Current management of patients with cutaneous melanoma with a positive sentinel lymph node / Tratamiento actual de pacientes con melanoma cutáneo y ganglio centinela positivo

Abstract Introduction : Immediate completion lymph node dissection (CLND) performed in patients with a positive sentinel lymph node biopsy (SLNB) cutaneous melanoma is not associated with improved melanoma specific survival versus active surveillance (AS) using nodal ul trasound. Clinical practice experience and outcomes of AS and adjuvant therapy is now starting to be published in literature. Methods : Retrospective analysis of patients with a positive-SLNB between June/2017-February/2022. Impact of management on any-site recurrence free survival (RFS), isolated nodal recurrence (INR), distant metasta sis-free survival (DMFS) and melanoma-specific survival (MSS) was evaluated. Results : From 126 SLNB, 31 (24.6%) were positive: 24 received AS and 7 CLND. Twenty-one (68%) received ad juvant therapy (AS, 67% and CLND, 71%). With a median follow-up of 18 months, 10 patients developed recur rent disease with an estimated 2-yr RFS of 73% (CI95%, 0.55-0.86) (30% in AS group vs. 43% in dissection group; P = 0.65). Four died of melanoma with an estimated 2-yr MSS of 82% (CI 95%, 0.63-0.92) and no differences between AS and CLND groups (P = 0.21). Estimated 2-yr DMFS of the whole cohort was 76% (CI 95%, 0.57-0.88) with no differences between groups (P = 0.33). Conclusion : Active surveillance strategy has been adopted for most positive-SLNB cutaneous melanoma patients. Adjuvant therapy without immediate CLND was delivered in nearly 70% of patients. Our results align with outcomes of randomized control trials and previous real-world data.

Resumen Introducción : La linfadenectomía inmediata (LI) re alizada en pacientes con biopsia de ganglio centinela (BGC) positivo por melanoma cutáneo no está asociada a mejoría en la supervivencia libre de enfermedad vs. vigilancia activa (VA). Resultados oncológicos y experi encia en la práctica clínica con dicha conducta asociados a tratamiento adyuvante comienzan a ser publicados en la literatura. Métodos : Análisis retrospectivo incluyendo paci entes con BGC-positiva por melanoma cutáneo entre junio/2017-febrero/2022. Se evaluó impacto del manejo en: supervivencia libre de recurrencia (SLR), recurren cia ganglionar aislada (RGA), supervivencia libre de metástasis a distancia (SLMD) y supervivencia libre de enfermedad (SLE). Resultados : De 126 pacientes, 31 (24.6%) fueron positi vos: en 24 se realizó VA y en 7 LI. Veintiún pacientes (68%) recibieron tratamiento adyuvante (VA, 67% y LI, 71%). Con una media de seguimiento de 18 meses, 10 pacientes presentaron recurrencia de la enfermedad con una SLR estimada a 2 años del 73% (CI95%, 0.55-0.86) (30% en VA vs. 43% en LI; P = 0.65). Cuatro murieron de melanoma con una SLE a 2 años del 82% (CI 95%, 0.63-0.92); sin diferencia entre ambos grupos (P = 0.21). La SLMD a 2 años de toda la cohorte fue de 76% (CI 95%, 0.57-0.88; P = 0.33). Conclusión : La vigilancia activa se ha adoptado como conducta para la mayoría de los pacientes con BGC-positivo. El tratamiento adyuvante sin linfadenectomía inmediata se realizó en cerca del 70% de nuestra serie. Los resultados de nuestra serie son similares a los re portados en la literatura.

The radiosensitization effect of STING agonist on cutaneous melanoma cells / 中华放射医学与防护杂志

Objective:To investigate the radiosensitizing effect and underlying mechanism of STING agonist (c-di-AMP) on cutaneous melanoma cells.Methods:Human cutaneous melanoma cells (A375) were divided into four groups: the control group, 10 μmol/L c-di-AMP group, X-ray irradiation group and X-ray irradiation combined with c-di-AMP group. The radiosensitizing effect of c-di-AMP on A375 cells was detected by CCK-8-based viability assay, lactate dehydrogenase (LDH) release assay, flow cytometry-based apoptosis assay, and colony formation assay. Western blot analysis was used to determine the expressions of cell death-related proteins.Results:In combination with 10 Gy X-ray irradiation, 10 μmol/L c-di-AMP showed significant radiosensitization effect in A375 cells, which was evidenced by decreased cell activity ( t=5.11, P<0.05), increased cytotoxicity ( t=10.15, P<0.05) and cell apoptosis ( t=4.41, P<0.05) and reduced clone viability( t=6.30, 3.55, 5.45, 3.55, P<0.05). The calculated radiosensitization ratio of c-di-AMP to A375 cells was 1.88. Moreover, 10 μmol/L c-di-AMP further increased the expressions of cell death-related proteins induced by radiation in A375 cells. Conclusions:The STING agonist c-di-AMP can be used as a radiosensitizer for cutaneous melanoma, which may provide a novel strategy for radiotherapy.

RITA selectively inhibits proliferation of BAP1-deficient cutaneous melanoma cells in vitro / 南方医科大学学报

OBJECTIVE@#To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion.@*METHODS@#Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting.@*RESULTS@#The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001).@*CONCLUSION@#Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.

Analysis on tumor immune microenvironment and construction of a prognosis model for immune-related skin cutaneous melanoma / 中南大学学报(医学版)

OBJECTIVES@#Malignant melanoma is a highly malignant and heterogeneous skin cancer. Although immunotherapy has improved survival rates, the inhibitory effect of tumor microenvironment has weakened its efficacy. To improve survival and treatment strategies, we need to develop immune-related prognostic models. Based on the analysis of the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Sequence Read Archive (SRA) database, this study aims to establish an immune-related prognosis prediction model, and to evaluate the tumor immune microenvironment by risk score to guide immunotherapy.@*METHODS@#Skin cutaneous melanoma (SKCM) transcriptome sequencing data and corresponding clinical information were obtained from the TCGA database, differentially expressed genes were analyzed, and prognostic models were developed using univariate Cox regression, the LASSO method, and stepwise regression. Differentially expressed genes in prognostic models confirmed by real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Survival analysis was performed by using the Kaplan-Meier method, and the effect of the model was evaluated by time-dependent receiver operating characteristic curve as well as multivariate Cox regression, and the prognostic model was validated by 2 GEO melanoma datasets. Furthermore, correlations between risk score and immune cell infiltration, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) score, immune checkpoint mRNA expression levels, tumor immune cycle, or tumor immune micro-environmental pathways were analyzed. Finally, we performed association analysis for risk score and the efficacy of immunotherapy.@*RESULTS@#We identified 4 genes that were differentially expressed in TCGA-SKCM datasets, which were mainly associated with the tumor immune microenvironment. A prognostic model was also established based on 4 genes. Among 4 genes, the mRNA and protein levels of killer cell lectin like receptor D1 (KLRD1), leukemia inhibitory factor (LIF), and cellular retinoic acid binding protein 2 (CRABP2) genes in melanoma tissues differed significantly from those in normal skin (all P<0.01). The prognostic model was a good predictor of prognosis for patients with SKCM. The patients with high-risk scores had significantly shorter overall survival than those with low-risk scores, and consistent results were achieved in the training cohort and multiple validation cohorts (P<0.001). The risk score was strongly associated with immune cell infiltration, ESTIMATE score, immune checkpoint mRNA expression levels, tumor immune cycle, and tumor immune microenvironmental pathways (P<0.001). The correlation analysis showed that patients with the high-risk scores were in an inhibitory immune microenvironment based on the prognostic model (P<0.01).@*CONCLUSIONS@#The immune-related SKCM prognostic model constructed in this study can effectively predict the prognosis of SKCM patients. Considering its close correlation to the tumor immune microenvironment, the model has some reference value for clinical immunotherapy of SKCM.

Ganglio centinela en el melanoma cutáneo / Sentinel node in cutaneous melanoma

La biopsia selectiva del ganglio centinela (BSGC) se ha desarrollado de tal manera que reemplazó a la linfadenectomía electiva en el tratamiento del melanoma cutáneo (MC). Numerosos estudios demostraron que el estado del ganglio centinela es un factor pronóstico independiente en relación con la supervivencia global y la supervivencia libre de enfermedad de los pacientes con melanoma. El objetivo del presente trabajo fue realizar una revisión bibliográfica para comprender la utilidad y las indicaciones de la BSGC en pacientes con MC a partir de la evidencia actual publicada.

Sentinel lymph biopsy (SLNB) has been developed in such a way that is has replaced elective lymphadenectomy in the treatment of cutaneous melanoma (CM). Numerous studies have shwn that sentinel node status is an independent prognostic factor in relation to overall survival and disease-free survival of patients with CM. The purpose of this article is to carry out a literature review to understand the usefulness and indications of SLNB in patients with CM based on the current evidence.

Cutaneous metastatic melanoma in a Siberian tiger (Panthera tigris altaica) - case report / Melanoma cutâneo metastático em um tigre-siberiano (Panthera tigris altaica) - relato de caso

A male 15-year-old captive Siberian tiger (Panthera tigris altaica) developed pelvic limb hypermetry over the past 10 years. Recently, an ulcerated black nodule located caudally to the right ear was observed. The animal was submitted to surgery for removing the tumor, but died during anesthetic recovery. At necropsy, another infiltrative nodule was observed caudally to the right ear. Histologically, both nodules corresponded to melanocytic neoplasia, varying from heavily pigmented to amelanotic, with metastasis to mediastinal lymph nodes, spleen and lung. Lipofuscinosis and corpora amylacea were histologically observed in the central nervous system. Macroscopic and histologic findings confirmed the diagnosis of skin metastatic melanoma in a captive adult Siberian tiger.(AU)

Um tigre-siberiano (Panthera tigris altaica) de cativeiro, macho, de 15 anos de idade, apresentou hipermetria dos membros pélvicos nos últimos 10 anos, e recentemente, foi observado um nódulo preto e ulcerado caudalmente à orelha direita. O animal foi submetido à cirurgia para remoção do nódulo e morreu durante a recuperação anestésica. À necropsia, outro nódulo infiltrativo, foi detectado caudalmente a orelha direita. Histologicamente, ambos os nódulos correspondiam à neoplasia melanocítica, com células variando de fortemente pigmentadas a amelanóticas, com metástase para linfonodos mediastinais, baço e pulmão. Havia lipofucsinose e corpora amilácea no sistema nervoso central. Os achados macroscópicos e histológicos confirmam o diagnóstico de melanoma cutâneo metastático em um tigre-siberiano adulto de cativeiro.(AU)

Interactome of vertebrate GAF/ThPOK reveals its diverse functions in gene regulation and DNA repair

GAGA associated factor (GAF) is a sequence-specific DNA binding transcription factor that is evolutionarilyconserved from flies to humans. Emerging evidence shows a context-dependent function of vertebrate GAF(vGAF, a.k.a. ThPOK) in multiple processes like gene activation, repression, and enhancer-blocking. Wehypothesize that context-dependent interaction of vGAF with a diverse set of proteins forms the basis for themultifunctional nature of vGAF. To this end, we deciphered the protein–protein interactome of vGAF andshow that vGAF interacts with chromatin remodelers, RNA metabolic machinery, transcriptional activators/repressors, and components of DNA repair machinery. We further validated the biological significance of ourprotein–protein interaction data with functional studies and established a novel role of vGAF in DNA repairand cell-survival after UV-induced DNA damage. One of the major risk factors for skin cutaneous melanoma isprolonged exposure of UV and subsequent DNA damage. vGAF is highly expressed in normal skin tissue.Interestingly, our analysis of high-throughput RNA-sequencing data shows that vGAF is heavily downregulated across all major stages of skin cutaneous melanoma suggesting its potential as a diagnostic biomarker.Taken together, our study provides a plausible explanation for the diverse gene regulatory functions of vGAFand unravels its novel role in DNA repair.

Comparación entre los melanomas de cabeza y cuello con los de tronco y extremidades / Comparison between head and neck melanomas with trunk and extremity melanomas

Antecedentes: los melanomas en cabeza y cuello (MCC) han sido asociados con factores pronósticos diferentes de aquellos en otras localizaciones. Objetivo: comparar características demográficas, clínicas y resultados del tratamiento quirúrgico de pacientes con MCC y pacientes con melanomas en tronco y extremidades (MTE). Material y métodos: se llevó a cabo una revisión retrospectiva de las historias clínicas de pacientes operados por melanoma entre enero de 2012 y diciembre de 2017. Quince pacientes (22,3%) tuvieron MCC y 52 (77,7%) MTE. Resultados: ambos grupos tuvieron edad similar (63,8 ± 21,1 versus 58,5 ± 16), pero los MCC mostraron una tendencia con predominio masculino (80% versus 61,3%). Los MCC tuvieron menor espesor tumoral que los MTE (2,07 versus 5,5 mm) y mayor porcentaje de melanoma in situ, 5 (33,3%) versus 8 (15,3%), pero requirieron vaciamientos ganglionares más a menudo (33% versus 25%) así como reconstrucción del defecto primario con colgajos locales y miocutáneos. Durante el seguimiento, en el grupo de MCC, dos pacientes desarrollaron recidivas locales que fueron extirpadas, y otros tres desarrollaron metástasis a distancia en pulmón, intestino delgado y abdomen y fallecieron por la enfermedad; en el grupo de MTE un paciente tuvo recidiva local y cinco fallecieron de metástasis sistémicas. El tamaño de la muestra no permitió aplicar pruebas de significación entre las diferencias encontradas. Conclusión: los MCC se presentan en un amplio rango de edad y estadios, y tuvieron algunas diferencias clínicas con el MTE. Los defectos producidos por la extirpación de la lesión primaria requieren procedimientos reconstructivos más complejos la mayoría de las veces y se aconseja un abordaje multidisciplinario.

Background: Head and neck melanomas (HNMs) have been associated with prognostic factors different from those on other locations. Objective: The goal of the present study was to compare the demographic and clinical characteristics and the outcomes of surgical treatment between patients with HNM and those with trunk and extremity melanoma (TEM). Material and methods: The clinical records of patients undergoing surgery for melanoma between October 2014 and April 2018 were retrospectively reviewed. Fifteen patients (22.3%) had HNM and 52 (77.7) presented TEM. Results: There were no differences in age between both groups (63.8 ± 21.1 versus 58.5 ± 16), but there was a trend toward higher percentage of men in the HNM group (80% versus 61.3%). Patients with HNM had lower tumor thickness than those with TEM (2.07 versus 5.5 mm), higher incidence of melanoma in situ [5 (33.3%) versus 8 (15.3%)]; lymph node resection was more common (33% versus 25%) as well as reconstruction of the primary defect with local and musculocutaneous flaps. During follow-up, two patients in the HNM group developed local recurrences that were excised and three presented distant metastases in the lung, small bowel and abdomen and finally died due to the disease. In the TEM group, one patient had local recurrence and five died due to systemic metastases. The sample size was not sufficient to assess statistically significant differences. Conclusion: Head and neck melanomas occur in a wide age range and stages and has some clinical differences with TEM. The defects produced after the excision of the primary lesion often require more complex procedures and should be managed with a multidisciplinary approach.

Melanoma cutáneo: algunas consideraciones actuales / Cutaneous melanoma: some current considerations

El melanoma cutáneo es una enfermedad grave y potencialmente mortal que afecta a la población de todo el orbe y que se encuentra condicionada por muchos factores de riesgo relacionados con algunos estilos de vida, que pueden ser modificables. El hallazgo oportuno y precoz de esta entidad clínica eleva la sobrevida de las personas afectadas y favorece el resultado terapéutico; sin embargo, en ocasiones no se diagnostica a tiempo. Actualmente ya se presenta en individuos más jóvenes de 25-29 años de edad y con gran probabilidad de generar metástasis, lo cual constituye una preocupación en el ámbito de la salud. Al respecto, se decidió efectuar esta revisión bibliográfica, con el fin de actualizar algunos elementos sobre el tema y darlos a conocer a la comunidad médica nacional y extranjera.

The cutaneous melanoma is a severe and potentially mortal disease that affects the population of the whole world and that is conditioned by many risk factors related to some lifestyles that can be modified. The opportune and early finding of this clinical entity elevates the survival of affected people and it favors the therapeutic result; however, it is not diagnosed on time occasionally. At present it is already presented in younger individuals with 25-29 years old and with great probability of generating metastasis, which constitutes a concern in the health field. In this respect, it was decided to make this literature review, with the purpose of to update some elements on the topic and to make them known in the national and foreign medical community.

Dynamic imaging of melanoma development in nude mice using high-frequency ultrasound and optical coherence tomography / 南方医科大学学报

OBJECTIVE@#To investigate the application of high-frequency ultrasound (HFUS) and optical coherence tomography (OCT) for monitoring the progression of cutaneous melanoma (CM) in nude mice.@*METHODS@#Twenty 4-week-old nude mice were randomly divided into CM group (=16) and control group (=4). In CM group, A375 cell suspension were injected subcutaneously on the back of the nude mice, and only culture medium was injected in the control group. The tumor growth was monitored by gross observation and with HFUS and OCT on a daily basis. The tumor formation rate, time, and size were recorded and melanoma visibility was assessed quantitatively using the contrast- to-background-noise ratio (CNR). Twentyfour days after cell implantation, the tumors were dissected for pathological examination.@*RESULTS@#The tumor formation rate was 87.5% in CM group. OCT detected tumor formation at an earlier time than HFUS. With the growth of the tumor, HFUS detected spots or bands of strong echoes, and flattening of the upper dermis could be observed in OCT; the of HFUS and OCT were obviously enhanced over time ( < 0.05). The tumor growth curve showed that OCT was more sensitive for measurement of the tumor thickness than HFUS. The length, depth and volume of the tumors measured by HFUS were significantly greater than those measured by OCT ( < 0.05).@*CONCLUSIONS@#HFUS and OCT can monitor the dynamic development of cutaneous melanoma in nude mice, and their imaging performance differs in different stages of tumor development.

Evaluation of ¹⁸F-FDG PET/CT Parameters for Detection of Lymph Node Metastasis in Cutaneous Melanoma / 대한핵의학회잡지

PURPOSE: The purpose of this study was to investigate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in the detection of regional lymph node (LN) metastasis in patients with cutaneous melanoma.METHODS: We evaluated patients with cutaneous melanoma who underwent FDG PET/CT for initial staging or recurrence evaluation. A total of 103 patients were enrolled, and 165 LNs were evaluated. LNs that were confirmed pathologically or by follow-up imaging were included in this study. PET parameters, including maximum standardized uptake value (SUVmax), total lesion glycolysis and tumour-to-liver ratio, were used to determine the presence of metastases, and the results were compared with CT-determined LN metastasis. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values of the FDG PET parameters.RESULTS: A total of 93 LNs were malignant, and 84 LNs were smaller than 10 mm. In all 165 LNs, an SUVmax of >2.51 showed a sensitivity of 73.1%, a specificity of 88.9%, and an accuracy of 80.0% in detecting metastatic LNs. CT showed a higher specificity (87.3%) and lower accuracy (65.5%). For non-enlarged regional LNs ( < 10 mm), an SUVmax cut-off value of 1.4 showed the highest negative predictive value (81.3%). For enlarged LNs (≥10 mm), an SUVmax cut-off value of 2.4 showed the highest sensitivity (90.7%) and accuracy (88.9%) in detecting metastatic LNs.CONCLUSIONS: In patients with cutaneous melanoma, an SUVmax of >2.4 showed a high sensitivity (91%) and accuracy (89%) in detecting metastasis in LNs ≥1 cm, and LNs < 1 cm with an SUVmax < 1.4 were likely to be benign.

Epigenetic signature of differentially methylated genes in cutaneous melanoma

Background: Cutaneous melanoma (CM) is the most aggressive subtype of skin cancer, with increasing incidence over the past several decades. DNA methylation is a key element of several biological processes such as genomic imprinting, cell differentiation and senescence, and deregulation of this mechanism has been implicated in several diseases, including cancer. In order to understand the relationship of DNA methylation in CMs, we searched for an epigenetic signature of cutaneous melanomas by comparing the DNA methylation profiles between tumours and benign melanocytes, the precursor cells of CM. Methods: We used 20 primary CMs and three primary cell cultures of melanocytes as a discovery cohort. The tumours mutational background was collected as previously reported. Methylomes were obtained using the HM450K DNA methylation assay, and differential methylation analysis was performed. DNA methylation data of CMs from TCGA were recovered to validate our findings. Results: A signature of 514 differentially methylated genes (DMGs) was evident in CMs compared to melanocytes, which was independent of the presence of driver mutations. Pathway analysis of this CM signature revealed an enrichment of proteins involved in the binding of DNA regulatory regions (hypermethylated sites), and related to transmembrane signal transducer activities (hypomethylated sites). The methylation signature was validated in an independent dataset of primary CMs, as well as in lymph node and distant metastases (correlation of DNA methylation level: r > 0,95; Pearson's test: p < 2.2e-16). Conclusions: CMs exhibited a DMGs signature, which was independent of the mutational background and possibly established prior to genetic alterations. This signature provides important insights into how epigenetic deregulation contributes to melanomagenesis in general (AU)

Relación entre ganglio centinela positivo y el espesor de Breslow en pacientes con melanoma cutáneo primario / Relationship between positive sentinel lymph node and Breslow's depth in patients with primary cutaneous melanoma

Introducción: es sabido que el pronóstico del melanoma cutáneo depende, entre otros factores, de la existencia de diseminación linfática a ganglios. La biopsia del ganglio centinela busca identificar metástasis ganglionares subclínicas. Objetivo: el presente estudio tuvo por objetivo analizar la asociación entre la presencia de ganglio centinela positivo, identificado mediante rastreo con radioisótopo 99mTc-coloide de Renio, y el espesor de Breslow hallado en la lesión primaria a nivel cutáneo. Metodología: se analizaron 52 pacientes. Se realizó la búsqueda del ganglio centinela por el método de rastreo con radioisótopo 99mTc-coloide de Renio y posterior biopsia del mismo, en pacientes tratados en el Instituto Nacional de Cancerología de México, entre enero de 2015 a agosto de 2016, con diagnóstico de melanoma cutáneo y espesor de Breslow mayor o igual a 1mm o con menor a 1mm y otros criterios de riesgo como la ulceración. Aquellos con biopsia positiva fueron sometidos a linfadenectomía. Además, se recogieron las siguientes variables: sexo, edad, localización, tipo de melanoma, espesor de Breslow y ulceración. Resultados: la edad media de la muestra fue 57 ± 15 años. El 63,5% de los pacientes fue del sexo masculino. El tipo histológico más frecuente fue el melanoma de extensión superficial (69,2%). Se detectó positividad del ganglio centinela en 46,2% y 28,8% presentó Breslow >4,0 mm. Se encontró relación entre la presencia de ganglio centinela positivo y espesor de Breslow (p=0,007). Conclusiones: a medida que aumenta el espesor de Breslow, lo hace también el encuentro de metástasis en ganglio centinela. Se recomienda realizar estudios de casos y controles para evaluar el factor predictivo que puede llegar a tener el encontrar ganglio centinela positivo.

Introduction: It is known that the prognosis of cutaneous melanoma depends, among other factors, on the existence of lymphatic spread to lymph nodes. Sentinel node biopsy seeks to identify subclinical lymph node metastases. Objective: The present study aimed to analyze the association between the presence of positive sentinel lymph node, identified by Rhenium 99mTc-colloid radioisotope tracing, and the Breslow´s depth found in the primary lesion at the cutaneous level. Methodology: 52 patients were analyzed. The sentinel lymph node was searched by the rhenium 99mTc-colloid radioisotope and subsequent biopsy of it in patients treated at the Instituto Nacional de Cancerología of Mexico, between January 2015 and August 2016, with a diagnosis of cutaneous melanoma and Breslow's depth greater-than or equal to 1mm or less-than 1mm and other risk criteria such as ulceration. Those patients with positive biopsy underwent lymphadenectomy. In addition, the following variables were collected: sex, age, location of the lesion, type of melanoma, Breslow's depth, and ulceration. Results: Mean age of the sample was 57±15 years. 63.5% of the patients were male. The most frequent histological type was superficial spreading melanoma (69.2%). 46.2% had positive sentinel lymph node. 28.8% presented Breslow >4.0 mm. A relationship was found between the presence of positive sentinel lymph node and Breslow's depth (p=0.007). Conclusions: As Breslow's depths increases, so does the metastasis encounter in sentinel lymphs nodes. It is recommended to carry out case-control studies to evaluate the predictive factor that may result in finding a positive sentinel lymph node.

Predictores de metástasis de ganglio centinela en melanoma cutáneo / Predictors for sentinel lymph node metastasis of cutaneous melanoma

Antecedentes: se han descripto múltiples factores de riesgo para el compromiso del ganglio centinela en melanoma cutáneo, pero existe discrepancia en cuanto a la importancia de cada uno de ellos. El objetivo de este estudio fue identificar factores predictores de metástasis del ganglio centinela en pacientes con melanoma cutáneo. Material y métodos: se incluyeron los mapeos linfáticos realizados en pacientes con melanoma cutáneo entre 2001 y 2013. Se evaluaron variables demográficas y características del tumor primario. Se realizaron análisis univariado y multivariado en busca de factores predictivos del compromiso del ganglio centinela. Resultados: en el período citado se efectuaron 117 mapeos linfáticos; 25 pacientes (21,3%) presentaron ganglio centinela positivo. La edad y la localización de la lesión primaria no se asociaron con riesgo de metástasis linfática. Los melanomas con espesor de 1 a 4 mm se asociaron con mayor compromiso ganglionar que aquellos con espesor menor de 1 mm, y aquellos con espesor mayor de 4 mm tuvieron aún mayor tasa de ganglio centinela positivo. La presencia de ulceración y el tipo histológico nodular tuvieron mayor compromiso del ganglio centinela. La regresión tumoral y el número de mitosis no se relacionaron con la positividad del ganglio centinela. En el análisis multivariado solo el índice de Bres-low mayor de 4 mm y el tipo histológico nodular presentaron significación estadística. Conclusiones: la ulceración, el índice de Breslow y el tipo histológico nodular se asocian a mayor compromiso del ganglio centinela. El índice de Breslow y el tipo histológico nodular serían predictores independientes de compromiso ganglionar en melanoma cutáneo.

Background: multiple risk factors have been described in order to predict sentinel lymph node (SLN) compromise in patents with cutaneous melanoma. However, there is no agreement as to the impor-tance of each of those factors. The aim of this study was to identify risk factors of SLN metastasis. Methods: consecutive SLN biopsies in patents with cutaneous melanoma in the period 2001-2013 were included. Demographic factors and primary tumor characteristics were evaluated and univariate and multivariate analyses were performed. Results: of 117 SLN biopsies, 25 patents (21.3%) had a positive SLN. Age and tumor locaton were not associated with risk of lymphatic metastasis. Patents with Breslow thickness 1-4 mm were associated with more nodal involvement than those with thickness < 1mm and those with > 4mm had even higher rate of positive SLN. Ulceraton and nodular histology showed higher SLN compromise. Tumor regres-sion and number of mitoses were not associated with positive SLN. In the multivariate analysis Breslow thickness > 4mm and nodular histologic type showed statstical significance. Conclusions: ulceraton, Breslow thickness and nodular histologic type are associated with the SLN status. Furthermore, Breslow thickness and nodular histologic type could be independent predictor factors of SLN involvement.

Bap1 y neoplasias melanocíticas / Bap1 and melanocytic neoplasms

El melanoma maligno cutáneo (MMC) es un cáncer genéticamente heterogéneo, en cuya patogénesis participarían varios genes. Algunos de estos activan la vía MAP kinasa (BRAF, NRAS, KIT, NF1), mientras que otros confieren una mayor susceptibilidad a melanoma familiar, como CDKN2A, CDK4, MITF y BAP1. BAP1 (BRCA1-associated-protein 1) ha sido descrito como una proteína que se une a BRCA1 para inhibir el crecimiento celular. Actualmente se sabe que es producto de un gen supresor de tumores (denominado BAP1) y que actúa como una enzima con actividad deubiquitinasa, la cual se asocia a varios complejos de proteínas, regulando diversas vías celulares relacionadas con el ciclo celular, diferenciación y muerte celular, así como también gluconeogénesis y respuesta a daño del ADN. Tanto su actividad deubiquitinasa como su localización nuclear son relevantes para su función en la supresión de tumores.

Malignant cutaneous melanoma (MMC) is a genetically heterogeneous cancer and various genes participate in its pathogenesis. Some of these genes activate the MAP kinase pathway (BRAF, NRAS, KIT, NF1) and others are related to a higher susceptibility to familial melanoma like CDKN2A, CDK4, MITF y BAP1. BAP1 (BRCA1-associated –protein 1) has been described as a BRCA1-binding protein inhibiting cell growth. This protein is a product of a gene with tumor suppressor activity, the protein being a deubiquitinase associated to multiple protein complexes regulating various cellular pathways, including the cell cycle, differentiation and cell death, as well as gluconeogenesis and DNA damage response. Both deubiquitinase activity and location to the nucleus are relevant to its tumor suppressor function.

Características del melanoma cutáneo primario en el Instituto Nacional de Cancerología 2006-2010 / Characteristics of primary cutaneous melanoma in the Colombian National Cancerology Institute 2006-2010

Objetivos: Describir las principales características del melanoma cutáneo en el Instituto Nacional de Cancerología, centro de referencia del cáncer, en Bogotá, Colombia. Materiales y métodos: Estudio descriptivo, retrospectivo, de las características demográficas, clínicas e histológicas de los pacientes con diagnóstico de melanoma cutáneo primario, en el Instituto Nacional de Cancerología entre 2006 y 2010. Resultados: Se incluyeron un total de 599 pacientes, de los cuales el 57,4% eran mujeres (n = 344) y el 42,6% hombres (n = 255). La edad media de diagnóstico fue de 60,8 años. La mayoría de los casos fueron procedentes de Bogotá, con el 56,3% (n = 329). Fue más frecuente el área urbana como sitio de residencia habitual (n = 500). La media de frecuencia anual fue de 115 casos nuevos por año. La localización más frecuente fue acral, con el 42,2% (n = 253), seguido de cabeza y cuello (n = 186). Concordando con la localización, el subtipo más frecuente fue el melanoma lentiginoso acral, con el 43,7% (n = 262), seguido por el lentigo maligno, con el 24% (n = 144). En cuanto a la profundidad, se observó una frecuencia igual de melanomas in situ y melanomas con Breslow > 4 mm, ambos con el 19% de los casos. Se encontró que la mayoría de los lentigos malignos, el 75% (n = 108), fueron in situ o con un Breslow ≤ 1 mm; por el contrario, los lentiginosos acrales y los nodulares tuvieron un Breslow > 4 mm con mayor frecuencia (con el 26,3%, n = 69, y el 45,4%, n = 10, respectivamente). El estadio más frecuente fue el III, con el 26,2% de los casos (n = 157). Conclusiones: Se evidenció un mayor porcentaje de melanomas en mujeres y mayor frecuencia de melanomas acrales. Un número importante de pacientes se ubicaron en estado avanzado, por lo que se requieren mayores acciones para la detección temprana del melanoma.

Objectives: To describe the main characteristics of cutaneous melanoma in the National Cancerology Institute, a cancer reference center in Bogota, Colombia. Materials and methods: A descriptive, retrospective study was conducted on the demographic, clinical and histological characteristics of patients diagnosed with primary cutaneous melanoma in the National Cancerology Institute between 2006 and 2010. Results: A total of 599 patients were included, of whom 57.4% were females (n= 344) and 42.6% males (n=255). The mean age at diagnosis was 60.8 years. The majority of cases, 56.3% (n=329), were from Bogota. It was also the most common urban area where the patients had their usual residence (n=500). The mean annual frequency was 115 new cases per year. The most frequent location was acral, with 42.2% (n=253), followed by head and neck (n=186). In accordance with the location, the most common sub-type was acral lentiginous melanoma, with con 43.7% (n=262), followed by lentigo maligna, with 24% (n=144). As regards the depth, a similar frequency was observed for melanomas in situ and melanomas with Breslow >4 mm, both with 19% of the cases. It was found that the large majority of the lentigo maligna, 75% (n=108) were in situ or with a Breslow ≤1 mm. On the other hand, acral lentiginous and nodular melanomas had a higher frequency of Breslow >4 mm (with 26.3% n=69 and 45.4% n=10, respectively). Stage III was the most common stage, with 26.2% (n=157) of the cases. Conclusions: A higher percentage of melanomas were observed in women, as well as a higher frequency of acral melanomas. A signifi cant number of patients were in an advanced stage, thus greater action is required for the early detection of melanoma.

Melanomas no cutáneos de cabeza y cuello enfermedad de pronóstico sombrío / Non-cutaneous melanoma of the head and neck disease of grim prognosis

Antecedentes: Los melanomas no cutáneos representan el 1-7% del total. Su pronóstico es malo, a pesar de lo cual, los avancestecnológicos pueden haber cambiado su evolución.Objetivo: Descubrir factores que permitan determinar los progresos de los últimos 20 años.Diseño: Retrospectivo, observacional.Lugar de aplicación: Hospital Público de atención terciaria.Población: 30/56 pacientes pertenecían al género masculino, con una relación 1.15/1. La edad media fue 61.07 años. El sitiodominante de los mucosos fue paladar con 22 (39.2%) y senos paranasales con 9 (16%). Los oculares con 24/56 representaron el(42.8%) de la muestra. El 94.6% se hallaban en E I.Métodos: La extensión de la cirugía varió desde la simple resección local en 13/56 -23.2%- pacientes, a la enucleación ocular en14/56 (25%), exenteración orbitaria en 5/56(9%), maxilectomía superior en 20/56 (35.7%), resección craneofacial en 3 y amputaciónnasal en 1.Resultados: La morbilidad fue 51.7% y la mortalidad 1.7%. El 67.8% desarrolló recurrencias. El análisis univariado para recurrenciademostró que los orígenes rinosinusal y conjuntival, influyeron desfavorablemente en el evento recurrencia. Al cierre de laobservación 42/56 (75%) habían fallecido, (85.8%) de ellos por causa específica. Solo 2/42 (4.7%) muertes se produjeron despuésde los 60 meses. La supervivencia libre de enfermedad a 5 años fue 31.9%. El paladar y el E I, fueron las variables que a su favorconservaron significación estadística.Conclusiones: Urgen nuevos paradigmas de tratamiento para esta enfermedad cuya evolución no se ha modificado sustancialmenteen los últimos 20 años.

Background: Non cutaneous are 1-7% of all melanoma. The prognosis is poor in spite of which, technological progress maychange the outcome.Objective: To discover factors which allow to define progress of last 20 years.Design: Retrospective, observational.Setting: Public Hospital of tertiary care.Population: 30/56 male patients with 1.15/1 rate. Mean age 61.07 years old. Priority sites in mucosal melanoma were palate with22-39.2% and paranasal sinus with 9 (16%). Ocular melanomas were 42.8% of the sample. 94.6% were EI.Methods: Extention of surgery was simple resection in 13/56 (23.2%), ocular enucleation in 14/56 (25%), orbit exenteration in 5/56(9%) maxilectomy in 20/56 (35.7%), craniofacial resection in 3 and nasal amputation in 1.Results: Morbility was 51.7% and mortality 1.7%. 67.8% of the sample recurred. Multivariate analysis for recurrence showed thatrinosinusal and conjuntival sites unfavorably influence on that event. At close of observation 42/56 (75%) was dead, 85.8% of themfor specific cause. Only 2 death happened after 60 months. Five years specific survival was 31.9%. Palate and stage I were favorablesites with statistic significance.Conclusions: Other paradigms of treatment are urgently necessary for this disease which outcome was not substantially modifiedin the last 20 years.

Melanoma dérmico hiperpigmentado de bajo grado de malignidad (melanoma de tipo animal): reporte de cuatro casos / Hyperpigmented dermal melanoma of low-grade of malignancy (animal-type melanoma): report of four cases

El melanoma animal o hiperpigmentado es un subtipo infrecuente de melanoma con células melanocíticas epitelioideas y fusadas muy pigmentadas. Esta entidad sería similar al llamado “melanoma de tipo equino”, una forma de melanoma de bajo grado de malignidad que afecta a los caballos grises. Se reportan cuatro casos, tres hombres y una mujer, cuyas edades variaron de 22 a 84 años; el estudio histopatológico confirmó melanoma dérmico hiperpigmentado; dos casos mostraron ganglio centinela positivo y un caso evolucionó con metástasis múltiples. Tres casos están en control o tratamiento sin evidencias de recidiva o metástasis. El melanoma animal es considerado un subtipo de melanoma de conducta poco agresiva y de mejor pronóstico, pese a su tendencia a las metástasis ganglionares. Los casos presentados mostraron una conducta menos agresiva que la esperada para el espesor de Breslow y estadio clínico en estos casos. Se requieren más estudios para poder identificar variables que permitan predecir el comportamiento biológico y así protocolizar el tratamiento de esta entidad, considerada por algunos como diferente del melanoma.

Animal type or hyperpigmented melanoma is an infrequent subtype of melanoma with heavily pigmented epithelioid and spindle melanocytes. This entity is similar to the so-called “equine-type melanoma”, an indolent variant of melanoma affecting gray horses. We report four cases, three males and one female, whose ages varied from 22 to 84 years; the histopathological study confirmed the diagnosis of hyperpigmented dermal melanoma; two cases showed positive sentinel lymph nodes and one case evolved with multiple metastases. Three cases are in control or under therapy without evidence of recurrences and/or metastases. Animal-type melanoma is considered a subtype of melanoma with indolent behavior and better prognosis, despite its tendence to develop lymph node metastases. The present cases showed a less aggressive behavior than expected for the Breslow’s thickness and clinical stage. More studies are needed to identify variables to predict its behavior and propose therapy protocols for this tumor, considered by some authors a different type of melanoma.

Melanoma cutáneo: mortalidad y características de los tumores incidentes en los dos extremos de la vida en la Argentina / Cutaneous melanoma in argentina: mortality and primary tumor

Objetivos. Conocer y comparar en la Argentina, en los jóvenes y adultos, la mortalidad por melanoma cutáneo (MC) y las características de casos incidentes para aportar información útil en el diseño y evaluación de acciones de prevención. Diseño. descriptivo y retrospectivo. Métodos. Se consideraron para el estudio: los jóvenes < 30 años (J) y adultos > 74 años (AM). Los datos de las defunciones para el cálculo de tasas de mortalidad en los períodos 1981-89, 90-98 y 99-07 fueron proporcionados por la Dirección de Estadísticas e Información de Salud del Ministerio de Salud. La información sobre los casos incidentes se obtuvieron del Registro Argentino de Melanoma Cutáneo (RAMC) para el período enero 2002- diciembre 2009. De ellos se estudió la localización, el espesor de Breslow y el tipo histológico.Resultados. En los sucesivos períodos las muertes por MC en J de ambos sexos fue 97, 93 y 123, y en AM 416, 654 y 1.307, respectivamente. En los AM las tasas de mortalidad aumentaron en el tiempo, y fueron siempre menores para las mujeres que para losvarones (varones: 6,3 muertes por MC promedio por cada 100.000 individuos por año en 81-89 a 13,4/100.000 99-07; mujeres: 4,4/100.000 81-89 a 7,5/100.000 en 99-07). El RAMC registró 4.100 casos, 258 fueron en J y 665 en AM. Fueron mujeres el 63% en J y el 47% en AM (p< 0,05). En las mujeres, el 56% de los MC en J y el 36% en AM tuvieron Breslow ≤ 1,00 mm (p< 0,004). En las mujeres predominaron las lesiones en piernas (el 43,4% en J y el 42,2% en AM), mientras que en los hombres fueron el 19,8% y el 12,4% respectivamente (p< 0,005). Conclusión. En las mujeres jóvenes, el menor espesor de Breslow al momento del diagnóstico y las menores tasas de mortalidad por MC con menor incremento temporal de las mismas podrían ser reflejo de una mayor influencia de las acciones de prevención y una mayor atención del propio cuerpo y de la salud por parte del género femenino. Cabe esperar que la continuidad de las actividades del ...

Objectives. To compare mortality rates and main features of cutaneous malignant melanoma(CMM) between two age groups in Argentina (young and elderly patients), in order to increaseknowledge as well as improve planning and preventive actions for this disease.Study design. descriptive and retrospective.Methods. Group J was defined as patients younger than 30 years of age and Group AM patientsover 74 years old. Death reports for periods 1981-89 / 90-98 / 99-07 were provided by theDepartment of Statistics of the Health Ministry and incident cases between 2002 and December2009 by the Argentine Registry of Cutaneous Malignant Melanoma (RAMC). Tumor location,Breslow thickness index and histopathology characteristics were analyzed for all cases.Results. For successive periods, the total number of CMM-associated deaths for both gendersin Group J was 97, 93 and 123 respectively; while these figures were for Group AM 416, 654 and1,307 respectively. On older patients an increase in mortality rates was observed over elapsedtime, being always lower for women than for men (mortality rates for men were 6.3 /100,000population per year during the period of 1981-1989 and 13.4/100,000 between the years1999-2007. Mortality rates for women were: 4.4/100,000 during 1981-1989 and 7.5/100,000and in 1999-2007). RAMC registered 4,100 new cases, of which 258 belonged to Group J and665 to Group AM. Women comprised 63% on group J and 47% on group AM (p<0, 05). Womencomprised 56% of CMM in Group J and 36% on Group AM, having a Breslow tumor thickness≤ 1.00mm (p<0,004). Primary tumors located on lower limbs were more frequently observedamong women (43.4% and 42.2% for Group J and AM respectively), whereas on men this was19.8% and 12.4%, respectively (p<0,005)...

Cutaneous malignant melanoma: clinical and histopathological review of cases in a Malaysian tertiary referral centre

Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superfi cial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.