Distintas características clínico-patológicas y pronósticas de los melanomas primarios nodulares delgados: un estudio internacional de 17 centros.

Dessinioti C , Dimou N , Geller AC , Stergiopoulou A , Lo S , Keim U , Gershenwald JE , Haydu LE , Ribero S , Quaglino P , Puig S , Malvehy J , Kandolf- Sekulovic L , Radevic T , Kaufmann R , Meister L , Nagore E , Traves V, Champsas GG , Plaka M, Dreno B , Varey E , Ramirez DM , Dummer R , Mangana J , Hauschild A , Egberts F , Peris K , Del Regno L , Forsea AM  , Zurac SA , Vieira R , Brinca A , Zalaudek I, Deinlein  , Linos E , Evangelou E , Thompson JF, Scolyer RA , Garbe C, Stratigos AJ 

Resumen

FONDO:

El melanoma nodular (NM) es más probable que sea fatal en comparación con otros subtipos de melanoma, un efecto atribuido a su mayor grosor de Breslow.

MÉTODOS:

Las características clínico-patológicas de NM y melanoma de propagación superficial diagnosticadas en 17 centros en Europa (n = 15), EE. UU. Y Australia entre 2006 y 2015 se analizaron mediante análisis de regresión logística multivariable, con énfasis en melanomas delgados (T1 ≤ 1,0 mm). El análisis de Cox evaluó la supervivencia específica del melanoma (MSS). Todas las pruebas estadísticas fueron de dos caras.

RESULTADOS:

En total, se incluyeron 20,132 melanomas (NM: 5,062, SSM: 15,070). En comparación con T1 SSM, T1 NM tuvo menos probabilidades de tener regresión (OR: 0,46, IC 95%: 0,29-0,72) o nevo remanentes histológicamente (OR: 0,60, IC 95%: 0,42-0,85), y es más probable que tenga mitosis (OR: 1.97, IC 95%: 1.33-2.93) y metástasis regionales (OR: 1.77, IC 95%: 1.02-3.05). T1 NM tuvo una tasa mitótica más alta que T1 SSM (media geométrica ajustada 2.2 [IC 95%: 1.9-2.4] frente a 1.6 [IC 95%: 1.5-1.7] por mm2, p <0.001). El análisis multivariado de Cox mostró un mayor riesgo de muerte específica por melanoma para NM en comparación con SSM para T1 (HR: 2,10; IC del 95%: 1,24-3,56) y melanomas T2 (HR: 1,30; IC del 95%: 1,01-1,68), mientras que después de tener en cuenta la heterogeneidad del centro, solo hubo significación estadística para T1 (HR: 2,20; IC del 95%: 1,28-3,78).

CONCLUSIONES:

T1 NM (en comparación con T1 SSM) se asoció con una constelación de características agresivas que pueden conferir un peor pronóstico. Nuestros resultados indican que el NM es un subtipo de melanoma de alto riesgo que debe considerarse para su inclusión en futuras clasificaciones de pronóstico del melanoma.

Fuente: PubMed

Distinct clinicopathological and prognostic features of thin nodular primary melanomas: an international study from 17 centers.

Abstract

BACKGROUND:

Nodular melanoma (NM) is more likely to be fatal compared to other melanoma subtypes, an effect attributed to its greater Breslow thickness.

METHODS:

Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), USA and Australia between 2006 and 2015, were analyzed by multivariate logistic regression analysis, with emphasis in thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival (MSS). All statistical tests were two-sided.

RESULTS:

In all, 20,132 melanomas (NM: 5,062, SSM: 15,070) were included. Compared to T1 SSM, T1 NM was less likely to have regression (OR: 0.46, 95% CI: 0.29-0.72) or nevus remnants histologically (OR: 0.60, 95% CI: 0.42-0.85), and more likely to have mitoses (OR: 1.97, 95% CI: 1.33-2.93) and regional metastasis (OR: 1.77, 95% CI: 1.02-3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean 2.2 [95% CI:1.9-2.4] vs 1.6 [95% CI:1.5-1.7] per mm2, p < 0.001). Cox multivariate analysis showed a higher risk for melanoma-specific death for NM compared to SSM for T1 (HR: 2.10, 95% CI: 1.24-3.56) and T2 melanomas (HR: 1.30, 95% CI: 1.01-1.68), while after accounting for center heterogeneity, there was statistical significance only for T1 (HR: 2.20, 95% CI: 1.28-3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis).

CONCLUSIONS:

T1 NM (compared to T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.

Biopsia de ganglio linfático centinela versus observación en melanoma grueso: un estudio de coincidencia de puntaje de propensión multicéntrico.

Boada A , Tejera-Vaquerizo A , Ribero S , Puig S , Moreno-Ramírez D, Descalzo-Gallego MA, Fierro MT, Quaglino P, Carrera C, Malvehy J, Vidal-Sicart S, Bennássar A, Rull R, Alos L , Requena C, Bolumar, Traves V, Pla Á, Fernández-Figueras MT, Ferrándiz C, Pascual I, Manzano JL, Sánchez-Lucas M, Giménez-Xavier P, Ferrandiz L, Nagore E

Resumen

El valor clínico de la biopsia de ganglio linfático centinela (SLN) en pacientes con melanoma grueso (Breslow> 4 mm) no se ha estudiado lo suficiente. El objetivo del estudio es evaluar si la biopsia de GLC aumenta la supervivencia en pacientes con melanoma cutáneo grueso y, como objetivo secundario, investigar las correlaciones entre la supervivencia y el estado de los ganglios linfáticos. 

Incluimos 1.211 pacientes consecutivos con melanomas gruesos (> 4 mm) registrados en las bases de datos de melanoma de los hospitales participantes entre 1997 y 2015. El seguimiento medio fue de 40 meses. De estos pacientes, 752 se emparejaron en pares según las puntuaciones de propensión según el sexo, la edad, la ubicación del tumor, las características histológicas del melanoma, el año de diagnóstico, el tratamiento hospitalario con interferón adyuvante. La biopsia de SLN frente a la observación se asoció con un mejor DFS [cociente de riesgo ajustado (AHR), 0,74; Intervalo de confianza (IC) del 95%: 0,61-0,90; p = 0.002] y OS (AHR, 0.75; IC del 95%, 0.60-0.94; p = 0.013) pero no MSS (AHR, 0.84; IC del 95%, 0.65-1.08; p = 0.165). Los pacientes con SLN negativo tuvieron mejores MSS a 5 y 10 años en comparación con los pacientes con SLN positivo (65.4 vs. 51.9% y 48.3 vs. 38.8%; p = 0.01, respectivamente). Como conclusión, la biopsia de SLN se asoció con una mejor DFS pero no MSS en pacientes con melanoma grueso después del ajuste por factores pronósticos clásicos. La biopsia de GLC es útil para estratificar a estos pacientes en diferentes grupos de pronóstico. La biopsia de SLN se asoció con una mejor DFS pero no con MSS en pacientes con melanoma grueso después del ajuste para los factores pronósticos clásicos. La biopsia de GLC es útil para estratificar a estos pacientes en diferentes grupos de pronóstico. La biopsia de SLN se asoció con una mejor DFS pero no con MSS en pacientes con melanoma grueso después del ajuste para los factores pronósticos clásicos. 

La biopsia de GLC es útil para estratificar a estos pacientes en diferentes grupos de pronóstico.

Fuente:PubMed

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

Abstract

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups.

Eficacia de nuevos regímenes de inmunoterapia en pacientes con melanoma metastásico con mutaciones de CDKN2A en la línea germinal .

Helgadottir H , Ghiorzo P , van Doorn R , Puig S , Levin M , Kefford R , Lauss M , Queirolo P , Pastorino L , Kapiteijn E , Potrony M , Carrera C , Olsson H , Höiom V , Jönsson G 

Resumen

FONDO:

La mutación heredada de CDKN2A es un fuerte factor de riesgo para el melanoma cutáneo. Además, se ha encontrado que los portadores tienen mala supervivencia específica para el melanoma. En este estudio, se evaluaron las respuestas a nuevos agentes de inmunoterapia en portadores de mutación CDKN2A con melanoma metastásico.

MÉTODOS:

Los portadores de la mutación CDKN2A que han desarrollado un melanoma metastásico y se han sometido a tratamientos de inmunoterapia se identificaron entre los portadores incluidos en estudios de seguimiento para el melanoma familiar. Las respuestas de los portadores se compararon con las respuestas informadas en ensayos clínicos de fase III para los inhibidores de CTLA-4 y PD-1. De los conjuntos de datos disponibles al público, los melanomas con mutación somática de CDKN2A se analizaron para determinar la asociación con la carga mutacional del tumor.

RESULTADOS:

Once de los 19 portadores (58%) respondieron a la terapia, una frecuencia significativamente mayor que la observada en los ensayos clínicos (p = 0.03, prueba binomial contra una tasa esperada del 37%). Además, 6 de los 19 portadores (32%) tuvieron una respuesta completa, una frecuencia significativamente mayor que la observada en los ensayos clínicos (p = 0,01, prueba binomial frente a una tasa esperada del 7%). En 118 melanomas con mutaciones somáticas de CDKN2A , se observaron números totales significativamente mayores de mutaciones en comparación con 761 melanomas sin mutación de CDKN2A (prueba de Wilcoxon, p <0,001).

CONCLUSIÓN:

Los pacientes con melanoma mutado CDKN2A pueden tener mejores respuestas de inmunoterapia debido al aumento de la carga mutacional del tumor, lo que resulta en más neoantígenos y respuestas inmunitarias antitumorales más fuertes.

Fuente: PubMed

https://www.ncbi.nlm.nih.gov/pubmed/30291219

Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline CDKN2A mutations.

Abstract

BACKGROUND:

Inherited CDKN2A mutation is a strong risk factor for cutaneous melanoma. Moreover, carriers have been found to have poor melanoma-specific survival. In this study, responses to novel immunotherapy agents in CDKN2A mutation carriers with metastatic melanoma were evaluated.

METHODS:

CDKN2A mutation carriers that have developed metastatic melanoma and undergone immunotherapy treatments were identified among carriers enrolled in follow-up studies for familial melanoma. The carriers' responses were compared with responCDKN2A mutation were analysed for association with tumour mutational load.

ses reported in phase III clinical trials for CTLA-4 and PD-1 inhibitors. From publicly available data sets, melanomas with somatic

RESULTS:

Eleven of 19 carriers (58%) responded to the therapy, a significantly higher frequency than observed in clinical trials (p=0.03, binomial test against an expected rate of 37%). Further, 6 of the 19 carriers (32%) had complete response, a significantly higher frequency than observed in clinical trials (p=0.01, binomial test against an expected rate of 7%). In 118 melanomas with somatic CDKN2A mutations, significantly higher total numbers of mutations were observed compared with 761 melanomas without CDKN2A mutation (Wilcoxon test, p<0.001).

CONCLUSION:

Patients with CDKN2A mutated melanoma may have improved immunotherapy responses due to increased tumour mutational load, resulting in more neoantigens and stronger antitumorous immune responses.

Diagnosis Dermatologica Clinic, skin cancer experts

Diagnosis Dermatologica Clinic,

https://youtu.be/hP2p-MoU9Go

Diagnosis Dermatologica is a pioneer center worldwide in the diagnosis and treatment of skin cancer.
Its professionals are experts with recognized international prestige in skin cancer and melanoma and are under the medical direction of the Dr. Susana Puig Sardá and Dr. Josep Malvehy Guilera, head of dermatology service and coordinator of the melanoma group respectively at the Hospital Clínic de Barcelona.

They are responsible for the introduction and validation of numerous diagnostic techniques, such as the digital monitoring method currently implemented around the world and are authors of more than 400 research articles in the most prestigious international journals.

The medical team is made up of dermatologists who are experts in imaging technology, in dermato-oncology and in dermatological therapeutics, being leaders in these fields at a national and international level. We also have a team of nursing professionals and image technicians specialized in the dermatological patient with extensive experience.

#josepmalvehy #susanapuig #skincancer #confocalexvivo #confocalinvivo #melanoma #carcinoma #cáncerdepiel #cedilp #microscopy #molemax #fotofinder #mavig #caliber #dermatologist #topdoctors

Dermoscopic Clues for Diagnosing Melanomas That Resemble Seborrheic Keratosis.

PubMed

Abstract

Importance:

Melanomas that clinically mimic seborrheic keratosis (SK) can delay diagnosis and adequate treatment. However, little is known about the value of dermoscopy in recognizing these difficult-to-diagnose melanomas.

Objective:

To describe the dermoscopic features of SK-like melanomas to understand their clinical morphology.

Design, Setting, and Participants:

This observational retrospective study used 134 clinical and dermoscopic images of histopathologically proven melanomas in 134 patients treated in 9 skin cancer centers in Spain, France, Italy, and Austria. Without knowledge that the definite diagnosis for all the lesions was melanoma, 2 dermoscopy-trained observers evaluated the clinical descriptions and 48 dermoscopic features (including all melanocytic and nonmelanocytic criteria) of all 134 images and classified each dermoscopically as SK or not SK. The total dermoscopy score and the 7-point checklist score were assessed. Images of the lesions and patient data were collected from July 15, 2013, through July 31, 2014.

Main Outcomes and Measures:

Frequencies of specific morphologic patterns of (clinically and dermoscopically) SK-like melanomas, patient demographics, and interobserver agreement of criteria were evaluated.

Results:

Of the 134 cases collected from 72 men and 61 women, all of whom were white and who had a mean (SD) age of 55.6 (17.5) years, 110 (82.1%) revealed dermoscopic features suggestive of melanoma, including pigment network (74 [55.2%]), blue-white veil (72 [53.7%]), globules and dots (68 [50.7%]), pseudopods or streaks (47 [35.1%]), and blue-black sign (43 [32.3%]). The remaining 24 cases (17.9%) were considered likely SKs, even by dermoscopy. Overall, lesions showed a scaly and hyperkeratotic surface (45 [33.6%]), yellowish keratin (42 [31.3%]), comedo-like openings (41 [30.5%]), and milia-like cysts (30 [22.4%]). The entire sample achieved a mean (SD) total dermoscopy score of 4.7 (1.6) and a 7-point checklist score of 4.4 (2.3), while dermoscopically SK-like melanomas achieved a total dermoscopy score of only 4.2 (1.3) and a 7-point checklist score of 2.0 (1.9), both in the range of benignity. The most helpful criteria in correctly diagnosing SK-like melanomas were the presence of blue-white veil, pseudopods or streaks, and pigment network. Multivariate analysis found only the blue-black sign to be significantly associated with a correct diagnosis, while hyperkeratosis and fissures and ridges were independent risk markers of dermoscopically SK-like melanomas.

Conclusions and Relevance:

Seborrheic keratosis-like melanomas can be dermoscopically challenging, but the presence of the blue-black sign, pigment network, pseudopods or streaks, and/or blue-white veil, despite the presence of other SK features, allows the correct diagnosis of most of the difficult melanoma cases.

https://www.ncbi.nlm.nih.gov/pubmed/28355453

#josepmalvehy  #aliciabarreiro  #aliciabarreiro #susanapuig #paulaaguilera #cristinacarrera, #cutaneousmelanoma #diagnosisofmelanoma #dermoscopic #seborrheickeratosis #keratosis, #dermoscopy #skincancer

Dermoscopy versus reflectance confocal microscopy for the diagnosis of lentigo maligna

PubMed

Dermoscopy versus reflectance confocal microscopy for the diagnosis of lentigo maligna

BACKGROUND:

Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques.

OBJECTIVE:

We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images.

METHODS:

223 facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical, dermoscopic and RCM examination were compared. Inter-investigator variability and confidence level in the diagnosis were also evaluated.

RESULTS:

Overall diagnostic accuracy of the two imaging techniques was good (area under the curve of the sROC function: 0.89). RCM was more sensitive (80%, versus 61%) and less specific (81% versus 92%) than dermoscopy for LM/LMM. In particular RCM showed a higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher inter-investigator agreement and a higher confidence level in the diagnosis than dermoscopy.

CONCLUSION:

RCM and dermoscopy are both useful techniques for the diagnosis of facial lesions and in particular LM/LMM. RCM is particularly suitable for the identification of hypomelanotic and recurrent LM/LMM. This article is protected by copyright. All rights reserved.

https://www.ncbi.nlm.nih.gov/pubmed/29341263

This article is protected by copyright. All rights reserved.

 

 

#confocal #cristinacarrera #josepmalvehy #susanapuig #skincancer #invivo #confocalinvivo #cutaneousmelanoma #lentigo #reflactanceconfocal #cedilp #pubmed #microscopy

 

Improving diagnostic sensitivity of combined dermoscopy and reflectance confocal microscopy imaging through double reader concordance evaluation in telemedicine settings: A retrospective study of 1000 equivocal cases

PubMed

Improving diagnostic sensitivity of combined dermoscopy and reflectance confocal microscopy imaging through double reader concordance evaluation in telemedicine settings: A retrospective study of 1000 equivocal cases

Abstract

BACKGROUND:

Reflectance confocal microscopy (RCM) is an imaging device that permits non-invasive visualization of cellular morphology and has been shown to improve diagnostic accuracy of dermoscopically equivocal cutaneous lesions. The application of double reader concordance evaluation of dermoscopy-RCM image sets in retrospective settings and its potential application to telemedicine evaluation has not been tested in a large study population.

OBJECTIVE:

To improve diagnostic sensitivity of RCM image diagnosis using a double reader concordance evaluation approach; to reduce mismanagement of equivocal cutaneous lesions in retrospective consultation and telemedicine settings.

METHODS:

1000 combined dermoscopy-RCM image sets were evaluated in blind by 10 readers with advanced training and internship in dermoscopy and RCM evaluation. We compared sensitivity and specificity of single reader evaluation versus double reader concordance evaluation as well as the effect of diagnostic confidence on lesion management in a retrospective setting.

RESULTS:

Single reader evaluation resulted in an overall sensitivity of 95.2% and specificity of 76.3%, with misdiagnosis of 8 melanomas, 4 basal cell carcinomas and 2 squamous cell carcinomas. Combined double reader evaluation resulted in an overall sensitivity of 98.3% and specificity of 65.5%, with misdiagnosis of 1 in-situ melanoma and 2 basal cell carcinomas.

CONCLUSION:

Evaluation of dermoscopy-RCM image sets of cutaneous lesions by single reader evaluation in retrospective settings is limited by sensitivity levels that may result in potential mismanagement of malignant lesions. Double reader blind concordance evaluation may improve the sensitivity of diagnosis and management safety. The use of a second check can be implemented in telemedicine settings where expert consultation and second opinions may be required.

https://www.ncbi.nlm.nih.gov/pubmed/29121636

#josepmalvehy  #carcinomabasocelular  #dermatoscopy #confocal #cancerdepiel #confocalinvivo, #microscopy #cutaneousmelanoma #squamouscellcarcinomas #carcinomas  #melanomas #reflectanceconfocal #telemedicine

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

https://www.ncbi.nlm.nih.gov/pubmed/28960289

Abstract

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups.


#melanoma #josepmalvehy #susanapuig #Mohs #dermoscopy #sentinellymphnode #skincancer #topdoctors #dermatologiabarcelona #cutaneousbarcelona #diagnosisdermatologica