ABSTRACT
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.
Subject(s)
Melanoma , Sarcoma , Skin Neoplasms , Soft Tissue Neoplasms , Humans , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Melanoma/pathology , Retrospective Studies , Sarcoma/diagnosisABSTRACT
BACKGROUND/AIMS: To review the clinicopathological features of caruncle biopsies carried out at a district general hospital in the United Kingdom (UK), and compare with other centres where data has been published. METHODS: Retrospective, single-centre, observational case series between 2004-2020. RESULTS: A total of 31 lesions from 31 patients were analysed. 18 of 31 patients were men (58%), and the age ranged from 12 to 91 years. 13 different histopathological types of lesions were identified in our case series, including 9 melanocytic nevi (29%), 7 benign squamous papillomas (23%), 5 skin adnexal lesions (16%), 3 chronic inflammation (10%), 3 epithelial cysts (10%), 1 basal cell carcinoma (3%), 2 malignant melanomas (6%) and l lymphoproliferative disorder (3%). Pre-operative suspected diagnoses were often vague but correct in 12 of 18 cases (67%), where data was available. CONCLUSION: The uncommon nature and variety of caruncular lesions make the diagnostic process difficult. Our case series is the first reported in the UK, showing a slightly higher proportion of malignant melanomas, in keeping with the population demographics. Excisional biopsies would, therefore, be prudent in the majority of cases to rule out any possible malignancy.
ABSTRACT
The sentinel lymph node (SLN) biopsy is a highly accurate staging procedure and the most important prognostic factor in melanoma patients. The European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group aimed to design an updated evolved SLN protocol for the histopathological workup and reporting. We herein recommend extending the distance between steps according to the short axis dimension of the lymph node and optimise both conventional sectioning and staining procedures including immunohistochemistry. We also provide guidance on the description of the spatial localisation of melanoma deposits in a SLN. The histopathological features to be reported include the following: presence or absence of the metastasis, the intranodal location of the metastasis (subcapsular, parenchymal, combined, extensive confluent and extensive multifocal), the number of the metastatic deposits (1, 2-5, 6-10, 11-20 and >20), the maximum dimension of the largest metastasis (indicating its site) and the presence of extracapsular extension and of naevus cells. This updated EORTC protocol is expected to clarify and simplify the existing procedures, ensuring a reasonable workload for the laboratory and for the pathologists resulting in cost saving with no loss, and possible increase, in accuracy.