tbuckley/cabot-search huggingface dataset:
BG02 A rare case of necrolytic migratory erythema
Authors: Arnav Katira, Sophie Gaikwad
Journal: British Journal of Dermatology (2024)

Abstract We present the case of a 72-year-old White man who had a several months’ history of multiple crusted annular plaques starting in the groin and spreading to the lower limbs and upper back. He also had an erythematous scaly rash on the face in a seborrhoeic distribution and a sore tongue. Systemic enquiry highlighted significant weight loss. Additionally, he had a recent diagnosis of borderline diabetes mellitus and later developed steatorrhoea. He also had a palpable mass behind his umbilicus. Laboratory studies showed a mild normocytic anaemia. Plasma glucagon levels were markedly raised at 230 pmol L−1. Levels of zinc, other trace metals and haematinics were normal. Computed tomography imaging identified a lesion to the body and tail of the pancreas, which was locally invasive and partly calcified. Histology from the rash showed confluent parakeratosis containing few neutrophils. The epidermis was mildly acanthotic with mild spongiosis and dyskeratotic cells and some vacuolated keratinocytes. There was mild lymphocytic exocytosis, but no significant lichenoid reaction. There were moderate perivascular lymphoplasmacytic infiltrates with mild oedema in the epidermis. No immune deposits were seen on direct immunofluorescence. He was referred to the general surgeons and the neuroendocrine multidisciplinary team (MDT). A well-differentiated neuroendocrine tumour, in keeping with a glucagonoma, was seen on histology of the tail of the pancreas. He was treated with zinc supplements and topical steroids, as well as having staging scans and further management of his glucagonoma. Necrolytic migratory erythema is a rare clinical entity usually occurring with a glucagonoma, an alpha-cell tumour of the pancreatic islets. The elevated glucagon levels may lead to diabetes mellitus, weight loss, diarrhoea, neuropsychiatric problems, venous thromboembolism and anaemia. The rash normally improves with management of the underlying tumour. This may include surgical management or suppression of raised glucagon levels by a glucagon antagonist. Patients should be referred to a specialist neuroendocrine MDT and have staging scans. Zinc supplementation may also improve the rash. Early diagnosis of the rash may help to prevent morbidity and mortality from the underlying neoplasia and reduce the chance of metastasis.
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: Stephanie Bowe, Claire Quigley, Liana Victory, Li Jie Helena Yoo, Eoin Storan
Journal: British Journal of Dermatology (2024)

Abstract 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: &amp;lt; 18 years (31, 7%), 18–35 years (105, 25%), 36–65 years (191, 45%) and &amp;gt; 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.
DP17 Alveolar soft part sarcoma: a not-so-common entity
Authors: Chia-Lun Li, Chen-Yi Wu
Journal: British Journal of Dermatology (2024)

Abstract A 24-year-old man presented with an asymptomatic mass on his left thigh that had been present for 1 month. On examination, a well-defined subcutaneous nodule measuring approximately 2.1 × 2.1 cm was observed on his left thigh, with no apparent epidermal change. Magnetic resonance image showed a hyperintense lesion over the left thigh with contrast enhancement. An incisional biopsy revealed nests of eosinophilic cells displaying nuclear pleomorphism, prominent nucleoli, and positive transcription factor enhancer (TFE)3 expression. A diagnosis of alveolar soft part sarcoma (ASPS) was made. ASPS, a rare sarcoma primarily occurring in young patients, typically affects deep soft tissues of the buttock and thigh. While it shows a relatively indolent clinical progression, ASPS often indicates a poor prognosis due to late-stage metastases upon diagnosis. Microscopically, ASPS is characterized by uniform nests of polygonal tumour cells within fibrovascular septa and vascular channels, displaying distinctive cellular dyscohesion, resulting in the characteristic ‘pseudoalveolar pattern’. The cells have defined borders, abundant eosinophilic to granular cytoplasm, and an epithelioid appearance. ASPS is caused by a specific unbalanced translocation, der(17)t(X:17)(p11;p25), forming an ASPSCR1–TFE3 fusion gene. In this patient, further imaging was arranged for tumour staging, which confirmed localized disease without lymph node or distant metastasis. The patient underwent wide excision and local flap surgery and has remained recurrence free during a 4-year follow-up. This case emphasizes the importance of recognizing the clinical features of ASPS in young patients and considering skin biopsy and image studies for long-standing subcutaneous nodules, as this can provide an early diagnosis and improve patient outcomes.
DP13 First case of distant metastases from a BAP1-inactivated melanocytoma with melanoma transformation
Authors: Jonathan Guckian, Bipin Mathew, Will Merchant, Andrew Muinonen-Martin, Angana Mitra, Hayley Smith
Journal: British Journal of Dermatology (2024)

Abstract A 43-year-old man presented with a long-standing back lesion causing irritation and bleeding. A presumed pedunculated seborrhoeic keratosis was shave excised by his general practitioner; however, histology revealed a BRCA1-associated protein (BAP1)-inactivated melanocytoma (BIM) with melanoma transformation. Histologically, BIMs are identified by the presence of a dermally located expansile clone of epithelioid melanocytes, sometimes associated with a pre-existent conventional naevus. Clones have abundant amphophilic cytoplasm and nuclear polymorphism with distinct cell membranes. BAP1 immunohistochemistry showing loss of nuclear expression in altered melanocytes confirms the diagnosis. BIMs typically harbour a BRAF V600E mutation as the initial oncogenic driver, with subsequent biallelic loss of the BAP1 gene leading to BAP1 protein inactivation. They typically run a benign, indolent course, with no cases with distant metastasis previously reported. Our case had BAP1-inactivated clones with typical BIM morphology. However, there was also a dominant, aggressive, BAP1-inactivated subclone with 15 mitoses, Ki67 &amp;gt; 10%, ulceration, P16 loss and PRAME positivity. These features are unusual for BIMs and are considered high risk in conventional melanoma subtypes. Overlying this was a junctional component with focal architectural and cytological atypia, bordering on melanoma in situ. Next-generation sequencing showed an NRAS driver mutation. DNA methylation profiling showed more than three copy number variations: 8q12.1q24.3, 90.2-Mb gain; whole chromosome 9 loss; 9p21.3, 3-Mb biallelic loss including CDKN2A and CDKN2B (whole genes); and 11q22.3q25, 31.7-Mb loss. There was no significant family history, and germline BAP1 genetic testing was negative. The patient underwent narrow margin excision followed by wide local excision. Sentinel lymph node biopsy was not offered due to previous pulmonary emboli and obesity. After 11 months he reported persistent abdominal pain. Computed tomography showed widespread metastatic disease (right axillary lymph nodes, brain and liver). Lymph node biopsy revealed atypical naevoid to epithelioid cells with focal cytoplasmic pigmentation and mitotic activity lying within fibrous stroma. Immunohistochemistry demonstrated strong diffuse expression of SOX-10 and melan-A, with loss of BAP1 expression. We report the first case of BIM with melanoma transformation (malignant BAP1 inactivated tumour) resulting in stage IV melanoma. Our centre has identified four further lesions in three patients with similar histological presentation. Two patients with three lesions developed locoregional recurrence. Our cases demonstrate that not all BIMs run a benign to indolent course. Identifying high-risk features as seen in these cases will aid future risk stratification.
DP22 An unusual presentation of acquired perforating dermatosis
Authors: Lisa Murphy, Caitriona Hackett
Journal: British Journal of Dermatology (2024)

Abstract Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) is a rare condition that can affect people of all ages and ethnicities. We present the case of a patient who presented with a rash consistent with vasculitis on his fingers and nose, and a number of keratotic papular lesions on his elbows. These lesions were pruritic and were clinically consistent with perforating dermatosis. Biopsy of a lesion on his left elbow showed skin with central dome-shaped epidermal ulceration in the epidermis with abundant cellular debris and collagen fibres. The features were in keeping with a perforating dermatosis. Initially, he was commenced on methylprednisolone, before being switched to rituximab infusions. His rash resolved, and he developed no further new lesions. Perforating dermatoses are characterized by the transepithelial elimination of dermal connective tissue through the epidermis. The acquired form is more common and typically presents in patients with diabetes mellitus and chronic renal disease. The lesions usually present as umbilicated, keratotic papules on the extremities. The histology of acquired perforating dermatoses typically demonstrates epidermal invagination with a keratotic plug consisting of collagen, keratin or elastic fibres. Perforating dermatosis in patients with granulomatosis with polyangiitis is very rare. Treatment for acquired perforating dermatosis is primarily centred on treating the underlying disease. Options include antihistamines, topical corticosteroids and keratolytic agents such as salicylic acid.
DP18 The histopathological diagnosis of primary, invasive, metastatic, extramammary Paget disease
Authors: James Waddell, Rakhee Gupta, ZiVo Chang, Freida Shaffrali, Helen Dilworth
Journal: British Journal of Dermatology (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 &amp;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.
DP12 Comparison of clinical, dermoscopic and histopathological characteristics of salt and pepper pigmentation in systemic sclerosis and vitiligo: a prospective controlled study
Authors: Parvathy Viswan, Biswanath Behera
Journal: British Journal of Dermatology (2024)

Abstract Systemic sclerosis (SS)-associated salt and pepper pigmentation (SAPP) and vitiligo are rather indistinguishable. This study aimed to compare the clinical, dermoscopic and histopathological characteristics of SAPP in SS with vitiligo. Twenty-one patients with SS-associated SAPP, and 43 patients with vitiligo attending the outpatient department were recruited. The clinical, dermoscopic and histopathological characteristics of the depigmented lesions were analysed for a predefined set of parameters by two dermatologists. Sites prone to friction, like the extensor aspect of the arms (P &amp;lt; 0.05), the flexor aspect of the thigh (P &amp;lt; 0.05) and the inguinal folds (P &amp;lt; 0.05), were more commonly involved in SAPP. Depigmentation or hypopigmentation of the palms and soles (P &amp;lt; 0.05) were invariably absent in SS. Clinically, perifollicular depigmentation (P = 0.02), confetti lesions (P ≤ 0.01), trichrome sign (P ≤ 0.01) and leucotrichia (P = 0.02) were seen in vitiligo, while perifollicular hyperpigmentation (P &amp;lt; 0.01) was seen in SAPP. Among dermoscopic features, trichrome sign (P &amp;lt; 0.01), dermoscopic leucotrichia (P = 0.02), perifollicular depigmentation (P = 0.02), lesional and perilesional pigment network (P &amp;lt; 0.01) and satellite white clod (P &amp;lt; 0.01) were characteristically present in vitiligo, whereas perifollicular hyperpigmentation over a background of depigmentation (P &amp;lt; 0.01), white network (P &amp;lt; 0.01), hypo- or depigmented structureless area with angulated border (P &amp;lt; 0.01), alternating hyper- and depigmentation longitudinally (P &amp;lt; 0.01), blue–grey dots (P &amp;lt; 0.01) and telangiectasia (P &amp;lt; 0.01) were more common in SAPP. The histopathological features of depigmented areas of SAPP and vitiligo showed the following significant differences: more epidermal lymphocytes (P &amp;lt; 0.05) and more dermal fibroblasts were seen in vitiligo (P &amp;lt; 0.01), while dermal sclerosis (P &amp;lt; 0.01) and periadnexal infiltrate (P &amp;lt; 0.01) were more common in SS. Histopathological features suggestive of dermal sclerosis such as pandermal sclerosis (P &amp;lt; 0.01), line sign (P &amp;lt; 0.01), square biopsy sign (P &amp;lt; 0.01), cookie cutter sign (P &amp;lt; 0.01), lone arrector pili sign (P &amp;lt; 0.01) and high eccrine gland sign (P &amp;lt; 0.01) were seen exclusively in SS. When in doubt, careful clinical, dermoscopic and histopathological examination of the depigmented lesions in SS and vitiligo will help in diagnosis. This study is limited by the small sample size, and only patients with Fitzpatrick skin types IV and V were studied.
CPC09 Two cases of late-onset dystrophic epidermolysis bullosa <i>COL7A1</i> mutations
Authors: Lisa O’Higgins, Jason Hynes, Cristina Grechin, Andrew Hudson, Muireann Roche, Marina O’Kane
Journal: British Journal of Dermatology (2024)

Abstract Epidermolysis bullosa pruriginosa (EBP) is a highly distinctive phenotype of dystrophic EB (DEB). It is characterized by pruritic hypertrophic papules, nodules and plaques usually on the lower extremities. Clinical findings are caused by mutations in the COL7A1 gene on chromosome 3p21.3, which encodes type VII collagen. It is a rare condition that was first described in the literature in 1994 in a series of eight cases (McGrath JA, Schofield OM, Eady RA. Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features. Br J Dermatol 1994; 130: 617–25). The condition usually presents in the neonatal period, during adolescence or early adulthood. There are &amp;lt; 100 documented cases to date (Kim WB, Alavi A, Pope E, Walsh S. Epidermolysis bullosa pruriginosa: case series and review of the literature. Int J Low Extrem Wounds 2015; 14: 196–9). Here, we present two cases of late-onset EBP. Case 1 is a 72-year-old woman with a 20-year history of a recalcitrant, pruritic violaceous eruption on her lower legs. Findings on biopsy were nonspecific, showing hyperkeratosis, mild epidermal spongiosis with a subepidermal split devoid of inflammatory cells. There was vascular proliferation in the superficial dermis and surrounding perivascular inflammation with an inflammatory infiltrate comprising lymphocytes, histiocytes and plasma cells. Differential diagnosis included venous stasis or DEB. Genetic sequencing was performed, revealing heterozygosity for a COL7A1 c.6007Gly&amp;gt;Arg mutation, confirming a diagnosis of autosomal dominant EBP. Case 2 is a 60-year-old woman who presented with pruritic coalescing nodules and papules. These had appeared initially on the buttocks and occipital scalp and subsequently developed on her wrists, elbows and lower legs. Hyperkeratotic toenails and a pincer nail on her left thumb were noted. A biopsy taken from her right thigh showed hyperkeratosis with acanthosis, and sub­epidermal cleavage containing mixed inflammatory cells. Genetic sequencing confirmed the heterozygous mutation IVS107–2delA in the COL7A1 gene, consistent with a variant of dystrophic EB highly suggestive of EBP. Both patients’ symptoms responded to dapsone. To our knowledge these mutations have not been reported elsewhere in the context of EBP. We highlight the potential for late onset of this rare condition, novel genetic mutations, and the role of genetic testing in situations of clinical uncertainty.
DP03 Melanoma detection in whole-slide images using a convolutional neural network for objective prognostic biomarker generation
Authors: Emily L Clarke, Derek Magee, Julia Newton-Bishop, William Merchant, Marlous Hall, Robert Insall, Nigel G Maher, Richard A Scolyer, Grace Farnworth, Anisah Ali, Gerald Saldanha, Mark Bamford, Eva Sitcova, Petr Kujal, Sally O’Shea, Darren Treanor
Journal: British Journal of Dermatology (2024)

Abstract 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 &amp;lt; 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 &amp;lt; 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.