ten years ago have been replaced by studies constantly improving survival in patients with advanced melanoma. Immune checkpoint inhibitors belong to one group of treatments and targeted therapy to another. Fifty percent of melanomas are BRAF mutation positive. Normally, the mitogen activated protein kinase or MAP kinase (Ras-BRAF-MEK-Erk chain) pathways translate external signals to intracellular growth and proliferation. In BRAF mutated melanoma cells, the mutated BRAF kinase is excessively active leading to autonomous proliferation and cancerous growth. This kinase can be blocked by BRAF-inhibitors. If given to BRAF negative melanoma patients, it may lead to disease progression because Ras is not inhibited in these cells. Development of Squamous cell carcinomas as a serious adverse event to BRAF inhibition may be caused by similar mechanisms in non BRAF mutated keratinocytes. A spontaneous and paradoxical loss of effect is seen with BRAF inhibitors due to various ways melanoma cells bypass BRAF. This is somewhat counteracted by the addition of a MEK1/2 inhibitor. Overall progression-free survival has increased from a median of two months for chemotherapy, via 7-8 months for BRAF inhibitor to 10-14 months for newer BRAF and MEK inhibitor combination therapy.

The Danish Melanoma Database.

AIM OF DATABASE: The aim of the database is to monitor and improve the treatment and survival of melanoma patients. STUDY POPULATION: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register. MAIN VARIABLES: The main variables include demographic, clinical, and pathological characteristics, including Breslow's tumor thickness, ± ulceration, mitoses, and tumor-node-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. DESCRIPTIVE DATA: The DMD is an old research database, but new as a clinical quality register. The coverage is high, and the performance in the five Danish regions is quite similar due to strong adherence to guidelines provided by the Danish Melanoma Group. The list of monitored indicators is constantly expanding, and annual quality reports are issued. Several important scientific studies are based on DMD data. CONCLUSION: DMD holds unique detailed information about tumor characteristics, the surgical treatment, and follow-up of Danish melanoma patients. Registration and monitoring is currently expanding to encompass even more clinical parameters to benefit both patient treatment and research.

Actinic keratosis: a cross-sectional study of disease characteristics and treatment patterns in Danish dermatology clinics.

OBJECTIVES: The incidence of actinic keratosis (AK) is increasing, and several treatment options are available. The aim of this study was to describe clinical characteristics and treatment patterns in patients with AK treated by Danish dermatologists. METHODS: A multicenter, non-interventional, cross-sectional study was conducted. Three dermatology hospital departments and seven private dermatology clinics enrolled eligible AK patients consecutively during one week. RESULTS: A total of 312 patients were included. Non-melanoma skin cancer (NMSC) was previously reported in 51.0% of patients and currently suspected in 9.4% of AK-affected anatomical regions. Lesions of AK were located primarily on the face (38.6%), scalp (12.8%), and hands (11.2%). Actinic keratosis commonly presented with multiple AK lesions (38.6%) and field cancerization (38.5%). The treatments used most frequently were cryotherapy (57.7%) and photodynamic therapy (PDT) with methyl aminolevulinate (17.1%) and imiquimod (11.2%). The likelihood of receiving cryotherapy was higher for men (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10-2.47) and increased with age (2.2% per year, 0.4-4.0%). PDT represented the most frequently applied treatment for severe actinic damage and was more likely to be prescribed to women (OR 4.08, 95% CI 2.22-7.47) and young patients (OR 0.97 per year, 95% CI 0.95-0.99). The prevalence of severe actinic damage (17.3% versus 9.6%) and intake of immunosuppressive medication (29.0 versus 2.0) were higher among hospital patients compared with those treated in private practices (P < 0.0001). CONCLUSIONS: The majority of AK patients in Danish dermatology clinics have a history of skin cancer, and NMSC is suspected in almost 10% of AK-affected regions. Cryotherapy is the most frequently used treatment overall, except in instances of severe actinic damage, in which PDT is the first-choice treatment.

[CDKN2A-mutation in a family with hereditary malignant melanoma].

Malignant melanoma (MM) is a frequent form of cancer with increasing incidence. 6-10% of patients with MM report a family history of MM, and in most populations 2% of unselected cases of MM carry a CDKN2A mutation. tvWe present a family with 24 cases of MM in nine persons from several generations, caused by a previously undescribed germ-line intronic mutation in CDKN2A. Through genetic counselling and genetic testing high-risk persons in the family are located and offered regular screening for MM.

Melanoma associated with the use of melanotan-II.

BACKGROUND: Unlicensed use of melanotan-II (MT-II) to promote skin pigmentation has become prevalent amongst young people attending fitness centres. We present a case where the melanocyte stimulation of MT-II in combination with the use of sun tanning beds coincided with cutaneous melanoma. OBSERVATION: A 20-year-old woman with Fitzpatrick skin type II was referred to a dermatology clinic. Clinical examination revealed a suspicious black melanocytic lesion in her left gluteal region. Furthermore, her skin was universally intensely pigmented. The melanocytic lesion was excised, and histology confirmed the diagnosis of melanoma. Three months prior to the excision the patient had conducted a 3- to 4-week course of self-injections with MT-II, intending an augmentation of sunbed tanning. CONCLUSIONS AND RELEVANCE: This observation brings attention to the potential risks related to the use of the cyclic α-melanocyte-stimulating hormone analogue MT-II. There are several hazardous aspects of the possible widespread use of MT-II. As the drug is unlicensed and incompletely tested, the extent and types of adverse effects are unknown. Clinicians are advised to be aware of the problem, and counsel their at-risk patients regarding the potential hazards related to the use of MT-II.