Multiple predictive biomarker testing in melanoma: another challenge for the optimal approach on cytological samples

Background: The management of cutaneous melanoma has dramatically changed in recent years thanks to the development of tyrosine kinase and immune-checkpoint inhibitors (ICIs). Thus, multiple biomarker testing is becoming ever more important to identify patients potentially eligible for these treatments. One reliable approach for molecular evaluation of metastatic melanoma is fine-needle cytology (FNC). To examine the utility of this approach for PD-L1 assessment, we evaluated the cellular adequacy of residual cell block (CB) material from metastatic melanomas previously tested for BRAF and NRAS mutations. Methods: We retrieved from our internal archives a series of FNC samples of metastatic melanoma subjected to molecular testing on residual CB material or dedicated needle rinse, between January 2016 and July 2022. Briefly, RT-PCR was adopted to assess BRAF and NRAS status, and SP263 assay was employed to assess PD-L1 expression level. Results: Overall n=19 cases were selected. Of these, 11 (57,9%) cases revealed a BRAF exon 15 p.V600E mutation, one case (5,3%) revealed NRAS mutation, and seven cases (36,8%) showed no mutations. Regarding PD-L1 assessment, 16/19 (84,2%) cases were deemed adequate, containing at least 100 viable cells. Conclusions: We highlighted the feasibility of PD-L1 assessment on residual CB material from metastatic melanomas previously tested for BRAF and NRAS mutations. Moreover, we pointed out that FNC needle rinses may be an alternative sources of nucleic acids for molecular testing, preserving CB material for ICC evaluation.