MED15::ATF1-Rearranged Tumor: A Novel Cutaneous Tumor With Melanocytic Differentiation.

We recently described novel dermal tumors with melanocytic differentiation and morphologic and biological similarities to cutaneous clear cell sarcoma, including CRTC1::TRIM11 cutaneous tumor, and clear cell tumors with melanocytic differentiation and either ACTIN::MITF or MITF::CREM. Here, we describe a series of 3 patients presenting with tumors reminiscent of CRTC1::TRIM11 cutaneous tumor, found to demonstrate a novel MED15::ATF1 fusion. All 3 patients were children (5-16 years old). Primary excision of case 1 showed a circumscribed wedge-shaped silhouette with peripheral intercalation into collagen fibers and scattered lymphoid aggregates. All 3 tumors abutted the epidermis; one showed a junctional component. Tumors were highly cellular and comprised of monomorphic, oval-to-round epithelioid cells arranged in vague nests and short fascicles in variably fibrotic stroma. Mitotic rate was high (hotspot 6-12/mm2), without atypical mitoses. Necrosis was focally present in case 3. All cases showed strong, diffuse nuclear staining for SOX10 and MITF (2/2) but showed variable expression for S100 protein (1/3) and other melanocytic markers-Melan-A (focal in 2/3), HMB45 (focal in 1/3), and Pan-Melanoma (patchy in 1/1). Whole-exome RNA sequencing demonstrated a MED15::ATF1 fusion without any other notable alterations. Cases 1 and 2 were completely excised without recurrence (12 months). Case 3 developed a grossly apparent regional lymph node spread shortly after primary biopsy. The patient was treated with wide excision, radiation, cervical lymph node dissection (4/46 with >75% lymph node replacement), and neoadjuvant and adjuvant nivolumab (alive without disease at cycle 11). This series is presented to aid in future diagnosis of this novel dermal tumor with melanocytic differentiation and emphasize the potential for aggressive biologic behavior, which should be considered in patient management planning.

Presumed incipient choroidal melanoma: proposed diagnostic criteria and management.

AIMS: To propose diagnostic criteria for a presumed incipient choroidal melanoma based on tumour growth rate and tumour doubling time (TDT) and to describe management of such tumours with transpupillary thermotherapy (TTT). METHODS: Retrospective interventional case series of nine consecutive presumed incipient uveal melanomas diagnosed and treated with TTT in 2010-2017. Growth rate in mm/year and per cent/year in largest basal diameter (LBD) and TDT were compared with published data for uveal melanomas and growing naevi that did not transform to melanoma under long-term follow-up. RESULTS: The median LBD and thickness were 1.6 mm (range 0.9-2.3) and 0.20 mm (range 0.15-0.29), respectively. The median age was 57 years (range 47-78). Seven tumours were classified as de novo melanomas and two as transformed naevi. The median time from first observation to diagnosis was 3.3 years (range 2.2-7.3), LBD growth rate 0.25 mm/year (range 0.11-0.72) and 34 per cent/year (range 10-1437), and TDT 609 days (range 97-1612). The estimates matched those reported for uveal melanoma (median TDT 521 days, 90th percentile 2192) and exceeded those for growing naevi (median growth rate 0.04 mm/year, 90th percentile 0.12; 1.1 per cent/year, 90th percentile 2.6). The predicted median age at de novo appearance was 51 years (range 32-63). No tumour grew after TTT during a median follow-up of 2.1 years (range 0.6-8.7). CONCLUSIONS: In this series, relative growth rate and TDT best qualified as diagnostic criteria for an incipient choroidal melanoma. Too small for brachytherapy, they could be managed with TTT.

Optic disc cupping after circumpapillary Pd-103 slotted plaque radiation therapy.

OBJECTIVE: To investigate vascular and morphologic optic disc changes after slotted plaque radiation therapy for choroidal melanoma involving the optic disc. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Thirty-nine patients with choroidal melanoma involving the optic nerve. METHODS: Each melanoma was treated with palladium-103 slotted plaque brachytherapy (incorporating and/or surrounding the optic nerve sheath) between 2005 and 2019. Imaging of the optic nerve before and after radiation allowed for documentation and evaluation of optic nerve pallor and cup-to-disc ratio (CDR) changes. Optical coherence tomography (OCT) CDR measurements and intraocular pressure (IOP) were recorded pretreatment and at follow-up. Of these patients, 22 also had OCT angiography (OCT-A) images with sufficient quality for evaluation of blood vessel density and length. Differences in cup-to-disc measurements were correlated with changes in OCT-A-measured vessel density and length. RESULTS: Following slotted plaque radiation therapy, there was no significant increase in IOP or optic nerve pallor. OCT and colour photography revealed significant increases (both p < 0.001) in CDR from pretreatment to the last follow-up. Increased CDRs on OCT were significantly correlated to OCT-A-measured change in vessel length (p = 0.027). Similarly, increased CDR ratios on fundus photography were significantly correlated with OCT-A-measured change in vessel density (p = 0.043) and length (p = 0.019). CONCLUSION: Fundus photography and OCT measurements revealed increased optic disc cupping following slotted plaque radiation therapy. Cupping was associated with OCT-A evidence of synchronous progressive peripapillary vascular occlusion and attenuation. Therefore, slotted plaque radiation-induced peripapillary and papillary ischemia was associated with increased CDR ratios and optic disc cupping.

BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting.

Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia. Notably, it recommends that pathologists reflexively order BRAF mutation testing whenever a patient is found to have American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III or IV melanoma (i.e., any metastatic spread beyond the primary tumour) and that patient's BRAF mutation status is hitherto unknown, even if BRAF mutation testing has not been specifically requested by the treating clinician (in Australia, Medicare-subsidised BRAFV600 mutation testing does not need to be requested by the treating clinician). When performed in centres with appropriate expertise and experience, immunohistochemistry (IHC) using the anti-BRAF V600E monoclonal antibody (VE1) can be a highly sensitive and specific means of detecting BRAFV600E mutations, and may be used as a rapid and relatively inexpensive initial screening test. However, VE1 immunostaining can be technically challenging and difficult to interpret, particularly in heavily pigmented tumours; melanomas with weak, moderate or focal BRAFV600E immunostaining should be regarded as equivocal. It must also be remembered that other activating BRAFV600 mutations (including BRAFV600K), which account for ∼10-20% of BRAFV600 mutations, are not detected with currently available IHC antibodies. For these reasons, if available and practicable, we recommend that DNA-based BRAF mutation testing always be performed, regardless of whether IHC-based testing is also conducted. Advice about tissue/specimen selection for BRAF mutation testing of patients diagnosed with stage III or IV melanoma is also offered in this article; and potential pitfalls when interpreting BRAF mutation tests are highlighted.

Assessing the Potential for Patient-led Surveillance After Treatment of Localized Melanoma (MEL-SELF): A Pilot Randomized Clinical Trial.

IMPORTANCE: Patient-led surveillance is a promising new model of follow-up care following excision of localized melanoma. OBJECTIVE: To determine whether patient-led surveillance in patients with prior localized primary cutaneous melanoma is as safe, feasible, and acceptable as clinician-led surveillance. DESIGN, SETTING, AND PARTICIPANTS: This was a pilot for a randomized clinical trial at 2 specialist-led clinics in metropolitan Sydney, Australia, and a primary care skin cancer clinic managed by general practitioners in metropolitan Newcastle, Australia. The participants were 100 patients who had been treated for localized melanoma, owned a smartphone, had a partner to assist with skin self-examination (SSE), and had been routinely attending scheduled follow-up visits. The study was conducted from November 1, 2018, to January 17, 2020, with analysis performed from September 1, 2020, to November 15, 2020. INTERVENTION: Participants were randomized (1:1) to 6 months of patient-led surveillance (the intervention comprised usual care plus reminders to perform SSE, patient-performed dermoscopy, teledermatologist assessment, and fast-tracked unscheduled clinic visits) or clinician-led surveillance (the control was usual care). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of eligible and contacted patients who were randomized. Secondary outcomes included patient-reported outcomes (eg, SSE knowledge, attitudes, and practices, psychological outcomes, other health care use) and clinical outcomes (eg, clinic visits, skin surgeries, subsequent new primary or recurrent melanoma). RESULTS: Of 326 patients who were eligible and contacted, 100 (31%) patients (mean [SD] age, 58.7 [12.0] years; 53 [53%] men) were randomized to patient-led (n = 49) or clinician-led (n = 51) surveillance. Data were available on patient-reported outcomes for 66 participants and on clinical outcomes for 100 participants. Compared with clinician-led surveillance, patient-led surveillance was associated with increased SSE frequency (odds ratio [OR], 3.5; 95% CI, 0.9 to 14.0) and thoroughness (OR, 2.2; 95% CI, 0.8 to 5.7), had no detectable adverse effect on psychological outcomes (fear of cancer recurrence subscale score; mean difference, -1.3; 95% CI, -3.1 to 0.5), and increased clinic visits (risk ratio [RR], 1.5; 95% CI, 1.1 to 2.1), skin lesion excisions (RR, 1.1; 95% CI, 0.6 to 2.0), and subsequent melanoma diagnoses and subsequent melanoma diagnoses (risk difference, 10%; 95% CI, -2% to 23%). New primary melanomas and 1 local recurrence were diagnosed in 8 (16%) of the participants in the intervention group, including 5 (10%) ahead of routinely scheduled visits; and in 3 (6%) of the participants in the control group, with none (0%) ahead of routinely scheduled visits (risk difference, 10%; 95% CI, 2% to 19%). CONCLUSIONS AND RELEVANCE: This pilot of a randomized clinical trial found that patient-led surveillance after treatment of localized melanoma appears to be safe, feasible, and acceptable. Experiences from this pilot study have prompted improvements to the trial processes for the larger trial of the same intervention. TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12616001716459.

Expanding Our Reach: the Value of Massage Therapists in Melanoma Identification.

Massage therapists are uniquely positioned to identify skin cancer. Seminal work in 2013 revealed that 40% of massage therapists do not receive any training in skin cancer identification (Campbell et al. J Cancer Educ 28:158-164, 2013). Limited work has been published assessing optimal training methodologies to close this educational gap. We present the results of a study in which students were given access to a 30-min self-driven web-based learning module designed to teach the high yield points of melanoma demographics and clinical features. The students completed pre- and post-testing, the results of which indicated improved knowledge levels and improved confidence in detecting suspected melanoma. We conclude that a 30-min learning module may be sufficient to improve massage therapists' ability and comfort level in identifying melanoma. The ease of delivery of web-based modules may make this an important approach in ensuring that massage therapists receive basic training in skin cancer identification.

Management of Transected Invasive Melanoma: A Single Institution Retrospective Review.

BACKGROUND: Deep transection of invasive melanoma precludes accurate measurement of Breslow depth, which may affect tumor staging. OBJECTIVE: To determine the frequency of upstaging of transected invasive melanomas after excision, characterize the impact on National Comprehensive Cancer Network (NCNN)-recommended treatment, and determine predictors of subsequent upstaging. MATERIALS AND METHODS: A retrospective review of invasive melanomas between January 2017 and December 2019 at a single institution. Deeply transected biopsy reports were compared with subsequent excisions to calculate the frequency of upstaging. RESULTS: Three hundred sixty (49.6%) of 726 invasive melanomas identified were transected. Forty-nine (13.6%) transected tumors had upstaging that would have altered NCCN-recommended management. "Broadly" transected tumors had upstaging that would have resulted in a change in the management in 5/23 cases (21.7%) versus 2/41 cases (4.9%) for "focally" transected tumors (p = .038). Breslow depth increased by 0.59 mm on average for "broad" transection versus 0.06 mm for "focal" transection (p =< .01). Of the 89 transected pT1a melanomas, specimens with gross residual tumor or pigment after biopsy were upstaged in 8/17 (47.1%) of cases versus 5/72 (6.9%) of specimens without (p =< .01). CONCLUSION: Upstaging of deeply transected invasive melanomas that would alter NCCN-recommended management occurred in 13.6% of cases. Broad transection and gross residual tumor or pigment after biopsy predicted higher likelihood of upstaging.

A Reminder of Skin Cancer During the COVID-19 Pandemic.

The year 2020 has been marked by the coronavirus disease 2019 (COVID-19) pandemic, caused by an RNA virus called SARS-COV2 (severe acute respiratory syndrome coronavirus). The fight against this epidemic has become the center of our daily clinical practice as well as of our private lives, in which avoiding infection has become one of our most important goals. Even though COVID-19 is a potentially lethal disease, especially for the elderly and people with chronic diseases, it did not cause all the other life-threatening diseases to vanish. On the contrary, many scheduled medical activities and procedures, especially preventive and non-urgent internal and surgical activities, had to be postponed due to COVID-19 crisis. This interruption in the health care system can negatively affect the diagnosis and management of our patients with other health issues, namely malignant skin tumors, of which melanoma is the most aggressive. In this letter, we as dermatovenereologists from the Croatian Referral Centre of The Ministry of Health for Melanoma needed to express our concern regarding the increasing number of patients with delayed diagnosis of skin cancer, with special emphasis on melanoma detection and treatment. In the last few months, a large number of our newly-diagnosed patients with melanoma, as well as those with non-melanoma skin cancers, reported that they had noticed a suspicious skin lesion a few months ago but decided not to seek help from dermatologist due to the worrisome epidemiologic situation. In the current environment, clinical skin examination may be viewed as less important and thus postponed, but neglecting melanoma throughout the virus outbreak may lead to increased rates of morbidity, mortality, and consequently a greater financial burden for the health system (1). There are several reasons for such a relaxed attitude towards skin health in our patients. Unlike cardiac, pulmonary, or digestive difficulties, which patients consider life-threatening and for which they seek emergency care despite the coronavirus pandemic, skin tumors do not cause great subjective or significantly noticeable objective symptoms. Moreover, all of the skin tumors and especially melanoma , mostly present as small changes of just a few millimeters in diameter in the early stage at which they are prognostically most favorable. For the average person with no medical education, such small lesions usually do not cause any concern as they have no awareness of the fact that small and inconspicuous skin lesions may be dangerous and potentially even lethal. According to the recommendations concerning patient management during COVID-19 pandemic, oncological examinations should still be performed regularly (2). In spite of that, the cancelation of appointments, especially by patients who are being monitored for high-risk lesions, is inevitable when COVID-19 is disrupting everyone's lives. With the pandemic evolving and no clear solutions in sight, now is the time to emphasize the importance of self-examination and teledermatology in early melanoma diagnosis. Even though diagnosing and managing pigmented skin lesions usually requires face-to-face examinations and dermoscopy as a crucial tool in early melanoma detection, in these times, and especially for people with a higher risk of SARS-COV2 infection, remote communication could prevent delays resulting in worse prognosis and could also eliminate the risk of infecting healthcare workers. Moreover, teledermatology can also be initiated by doctors asking patients to monitor lesions between clinical visits (3). However, we should not rely solely on this technology but should instead assess every patient individually and insist on a face-to-face examination for those at greater risk, with the aim that, if necessary, surgery be performed in timely manner. The collaboration between general practitioners and dermatologists represents an important aspect of achieving the most rational and effective health care in terms of performing triage of patients who can be assessed by teledermatology as well as referring to hospital centers those who need face-to-face examination and further treatment. During the first breakout of the epidemic in March 2020, the multidisciplinary team for melanoma from the Croatian National Referral Melanoma Centre provided recommendations for the management of patients with melanoma during COVID epidemic, designed according to the guidelines of the National Comprehensive Cancer Network (NCCN) (4) and considering the specifics of health care and clinical practice in the Republic of Croatia. Due to epidemic circumstances, preventive actions such as Euromelanoma and many other campaigns that included massive preventive skin examinations of the population and which were conducted for years by Croatian dermatologists throughout the country, could not be organized this year. This is particularly worrisome because on average about 800 patients are diagnosed with melanoma annually in Croatia, of which 60 during public health preventive actions. Despite these circumstances, we were able to maintain public awareness of the importance of early skin cancer recognition by sending the message through different media such as newspapers, television, and social media (Facebook and Instagram). We find that now more than ever it is essential to remind and teach the population about the importance of regular monthly skin self-examinations and recognition of atypical lesions. Clearly, a thorough dermatological examination includes full skin examination from head to toe. Herein we would also like to remind our readers that most skin cancers develop in the head and neck area, which is the most UV-exposed part of the body. Therefore, despite the epidemic conditions, the removal of patients' masks and thorough inspection of the face is mandatory. We find it most practical and efficient to perform the body and scalp examination first, followed by the face examination after the patient gets dressed. Prior to removal of the mask, we ask the patient not to talk during close examination. Even though this could make dermoscopic examination harder to perform, we strongly suggest wearing a protective shield and mask during close examination whenever possible. Between patients, the examining room should be disinfected and ventilated. As doctors, we live in uncertain times when we are heavily burdened by the currently unstoppable COVID epidemic, always awaiting new instructions from the state administration every day and wondering whether perhaps tomorrow we dermatologists will be assigned solely to the service of patients with COVID-19. In the end, we would like to once again remind you that despite the ravaging COVID pandemic and all the epidemiological measures that come with it, other diseases still exist. It is expected of us to draw attention to the still growing incidence of skin cancers and the serious consequences that can occur as a result of a delayed diagnosis.

Impact of personal genomic risk information on melanoma prevention behaviors and psychological outcomes: a randomized controlled trial.

PURPOSE: We evaluated the impact of personal melanoma genomic risk information on sun-related behaviors and psychological outcomes. METHODS: In this parallel group, open, randomized controlled trial, 1,025 Australians of European ancestry without melanoma and aged 18-69 years were recruited via the Medicare database (3% consent). Participants were randomized to the intervention (n = 513; saliva sample for genetic testing, personalized melanoma risk booklet based on a 40-variant polygenic risk score, telephone-based genetic counseling, educational booklet) or control (n = 512; educational booklet). Wrist-worn ultraviolet (UV) radiation dosimeters (10-day wear) and questionnaires were administered at baseline, 1 month postintervention, and 12 months postbaseline. RESULTS: At 12 months, 948 (92%) participants completed dosimetry and 973 (95%) the questionnaire. For the primary outcome, there was no effect of the genomic risk intervention on objectively measured UV exposure at 12 months, irrespective of traditional risk factors. For secondary outcomes at 12 months, the intervention reduced sunburns (risk ratio: 0.72, 95% confidence interval: 0.54-0.96), and increased skin examinations among women. Melanoma-related worry was reduced. There was no overall impact on general psychological distress. CONCLUSION: Personalized genomic risk information did not influence sun exposure patterns but did improve some skin cancer prevention and early detection behaviors, suggesting it may be useful for precision prevention. There was no evidence of psychological harm.

Local and regional therapy for primary and locally recurrent melanoma.

In the vast majority of cases, cutaneous melanoma presents as localized disease and is treated with wide excision and sentinel lymph node biopsy, with shared decision making regarding completion lymph node dissection and adjuvant systemic therapy. The treatment of recurrent and in-transit disease is more complex, with further options for regional and systemic therapies and multiple variables to be factored into decisions. Rates of overall and complete response to regional therapies can be quite high in carefully chosen patients, which limits the need for systemic therapies and their inherent side effects. Ongoing trials aim to assess the efficacy of combination regional and systemic therapies and assist in deciding among these options. This review discusses the treatment of primary melanoma and regional nodal disease and offers an in-depth discussion of options for the treatment of recurrent melanoma and in-transit melanoma.

Discordance in Diagnosis of Melanocytic Lesions and Its Impact on Clinical Management.

CONTEXT.­: Accurate diagnosis of melanocytic lesions is fundamental for appropriate clinical management. OBJECTIVE.­: To evaluate the degree of discordance, if any, between histopathologic diagnoses of melanocytic lesions at referring institutions and at a tertiary referral cancer center and the potential impact of such discordance on clinical management. DESIGN.­: We retrospectively identified all patients referred to our comprehensive cancer center for evaluation of a melanocytic lesion from January 2010 to January 2011. For each patient, the histopathologic diagnosis from the referring institution was compared with the histopathologic diagnosis from a dermatopathologist at our center. Discordances were classified as major if they resulted in a change in clinical management and minor if they did not. RESULTS.­: A total of 1521 cases were included. The concordance rates were 72.2% (52 of 72) for dysplastic nevus, 75.0% (15 of 20) for all other types of nevi, 91.1% (143 of 157) for melanoma in situ, 96.1% (758 of 789) for invasive melanoma, and 99.6% (478 of 480) for metastatic melanoma. Major discordances were found in 20.2% of cases (307 of 1521), and minor discordances were found in 48.8% of cases (742 of 1521). Compared with the guideline-based treatment recommendation based on the referring-institution diagnosis, the guideline-based treatment recommendation based on the cancer center diagnosis was more extensive in 5.9% (89 of 1521) of patients and less extensive in 5.0% (76 of 1521) of patients. CONCLUSIONS.­: Our findings underscore the importance of secondary histopathologic review of melanocytic lesions by expert dermatopathologists because significant changes in the diagnosis, tumor classification, and/or staging may be identified, thus, resulting in critical changes in recommendations for clinical management.

Clinical Characteristics of UM and Association of Metastasis of Uveal Melanoma with Congenital Oculocutaneous Melanosis in Asian Patients: Analysis of 1151 Consecutive Eyes.

PURPOSE: To analyze the clinical characteristics of uveal melanoma (UM) and evaluate the relationship of congenital oculocutaneous melanosis (OCM) to the prognosis of Asian patients with UM. DESIGN: Retrospective cohort study. PARTICIPANTS: We included a total of 1151 Asian patients with UM who were managed at the Beijing Tongren Hospital from June 26, 2005, to July 27, 2020. METHODS: I-125 plaque brachytherapy, local resection, thermotherapy, or enucleation. MAIN OUTCOME MEASURES: Melanoma-related metastasis and death. RESULTS: Of 1151 Asian patients with UM, congenital OCM was present in 23 (0.20%). The melanocytosis involved the conjunctiva (78%), sclera (74%), eyelid (70%), face (26%), forehead (2.2%), iris (0.87%), choroid (0.87%), and auricle (0.4%). Univariate analysis of Cox proportional hazards regression model showed that age, tumor thickness, largest tumor basal diameter, and ciliary body involvement were the risk factors for the poor prognosis of Asian patients with UM. By multivariable analysis, the only factor predictive of melanoma-related metastasis and death was the largest tumor basal diameter (hazard ratio [HR], 1.21 [1.11-1.33], P < .001; 1.17 [1.01-1.35], P = 0.033). Probability-of-censoring weighted (IPW) estimation was used to mitigate selection bias due to loss to follow-up. Probability-of-censoring weighted estimation revealed the largest tumor basal diameter and ciliary body involvement were associated with metastasis (HR, 1.29 [1.15-1.45], P < 0.001; HR, 2.64 [1.01-6.90], P < 0.048). During the median follow-up period of 53 (33-67) months, 2 patients with OCM (8.7%) developed melanoma-related metastasis. By using nested case-control design and matched with the factors of age, largest tumor basal diameter, tumor thickness, and ciliary body involvement, Kaplan-Meier survival analysis showed that UM combined with OCM did not increase the risk of melanoma-related metastasis and death (P = 0.68, log-rank test). CONCLUSIONS: The prominent risk for metastasis from UM was the largest tumor basal diameter in Asian patients. Estimation of IPW revealed that the largest tumor basal diameter and ciliary body involvement were the risk factors for UM metastasis. Patients with UM combined with OCM had a similar risk for metastasis compared with those with no OCM.

Melanoma Risk is Increased in Patients with Mycosis Fungoides Compared with Patients with Psoriasis and the General Population.

Patients with mycosis fungoides (MF) are thought to be at increased risk of melanoma. However, studies addressing surveillance-bias and treatments as a possible confounder are lacking. This retrospective study compared the prevalence and risk of melanoma between 982 patients with MF, and 3,165 patients with psoriasis attending tertiary cutaneous-lymphoma/psoriasis clinics during 2009 to 2018. Melanoma was diagnosed in 47 patients with MF (4.8%; 43 early-stage) and in 23 patients with psoriasis (0.7%) (odds ratio 6.6, p < 0.0001). In 60% of patients, MF/psoriasis preceded melanoma diagnosis. Hazard ratio (HR) for a subsequent melanoma in MF vs psoriasis was 6.3 (95% confidence interval (95% CI) 3.4-11.7, p < 0.0001). Compared with the general population, melanoma standardized incidence ratios were 17.5 in patients with MF (95% CI 11.0-23.9, p < 0.0001), and 2.2 (95% CI 0.6-3.8, p = 0.148) in patients with psoriasis. Narrow-band ultraviolet B was not a contributory factor (HR 1.15, 95% CI 0.62-2.14, p = 0.66). These findings add evidence that patients with MF have a significantly higher risk of melanoma, not only compared with the general population, but also compared with patients with psoriasis. This comorbidity may be inherent to MF.

Melanoma and COVID-19: A narrative review focused on treatment.

Melanoma is the most severe form of skin cancer and its incidence has increased over the past few decades. COVID-19 pandemic affected the diagnosis and management of many diseases including melanoma. In this study, we aimed to provide a review focused on the diagnosis and management of melanoma in the era of COVID-19. A comprehensive search was conducted on PubMed, Web of Science, and Google Scholar databases using the keywords "melanoma," "coronavirus," "COVID 19," and "SARS-CoV-2." The relevant guidelines published by the European Society for Medical Oncology and the National Comprehensive Cancer Network were also included. The current guidelines recommend that surgical interventions for new diagnosis of invasive primary melanoma, patients with postoperative complications, wide resection and sentinel lymph node biopsy for newly diagnosed T3-T4 melanoma, and planned surgical procedures for patients in neo-adjuvant trials should be prioritized. Surgical treatment of T3/T4 melanomas should be prioritized over T1/T2 melanomas except for any melanoma in which large clinical residual lesion is visible. Adjuvant therapies can be postponed for up to 12 weeks depending on the local center circumstances. PD-1 inhibitor monotherapy is recommended for patients starting immunologic therapy. Combination immunotherapy is still considered suitable for patients with higher-risk disease. Encorafenib and binimetinib should be prioritized for patients requiring BRAF-targeted therapy due to the lower chance of symptoms mimicking COVID-19 infection.

Uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UMs are usually initiated by a mutation in GNAQ or GNA11, unlike cutaneous melanomas, which usually harbour a BRAF or NRAS mutation. The annual incidence in Europe and the USA is ~6 per million population per year. Risk factors include fair skin, light-coloured eyes, congenital ocular melanocytosis, ocular melanocytoma and the BAP1-tumour predisposition syndrome. Ocular treatment aims at preserving the eye and useful vision and, if possible, preventing metastases. Enucleation has largely been superseded by various forms of radiotherapy, phototherapy and local tumour resection, often administered in combination. Ocular outcomes are best with small tumours not extending close to the optic disc and/or fovea. Almost 50% of patients develop metastatic disease, which usually involves the liver, and is usually fatal within 1 year. Although UM metastases are less responsive than cutaneous melanoma to chemotherapy or immune checkpoint inhibitors, encouraging results have been reported with partial hepatectomy for solitary metastases, with percutaneous hepatic perfusion with melphalan or with tebentafusp. Better insight into tumour immunology and metabolism may lead to new treatments.

Internal Pathology Review of Invasive Melanoma: An Academic Institution Experience.

BACKGROUND: Prior studies of internal pathology review (IPR) for melanoma have shown that changes in the pathology analysis are common. How these changes impact clinical management of melanoma or how the margin status reports may modify has not been evaluated. Our goal was to determine what changes to staging and surgical management occurred after IPR of newly diagnosed melanomas and to determine how the final surgical pathology report may correlate with the IPR. METHODS: A retrospective study was conducted from 2014 to 2016 of newly diagnosed invasive melanomas referred to a single National Comprehensive Cancer Network tertiary care center. RESULTS: A total of 370 cases met inclusion criteria. The most common feature changed after internal review was mitotic rate, in 155 (41.7%) patients, followed by Breslow depth in 99 (26.9%) patients. Tumor staging was changed in 45 (12.2%) patients. The most common change was a T1a lesion being upgraded to a T1b lesion. These tumor staging changes lead to 38 (10.3%) overall staging differences. A biopsy's deep margin status was changed in 27 (7.3%) patients. Outside hospital reports lacked information about deep margin status in 71 (19.2%) of specimens. Based on the National Comprehensive Cancer Network guidelines, 22 (5.9%) patients had changes in their sentinel lymph node biopsy recommendations and one of these patients had a positive node found on pathology. Of those patients who had changes in the T-stage, 16 (4.3%) of them also had changes in the recommended wide local excision radial margin. CONCLUSIONS: IPR of invasive melanoma leads to both changes in staging and the surgical management of melanoma and should remain an important component of care of melanoma patients at a tertiary referral center.

Nomogram for visual acuity outcome after iodine-125 plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma in 1131 patients.

AIMS: To develop a nomogram for prediction of visual acuity outcome following plaque radiotherapy for uveal melanoma. METHODS: Retrospective review of uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab injections at 4-month intervals for 2 years duration. Two nomograms for poor visual acuity outcome (Snellen <20/200) were developed based on (1) Clinical risk factors. (2) Or clinical and treatment risk factors. RESULTS: There were 1131 included cases. The most important clinical risk factors (points for nomogram) for poor visual acuity outcome included subretinal fluid involving four quadrants (100), tumour thickness >4 mm (69), presenting visual acuity ≤20/30 (65), non-Caucasian race (58), tumour shape mushroom, bilobed, or multilobulated (57), and insulin-dependent diabetes (54). Risk of poor visual acuity at 2 years and 4 years increased from 11% and 24% with 40 points to 97% and >99% with 304 points. A second analysis was performed using both clinical and treatment risk factors. The most important factors included presenting visual acuity ≤20/30 (100), tumour largest basal diameter >11 mm (80), radiation dose rate to tumour base ≥164 cGy/hour (78), tumour thickness >4 mm (76), insulin-dependent diabetes (75) and abnormal foveolar status by optical coherence tomography at presentation (72). Risk of poor visual acuity at 2 years and 4 years increased from 6% and 14% with 56 points to 88% and 99% with 496 points. CONCLUSIONS: A nomogram using clinical or treatment risk factors can predict visual acuity outcome following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma and is available online at https://fighteyecancer.com/nomograms/.

Management of Melanoma Patients by Non-Dermatologists in the Military Health System: A Retrospective Observational Study.

INTRODUCTION: Compared to their civilian counterparts, military personnel can have more exposure to sunlight and, as recent studies have shown, do have an increased incidence of melanoma. Given the inherent challenges service members may face in getting appropriate care whether because of operational tempo, deployments, and/or austere locations, many are initially diagnosed by specialties other than dermatology. In this study, we sought to determine if patients within the military health system were receiving appropriate follow-up management after biopsies by non-dermatologists led to the diagnosis of melanoma by pathology. MATERIALS AND METHODS: Using the Co-Path system, 1,000 patients were identified who had first time biopsies positive for melanoma. Of these, 73 were originally biopsied by non-dermatologists. Retrospective medical record review was performed to determine specialties of the non-dermatologists, staging of melanoma at diagnosis, referrals to specialists and dermatologists, and adherence to National Comprehensive Cancer Network guidelines. The study protocol was approved by the Walter Reed National Military Medical Center Institutional Review Board, protocol number WRNMMC-EDO-2017-0030, in compliance with all applicable federal regulations governing the protection of human subject research. RESULTS: Family medicine physicians made up the majority of non-dermatologists involved in performing biopsies that led to the diagnosis of melanoma in this study. Most patients were Stage I (pT1a), and the average time from initial biopsy to further wide excision biopsy was 18 days. Sixty-seven of the 73 patients biopsied by non-dermatologists received referrals to dermatologists, and 55 of the 67 patients followed through with being seen. Follow-up full body skin exams were performed on 55 of the 73 patients, with dermatologists conducting the majority of them. National Comprehensive Cancer Network guidelines were followed in 45 of the 73 patients, with an additional 24 patients having insufficient evidence to determine if guidelines were adhered to. CONCLUSION: Our study demonstrated that a number of different specialties outside of dermatology are involved in performing biopsies on patients in which melanoma is a concern. Although the results show that the majority of patients biopsied by non-dermatologists received appropriate follow-up care, there is still room to improve to ensure that all melanoma patients receive referrals to and are seen by dermatologists after a diagnosis of melanoma.