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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.

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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.

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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.

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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.

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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.

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