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Evaluation of clonality in lentigo maligna
Sophie Soyeon Lim1, Peinan Zhao2, Nicholas C Wong3
1Department of Cancer Medicine, Monash University, Clayton, Australia; Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Oncology, Alfred Hospital, Melbourne, Australia.
The Journal of Investigative Dermatology
|December 26, 2025
Summary
Local recurrences of lentigo maligna (LM) commonly arise from residual disease after surgery, not new primary tumors. Genetic analysis confirms incident LMs are clonally related to their post-operative recurrences.
Area of Science:
- Dermatology
- Oncology
- Genetics
Background:
- Lentigo maligna (LM) is an in situ melanoma with frequent local recurrence after surgical removal.
- Distinguishing between inadequate excision and new primary tumors is crucial for patient management.
Purpose of the Study:
- To investigate the clonal relationship between incident lentigo maligna and its local recurrences.
- To understand the genetic basis of LM recurrence.
Main Methods:
- Whole exome sequencing of incident LMs, recurrent LMs, and invasive lentigo maligna melanomas (LMMs).
- Laser microdissection for DNA extraction from tumor samples.
- Analysis of clonal relationships using genetic sequencing data.
Main Results:
- All analyzed incident LMs were found to be clonally related to their post-operative local recurrences.
- LM/LMMs exhibit high mutational burden, UVR signature, copy number alterations, and DNA repair gene defects.
- Recurrent lesions share mutational landscapes typical of chronic sun exposure, with some late-stage melanoma features.
Conclusions:
- Local recurrences of LM predominantly stem from subclinical residual disease left after surgical resection.
- Understanding the clonal origin of recurrences impacts clinical management strategies for LM.
