TY - JOUR
T1 - Clinical, histopathological and molecular features of dedifferentiated melanomas
T2 - An EORTC Melanoma Group Retrospective Analysis
AU - EORTC Melanoma Group
AU - Hench, Juergen
AU - Mihic-Probst, Daniela
AU - Agaimy, Abbas
AU - Frank, Stephan
AU - Hultschig, Claus
AU - Simi, Sara
AU - Alos, Lucia
AU - Balamurugan, Thiagarajah
AU - Blokx, Willeke
AU - Bosisio, Francesca
AU - Cappellesso, Rocco
AU - Griewank, Klaus
AU - Hadaschik, Eva
AU - van Kempen, Leon C
AU - Kempf, Werner
AU - Lentini, Maria
AU - Mazzucchelli, Luca
AU - Rinaldi, Gaetana
AU - Rutkowski, Piotr
AU - Schadendorf, Dirk
AU - Schilling, Bastian
AU - Szumera-Cieckiewicz, Anna
AU - van den Oord, Joost
AU - Mandalà, Mario
AU - Massi, Daniela
N1 - Copyright © 2023 Elsevier Ltd. All rights reserved.
PY - 2023/7
Y1 - 2023/7
N2 - PURPOSE: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.PATIENTS AND METHODS: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out.RESULTS: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome.CONCLUSIONS: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.
AB - PURPOSE: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.PATIENTS AND METHODS: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out.RESULTS: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome.CONCLUSIONS: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.
U2 - 10.1016/j.ejca.2023.03.032
DO - 10.1016/j.ejca.2023.03.032
M3 - Article
C2 - 37098294
SN - 0959-8049
VL - 187
SP - 7
EP - 14
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -