bluuebunny/crossref_metadata_2025 huggingface dataset:
P103 Clinical clues for frontal fibrosing alopecia: a case series describing prominent, depressed forehead veins
Authors: Bala Laksha , Tsang Christie , Agarwal Vani , Elshimy Noha
Published: June 2024

Frontal fibrosing alopecia (FFA) is a lymphocytic, scarring alopecia characterized by progressive frontotemporal hairline recession, most frequently in postmenopausal women. It is considered a subtype of lichen planopilaris, given the shared histopathological findings of perifollicular lymphocytic infiltration and fibrosis. FFA is a recently reported entity and one of the most common causes of cicatricial alopecia worldwide. Its pathogenesis is not well understood, with immune dysregulation, and hormonal, genetic and environmental factors all postulated to play a role. Clinical features include the characteristic bandlike frontotemporal scarring hair loss, perifollicular hyperkeratosis and erythema (active inflammation), the ‘lonely hair’ sign (terminal hairs within a band of alopecia), loss of eyelashes and eyebrows, and facial lesions (most commonly papules). Visible vascular abnormalities with prominent and/or depressed forehead veins are a much less recognized entity, with only three publications to date reporting this finding (Heymann WR. Vascular abnormalities in FFA, artificial intelligence and Winston Churchill. Dermatol World Insights Inquiries 2023; 5: Aug 23). We present a case series of 15 patients with FFA presenting to our tertiary centre hair clinic, who displayed prominent and/or depressed forehead veins. To the unsuspecting clinician, visibility of frontal veins may mistakenly be attributed to steroid atrophy (in patients receiving corticosteroid treatment). Instead, it has been hypothesized that FFA itself may be responsible. The pathogenesis of FFA involves concentric perifollicular fibrosis, thought to culminate in fibrous tract formation and progressive vertical contraction with dermal constriction. This may be more marked around vasculature, resulting in the characteristic appearance of frontal veins in FFA. Steroids may exacerbate this process, but are not thought to be pathogenic (Vañó-Galván S, Rodrigues-Barata AR, Urech M, Jiménez-Gómez N et al. Depression of the frontal veins: a new clinical sign of frontal fibrosing alopecia. J Am Acad Dermatol 2015; 72: 1087–8). Therapeutic approaches for FFA largely focus on suppression of inflammation driving perifollicular fibrosis. Common therapies include topical corticosteroids or calcineurin inhibitors, corticosteroid injections, and systemic therapies such as oral tetracyclines or hydroxychloroquine. Prominent vasculature in FFA can be challenging to treat, with one study supporting the use of Nd:YAG laser as a potentially safe and effective treatment. The reason for the presence of prominent, depressed forehead veins in FFA and, indeed, the preferential targeting of follicles along the frontal hairline in this disease remains unknown and merits further research. Nevertheless, this clinical sign may serve as a helpful diagnostic tool for the perceptive dermatologist.
P108 Acne as an adverse effect of upadacitinib treatment for atopic dermatitis in adults and adolescents: a systematic review of short-term analysis
Authors: Sarto Rubiana , Dornelas Luana Baptistele , Monteiro Sara Baldé , Ricardo Naína Oliveira
Published: June 2024

Atopic dermatitis (AD) is a chronic, recurrent, immune-mediated inflammatory skin disease characterized by eczema and intense itching. There are many drugs used in patients with AD, but none of them is preferential. In this context, upadacitinib, an oral Janus kinase inhibitor, has been suggested for AD treatment. However, acne has been described as a potential adverse effect of this drug. We aim to compare the incidence of acne among patients treated with upadacitinib and placebo through randomized clinical trials (RCTs) in adolescents and adults with moderate-to-severe AD. The PubMed, Scopus and Cochrane databases were used to search for RCTs comparing upadacitinib and placebo in adolescents and adults with moderate-to-severe AD. The outcome assessed was acne. We included four RCTs: Measure Up 1 and Measure Up 2 (together abbreviated here as MUp), AD Up (ADUp) and Rising Up (RUp). These involved 2855 patients allocated to receive placebo, upadacitinib 15 mg or upadacitinib 30 mg. Of these patients, 269 had acne as an adverse event. The follow-up period was 16 weeks. Acne was predominant in the upadacitinib 30-mg group (19.8% in RUp, and 15.2% in MUp + ADUp). Patients aged 18–40 years were the most affected by acne, especially those in the upadacitinib 30-mg group. The body area most affected by acne was the face in all groups and studies (placebo: 80% in RUp and 89.5% in MUp + ADUp; upadacitinib 15 mg: 83.3% in RUp and 96.4% in MUp + ADUp; upadacitinib 30 mg: 94.4% in RUp and 96.2% in MUp + ADUp). The most common presentation of acne was as inflammatory papules (placebo: 100% in RUp and 84.2% in MUp + ADUp; upadacitinib 15 mg: 83.3% in RUp and 91.7% in MUp + ADUp; upadacitinib 30 mg: 88.9% in RUp and 8.4% in MUp + ADUp). There were two episodes of medication discontinuation due to acne, each in the RUp study in the upadacitinib 15-mg and 30-mg groups. Our ana­lysis suggest that acne as an adverse effect was more intense in the upadacitinib 30-mg group in all studies. Also, the face was the most common site of manifestation, and the most common presentation was as papules.
BH12 A case of reverse ageing phenomenon of the hair secondary to vitamin B supplementation
Authors: Amoafo Emma , Rao Archana
Published: June 2024

An 80-year-old woman is known to the dermatology department with darkening of previously grey hair. She was initially referred to the dermatology department for scalp pruritus. Her past medical history included atrial fibrillation and heart failure. Regular medications included furosemide, omeprazole, ferrous fumarate, and over-the-counter supplements, namely vitamin B, vitamin D, zinc, magnesium, cod liver oil, glucosamine and chondroitin. Examination of the scalp revealed erythema, scaling and crusting on the crown with no alopecia. Initial blood tests revealed normal full blood count, renal function, liver function, thyroid function, vitamin D and iron studies, and a raised vitamin B12 level. The scalp pruritus was attributed to seborrhoeic dermatitis and was treated successfully with topical steroids and antifungal shampoo. Changes in hair colour have been described in the literature. Overnight white hair has been attributed to alopecia areata. Conversely, darkening of hair has been reported secondary to vitamin B supplementation. Vitamin B has been reported to repigment grey or white hair in both premature and age-related achromotrichia. Hair repigmentation can begin as early as within 1 month of supplementation. A 2020 review of the literature suggests that vitamin B supplementation is only useful to reverse hair greying where there was underlying vitamin B deficiency initially (Yale K, Juhasz M, Atanaskova Mesinkovska N. Medication-induced repigmentation of gray hair: a systematic review. Skin Appendage Disord 2020; 6: 1–10). The mechanism for hair greying and repigmentation with vitamin B supplementation is incompletely understood, but some authors have hypothesized a ‘free radical theory of ageing’. This is where the production of free radicals increases while endogenous defence mechanisms decrease with age. It has been suggested that the antioxidant properties of orally ingested B vitamins in targeting these free radicals may explain the reverse ageing phenomenon (Trüeb RM. Oxidative stress in ageing of hair. Int J Trichol 2009; 1: 6–14). Other medications that have been reported to cause reverse ageing of the hair include thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, ciclosporin, cisplatin-based chemotherapy, interferon-α, psoralen, latanoprost, erlotinib, imatinib, tamoxifen, levodopa, clofazimine and captopril (Yale et al.). Further studies and trials into this unique phenomenon could prove extremely beneficial to a society that is significantly focused on antiageing.
BH17 A case of talquetamab-induced onychomadesis with associated palmoplantar keratoderma and desquamation
Authors: Quigley Claire , Qassabi Al Mutasim Al , Murphy Lisa , Long Amy , Timoney Irene , Barry Rory , Diong Sophie , O’Gorman Susan
Published: June 2024

Herein we present the case of a 59-year-old woman who presented to our department with shedding of nails on all 10 fingers and toes, as well as desquamation of the skin on the palms of her hands and soles of her feet. She had a background history of relapsing refractory multiple myeloma and had not responded to multiple other lines of therapy. However, she had biochemical and clinical remission of her multiple myeloma with a new monoclonal antibody agent, talquetamab. She presented to our clinic with significant nail and skin changes that occurred 2 weeks into treatment with talquetamab. She reported shedding of the nails on all 10 fingers and toes, with recurrent cycles of regrowth and shedding. She also reported increased thickened scale and peeling of the skin on the palms of her hands and soles of her feet. Examination revealed onychomadesis of all nails and toenails as well as palmoplantar keratoderma and desquamation. Talquetamab is a bispecific monoclonal antibody targeting human CD3 surface antigen, and GPRC5D tumour-associated antigen. It was approved as a conditional monotherapy for relapsing refractory multiple myeloma in August 2022. In trials, nail-related adverse events occurred in 57% of patients receiving talquetamab and skin-related adverse events occurred in 67% of recipients. To our knowledge, there has been only one other case report of onychomadesis described in relation to talquetamab therapy. It is postulated that the target protein GPRC5D is also present in nails, with talquetamab treatment leading to nail matrix arrest and subsequent nail shedding. These changes have impacted on our patient’s quality of life, including affecting her manual dexterity. Treatment with ultrapotent topical steroids has provided only modest benefit.
PD09 Delving deeper into sunburn
Authors: Christou Evangelos A A , Kerr Alastair , Lehmann Alan , Sarkany Robert , Fassihi Hiva , Ibbotson Sally H
Published: June 2024

A 25-year-old woman was referred to a tertiary photodiagnostic service following ‘severe sunburn’ after minutes of sun exposure on an overcast day. She described a prickling sensation on exposed forearms and later developed erythema, vesicles and large unilocular blisters, requiring attendance at accident and emergency and a burns unit. The episode resolved over weeks with exfoliation, but no scarring. With hindsight, she reported five other severe episodes since the age of 7 years, requiring accident and emergency visits and bandaging, so had avidly avoided the sun. She was medically well, on no medications, with no personal or family history of skin cancer. Skin examination was normal, with no skin dyspigmentation or lentigines. Monochromator phototesting showed mild delayed ultraviolet (UV)B and UVA2 sensitivity, with enhanced responses at 48 h. UVB TL-01 minimal erythemal dose, broadband UVA provocation testing, sunscreen photopatch testing, connective tissue disease screen, human leucocyte antigen typing, plasma and red cell porphyrins were normal or negative, and vitamin D levels were markedly deficient. Biopsy of an abnormal phototesting site revealed apoptotic keratinocytes, lymphocytic infiltrate and dermal oedema. Due to the severity of the ‘sunburn’ episodes, functional DNA repair studies were performed and could not rule out xeroderma pigmentosum (XP), although they excluded XP-variant. Genotyping showed homozygosity of an ERCC4 pathogenic variant [NM_005236.2(ERCC4): c.1135C>T (p.Pro379Ser)], consistent with XP complementation group F (XP-F). XP-F is a rare form of XP and is significantly underdiagnosed due to its often milder clinical manifestations. Our case is the fourth case of XP-F that is reported in the UK, and shares similar characteristics with the other three published cases (Fassihi H, Sethi M, Fawcett H et al. Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect. Proc Natl Acad Sci U S A 2016; 113: E1236–45). Notably, the identified pathogenic variant has an allele frequency of 0.3%, suggesting that around 10 individuals per million could be homozygous for this variant, equivalent to roughly 600 cases of XP-F currently in the UK. This case raises the importance of not underestimating ‘sunburn’ – attending accident and emergency with severe episodes following relatively minor sun exposure should be a red flag, requiring consideration of DNA repair diseases, even in the absence of any other features of XP. Moreover, it underscores the need to refer patients with abnormal photosensitivity to a specialist photodiagnostic service for comprehensive assessment and, where required, to the national XP service. It is likely that there is a significant number of ‘easy sunburners’, who are not currently recognized as having XP-F due to underdiagnosis, so we wish to raise awareness of this important condition.
PD14 Trends, knowledge and practice on sunscreen use in patients referred via the suspected cancer pathway: a multisite survey
Authors: McAllister Lucy , Ifan Erin , Hiranput Siwaporn , Yesudian Paul Devakar
Published: June 2024

Sunscreens are widely accepted as a safe and effective method for reducing skin cancer incidence and addressing photoageing and sun-induced pigmentary changes. Market research indicates a worldwide increase in sunscreen sales; however, real-world data on consumer understanding, selection and use of these products remain scarce. A questionnaire was distributed to patients attending clinics in five hospital sites after referral for suspected skin cancers. Data collected included demographics, occupation and previous dermatological diagnosis. Sunscreen use, sun protection factor (SPF), ultraviolet star rating, presence of a visible light filter, and frequency and anatomical areas of application were also recorded. Understanding of SPF definition was assessed using a multiple-choice question. Data were analysed using SPSS software (IBM, Armonk, NY, USA), and a χ2-test was applied to identify associations between patient characteristics and sunscreen use. In total, responses were received from 126 patients; 54 (43%) were male and 72 (57%) female. The most frequent age category was 61–70 years (n = 31, 25%) and, where data on skin type were captured, Fitzpatrick types I and II were most prevalent (n = 62, 84%). Of the responses regarding employment, 16 (29%) worked in outdoor occupations. Overall, 63 patients had no prior dermatoses (49%). Of the 126 respondents, 97 stated regular use of a sunscreen product, which was significantly associated with female sex: χ2 (1, n = 126) = 14.4, P < 0.001. No relationship was identified between age or occupation and sunscreen use. Products were applied in sunny weather (n = 76, 66%), rather than daily. SPF 50 was the most frequent factor used (n = 39, 41%). In total, 84 (87%) did not know whether their product contained a visible light filter. The scalp was a frequently missed site of application (n = 17, 16% applied to the scalp). Approximately half of responses (n = 47, 53%) reported the correct definition of SPF. Evidence suggests that those with previous cutaneous malignancy tend to be better educated on SPF properties of sunscreen than the general population. However, there are very limited data available on understanding of visible light blockage. In this survey only 13% knew whether their sunscreen contained a visible light filter, which confers major advantages in reducing hyperpigmentation and photoageing. As ultraviolet vs. visible light protection varies between products, targeted education may enable better choices. Men are statistically more likely to develop skin cancers, yet they underutilize sunscreens, frequently omitting high-risk sites for carcinogenesis, which our findings corroborate.
PD15 Ultraviolet overexposure in solar urticaria: beyond the rash
Authors: Ross Hannah , Parkin Donna , Ayer Jean
Published: June 2024

Solar urticaria is a rare photodermatosis characterized by an immediate type I hypersensitivity reaction, usually to ultraviolet (UV)A and visible light, and less commonly to ultraviolet B (UVB). Symptoms of itch and burning to exposed sites occur after seconds of sun exposure and are followed by erythema and often wealing of the skin. Patients can report associated systemic symptoms including headache, hypotension, nausea and syncope following significant exposure. We describe the rare case of a 54-year-old white British man with a diagnosis of solar urticaria who experienced vasomotor collapse following sunbed use. The patient had previously undergone monochromated light testing, which demonstrated exquisite photosensitivity to both UVB and UVA from 300 to 370 nm and severity in the visible range from 400 nm. Treatment options for solar urticaria are limited, with avoidance of sunlight, photoprotective measures and antihistamines being the mainstay of management. Omalizumab is a more recent therapy; however, access to this at present is limited to tertiary centres for this indication. Phototherapy can be considered to induce skin hardening; however, this is used only in a controlled setting with the choice of treatment dependent on the provoking wavelengths. Our patient used a commercial sunbed in a desperate effort to self-treat his solar urticaria. Shortly after use, while sitting upright in a car, he become unresponsive and displayed involuntary movements, urinary incontinence and tongue biting, resulting in assessment at a local emergency department. He went on to have an unremarkable magnetic resonance imaging scan of the brain and electroencephalogram. Later review resulted in a diagnosis of an anoxic seizure. This was felt to be caused by hypotension and reduced cerebral perfusion, secondary to sunbed use and further exacerbated by his upright seated position in the car passenger seat. The case highlights the complexity of solar urticaria and the potentially fatal consequences of significant UV and visible light exposure.
CD02 What is the relevance of epoxy resin in the baseline series?
Authors: Phillips Peter , Divekar Preshita
Published: June 2024

Epoxy resin is used widely in adhesives, aircraft construction, boatbuilding, flooring and electrical encapsulation. It has been largely an occupational sensitizer in men. There have been recent reports of nonoccupational sensitization in women, due to exposure to crafting materials (Dios-Guillán V, Matellanes-Palacios M, Bou-Boluda L et al. Non-occupational, recreational epoxy resin contact allergy: report of two cases. Contact Dermatitis 2021; 85: 257–9) and the modern trend of ‘cosplaying’ (Samaran Q, Strizzolo R, Dereure O, Raison-Peyron N. Non-occupational allergic contact dermatitis to epoxy resin in a cosplayer. Contact Dermatitis 2023; 89: 122–4). We reviewed our patch test database for the 13-year period between 2009 and 2022, to identify patients with positive reactions to 1% epoxy resin tested routinely in the British Society for Cutaneous Allergy baseline series. Most patients had also been patch tested to at least one or two extended series including epoxy series. In total, 2445 patients (1701 female, 744 male) had been tested to epoxy resin. Fifteen patients (0.6%) (mean age 59.8 years, range 23–84) had tested positive (nine male, 1.2%; six female, 0.4%). The grade of reaction was +++ in two, ++ in eight and + in five. Of the fifteen, four were also sensitized to bisphenol F, two to 1,6-hexanediol diglycidyl ether and one each to BIS-GMA, 2-phenylglycidyl ether, triethylenetetramine, 1,4-butanediol diglycidyl ether, and phenol formaldehyde resin. Ten had dermatitis of the hands and/or forearms; four had involvement of the head and neck. The mean duration of dermatitis was 42 months (range 2–180). Eight had a history of atopy. Nine patients had known current or previous exposure to epoxy resins, four of whom had ongoing relevant exposure. Seven had occupational exposure (five male, two female). Two worked in boatbuilding or repair (wooden boatbuilder and boat painter), two in construction (decking builder and engineer) and two in art, and one was a lighthouse keeper and airport ground worker. An eighth patient had possible occupational exposure in gardening and a ninth had reacted to dental restorations. Both of the occupationally sensitized women had been exposed as artists working with epoxy resins. Relevance was unknown in six. The predominance of men in this audit is in accordance with previous publications. We found no patient of either sex sensitized through use of crafting kits. We could see no trend towards a reduction in the prevalence of sensitization to epoxy resin during this time period, nor a change in clinical relevance. The sensitization rate of 0.6% in unselected patients (1.2% male, 0.4% female) suggests that epoxy resin remains a relevant allergen, and we recommend that it remain in the baseline patch test series.
CD12 A case of occupational acrylate allergy: a success story!
Authors: Khan Yasmin , Latheef Faheem
Published: June 2024

A 35-year-old nail and beauty technician presented with severe hand and finger dermatitis. She had a 5-year history of eczema on her neck and trunk, which had improved with avoidance of balsam of Peru, to which she had previously tested positive on patch testing. Unfortunately, the patient began experiencing debilitating hand symptoms 2 years ago, escalating into painful, cracked, excoriated and fissured hands. Further patch testing revealed positive reactions to acrylates, specifically 2-hydroxyethyl methacrylate, ethylene glycol dimethacrylate, 2-hydroxyethyl acrylate, and triethylene glycol diacrylate – common components in acrylic, gel and shellac nail products used daily in her profession. Advised on strict allergen avoidance, the patient hesitated, citing practicality concerns given her lack of alternative income sources and qualifications. Reluctant to undergo a period of avoidance, she grappled with accepting her occupation as a likely source of her hand dermatitis and was keen to explore alternative options. Occupational acrylate allergy poses challenges for nail technicians, with symptoms often proving difficult to control once sensitized. Rapid acrylate penetration through most glove types complicates protective measures. Nitrile gloves offer marginally longer protection compared with latex, while laminate 4H gloves provide superior defence but limit manual dexterity. A study exploring an in vivo model for glove efficacy used open chambers filled with the acrylate gels, which were applied to the back with tape, and gloves attached as a membrane between the gel and the skin [Ursberg AM, Bergendorff O, Thorsson AC, Isaksson M. Is there a good in vivo method to show whether gloves are sufficiently protective when a nail technician is exposed to (meth)acrylates? An in vivo pilot study. Contact Dermatitis 2016; 75: 62–5]. The glove materials were then tested at four exposure times. This study showed promise in ascertaining which gloves offered appropriate protection for an individual, but is limited in practicality due to its prolonged duration. Applying the results from the study to clinical practice, the patient was first treated with oral steroids to clear her hands, and was then recommended to double glove during procedures. She was advised to ensure that she spent no more than 20 min with each client, in order to reduce penetration time of the acrylate through the gloves. This, along with frequent handwashing in between clients and regular workspace cleaning, has allowed her to successfully continue her career for the last 3 years. This case underscores the importance of finding collaborative solutions with patients, even if not medically ideal, and offering practical approaches for individuals facing challenging allergens to avoid. This case also highlights the usefulness of applying basic science research to clinical practice for the benefit of patients.
DS05 Overtreatment of skin cancer: how can we ensure those treated for basal cell carcinoma receive more benefit than harm?
Authors: Venables Zoe C , van Bodegraven Birgitta , Powell James B
Published: June 2024

For over a decade, international reports have highlighted how thousands of patients treated for basal cell carcinoma (BCC) die within a few years of a diagnosis, which questions how much benefit surgical treatment had. The current British Association of Dermatologists guidelines for basal cell carcinoma (BCC) have limited discussions on conservative, active surveillance, or no-treatment options. BCCs are often slow growing and minimally symptomatic, and therefore treatments such as curettage, cryotherapy, radiotherapy or topical therapy may be more appropriate in patients with limited life expectancy. Although associated with higher risk of recurrences, these treatments can be performed closer to home and may have lower associated morbidity than a complex excision. This abstract reports the incidence and survival following a first BCC diagnosis in England from the National Disease Registration Service Get Data Out (GDO) website, stratified by age. Survival is reported for first-ever tumours only, so subsequent tumours are excluded. For those aged ≥ 80 years, GDO reporting is separated by site; we chose facial BCC to represent survival outcomes in this age group. From 2013 to 2015 in England there were 271 473 first BCCs, of which 68 869 (25.4%) occurred in those aged ≥ 80 years. Kaplan–Meier overall survival rates at 3 and 5 years for patients of all ages following a first BCC were 90.3% [95% confidence interval (CI) 90.2–90.4] and 83.1% (95% CI 82.9–83.2), respectively. For those aged ≥ 80 years with a facial BCC, Kaplan–Meier overall survival rates at 3 and 5 years survival fell to 73.9% (95% CI 73.4–74.4) and 56.2% (95% CI 55.7–56.8), respectively, with similar findings at other sites. Net survival was consistently around 100% for various sites and age groups for first BCC; for example, in those aged 70–79 years with a facial BCC, 5-year net survival is 100.5% (95% CI 100.1–101). Net survival uses published life tables to compare survival of a person with a BCC to a person without a BCC accounting for variables including age, sex, deprivation and geography. The 5-year net survival for BCC was consistently around 100%. This implies that BCCs do not affect survival, and therefore, when considering BCC treatment, we must consider primarily the morbidity of no treatment vs. treatments. Overall survival analysis identified that 26.1% of patients aged ≥ 80 years with facial BCC die within 3 years and 43.8% die within 5 years of diagnosis. Better understanding this cohort of patients with limited life expectancy, who are less likely to benefit from treatment, is critical to patient care. Age alone is an incomplete predictor of limited life expectancy, but validated frailty scoring tools can assist in identifying patients who would benefit from a more informed conversation about the risks and benefits of treatment.
DS08 (P054) National incidence and survival of extramammary Paget disease 2013–2020 in England: reporting a total of 740 cases
Authors: Karkara Shweta , Khan Farishta , van Bodegraven Birgitta , Venables Zoe C
Published: June 2024

Extramammary Paget disease (EMPD) is a rare disease affecting the rich apocrine gland-bearing areas commonly involving the genital and perianal skin. It was first described in 1889 by Radcliffe Crocker. Clinical features of EMPD are insidious and nonspecific, frequently resulting in delayed diagnosis. Diagnosis of EMPD is important due to its association with an underlying malignancy, most commonly urothelial or anorectal, but it may also be cervical, prostatic, ovarian or endometrial in 10–30% cases. Until recently, there were limited national epidemiological data on incidence and survival. National data on EMPD incidence and 5-year survival in England from 2013 to 2020 were extracted from report-level data published openly by the ‘Get Data Out’ National Disease Registration Service programme. Crude incidence rates are reported per 100 000 person-years (PY). Survival is reported as overall Kaplan–Meier survival and net survival with associated 95% confidence intervals (CIs). Data for 2020 vs. 2019 incidence rate ratios with 95% CIs were calculated using the exact Poisson method. In total, 740 new cases of EMPD were diagnosed between 2013 and 2020, with a mean of 93 cases per year. The average crude incidence rate of EMPD per year was 0.17 per 100 000 PY (95% CI 0.14–0.21). The crude incidence rate in 2013 was 0.16 per 100 000 PY (95% CI 0.13–0.20), which increased nonsignificantly in 2019 to 0.20 per 100 000 (95% CI 0.16–0.24). During 2020, the first year of the COVID-19 pandemic, incidence decreased to 0.14 per 100 000 (95% CI 0.11–0.18). The incidence rate ratio between 2020 and 2019 was 0.73 (95% CI 0.54–0.98), with a P-value of 0.03. The 5-year overall Kaplan–Meier survival was 74.1% (95% CI 63.4–82.1) for EMPD diagnosed in 2013. Important limitations include lack of published data on site, age group, depth of invasion and associated comorbidities including malignancies due to small numbers. The reported net survival for EMPD is comparable with that for melanoma and prostate and breast cancer, presumably a result of its association with other underlying malignancies. The increase in crude incidence rates likely represents the ageing population, and one might expect age-standardized rates to be relatively static. The apparent decrease in the crude incidence rate of EMPD during 2020 demonstrates the impact of the pandemic on skin cancer services, as also shown for melanoma and other cancers. A study in The Netherlands assessed 178 cases of invasive and 48 cases of in situ EMPD and found an overall relative 5-year survival of 72% for invasive tumours and an incidence rate of 0.11 per 100 000 PY for EMPD. These data are important in better understanding the trends and outcomes of this rare and poorly understood tumour.
DS19 Assessing the attitudes to biobanking of patients attending a pigmented lesion clinic and healthcare staff employed in an academic hospital: a quantitative study
Authors: Bowe Stephanie , Quigley Claire , Victory Liana , Yoo Li Jie Helena , Storan Eoin
Published: June 2024

A biobank is a collection of biospecimens or biological samples and corresponding patient data points, which are used for the purposes of medical research. Patient participation and support are imperative to biobank research. We aimed to quantitatively assess the attitudes to biobanking of Irish patients attending a pigmented lesion clinic in an Irish dermatology centre and staff working at an academic teaching hospital. A questionnaire was distributed to healthcare staff working in an academic hospital and members of the Irish Association of Dermatologists via their hospital email address. Patients who attended the pigmented lesion clinic between January and April 2023, and patients who had previously been diagnosed with melanoma between January 2019 and January 2021 were asked to complete the questionnaire. Respondents from a market research company, Bounce Insights, were sent a modified questionnaire via a survey platform. A research grant was obtained from Amgen to incorporate the Bounce Insights market research group. In total there were 426 respondents, with the following ages: < 18 years (31, 7%), 18–35 years (105, 25%), 36–65 years (191, 45%) and > 65 years (99, 23%). There were 166 (39%) male and 260 (61%) female patients. Of the 426 total respondents there were 180 (42%) previous healthcare workers. The number of total participants who were aware of biobanks was 130 (31%), with 283 (66%) replying ‘no’ and 13 (3%) ‘not sure’. Around 20% of participants (84) had donated a biospecimen previously. Healthcare workers reported a positive response in 84% of cases (102), but only 46% (72) of the Bounce marketing respondents felt similarly (P ≤ 0.001). Over 60% of healthcare staff, 16% of all patients and 21% of the Bounce marketing group were aware of biobanks. In total, 83% (352) of all respondents were willing to donate a biospecimen following a medical procedure, but 78% (331) were willing to donate an additional blood sample. That number fell to 57% (242) when respondents were asked if they would donate an additional tissue sample purely for the purposes of research. The number who would encourage a family member to donate a biospecimen was 241 (56.6%, ‘yes’), with 41 (9.6%) replying ‘no’ and 144 (33.8%) ‘not sure’. Interestingly, age was related to individuals’ initial impression of biobanks [χ2 (6, n = 426) = 32, P ≤ 0.001], to a willingness to donate a biospecimen (P = 0.04) and to a desire to be informed if their specimen was disposed of (P ≤ 0.001). In conclusion, in Ireland, the majority of patients, healthcare workers and other members of the public are willing to donate biospecimens for the purposes of research.
DP02 Expression of AMBRA1 and loricrin in the epidermis overlying benign cutaneous naevi, including blue and dysplastic naevi, is similar to that seen in normal skin, but expression may rarely be altered in melanoma in situ
Authors: Husain Akhtar , Lovat Penny , Richardson Grant , Ness Thomas , Jones Claire , Graham Catherine , Labus Marie , Sloan Philip
Published: June 2024

The epidermal expression of AMBRA1 and loricrin overlying primary melanomas has recently been validated as a prognostic biomarker able to identify genuinely low risk nonulcerated American Joint Committee on Cancer stage I/II tumours. We have previously shown that the loss of these biomarkers is due to secretion of transforming growth factor-β2 by the underlying tumour cells, and hypothesize that this mechanism is used by melanomas at risk of metastasis to facilitate premalignant dissemination. The aim of the present study was to evaluate the potential for the combined expression of AMBRA1 and loricrin to characterize a range of melanocytic naevi and melanoma in situ as benign or malignant. Formalin-fixed paraffin-embedded tissue sections were obtained derived from a representative selection of benign naevi and melanoma in situ from the cellular pathology archive of Newcastle upon Tyne Hospitals NHS Foundation Trust. These comprised 5 intradermal naevus, 16 dysplastic naevus (severe/moderate), 5 junctional naevus, 5 compound naevus, 6 common blue naevus, 5 cellular blue naevus, 2 combined naevus, 1 melanocytoma and 26 melanoma in situ. All sections were subjected to automated immunohistochemical analysis for AMBRA1 and loricrin expression. Staining patterns and expression were evaluated using consensus scoring by the study cellular pathologists (A.H., P.S.). All of the benign and dysplastic melanocytic naevi examined showed maintenance of both AMBRA1 and loricrin in the epidermis overlying the lesion, in line with their expression in normal skin. A maintained pattern was also seen in 24 of 26 cases of melanoma in situ, but two cases displayed focal losses of both AMBRA1 and loricrin. On review, both cases showed no evidence of melanoma in further levels and there was no clinical progression. The maintained pattern of AMBRA1 and loricrin was expected in the melanocytic naevi and is consistent with their benign nature. However, loss of expression of AMBRA1 and loricrin in two cases of melanoma in situ was unexpected, suggesting that some cases of melanoma in situ may contain melanocytes with malignant potential. Collectively these data warrant the further investigation of AMBRA1 and loricrin expression in a larger cohort to investigate their potential as biomarkers to distinguish between benign melanocytic lesions and those at risk of malignant progression. This study is funded by the Innovate UK Combined Investor Partnerships Award Round 11 (reference 10083008-1586) awarded to AMLo Biosciences.
DP03 Melanoma detection in whole-slide images using a convolutional neural network for objective prognostic biomarker generation
Authors: Clarke Emily L , Magee Derek , Newton-Bishop Julia , Merchant William , Hall Marlous , Insall Robert , Maher Nigel G , Scolyer Richard A , Farnworth Grace , Ali Anisah , Saldanha Gerald , Bamford Mark , Sitcova Eva , Kujal Petr , O’Shea Sally , Treanor Darren
Published: June 2024

The current melanoma staging system is predictive of 74% of the variance in survival, with prognostic biomarkers subject to high levels of interobserver and intraobserver variation. Melanoma morphology appears to be of greater significance than in other solid tumours, with Breslow thickness remaining the strongest prognostic indicator. The application of convolutional neural networks (CNNs) to whole-slide images (WSIs) may reveal new insights into tumour morphology and therefore patient prognosis. This work outlines the development and evaluation of a CNN for invasive cutaneous melanoma detection in WSIs, to enable the creation of objective prognostic biomarkers based on the tissue morphology. In total, 1157 WSIs containing cutaneous melanoma from five sources have been used in the initial development and evaluation of a custom-designed two-class tumour segmentation network with a fully convolutional architecture. The CNN detected and located invasive melanoma tissue of no specific type with an average per-pixel sensitivity and specificity of 97.6% and 99.9%, respectively across, the five test sets (three external). There were no statistical differences between tumour dimensions generated by the CNN compared with manual annotation. Similarly, there were no statistically significant differences between CNN-generated tumour dimensions across three scanning platforms. Furthermore, we have identified that this CNN can be used to calculate the ‘digital Breslow thickness’, which is a strong independent prognostic predictor of overall survival and melanoma-specific survival, across three test sets with follow-up data (hazard ratio 1.26, 95% confidence interval 1.19–1.34, P < 0.001). We have also shown that the ‘nodularity index’ determined by the tumour shape, independently of size, is predictive of survival; the rounder the tumour the worse the outcome (hazard ratio 0.71, 95% confidence interval 0.60–0.83, P < 0.001). We have developed and performed initial evaluation of a CNN that accurately detects invasive cutaneous melanoma in WSIs, enabling an objective evaluation of tumour morphology. This CNN has afforded the development of the first objective biomarkers based on the tumour’s architectural morphology. The utility of these biomarkers will be further evaluated on WSIs from additional institutions – this work is currently underway.
DP18 The histopathological diagnosis of primary, invasive, metastatic, extramammary Paget disease
Authors: Waddell James , Gupta Rakhee , Chang ZiVo , Shaffrali Freida , Dilworth Helen
Published: June 2024

We present a diagnostic journey for an extremely rare presentation of primary, invasive, metastatic extramammary Paget disease (EMPD) arising directly from the adnexal structures of the skin. An 84-year-old male patient presented with an asymptomatic, unilateral, intertriginous rash of the left groin, of ambiguous provenance and unresponsive to conventional treatments. Following the appearance of a fleshy nodule within the rash, two biopsies were taken. Shortly thereafter the patient was admitted with confusion. Computed tomography scanning demonstrated significant metastatic disease in the liver with lucencies in the central canal of T9. It did not identify an alternative primary source. The patient unfortunately deteriorated and required palliation. Given the extreme rarity of the condition, histopathological diagnosis relied on a remarkable cascading series of immunocytochemical stains. Initial pathology demonstrated atypical epithelioid cells with abundant cytoplasm forming a 4.5-mm tumour extending from the superficial to deep dermis. Immunocytochemistry showed positivity for AE1/3, cytokeratin (CK)7 and epithelial membrane antigen, common markers of epithelial cell origin. Pagetoid spread was identified and, as staining for P40, CK5/6, melan-A and S100 were negative, excluding a squamous or melanocytic source, the lesion was felt best described as an invasive CK7+ carcinoma. The histological features, site and immunophenotype raised the possibility of a rare diagnosis of EMPD, although metastatic spread from another site had yet to be excluded. Carcinoembryonic antigen staining was positive, which would be anticipated in EMPD, although this marker of epithelial cell dysfunction is also expressed in colonic and lung adenocarcinomas. Therefore, although supportive, it was not definitive. Positive expression of gross cystic disease fluid protein-15, typically expressed in mammary ducts but also in EMPD, leant further weight to the diagnosis. Lack of expression of further site-specific markers (thyroid transcription factor-1, CDX2 and NKX3.1) made a primary from the lung, gastrointestinal tract or prostate, respectively, very unlikely. Taken with the initial negativity of P40, the most appropriate diagnosis was felt to be a primary, invasive, metastatic EMPD arising directly from the skin. EMPD accounts for < 1% of all anogenital cancers. Primary cases are rarer, and the incidence reduces further when considering cases with proven invasive and metastatic disease. A study from the Mayo Clinic in 2016 identified only 10 such cases on their registry over a 14-year period, only five of which were confirmed (Padrnos L, Karlin N, Halfdanarson TR. Mayo Clinic Cancer Center experience of metastatic extramammary Paget disease 1998–2012. Rare Tumours 2016; 8: 6804). This case is therefore a fascinating account of the histopathological process for identifying this exceptionally rare tumour.
PA09 Clinical characterization of a cohort of KRAS-associated low-flow vascular anomalies
Authors: Ramwani Miteshkumar , O’Neill Claire , Solman Lea , Barnacle Alex , Glover Mary , Polubothu Satyamaanasa
Published: June 2024

Low-flow vascular malformations with associated overgrowth are most often caused by somatic activating variants in the gene PIK3CA. Discovering the genetic basis in this cohort has transformed treatment prospects and enabled targeted medical therapy with inhibitors of the phosphoinositide 3-kinase–AKT–mammalian target of rapamycin pathway. However, a small number of patients are negative for PIK3CA mutations, and identification of such individuals is important to enable stratification for appropriate targeted medical therapies. We report here three patients with low-flow vascular anomalies secondary to somatic activating KRAS variants, highlighting key clinical features and the clinical course in this cohort. Case 1 is an 18-year-old man with a left-leg low-flow vascular malformation associated with overgrowth and notably prominent distended tortuous superficial veins and hyperpigmentation. He previously underwent epiphysiodesis and is currently being treated conservatively with a shoe raise and compression garments. Next-generation sequencing of DNA extracted directly from affected skin demonstrated a mosaic KRAS c.35G>A, p.Gly12Asp variant in 6% of reads. Case 2 is a 13-year-old girl with a capillary malformation of the left leg with overlying hyperpigmentation, and prominent distended veins associated with prominent leg length discrepancy (left longer than right). She is currently pending epiphysiodesis and reports frequent left-knee pain. Next-generation sequencing of DNA extracted directly from affected skin demonstrated a KRAS c.64C>A, p.Gln22Lys variant in 3% of reads. Case 3 is a 17-year-old girl with a capillary malformation of the left leg with associated with overgrowth, hyperpigmentation and distended superficial veins. She required epiphysiodesis to correct leg length discrepancy and reports significant pain in her left knee. She also has left-sided visual impairment and previous focal seizures. Next-generation sequencing of DNA extracted directly from affected skin demonstrated a mosaic KRAS c.35G>T, p.Gly12Val variant in 2% of reads. We describe a cohort of three patients with low-flow vascular malformations secondary to somatic variants in KRAS. Clinical features common to our three patients and potential clues to the underlying genetic diagnosis were associated hyperpigmentation, the progressive development of superficial dilated veins, and progressive overgrowth of the affected limb requiring surgical intervention. Targeted therapy in this cohort could potentially be achieved with the use of mitogen-activated protein kinase kinase inhibitors, which have been shown to be effective in the treatment of KRAS-driven arteriovenous and lymphatic malformations. This series highlights the importance of early genotyping in patients with segmental overgrowth syndromes and vascular anomalies to inform prognosis and to stratify patients for targeted medical therapies.
PA20 Follicular Becker naevus: an unusual presentation
Authors: Mackie Lucy , Herath Dimalee , Felton Jessie
Published: June 2024

A 16-year-old girl presented with an asymptomatic hyperpigmented patch on the left chest, growing with her since the age of 7 years. Her medical history was unremarkable. Examination revealed a 9 × 5-cm lesion extending from the left areola to the left shoulder and one-third of the way round the midback. Dermoscopy revealed discrete < 5-mm dark-brown perifollicular macules, with some areas coalescing towards the back. Mild hyperkeratosis was present, with no hypertrichosis. This was diagnosed as a follicular Becker naevus, which is a novel variant not previously described in the UK. Becker naevus, also known as Becker melanosis and Becker pigmentary haematoma, was first described in 1949 by Samuel William Becker. It is a relatively common benign late-onset epidermal naevus, with proliferation of the epidermis, melanocytes and hair follicles. Occasionally it forms part of an epidermal naevus syndrome, known as Becker naevus syndrome. Traditionally, pigment networks in Becker naevus are described as even, but since 2020 seven follicular cases have been described in Kuwait, India and China. Six of the seven patients were male, all had skin of colour, and they were between the ages of 16 and 37 years. None had Becker naevus syndrome. There have been recent breakthroughs in understanding of the aetiology of Becker naevus. Cai et al. demonstrated postzygotic mutations in the ACTB gene (Cai ED, Sun BK, Chiang A et al. Postzygotic mutations in beta-actin are associated with Becker’s nevus and Becker’s nevus syndrome. J Invest Dermatol 2017; 137: 1795–8). There could be heterogeneity in mutations playing a role in the development of follicular lesions. Other recent advances include in the role of hormones. It has long been known that there is androgen dependence, but Sheng et al. have shown that oestrogen and progesterone receptors are also overexpressed in lesional skin and hair follicles (Sheng P, Cheng YL, Cai CC et al. Overexpression of androgen, oestrogen and progesterone receptors in skin lesions of Becker’s naevus. Acta Derm Venereol 2018; 98: 867–72). These advances raise interesting questions for genetics, pigmentation and hair research. Lesions are benign but the appearance can lead to psychological distress, affecting confidence and choice of clothing. Our patient was referred for cosmetic camouflage. Knowledge of this unusual diagnosis is important for being able to reassure patients and treat them appropriately.