Online prediction tools for melanoma survival: A comparison.

BACKGROUND: Breslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that accurately considers these and other predictors could be valuable for clinicians managing melanoma patients. OBJECTIVE: To compare online melanoma survival prediction tools that request user input on clinical and pathological features. METHODS: Search engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared. RESULTS: Three tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival. LIMITATIONS: The authors did not have access to the base data used to compile various prediction tools. CONCLUSION: The LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects.

Intralesional photodynamic therapy induces apoptosis in basal cell carcinoma and Bowen's disease through caspase 3 and granzyme B.

BACKGROUND: Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor. OBJECTIVES: To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease). METHODS: Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK. RESULTS: Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT. CONCLUSION: Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h.

The peculiar dermatoscopic pattern of scalp melanoma.

BACKGROUND: Melanomas developing on anatomic sites other than the trunk and extremities have a special pathogenetic and mutational profile, morphologic characteristics and biologic behaviour. OBJECTIVE: By retrospectively screening the databases of our centres, we aimed to investigate the dermatoscopic morphology of early scalp melanoma, including in situ and invasive tumours with a Breslow thickness up to 1 mm. METHODS: The databases of three specialized centres for skin cancer diagnosis and management in Greece were retrospectively evaluated to retrieve dermatoscopic images of scalp melanomas. Patients' age and sex were recorded, as well as the precise location of the tumour, using 6 possible sub-locations: frontal, parietal, occipital, temporal, nuchal scalp and vertex. The dermatoscopic images were evaluated by 3 independent investigators for the presence of pre-defined criteria. The dermatoscopic criteria included in the evaluation were selected based on available literature and were categorized in 2 groups: 'classic melanoma criteria' and 'lentigo maligna (LM) criteria'. RESULTS: Of 38 melanomas, 37 (97.4%) displayed brown colour and 23 (60.5%) displayed additional grey or blue colour. The most frequent dermatoscopic criteria were regression (18/38, 47.4%), grey dots/globules (17/38, 44.7%), atypical network (16/38, 42.1%), obliterated follicles (16/38, 42.1%) and angulated lines (15/38, 39.5%). Of 38 melanomas, 28 (73.7%) displayed at least 1 classic melanoma criterion plus at least 1 LM criterion. Of the remaining melanomas, 8 (21.1%) displayed only classic melanoma criteria, 1 (2.6%) only LM criteria and 1 (2.6%) did not exhibit any of the evaluated criteria. CONCLUSIONS: This study demonstrates that early scalp melanoma combines classic with LM criteria in terms of colours and structures.

Dermoscopic spectrum of mycosis fungoides: a retrospective observational study by the International Dermoscopy Society.

BACKGROUND: The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited. OBJECTIVE: To evaluate dermoscopic morphology and dermoscopic-pathological correlations of classic MF stages and investigate dermoscopic features of MF variants. METHODS: Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic-pathological correlation assessment of different stages of classic MF were performed. RESULTS: A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF and 8 poikilodermatous MF). Linear/linear-curved vessels and white scales in the skin furrows were significantly associated with patch-stage MF, while clustered dotted vessels were related to plaque-stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumour-stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumours, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumours), bright white lines/structureless areas to dermal fibrosis and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines. CONCLUSION: Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants.

Clinical and dermatoscopic predictors of squamous cell carcinoma of the lips: a case-control, multicentric study.

BACKGROUND: Squamous cell carcinoma of the lip accounts for 20% of all oral carcinomas. Its diagnosis may be challenging because it clinically resembles actinic cheilitis and inflammatory lesions of the lips. OBJECTIVES: To determine clinical and dermatoscopic predictors of squamous cell carcinoma of the lip vs. other lip lesions. METHODS: Multicentre retrospective morphological study, including histologically confirmed cases of squamous cell carcinoma of the lip and controls consisting of actinic cheilitis and inflammatory lesions of the lips. Clinical and dermatoscopic images were evaluated for the presence of predefined criteria. Crude and adjusted odds ratios and corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression respectively. RESULTS: A total of 177 lip lesions were evaluated, 107 (60.5%) were squamous cell carcinomas and 70 (39.5%) were controls. The most frequent dermatoscopic criteria of lip squamous cell carcinoma were scales (100%), white halos (87.3%) and ulceration (79.4%). The majority of squamous cell carcinomas displayed polymorphic vessels (60.8%), with linear (68.6%) and hairpin (67.6%) being the most frequent types. Multivariate logistic regression analysis showed that clinical predictors of lip squamous cell carcinoma were exophytic appearance and clinical hyperkeratosis, with 43-fold and 6-fold higher probability respectively. White clods and ulceration in dermoscopy presented a 6-fold and 4-fold increased risk for squamous cell carcinoma respectively. CONCLUSIONS: A scaly lesion with exophytic growth, dermatoscopically displaying white clods, ulceration and linear and hairpin vessels is very likely a squamous cell carcinoma of the lip.

Not all melanomas are created equal: a review and call for more research into nodular melanoma.

Among the histogenic subtypes of melanoma, nodular melanoma (NM) is the major contributor for thicker and fatal melanomas and it has been associated with melanoma-specific death in thin tumours, highlighting an important subgroup of 'aggressive thin' melanomas. This review provides a synthesis of the distinct characteristics of NM, with respect to epidemiology and risk factors, clinical presentation, histopathology, molecular and dermoscopic aspects, and screening practices. The real challenges are to find better biomarkers of aggressiveness and to know whether the control of such aggressive melanomas can be influenced by targeted interventions such as early detection, drug interventions and preventive strategies.

The impact of anatomical location and sun exposure on the dermoscopic recognition of atypical nevi and early melanomas: usefulness of an integrated clinical-dermoscopic method (iDScore).

BACKGROUND: The anatomical location of atypical melanocytic skin lesion (aMSL) was never combined into an algorithm for discriminating early melanomas (EM) from atypical nevi (AN). AIMS: To investigate the impact of body location on the intuitive diagnosis performed in teledermoscopy by dermatologists of different skill levels. A further aim was to evaluate how the integration of the body location could improve an algorithm-aided diagnosis. METHODS: We retrospectively collected 980 standardized dermoscopic images of aMSL cases (663 AN, 317 EM): data on the anatomical location were collected according to 15 body sites classified into 4 macro-areas of chronically/frequently/seldom/rarely exposure. Through a teledermatology web platform, 111 variously skilled dermoscopists performed either the intuitive diagnosis and 3 algorithm-assisted diagnostic tests (i.e. iDScore, 7-point checklist, ABCD rule) on each case, for a total of 3330 examinations. RESULTS: In the rarely photoexposed area (side, bottom, abdomen), AN were the most tricky (i.e. highest quote of false positives), due to a frequent recognition of dermoscopic features usually considered as suggestive for melanoma in these lesions; the EM at these sites received the highest quote of false negatives, being generally interpreted as 'featureless' according to these traditional parameters, that were more frequently displayed on the chronically photoexposed area. In rarely and seldom photoexposed area, intuitive diagnosis fails to achieve adequate accuracy for all aMSLs, as the ABCD rule and the 7-point checklist; by applying the iDScore algorithm the diagnostic performance was increased by 15% in young and 17% in experts. CONCLUSIONS: The body location of an aMSL can affect the quality of intuitive dermoscopic diagnosis, especially in sun-protected areas. Accuracy can be improved by using the iDScore algorithm that assigns a different partial score of each body site.

Which medical disciplines diagnose and treat melanoma in Europe in 2019? A survey of experts from melanoma centres in 27 European countries.

BACKGROUND AND OBJECTIVES: The incidence of melanoma is increasing. This places significant burden on societies to provide efficient cancer care. The European Cancer Organisation recently published the essential requirements for quality melanoma care. The present study is aimed for the first time to roughly estimate the extent to which these requirements have been met in Europe. MATERIALS AND METHODS: A web-based survey of experts from melanoma centres in 27 European countries was conducted from 1 February to 1 August 2019. Data on diagnostic techniques, surgical and medical treatment, organization of cancer care and education were collected and correlated with national health and economic indicators and mortality-to-incidence ratio (MIR) as a surrogate for survival. Univariate linear regression analysis was performed to evaluate the correlations. SPSS software was used. Statistical significance was set at P < 0.05. RESULTS: The MIR was lower in countries with a high health expenditure per capita and with a higher numbers of general practitioners (GPs) and surgeons (SURG) per million inhabitants. In these countries, GPs and dermatologists (DER) were involved in melanoma detection; high percentage of DER used dermatoscopy and were involved in the follow-up of all melanoma stages; both medical oncologists (ONC) and dermato-oncologists administered systemic treatments; and patients had better access to sentinel lymph node biopsy and were treated within multidisciplinary tumour boards. CONCLUSION: Based on these first estimates, the greater involvement of GPs in melanoma detection; the greater involvement of highly trained DER in dermatoscopy, dermatosurgery, follow-up and the systemic treatment of melanoma; and the provision of ongoing dermato-oncology training for pathologists, SURG, DER and ONC are necessary to provide an optimal melanoma care pathway. A comprehensive analysis of the melanoma care pathway based on clinical melanoma registries will be needed to more accurately evaluate these first insights.

Dermatoscopy of combined blue nevi: a multicentre study of the International Dermoscopy Society.

BACKGROUND: Combined blue nevi (CBN) may mimic melanoma and are relatively often biopsied for diagnostic reasons. OBJECTIVE: To better characterize CBN and to compare it with melanoma. METHODS: We collected clinical and dermatoscopic images of 111 histologically confirmed CBN and contrasted their dermatoscopic characteristics with 132 partly blue coloured melanomas. Furthermore, we compared the accuracy of human experts using pattern analysis with a computer algorithm based on deep learning. RESULTS: Combined blue nevi are usually flat or slightly elevated and, in comparison with melanoma, more frequent on the head and neck. Dermatoscopically, they are typified by a blue structureless part in combination with either brown clods (n = 52, 46.8%), lines (n = 28, 25.2%) or skin-coloured or brown structureless areas (n = 31, 27.9%). In contrast with melanoma, the blue part of CBN is more often well defined (18.9% vs. 4.5%, P < 0.001) and more often located in the centre (22.5% vs. 5.3%, P < 0.001). Melanomas are more often chaotic (OR: 28.7, 95% CI: 14.8-55.7, P < 0.001), have at least one melanoma clue (OR: 10.8, 95% CI: 5.2-22.2 P < 0.001) in particular white lines (OR: 37.1, 95% CI: 13.4-102.9, P < 0.001). Using simplified pattern analysis (chaos and clues), two raters reached sensitivities of 93.9% (95% CI: 88.4-97.3%) and 92.4% (95% CI: 86.5-96.3%) at corresponding specificities of 59.5% (95% CI: 49.7-68.7%) and 65.8% (95% CI: 56.2-74.5%). The human accuracy with pattern analysis was on par with a state-of-the-art computer algorithm based on deep learning that achieved an area under the curve of (0.92, 95% CI: 0.87-0.96) and a specificity of 85.3% (95% CI: 76.5-91.7%) at a given sensitivity of 83.6% (95% CI: 72.5-91.5%). CONCLUSION: CBN usually lack melanoma clues, in particular white lines. The accuracy of pattern analysis for combined nevi is acceptable, and histopathologic confirmation may not be necessary in exemplary cases.

The evolving field of Dermato-oncology and the role of dermatologists: Position Paper of the EADO, EADV and Task Forces, EDF, IDS, EBDV-UEMS and EORTC Cutaneous Lymphoma Task Force.

BACKGROUND: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society. OBJECTIVE: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology. DISCUSSION: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients. CONCLUSION: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology.

Dermatoscopic features of thin (≤2 mm Breslow thickness) vs. thick (>2 mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non-melanoma tumours: a multicentric collaborative study by the International Dermoscopy Society.

BACKGROUND: Thin nodular melanoma (NM) often lacks conspicuous melanoma-specific dermatoscopic criteria and escapes clinical detection until it progresses to a thicker and more advanced tumour. OBJECTIVE: To investigate the dermatoscopic morphology of thin (≤2 mm Breslow thickness) vs. thick (>2 mm) NM and to identify dermatoscopic predictors of its differential diagnosis from other nodular tumours. METHODS: Retrospective, morphological case-control study, conducted on behalf of the International Dermoscopy Society. Dermatoscopic images of NM and other nodular tumours from 19 skin cancer centres worldwide were collected and analysed. RESULTS: Overall, 254 tumours were collected (69 NM of Breslow thickness ≤2 mm, 96 NM >2 mm and 89 non-melanoma nodular lesions). Light brown coloration (50.7%) and irregular brown dots/globules (42.0%) were most frequently observed in ≤2 mm NMs. Multivariate analysis revealed that dotted vessels (3.4-fold), white shiny streaks (2.9-fold) and irregular blue structureless area (2.4-fold) were predictors for thinner NM compared to non-melanoma nodular tumours. Overall, irregular blue structureless area (3.4-fold), dotted vessels (4.6-fold) and serpentine vessels (1.9-fold) were predictors of all NM compared to non-melanoma nodular lesions. LIMITATIONS: Absence of a centralized, consensus pathology review and cases selected form tertiary centres maybe not reflecting the broader community. CONCLUSIONS: Our study sheds light into the dermatoscopic morphology of thin NM in comparison to thicker NM and could provide useful clues for its differential diagnosis from other non-melanoma nodular tumours.

The presence of eccentric hyperpigmentation should raise the suspicion of melanoma.

BACKGROUND: Melanocytic lesions with eccentric hyperpigmentation (EH), even though without other dermatoscopic features of melanoma, are often excised. OBJECTIVE: Aiming to understand whether the EH in a pigmented lesion is an accurate criterion of malignancy, we evaluated the capability of two evaluators, with different expertise, to correctly diagnose a melanoma when analysing a given lesion in toto versus a partial analysis, with only the EH or the non-hyperpigmented portion (non-EH) visible. METHODS: Dermatoscopic images of 240 lesions (107 melanomas and 133 nevi) typified by EH were selected. Facial, acral, mucosal lesions and lesions showing clear-cut features of melanoma (except for atypical network) were excluded. Clinical and dermoscopic features (main pattern and numbers of colours) were described for all cases. Each image was split in two through a software so that only the EH or the non-EH was visible. Two blinded evaluators examined three sets of images, two with customized images and one with the non-modified ones: they were asked to give a dichotomous diagnosis (melanoma or nevus) for each image. RESULTS: Melanomas were significantly more frequently typified by colour variegation (3 colours in 44.8% and 4 colours in 41.1% of cases) and atypical network (88.1% in the EH). No significant differences in diagnostic accuracy emerged between the two evaluators. Sensitivity improved in the evaluation of the whole lesions (mean sensitivity 89.7%) in comparison with the evaluation of EH or non-EH alone (72.7-62.6%). Specificity increased when evaluating the EH (54.1%). Positive predictive value (PPV) and likelihood ratio (LR+) of EH resulted 52.3% and 1.4, meaning that in one case out of two with EH is a melanoma. CONCLUSIONS: Lesions with EH are challenging, regardless of dermoscopic experience. The EH is a robust criterion for malignancy, since the evaluation of the whole lesion, through an intralesional comparative approach, increases sensitivity.