L’identificazione della mutazione BRAF nel melanoma ha portato allo sviluppo di nuovi farmaci efficaci nella cura del tumore in fase avanzata. Parallelamente, è cresciuto l’interesse per l’influenza delle alterazioni genetiche sull’espressività clinica del tumore. Diversi studi hanno analizzato le caratteristiche cliniche, dermoscopiche e istopatologiche del melanoma in rapporto alle alterazioni molecolari. Tuttavia poco si conosce riguardo ai pazienti con melanoma primitivo multiplo (MPM).
Lo scopo dello studio è stato quello di analizzare le caratteristiche cliniche, dermoscopiche e confocali di una serie di melanomi in pazienti con MPM e correlarle con la presenza della mutazione BRAF.
Il campione in studio è stato di 62 pazienti, 36 uomini (58%) e 136 melanomi. L’età media era 53 anni (15-88). La maggior parte dei pazienti presentava 2 melanomi (n=48; 77.4%), 11 pazienti avevano 3 lesioni (17.8%); 2 ne presentavano 4 (3.2%) e 1 paziente era affetto da 5 melanomi primitivi. In 18 casi lesioni erano sincrone; in 21 localizzate nella stessa sede corporea.
La mutazione BRAF è stata riscontrata nel 38% dei casi; 85 lesioni erano BRAF wild type. La concordanza dello stato mutazionale BRAF è stata riscontrata in 13/62 (20.9%) pazienti. In 31/62 (50.0%) i pazienti presentavano 2 melanomi BRAF wild type. In 18/62 (29.1%) di casi non si è riscontrata consistenza nel profilo mutazionale dei melanomi multipli.
La concordanza mutazionale è risultata associata alla similitudine dermoscopica. In particolare, melanomi con alta concordanza dermoscopica avevano maggiore probabilità di presentare uno stato mutazionale concordante.
The identification of BRAF mutations in melanoma has led to the development and implementation of new and effective therapies for advanced melanoma. Moreover, with the advances in knowledge of the molecular background of melanoma, the interest in the link between different molecular alterations and distinct melanoma subtypes has been rising. Two recent observational retrospective studies investigated clinical, histopathological and dermoscopic characteristics of primary melanomas according to BRAF mutational status. However, little is known about BRAF mutational status and clinical, histopathological and dermoscopic characteristics in multiple primary melanomas (MPM). The aim of the present study is to investigate the clinical, histopathological and dermoscopic characteristics of MPM according to BRAF mutational status, in order to asses if MPM in a given patient tend to harbor the same BRAF status, and whether BRAF mutational status may influence the occurrence of dermoscopically similar or different MPM. From the databases of 3 pigmented skin-lesion clinics in Italy, the dermoscopic images of melanomas in patients diagnosed with MPM were collected. Histopathological specimens were reviewed, and BRAF mutation status of MPM was investigated according to the protocol reported below.
The association between BRAF status (BRAF mutated concordance; BRAF wild type concordance; BRAF mutation discordant) of the first and second primary melanoma for each patient and dermoscopic similar appearance was evaluated.
Statistical analysis was performed using the Fisher exact test or v2 analysis, where appropriate, in order to evaluate the association between the dermoscopic features of the melanomas (similar or different) and the given parameters.
The study sample was composed of 62 patients (36 males, 58%) and 136 melanomas. Mean age at the time of first melanoma was 53 years (range 15-88). The majority of patients had 2 melanomas (n=48; 77.4%), 11 patients had 3 melanomas (17.8%); 2 had 4 melanomas (3.2%), and 1 had 5 (1.6%) primary tumors. In 18 cases the melanomas were synchronous; 21 shared the same location. (Table 1)
Genotype was analyzed in all melanomas for which a dermoscopic image was available (n= 136). BRAF mutations were found in 38% of cases and included the following genotypes: V600E (n=50); V600R (n=1). A total of 85 (62%) cases harbored the BRAF wild type. BRAF mutational status concordance between first and second melanoma was observed in 13/62 (20.9%) patients. In 31/62 (50.0%) cases, patients had 2 melanomas BRAF wild type. In 18/62 (29.1%) there was no consistency between mutation pattern of first and subsequent melanoma.
None of the patients with more than 2 melanomas had a concordant BRAF status in all lesions except one patient with 3 melanomas all harboring the V600E mutation.
Regarding dermoscopy features, there was a good concordance between the two methods used for the definition of the dermoscopic similarity. Both the “scoring method” and the “prevalent pattern method” resulted in the same conclusion regarding the definition of “similar or different” melanomas.
In 24 cases the first and second melanomas of a given patient shared the same prevalent pattern. Interestingly, when both melanomas were BRAF mutated, they had a higher chance to be dermoscopically similar. In detail, when using the scoring method, melanomas having a concordance score > 5 had a 4-fold probability to have a concordant mutational status (OR: 4,616; 95%CI 1.397-15.253; P: .012). Moreover, synchronous melanomas had a 6-fold probability of sharing the same mutational status (OR: 5,860; 95%CI 1.396-24.599; P: .016). Similarly, melanomas with same prevalent pattern had a higher probability of sharing the same mutational status.