bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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 &lt; 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

Abstract
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&gt;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&gt;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&gt;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

Abstract
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 &lt; 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.
PA21 A child with longitudinal melanonychia secondary to subungual naevus showing regression during treatment with a single-agent MEK inhibitor (trametinib)
Authors: Guckian Jonathan , Picton Susan , Muinonen-Martin Andrew , Mitra Angana , Shanmugam Sangeetha 
Published: June 2024

Abstract
A 3-year-old boy with type IV skin presented in May 2021 with a 5-month history of a pigmented line in his right fourth fingernail. Examination revealed a 1-mm uniform darkly pigmented band (1.2 mm at proximal aspect) of triangular longitudinal melanonychia with positive pseudo-Hutchinson and negative Hutchinson sign. A clinical diagnosis of benign subungual naevus was made. The patient had a background of neurofibromatosis type 1 and ganglioglioma of the brainstem and right cerebellar peduncle treated with chemotherapy. First- and second-line regimens – vincristine plus carboplatin in 2019–2020, and TPCV (thioguanine, procarbazine, lomustine and vincristine) in 2020 to April 2021 – had been trialled unsuccessfully before dermatology review. In October 2021, the patient commenced trametinib 0.5 mg once daily for his progressive ganglioglioma. Within 4 months, the longitudinal melanonychia had involuted significantly. Dermoscopy demonstrated faded melanonychia with a small residual blueish linear pigmentation remaining proximally (reduced to 0.8 mm). Pseudo-Hutchinson sign was now negative. The patient’s trametinib was discontinued for around 10 days in July 2022 due to mucositis and sepsis and his melanonychia subsequently darkened and extended further distally over the following 3 months. In November 2022 his trametinib dose was decreased to 0.37 mg due to ongoing mucositis and infection. However, the dark band was not as pronounced as at the initial presentation. He remained on the reduced trametinib dose, and by January 2024 the melanonychia had faded and appeared as a 1-mm uniform pale-brown longitudinal streak. He also developed multiple new naevi on his face, trunk, buttocks and genital area during this period. Trametinib, a mitogen-activated protein kinase kinase (MEK) inhibitor, has been used in targeted therapies against various malignancies, including in combination with BRAF inhibitors against metastatic melanoma. A lesser-reported complication of targeted therapies includes ‘lightening’ of pigmented naevi. Hypopigmentation, or involution or regression has been reported in patients receiving single-agent BRAF inhibitor or combined BRAF–MEK therapy. However, ours is the first reported case of a single-agent MEK inhibitor causing regression of a subungual naevus as a side-effect. The mechanism behind naevus involution in patients receiving targeted therapy is unclear, with proposed models focusing on the impact of BRAF rather than MEK inhibition. This case highlights a stark temporal relationship between trametinib therapy and the involution and subsequent redevelopment of a benign longitudinal melanonychia. This adds to our growing understanding of the impact of targeted therapies on melanocytic naevi, which patients and doctors should be aware of.
PA31 Traction alopecia in the paediatric Sikh population
Authors: Sharma Akash , Halpern James , Cuell Alexis , Ramesh Raakhee , Hunjan Manrup 
Published: June 2024

Abstract
Sikh boys and girls, traditionally, keep their hair long and tend to tie it up in a knot over the vertex of their scalp; this is colloquially referred to as a ‘jura’. The repeated traction on the hair coupled with the weight of hair often leads to a distinct hair loss pattern that can be concerning and distressing for patients and parents alike. We describe two cases of traction alopecia in young Sikh boys, who presented to our tertiary paediatric service. The first case is 14-year-old boy who presented with reduced hair density of hair follicles and recession of the frontotemporal hairline. Similarly, the second case was a 14-year-boy, who presented with increasing hair loss over the frontal scalp. He had been tying his hair in a jura since the age of 4 years. He was also vitamin B12 deficient and on replacement treatment. With both cases the hair loss was particularly prominent over the frontotemporal scalp and was distributed in a bandlike pattern. There was sparing of the eyebrows, eyelashes and body hair. Trichoscopy findings included mild perifollicular scale without erythema, single follicular hair units and perifollicular inflammation. In both patients the initial diagnosis was traction alopecia with coexisting seborrhoeic dermatitis. Histology from scalp biopsies demonstrated intrafollicular coverage and follicular distortion with absence of inflammatory infiltrate. This was in keeping with the clinical impression of traction alopecia. Hair loss can have a profound impact on quality of life in both the paediatric and adult populations. In those with traction alopecia, early intervention is paramount in order to prevent progression and aid recovery of hair. Thus, we advised our patients to avoid putting their hair up in a tight jura for long periods of time, whenever feasible, as well as advising that hair be left open or loosely tied in a bun or ponytail. For topical treatment, minoxidil 2% or 5% foam can be tried to see whether it will help regrowth; however, this is within the remits of tolerability. Any coexisting diagnoses, such as seborrhoeic dermatitis, should be treated, and if there are doubts with regards to diagnosis, or features of a scarring alopecia, then it would be prudent to do a biopsy. These cases highlight a pattern of reversible hair loss seen in the Sikh paediatric population. It is important for dermatologists to recognize this, in order for early intervention and education on a potentially reversible condition.
BI10 Nonmelanoma skin cancers and immunosuppression: identifying keratinous red flags
Authors: Tuckwell William , Omenyo Ruth , Malladi Nitya , Patel Girish 
Published: June 2024

Abstract
Immunosuppression increases the risk of keratinocyte carcinomas, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), notably among organ transplant recipients on immunosuppressant therapies (Lanz J, Bouwes Bavinck JN, Westhuis M et al. Aggressive squamous cell carcinoma in organ transplant recipients. JAMA Dermatol 2019; 155: 66–71). Whether actinic keratoses (AKs), as treatable precursors for keratinocyte carcinoma, are more frequently associated with SCC and BCC in patients who are immunosuppressed remains to be determined. Our null hypothesis was that the AK frequency and grading should be similar between immunocompetent and immunosuppressed individuals with SCC and BCC. All keratinocyte carcinoma excisions for 2021 were retrospectively reviewed. Immunosuppressed individuals were identified from electronic records using the terms ‘immunosuppression’, ‘transplant’, ‘lymphoma’ and ‘chemotherapy’ and a review of current medication. Patient photographs were used to identify, enumerate and grade (Olsen grading) AKs in the surrounding anatomical region. A two-tailed χ2-test of independence was used to test the null hypothesis. A total of 827 keratinocyte carcinomas were excised in this centre, for which medical photography before excision was available for 728 keratinocyte carcinomas. Of the 286 patients with SCC and 432 patients with BCC, AKs were present in the anatomical region in 226 patients with SCC (79.0%) and 260 patients with BCC (60.2%). The head and neck was the most common site of keratinocyte carcinoma [202 patients with SCC (70.6%); 240 patients with BCC (55.6%)]. A total of 93 individuals (13%) were defined as immunosuppressed [61 patients with SCC (21%); 32 patients with BCC (7%)]. The frequency of AKs surrounding SCC was 1.11-fold greater in immunosuppressed (44 of 51, 86%) vs. immunocompetent (182 of 235, 77.4%) patients, but did not reach statistical significance. Olsen grade 3 AKs were more prevalent in immunosuppressed individuals with SCC (P &lt; 0.05). Among patients with BCC, 85% (n = 23) of immunosuppressed and 59% (n = 237) of immunocompetent patients had AKs within the anatomical region (P &lt; 0.01). Keratinocyte carcinomas in immunosuppressed individuals often have AKs within the surrounding anatomical region, which are often hyperkeratotic. Therefore, strategies for treating field cancerization in immunosuppressed individuals should also address the presence of hyperkeratotic AKs.
BI39 Oncological therapies and hair disorders: a narrative approach on permanent chemotherapy-induced alopecia. A literature review of cancer-related therapies and their associated hair and scalp disorders
Authors: Goncalves Rui , O’Donoghue Nuala , Harries Matthew , Asfour Leila 
Published: June 2024

Abstract
Alopecia is known to be one of the most psychologically distressing side-effects of chemotherapy. Patients view it as a constant reminder of the illness and it is frequently associated with distorted self-perception and social isolation. Studies suggest that 8% of women would decline chemotherapy because of their concerns regarding hair loss (Freites-Martinez A, Shapiro J, van den Hurk C et al. Hair disorders in cancer survivors. J Am Acad Dermatol 2019; 80: 1199–213). Permanent chemotherapy-induced alopecia (pCIA), with an incidence of 15–30% in patients with breast cancer, is a nonscarring, diffuse alopecia often resembling androgenetic alopecia. This patient-led narrative focuses on the experiences of two women with chemotherapy-induced alopecia regarding information and advice received pretreatment, the impact on self-esteem and suggestions for improving support for patients in similar circumstances. We present these patients to highlight this increasingly recognized phenomenon. We report patients’ perspective on pCIA in a 31-year-old who was treated with chemotherapy at the age of 15 years for aplastic anaemia and a 60-year-old who received chemotherapy for breast cancer. Both patients stated they were not informed of the impact and duration of alopecia, which they felt was presented as a ‘simply cosmetic side-effect’ that ‘would grow back’. This led to them thinking it would be a temporary consequence, easily amendable with ‘being fitted for a wig (to use) for a short period’. When they experienced alopecia, the impact was severe and disabling: ‘I felt like being hit by a train when I realized this was permanent’; ‘had a nervous breakdown’. Additionally, commonly used measures to overcome this side-effect were not seen as helpful: ‘Initially I struggled to wear wigs as I felt they were uncomfortable and did not look natural.’ Alopecia affected their sense of femininity and limited their activities because of the anxiety caused by wearing a wig or hat in social contexts. In addition to contributing to increased levels of social anxiety, the effects on self-esteem were profound: ‘I often do not feel “womanly” or feminine due to the hair loss. I feel it makes me look old, ill and witch-like. Whilst wigless, I view myself as disgusting.’ Both patients have been keen to trial pharmacotherapies to help address their hair loss. There is an increased awareness in mainstream and social media in relation to cancer-related therapies affecting hair growth permanently. With growing numbers of people surviving cancer, increasing emphasis is appropriately now placed on post-treatment quality of life. Our presentation aims to highlight the different hair and scalp disorders associated with chemotherapy-, radiotherapy- and immunotherapy-related treatments to support dermatologists in managing these patients and advising oncology teams.
BI40 A common conclusion to an uncommon case
Authors: Liu Bo , Khan Farishta , Lee Ava 
Published: June 2024

Abstract
Dermatophytes are a prevalent cause of superficial skin infections, affecting approximately 20–25% of the global population. Mortality as a result of dermatophytes is low; however, rising cases of recurrent and recalcitrant dermatophytoses owing to emerging antifungal resistance pose a significant health challenge. Early diagnosis and adequate treatment can significantly reduce morbidity and improve patients’ quality of life. We present the case of a 57-year-old woman with a background of precursor B-cell acute lympho­blastic leukaemia diagnosed in 2019. Her disease was stabilized on ponatinib over the last 1.5 years following failed treatment with conventional chemotherapy, allogeneic bone marrow and T-cell transplants and multiple tyrosine kinase inhibitors. She was referred by the haematology team, with a 3-week history of a symmetrically distributed erythematous annular rash that was well demarcated and scaly on her face, trunk and limbs, with large islands of sparing on her trunk. The rash had a burning and itchy quality. Prior to referral, she had 8 days of oral prednisolone 20 mg once daily for what was initially suspected to be graft-versus-host disease and her skin improved slightly with less inflammation. The differential diagnosis list remained broad. She was initiated on Dermovate ointment. Biochemistry and immunology lab investigations were unremarkable. Mycology cultures of skin scrapings were negative; however, a skin punch biopsy taken from a fresh erythematous edge showed histological features in keeping with a dermatophyte infection. She achieved full clearance of her rash following a 6-week course of oral terbinafine and fluconazole at intervals. This case demonstrates the atypical presentation of a common skin infection in an immunocompromised host that can mimic many dermatological conditions. This is particularly important when the addition of steroid treatment could alter a common presentation even further. This case reminds us that common causes can still be common, including in atypical presentations, where treatment outcomes can be satisfying and rewarding when combined with good clinical history taking. Importantly, to combat rising resistant dermatophyte infections, it is now even more prudent to not miss this common diagnosis.