International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Dermoscopy of Umbilical Lesions-A Systematic Review.

Background: The umbilicus is a fibrous remnant located in the centre of the abdomen. Various entities may be encountered in this special anatomical location; however, little is known about their dermoscopic presentation. The aim of this study was to provide a comprehensive summary of existing evidence on dermoscopic features of umbilical lesions. Methods: Studies assessing dermoscopic images of umbilical lesions were included in this study. No age, ethnicity or skin phototype restrictions were applied. Papers assessing lesions outside of the umbilical area, lacking dermoscopic images and/or dermoscopic description and not related to the topic were excluded. Embase, Medline and Cochrane Library were searched from inception to the end of May 2023. The Joanna Briggs Institute critical appraisal tools were used to evaluate the risk of bias of the selected studies. The quality and the level of evidence of included studies were assessed according to the Oxford 2011 Levels of Evidence. Thirty-four studies reporting a total of 39 lesions met the inclusion criteria and were included in qualitative analysis. Results: A qualitative synthesis of the following entities was performed: melanoma, nevi, basal cell carcinoma, fibroepithelioma of Pinkus, Sister Mary Joseph nodule, mycosis fungoides, dermatofibroma, endometriosis, epidermal cyst, granuloma, intravascular papillary endothelial hyperplasia, lichen planus, omphalolith, seborrheic keratosis, and syringoma. Conclusions: Dermoscopy is a non-invasive technique that may be useful in the differential diagnosis of umbilical lesions. The main limitations of this study were lack of a high level of evidence in the studies and the lack of uniformity in applied dermoscopic terminology between included studies.

Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

BACKGROUND: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. OBJECTIVES: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. METHODS: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. RESULTS: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. CONCLUSIONS: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

Lentigo maligna and lentigo maligna melanoma in patients younger than 50†years: a multicentre international clinical-dermoscopic study.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) is usually diagnosed in older patients, when lesions are larger. However, it is important to detect it at an earlier stage to minimize the area for surgical procedure. OBJECTIVES: To determine and define clinical, dermoscopic and reflectance confocal microscopy (RCM) features of LM/LMM in patients < 50 years old. METHODS: This was a multicentre study involving tertiary referral centres for skin cancer management. The study included cases of consecutively excised LM/LMM arising in patients < 50 years of age with a histopathological diagnosis of LM/LMM and a complete set of clinical and dermoscopic images; RCM images were considered when present. RESULTS: In total, 85 LM/LMM of the face from 85 patients < 50 years were included in the study. A regression model showed a direct association with the size of the lesion (R2 = 0.08; P = 0.01) and with the number of dermoscopic features at diagnosis (R2 = 0.12; P < 0.01). In a multivariable analysis, an increasing number of dermoscopic features correlated with increased patient age (P < 0.01), while the presence of grey colour was a predictor of younger age at diagnosis (P = 0.03). RCM revealed the presence of melanoma diagnostic features in all cases (pagetoid cells and atypical nesting). CONCLUSIONS: LM is not a disease limited to older people as previously thought. LM presenting in young adults tends to be smaller and with fewer dermoscopic features, making its diagnosis challenging. Careful evaluation of facial pigmented lesions prior to cosmetic procedures is imperative to avoid incorrectly treating early LM as a benign lesion.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.

Seven Plus One Steps to Assess Pigmented Nail Bands (Melanonychia Striata Longitudinalis).

Melanonychia striata longitudinalis might involve one or more fingers and/or toes and might result from several different causes, including benign and malignant tumors, trauma, infections, and activation of melanocytes that might be reactive or related to the pigmentary trait, drugs and some rare syndromes. This broad differential diagnosis renders the clinical assessment of melanonychia striata particularly challenging. Nail matrix melanoma is relatively rare, occurs almost always in adults involves more frequently the first toe or thumb. The most common nail unit cancer, squamous cell carcinoma / Bowen disease (SCC) of the nail matrix is seldom pigmented. Histopathologic examination remains the gold standard for melanoma and SCC diagnosis, but excisional or partial biopsies from the nail matrix require training and is not routinely performed by the majority of clinicians. Furthermore, the histopathologic evaluation of melanocytic lesions of the nail matrix is particularly challenging, since early melanoma has only bland histopathologic alterations. Dermatoscopy of the nail plate and its free edge significantly improves the clinical diagnosis, since specific patterns have been associated to each one of the causes of melanonychia. Based on knowledge generated and published in the last decades, we propose herein a stepwise diagnostic approach for melanonychia striata longitudinalis: 1) Hemorrhage first 2) Age matters 3) Number of nails matters 4) Free edge matters 5) Brown or gray? 6) Size matters 7) Regular or irregular and, finally, "follow back".

Evaluation of the Knowledge of Primary Care Physicians About Important Nail Diseases Before and After a Short Online Training.

INTRODUCTION: Nail diseases are often diagnosed late with a potential prognostic and functional impact. This could be partly due to knowledge gaps among primary care physicians (PCPs). OBJECTIVES: To evaluate the knowledge about diagnosis and management of ten common/important nail conditions in a population of French PCPs and its improvement after a 31-minute online training session. METHODS: We submitted 10 pre-test and post-test clinical cases and an educative online course on the diagnosis and the management of nail diseases to 138 volunteer PCPs; 73 completed the whole training path. RESULTS: Compared to pre-test, more PCPs in the post-test required an urgent second opinion to dermatologist for pigmented melanoma (100% versus 80.3%; P <0.05) and use of inappropriate/dangerous systemic treatment for trauma-induced nail changes was reduced after the training program (0% versus 6.8%; P <0.05). A lack of knowledge remained after training for amelanotic melanoma with an increase of mycological/bacteriological tests (9.6% versus 0%; P <0.05). CONCLUSIONS: Management of nail diseases by our panel of PCPs was suboptimal and was improved after a short online training.

Delphi Consensus Among International Experts on the Diagnosis, Management, and Surveillance for Lentigo Maligna.

INTRODUCTION: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. OBJECTIVES: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. METHODS: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as >75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. RESULTS: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. CONCLUSIONS: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient.

Junctional Nevus and Early Melanoma on Sun-Damaged Skin of the Head/Neck: a Clinico-Pathologic Challenge.

INTRODUCTION: Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi. OBJECTIVES: This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi. METHODS: From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal. RESULTS: Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna. CONCLUSIONS: Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient.

Stardust Pattern as Evolution of Pigmented Spitz Nevi During Childhood.

INTRODUCTION: Spitz nevi (SN) are benign melanocytic proliferations frequently occurring in children. Some pigmented SN with a starburst pattern evolve into the "stardust" one, which is characterized by a central, black to gray, hyperpigmented area and remnants of a brown network at the periphery. These dermoscopy changes are often the first alert to induce excision. OBJECTIVES: The aim of this study is to enlarge the case series of stardust SN in children, in order to increase confidence with this new dermoscopic pattern and reduce unnecessary excisions. METHODS: This retrospective observational study was conducted with SN cases received from IDS members. The inclusion criteria were: clinical and/or histopathologic diagnosis of Spitz naevus with starburst appearance in children <12 years old, availability of a dermoscopic image at baseline and after follow-up of at least 1 year, availability of patient data. The dermoscopic images and their changes over time were assessed by three evaluators in consensus. RESULTS: 38 SN were enrolled, with a median age of 7 years and a median FUP duration of 15,5 months. Comparing the evolution with time of FUP, no significant differences were found between growing and involuting lesions in terms of patient age and sex, location and palpability of lesions. CONCLUSIONS: The long follow-up reported in our study could really support the concept of benignity of changing SN. A conservative approach is acceptable for nevi showing the stardust pattern, because it may be considered a physiological evolution of pigmented Spitz nevus, and urgent surgeries could be avoided.

Validation of 3D Knee Kinematics during Gait on Treadmill with an Instrumented Knee Brace.

To test a novel instrumented knee brace intended for use as a rehabilitation system, based on inertial measurement units (IMU) to monitor home-based exercises, the device was compared to the gold standard of motion analysis. The purpose was to validate a new calibration method through functional tasks and assessed the value of adding magnetometers for motion analysis. Thirteen healthy young adults performed a 60-second gait test at a comfortable walking speed on a treadmill. Knee kinematics were captured simultaneously, using the instrumented knee brace and an optoelectronic camera system (OCS). The intraclass correlation coefficient (ICC) showed excellent reliability for the three axes of rotation with and without magnetometers, with values ranging between 0.900 and 0.972. Pearson's r coefficient showed good to excellent correlation for the three axes, with the root mean square error (RMSE) under 3° with the IMUs and slightly higher with the magnetometers. The instrumented knee brace obtained certain clinical parameters, as did the OCS. The instrumented knee brace seems to be a valid tool to assess ambulatory knee kinematics, with an RMSE of <3°, which is sufficient for clinical interpretations. Indeed, this portable system can obtain certain clinical parameters just as well as the gold standard of motion analysis. However, the addition of magnetometers showed no significant advantage in terms of enhancing accuracy.

Dermoscopy of haemosiderotic/aneurysmal dermatofibroma: A morphological study of 110 cases.

BACKGROUND: Haemosiderotic and aneurysmal dermatofibromas are uncommon and frequently misdiagnosed lesions, which can be considered as different histopathological stages of the same tumour. A dermoscopic diagnosis testing accuracy has not been performed for these tumours to date. OBJECTIVES: To determine the diagnostic significance of dermoscopic structures and patterns associated with haemosiderotic/ aneurysmal dermatofibromas in a large series. METHODS: Dermoscopic images of histopathologically proven cases of 110 haemosiderotic/ aneurysmal dermatofibromas and 501 other tumours were collected. The frequency, sensitivity, specificity, positive predictive value and negative predictive value of the dermoscopic structures and patterns associated with these lesions were calculated. RESULTS: Haemosiderotic/ aneurysmal dermatofibromas are mostly symmetric lesions (86.5%), and a prominent homogeneous area was present in 100% of them. The presence of vascular structures was very common (86.4%), and dotted vessels were predominant (58.2%). Shiny white structures were seen in 85.5% of lesions, while a peripheral delicate pigment network was present in 69.1%. The most significant pattern was the one composed of a prominent homogeneous area and peripheral delicate pigment network, which showed a specificity of 100% with a relatively good sensitivity (69.1%). All the patterns containing a peripheral delicate pigment network showed very good specificities, positive predictive values and negative predictive values. Those patterns without a peripheral delicate pigment network showed the highest sensitivities, but they showed a significant overlap with other tumours, mainly with melanoma. CONCLUSIONS: Dermoscopy is helpful in improving the diagnostic accuracy of haemosiderotic/ aneurysmal dermatofibromas. However, there is a considerable dermoscopic overlap between these tumours and melanoma, specifically when the peripheral delicate pigment network is absent.

Indications for Digital Monitoring of Patients With Multiple Nevi: Recommendations from the International Dermoscopy Society.

Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring. Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

Significance of Primary Melanoma Regression on Local Infiltrate and Outcome.

INTRODUCTION: The characteristics and the prognostic value of regression in primary melanomas are controversial. OBJECTIVES: To further characterize "hot" and "cold" tumor's stromas and to investigate the association between dermoscopy, pathology, and the prognostic implications of regression. METHODS: A 14-year-collection-based retrospective analysis was carried out on 40 patients with confirmed regressive melanomas. RESULTS: The extent of regression in dermoscopy was associated with the stage of the regression (P = 0.05) and with the MelanA patterns in histology (P = 0.02). Blue-gray and gray-brown color of the peppering (P = 0.01), and the eccentric, multifocal character of the dermoscopic regression (P = 0.05) were associated with "hot" stromas (CD8+, Granzym B+). Focal histologic regression (regressing melanomas) was associated with a good outcome (P < 0.001), while a complete regression (regressed melanomas) was associated with melanoma-related death (P < 0.001). "Hot" stromas (CD8+ were significantly associated with survival at 10 years (P = 0.044), while "hot" stromas (Granzyme B+) were associated with the locoregional extension (P = 0.016), and the initial distant metastasis (P = 0.016). CONCLUSIONS: Dermoscopic features of regression in primary melanomas were associated with the stage of regression, its extent, and the "hot" or "cold" nature of the tumor stroma, with prognostic implications.

The Usefulness of Dermoscopy for the Recognition of Malignant Collision Tumors.

BACKGROUND: Preoperative diagnosis of malignant collision tumors (MCT) is extremely difficult. The value of dermoscopy to improve the correct detection of these tumors has not been previously studied. This study aims to evaluate the diagnostic accuracy of MCT with and without dermoscopy and to describe the dermoscopic features of a large series of MCT. METHODS: Dermoscopic images of 161 MCT were evaluated. Clinical and dermoscopic images of histopathologically proven MCT intermingled with other tumors were randomly presented to clinicians with different levels of experience, blinded to the diagnosis and objective of the study. The clinical and dermoscopic diagnostic accuracies were measured separately. RESULTS: A total of 161 histopathologically proven cases of MCT were collected. The most frequent MCT was basal cell carcinoma-seborrheic keratosis collision tumor (CT; 37.9%), followed by basal cell carcinoma-melanocytic nevus CT (19.9%), and melanoma-seborrheic keratosis CT (6.8%). Diagnostic accuracy among experts on dermoscopy was 71.4%. The study included 119 participants. The percentage of correct diagnoses was 8% by naked eye examination and 36.4% by dermoscopy (p < 0.001). The presence of the malignant component in the cases of MCT was not recognizable in 19.1% of cases by naked eye examination and in 11.8% of cases by dermoscopy (p < 0.001). CONCLUSIONS: The diagnosis of MCT can be assisted and clarified by dermoscopy. However, many of these lesions manifest complex morphologies and continue to be challenging, even for experts on dermoscopy. Atypical, uncertain, or non-classifiable lesions still need a complete excision for the final diagnosis.

5-Year Outcomes with Cobimetinib plus Vemurafenib in BRAFV600 Mutation-Positive Advanced Melanoma: Extended Follow-up of the coBRIM Study.

PURPOSE: The randomized phase III coBRIM study (NCT01689519) demonstrated improved progression-free survival (PFS) and overall survival (OS) with addition of cobimetinib to vemurafenib compared with vemurafenib in patients with previously untreated BRAFV600 mutation-positive advanced melanoma. We report long-term follow-up of coBRIM, with at least 5 years since the last patient was randomized. PATIENTS AND METHODS: Eligible patients were randomized 1:1 to receive either oral cobimetinib (60 mg once daily on days 1-21 in each 28-day cycle) or placebo in combination with oral vemurafenib (960 mg twice daily). RESULTS: 495 patients were randomized to cobimetinib plus vemurafenib (n = 247) or placebo plus vemurafenib (n = 248). Median follow-up was 21.2 months for cobimetinib plus vemurafenib and 16.6 months for placebo plus vemurafenib. Median OS was 22.5 months (95% CI, 20.3-28.8) with cobimetinib plus vemurafenib and 17.4 months (95% CI, 15.0-19.8) with placebo plus vemurafenib; 5-year OS rates were 31% and 26%, respectively. Median PFS was 12.6 months (95% CI, 9.5-14.8) with cobimetinib plus vemurafenib and 7.2 months (95% CI, 5.6-7.5) with placebo plus vemurafenib; 5-year PFS rates were 14% and 10%, respectively. OS and PFS were longest in patients with normal baseline lactate dehydrogenase levels and low tumor burden, and in those achieving complete response. The safety profile remained consistent with previously published reports. CONCLUSIONS: Extended follow-up of coBRIM confirms the long-term clinical benefit and safety profile of cobimetinib plus vemurafenib compared with vemurafenib monotherapy in patients with BRAFV600 mutation-positive advanced melanoma.

Decreased survival in patients treated by chemotherapy after targeted therapy compared to immunotherapy in metastatic melanoma.

BACKGROUND: Cytotoxic chemotherapy (CC) is currently used in metastatic melanoma after patients have developed resistance to immune checkpoint inhibitors (ICI) and/or Mitogen-Activated Protein Kinase inhibitors (MAPKi). We sought to evaluate if a previous treatment by ICI or MAPKi influences clinical outcomes in patients treated by CC in metastatic melanoma. METHODS: Eighty-eight patients with a metastatic melanoma, treated by CC after a previous treatment by ICI or MAPKi between January 2009 and October 2019, were retrospectively analyzed. Progression-Free-Survival (PFS), Overall Survival (OS), Overall Response Rate (ORR), and Disease Control Rate (DCR) were evaluated in patients treated by CC according to their prior treatment by ICI or MAPKi. RESULTS: Patients treated by CC after ICI tended to have a better median PFS (2.81 months (2.39-5.30) versus 2.40 months (0.91-2.75), p = 0.023), median OS (6.03 months (3.54-11.54) versus 4.44 months (1.54-8.59), p = 0.27), DCR (26.0% vs. 10.5%, p = 0.121) and ORR (22.0% vs. 7.9% p = 0.134) than those previously treated by MAPKi. CONCLUSIONS: A prior treatment by an MAPKi may be associated with a worse response to CC than ICI, and further investigations should be performed to confirm if there is a clinical benefit to propose CC in this setting.