Evaluation of clonality in lentigo maligna.

Abstract

Background: Lentigo maligna (LM), a type of in situ melanoma, has a high rate of local recurrence. Although such recurrences might be redevelopment of inadequately excised LMs, an alternative possibility is that apparent recurrences are in fact new primary LMs developing from distinct melanocytic clones in the same anatomic regions. Although distinguishing these possibilities has implications for patient management, they have never been formally tested. The primary objective of this project was thus to understand clonal relationships between incident LMs and their post-operative local recurrences. We also aimed to identify distinguishing features of incident LMs that recur as lentigo maligna melanoma (LMM). Method(s): Formalin-fixed paraffin-embedded (FFPE) sections of incident and recurrent LM/LMMs were laser microdissected for DNA extraction. Tumour and matched germline DNA underwent whole exome sequencing. Data were processed to identify somatic single nucleotide variants (SNVs), copy number alterations (CNAs) and the clonality of each sample. Result(s): 4 cases of recurrent LM and 3 cases of recurrent LMM were sequenced. All incident LMs were clonally related to their recurrences. Moreover, LMs with recurrent LMM appeared more clonally heterogeneous than LMs with recurrent LM (p = 0.11). Conclusion(s): We found that local recurrence of LM arises from residual disease, confirming that adequate excision margins are important in preventing recurrence. Clonal heterogeneity is worth exploring as a prognostic marker in LM.