Dysplastic Naevi Research Articles

Overtreatment of dysplastic naevi: results of a multiregional UK questionnaire study.

Overtreatment of dysplastic naevi: results of a multiregional UK questionnaire study.

Melanoma imaging and diagnosis: What does the future hold?

In Australia, artificial intelligence (AI) is increasingly being used in the field of melanoma diagnosis. Early diagnosis is arguably the most important prognostic factor for melanoma survival. The use of digital monitoring of naevi, especially dysplastic naevi, might reduce the number of biopsies needed in managing patients at risk of melanoma, especially in patients with high naevi counts. This article discusses advances in imaging and early diagnosis including the use of AI in this process. The benefits of performing biopsies must be balanced with the potential to cause harm. Whole-body imaging can assist with more accurate detection of changing lesions and enable clinicians to focus on lesions where change is detected.

P062 A multicentre retrospective observational study reviewing the management of severely dysplastic naevi

P062 A multicentre retrospective observational study reviewing the management of severely dysplastic naevi

Parallelogram Excision: An Algorithmic Approach for Excision Designs in High-Tension Skin Areas.

The excision of lesions that are not oriented along the skin tension lines may cause the surgeon to design extremely broad elliptical preoperative markings, with the intent to follow the tension lines as recommended for the best postoperative course and the best quality scars. The aim of this study is to describe and clinically apply a new surgical technique called the parallelogram excision technique, in which the traditional ellipse with a major axis parallel to the tension lines is converted into a parallelogram whose lesser sides are coincident with the local skin tension lines. This technique was specifically conceived for lesions whose major axis is non-coincident with skin tension lines, and the primary advantage is that it reduces the amount of healthy tissue excised. Preliminarily to this clinical study, a comparative geometrical analysis was conducted between various excision shapes and angles using Geometry Pad version 2.7.10 (Bytes Arithmetic LLC) and verifying the data obtained through AutoCAD 2D 2016 (Autodesk, San Rafael, CA, USA), with the purpose of optimizing the technique from a geometrical point of view. A comparison was performed between the theoretical traditional elliptical excision and the hypothetical parallelogram excision. A pilot proof of concept clinical study was performed to verify the validity of the excisional design proposed. The patients considered for parallelogram excision suffered from skin lesions with a diameter no greater than 4 cm and oriented 45° to 60° with respect to tension lines. In order to limit variability, patients' ages were between 40 and 80, and the selected areas were limbs, sternum and dorsum. Scar quality was assessed with the validated POSAS method at 6 months post-operation. The geometrical analysis of the parallelogram's design showed that it allows a diminution of the excised healthy skin compared to the traditional ellipse. The clinical series included 16 patients, with a mean age of 63.5. Of these, nine patients were men and seven were women. Diagnoses included basal cell carcinoma in seven cases, dysplastic naevus in five patients, Bowen's disease in three individuals, and one case where a wider excision of a malignant melanoma was performed. Six-month follow up results showed: (1) an uneventful postoperative course; (2) good scar healing with an observer's POSAS median score of 16 and a patient's POSAS median score of 19; and (3) complete excision of lesions. When indicated, the parallelogram excision technique appears to be a good option for the excision and primary closure of skin lesions that are not parallel to skin tension lines, since it allows a reproducible and surgeon-friendly method of preoperative marking and implies a favorable use of the local tension, which determines good quality scars. The amount of healthy tissue removed is smaller compared to traditional elliptic excisions.

Wanita 74 Tahun Dengan Metastasis Pada Lobus Parieto-Oksipital Pada Melanoma Maligna

Melanoma is a tumor that is produced by the malignant transformation of melanocyte cells. Melanoma is the leading cause of premature death from cancer. Known risk factors include personal or family history of melanoma, large numbers of naevi and/or dysplastic naevi, congenital melanocytic naevi, sun-damaged skin, history of non-melanoma skin cancer, and immunodeficiency. Based on the Basic Health Research Results (Riskesdas) report, skin cancer as a whole ranks 3rd in Indonesia. Epidemiological studies of skin cancer have reported in Jakarta in 2014–2017, where out of 263 cases of skin cancer, malignant melanoma ranks third with the highest incidence of skin cancer (5.7%). Diagnosis of melanoma can be made by assessing the skin lesions with the naked eye and also by the patient's clinical symptoms. A person's risk of metastases is directly related to the depth of invasion and ulceration of their primary lesion. Among solid tumors, melanoma has one of the highest propensities to cause brain metastases with a proportion of more than 25% of patients. Although the current cancer treatment paradigm may reflect a combination of surgery, chemotherapy, radiotherapy, and immunotherapy with medical management, options for the treatment of metastatic brain cancer remain limited.

DP01 Survey on the management of dysplastic naevus

Abstract Although dysplastic naevus (DN) is a frequent diagnosis, there is significant controversy on its definition and gradation and its relationship to melanoma risk. Therefore, there is no consensus over optimal management, and surveys from Australia, Canada and the USA have shown variation in clinical practice. Dysplastic naevus with involved histological margins has not been shown to progress to melanoma. To assess UK management of DN depending on the grade of atypia and reported excision margin, we circulated a questionnaire via email to dermatologists in Scotland, north Wales, Liverpool and Manchester. Seventy-two responded, of whom 46 (64%) were consultants. The cohort was generally highly experienced, with 10 (14%) responders with 1–5 years’ dermatology experience, 15 (21%) with 6–10 years, 27 (37%) with 11–20 years and 20 (28%) with > 20 years’ experience. Management of DN varied greatly. For mild DN excised with < 1-mm margin, 59 (82%) agreed that no further management was required. Opinions were divided when margins were involved in mild DN, with 14 (19%) agreeing that no further management was required, 42 (58%) choosing to re-excise and six (8%) to re-excising only any residual pigmentation. Most dermatologists reassured patients with moderately DN with margins < 1 mm (49, 68%); 18 (25%) preferred to re-excise. For moderate DN with involved margins, six respondents (8%) felt that no further management was necessary and 54 (75%) would re-excise. For severe DN with margins > 1 mm, 16 (22%) would still re-excise and six (8%) would agree management in the multidisciplinary team meeting (MDT). For severe DN with margins < 1 mm, 41 (57%) would re-excise and seven (10%) would agree management in the MDT. Lastly, for severe DN with involved margins, 62 (86%) would re-excise and seven (10%) would agree management in the MDT. This study has shown comparable results with those from Australia and the USA, whereby most dermatologists would re-excise moderate and severe DN with involved margins. Significant numbers indicated that they would re-excise in the case of close histological margins: this is unnecessary, and more standardized management may reduce expenditure. Limitations of the study include the usual potential sources of bias in a questionnaire survey; it should be noted that reported behaviour may differ from actual practice. However, this is the first UK study on this common clinical scenario. The move to report DN as low- or high-grade may help to reduce variation, but our survey suggests that some patients are currently undergoing unnecessary procedures.

BT18 Evaluation of a teledermatology service for lesion monitoring

Abstract Teledermatology (TD) is an established diagnostic and triage tool for the initial assessment of skin lesions and is increasingly being used for monitoring. A previous study conducted at our trust found that 5% of our 2-week wait (2WW) referrals required follow-up for lesion monitoring. We therefore established a TD follow-up pathway to accommodate these patients and increase capacity for face-to-face (F2F) appointments. We retrospectively reviewed the outcomes of all TD follow-up patients seen from 1 April 2022 to 22 December 2022. The TD follow-up is usually requested 4 months after an initial assessment. We evaluated the proportion of benign lesions and those requiring further follow-up or surgery. In total, 3796 patients were assessed via TD, with 319 (8.4%) comprising TD follow-up. Altogether, 292 (91.5%) patients were initially reviewed via TD 2WW referral and 27 (8.5%) were referred from the clinic. Forty-eight (15.0%) did not attend (DNA) their follow-up and were discharged. Of the remaining 271 patients, seven (2.6%) who failed to attend their TD follow-up were rebooked, 179 (66%) were discharged after one TD follow-up assessment, 16 (5.9%) were booked for further TD follow-up, 19 (7.0%) were booked for routine F2F follow-up and five (1.8%) were booked for an urgent 2WW F2F appointment. Patients were also referred directly for excision, with 21 (7.7%) referred routinely and 24 (8.8%) referred urgently. From the 24 lesions excised urgently, five (21%) were dysplastic naevi, one (4%) was a moderately differentiated squamous cell carcinoma, 11 (46%) were benign (naevi, seborrhoeic keratoses or dermatofibroma) and for seven (29%), histology was unavailable (DNA appointment, sought private treatment or excision pending) at the time of data collection. No lesions were confirmed histologically as melanoma. Of the five dysplastic lesions, dermoscopic changes noted at follow-up included new atypical amorphous streaks, new and darker globules, loss of pigment and erythema. Our data suggest that TD for lesion monitoring may offer a suitable and time-efficient approach to follow-up, helping to alleviate pressure on services. Three to six months of follow-up has previously been considered an appropriate time period for short-term lesion monitoring; however, the optimal duration remains debatable. The low numbers of malignant lesions detected suggest an encouraging safety profile. However, with 66% of patients being discharged after TD follow-up, we plan to pilot a collaborative team approach to initial decision-making through mega processing clinics with the aim of improving specificity and ‘getting it right first time’ for patients. Longer-term data and cost-effectiveness analyses are required to further evaluate the sustained safety and efficacy of this service.

The anatomical distribution of lentiginous melanoma (lentigo maligna and lentigo maligna melanoma): Differences according to sex.

The anatomical distribution of lentiginous melanoma (lentigo maligna and lentigo maligna melanoma): Differences according to sex.

Terahertz imaging of human skin pathologies using laser feedback interferometry with quantum cascade lasers.

Early detection of skin pathologies with current clinical diagnostic tools is challenging, particularly when there are no visible colour changes or morphological cues present on the skin. In this study, we present a terahertz (THz) imaging technology based on a narrow band quantum cascade laser (QCL) at 2.8 THz for human skin pathology detection with diffraction limited spatial resolution. THz imaging was conducted for three different groups of unstained human skin samples (benign naevus, dysplastic naevus, and melanoma) and compared to the corresponding traditional histopathologic stained images. The minimum thickness of dehydrated human skin that can provide THz contrast was determined to be 50 µm, which is approximately one half-wavelength of the THz wave used. The THz images from different types of 50 µm-thick skin samples were well correlated with the histological findings. The per-sample locations of pathology vs healthy skin can be separated from the density distribution of the corresponding pixels in the THz amplitude-phase map. The possible THz contrast mechanisms relating to the origin of image contrast in addition to water content were analyzed from these dehydrated samples. Our findings suggest that THz imaging could provide a feasible imaging modality for skin cancer detection that is beyond the visible.

Do we need to rethink the diagnoses melanoma in situ and severely dysplastic naevus?

Do we need to rethink the diagnoses melanoma in situ and severely dysplastic naevus?

Subungual melanoma with blue naevus-like morphological features: a clinicopathological retrospective analysis of nine cases

Melanocytic lesions in the nail apparatus are often challenging. Both subungual melanomas (SUM) and blue naevus of the nail are very rare. Occasionally, melanomas may mimic blue naevus histologically. Benign and malignant blue melanocytic lesions are commonly associated with G protein mutations, a distinct abnormality not associated with conventional subungual melanomas. We describe the clinical, histological and immunohistochemical features of nine cases of SUM with blue naevus-like morphological features. Mutations in exon 4 and 5 of GNAQ and GNA11 were investigated in two cases, which showed no mutations. RNA-seq of one case revealed unknown mutations along with mutations in ATM, METK and ARID1A. Our study delineates a variant of SUM that mimics blue naevus. Awareness of this pitfall is important when evaluating heavily pigmented lesions around the nail in order to avoid misdiagnosis. Appropriate sampling of subungual lesions and clinicopathological correlation are paramount to reach the correct diagnosis.

Incidence of cutaneous melanoma in patients with histologically confirmed dysplastic naevus: A follow-up study in a large UK Healthcare Trust.

Incidence of cutaneous melanoma in patients with histologically confirmed dysplastic naevus: A follow-up study in a large UK Healthcare Trust.

Melanocytic lesions with peripheral globules: results of an observational prospective study in 154 high-risk melanoma patients under digital dermoscopy follow-up evaluated with reflectance confocal microscopy.

The management of melanocytic lesions with peripheral globules (MLPGs) is usually age-dependent and can be challenging in high-risk melanoma patients. To evaluate clinical, dermoscopic and reflectance confocal microscopy (RCM) features of MLPG in patients under digital dermoscopic surveillance. To know whether dermoscopic or RCM findings correlate with histologic diagnosis and the accuracy of the dermoscopy-RCM compared with histopathology. During 24 months, we prospectively enrolled MLPG in patients under digital dermoscopy follow-up. All were evaluated by dermoscopy and RCM and excised for histologic examination. We enrolled 154 patients, mean age 42.45years (18.78-73.19). Three melanomas and 19 dysplastic naevi (DNs) were diagnosed. There were no significant differences in the age of the patients (P=0.662). MLPGs with diameter of 6mm or more and asymmetry in two axes were associated with melanoma (P=0.01, P=0.003). Patients with more than one MLPG were less likely to have melanoma. Blue-grey and red colours were more frequent in melanoma (P=0.013 and P=0.000). Different sizes and shapes of PG were associated with DN and melanoma (P=0.000 and P=0.001). In a new lesion, PG in <25% of the circumference was related to malignancy (P=0.010). RCM signs of malignancy were related to melanoma: pagetoid cells (P=0.000), non-edged papillae (P=0.001), atypical junctional thickenings (P=0.000) and atypical cells at the dermal-epidermal junction (P=0.000). Dense irregular nests were associated to melanoma (P=0.019). Dermoscopy and confocal evaluation were able to diagnose 100% of melanomas and 84.21% of DNs. The kappa coefficient between dermoscopy-RCM vs. histology was 0.76. We recommend to excise a MLPG when it presents asymmetry in two axes, 6 or more mm, new lesion with PG in less than the 25% of the circumference, irregular size and shape PGs and irregular dense nests on RCM, regardless of the patient's age.

The differential expression of micro-RNAs 21, 200c, 204, 205, and 211 in benign, dysplastic and malignant melanocytic lesions and critical evaluation of their role as diagnostic biomarkers

Overlapping histological features between benign and malignant lesions and a lack of firm diagnostic criteria for malignancy result in high rates of inter-observer variation in the diagnosis of melanocytic lesions. We aimed to investigate the differential expression of five miRNAs (21, 200c, 204, 205, and 211) in benign naevi (n = 42), dysplastic naevi (n = 41), melanoma in situ (n = 42), and melanoma (n = 42) and evaluate their potential as diagnostic biomarkers of melanocytic lesions. Real-time PCR showed differential miRNA expression profiles between benign naevi; dysplastic naevi and melanoma in situ; and invasive melanoma. We applied a random forest machine learning algorithm to classify cases based on their miRNA expression profiles, which resulted in a ROC curve analysis of 0.99 for malignant melanoma and greater than 0.9 for all other groups. This indicates an overall very high accuracy of our panel of miRNAs as a diagnostic biomarker of benign, dysplastic, and malignant melanocytic lesions. However, the impact of variable lesion percentage and spatial expression patterns of miRNAs on these real-time PCR results was also considered. In situ hybridisation confirmed the expression of miRNA 21 and 211 in melanocytes, while demonstrating expression of miRNA 205 only in keratinocytes, thus calling into question its value as a biomarker of melanocytic lesions. In conclusion, we have validated some miRNAs, including miRNA 21 and 211, as potential diagnostic biomarkers of benign, dysplastic, and malignant melanocytic lesions. However, we also highlight the crucial importance of considering tissue morphology and spatial expression patterns when using molecular techniques for the discovery and validation of new biomarkers.

Associations of pigmentary and naevus phenotype with melanoma risk in two populations with comparable ancestry but contrasting levels of ambient sun exposure.

BackgroundPeople at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes.ObjectiveWe examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population‐based, case–control studies with comparable ancestry but different ambient sun exposure.MethodsData were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case–control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders.ResultsHair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self‐reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk.ConclusionsClassifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self‐reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development.

Massively parallel sequencing analysis of benign melanocytic naevi.

Melanocytic naevi are benign lesions of the skin or mucosa that may constitute non-obligate precursors of malignant melanoma, particularly when they show lentiginous and dysplastic features. The aim of this study was to investigate the repertoire of somatic genetic alterations in melanocytic naevi. DNA extracted from 12 melanocytic naevi and DNA from matching normal tissue were separately microdissected and subjected to targeted massively parallel sequencing of ≥300 cancer genes. A median of 5.5 (range 1-12) non-synonymous somatic mutations were detected, with 10 cases harbouring mutually exclusive BRAF V600E (6/12) or NRAS (4/12) clonal hotspot mutations. One of the two cases lacking BRAF and NRAS mutations was a dysplastic naevus harbouring an HRAS Q61L hotspot mutation. Analysis of the laser-capture microdissected components of a naevus synchronously diagnosed with in-situ and invasive malignant melanoma revealed a truncal, clonal BRAF V600E mutation, and the acquisition of a CDKN2A homozygous deletion in the invasive component, in conjunction with additional clonal mutations affecting NF2, FAT4 and KDR in both in-situ and invasive malignant components. Melanocytic naevi harbour recurrent BRAF V600E or NRAS hotspot mutations with low mutational burdens. Our findings also show that progression from naevi to malignant melanoma may be driven by the acquisition of additional genetic alterations, including CDKN2A homozygous deletions.

Dysplastic/Clark naevus in the era of molecular pathology.

Dysplastic naevus has been a controversial entity since its first description by Clark in 1978. Despite a recent paradigm shift from the initially proposed notion that dysplastic naevus is a precursor to melanoma, its management has been increasingly more aggressive in the last decade. The latter is due to an unresolved uncertainty regarding its biological nature which necessitates further clarification. Recent molecular genetics, epigenetic and transcriptomic discoveries have revealed that a subset of dysplastic naevi exhibits a genomic profile which is intermediate between that of benign naevus and melanoma. This group of lesions often shows somatic mutations in non-V600E BRAF, NRAS and TERT and hemizygous deletion of CDKN2A gene as well as upregulation of genes involved in proliferation, cell adhesion and migration, and epidermal and follicular keratinocyte-related genes. These new genomic insights suggest that a proportion of dysplastic naevi have a greater propensity to evolve to melanoma; however, the clinical and histopathological features of this proposed intermediate category are still to be elucidated by further research.

19. Examining discordance between histopathology diagnoses of thin melanoma compared to dysplastic naevi

Background: Dysplastic naevi (DN) and thin melanomas may be difficult to distinguish histologically.

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin.

Dysplastic naevi (DN) are benign lesions with atypical features intermediate between that of common melanocytic naevi (CMN) and malignant melanoma (MM). Debate remains over whether DN represent progressive lesions from CMN. Through gene expression profiling and analysis of molecular gene signatures, our study revealed progressive increases in immune activation and regulation, along with pathways implicated in melanomagenesis, from CMN to DN to MM. Using criteria of 1.5-fold change and false discovery rate ≤0.05, we found differential expression of 7186 probes (6370 unique genes) with the largest difference detected between DN and MM from the standpoint of genomic melanoma progression. Despite progressive increases in the T-helper type 1 (Th1)-inducing gene (IL-12), RT-PCR indicated impaired Th1 or cytotoxic T-cell response (decreased IFN-γ) in MM. Concordantly, our results indicated progressive increases in molecular markers associated with regulatory T cells, exhausted T cells and tolerogenic dendritic cells, including detection of increased expression of suppressor of cytokine signalling 3 (SOCS3) in dendritic cells associated with MM. All together, our findings suggest that the increased immunosuppressive microenvironment of melanoma may contribute to unhampered proliferation of neoplastic cells. In addition, the detection of increased markers associated with tolerogenic dendritic cells in MM suggests that targeting these suppressive immune cell types may represent an alternative avenue for future immunotherapy.

Methods of melanoma detection and of skin monitoring for individuals at high risk of melanoma: new Australian clinical practice.

The evidence-based national clinical practice guidelines for the management of cutaneous melanoma published in 2008 are currently being updated. This article summarises the findings from multiple chapters of the guidelines on different methods of melanoma detection and of monitoring the skin for patients at high risk of melanoma. Early detection of melanoma is critical, as thinner tumours are associated with enhanced survival; therefore, strategies to improve early detection are important to reduce melanoma-related mortality. Clinicians who perform skin examinations for the purpose of detecting skin cancer should be trained in and use dermoscopy. The use of short term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual melanocytic lesions of concern. The use of long term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual or multiple melanocytic lesions for routine surveillance of high risk patients. The use of total body photography should be considered in managing patients at increased risk for melanoma, particularly those with high naevus counts and dysplastic naevi. There is insufficient evidence to recommend the routine use of automated instruments for the clinical diagnosis of primary melanoma. Determining the relative indications for each diagnostic method and how each method should be introduced into the surveillance of a patient requires careful consideration and an individualised approach.