A recent study examined the real-world prevalence of highly pigmented advanced melanomas (HPMel) and their signature clinicopathologic, genomic and ICPI biomarkers.

The study comprised clinical melanoma samples, which the physicians sent testing for both PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP). The samples underwent further screening for HPMel and nonpigmented or lightly pigmented advanced melanoma cases (LPMel).

The study showed:

• Of the 1,268 consecutive melanoma biopsies submitted for PD-L1 IHC, 13.0% were HPMel and 87.0% were LPMel.
• HPMel cohort showed a significantly lower tumor mutational burden (TMB, median 8.8 mutations/Mb) than the LPMel group (11.4 mut/Mb), with substantial overlap.
• Characteristic secondary genomic alterations (GA) showed the frequencies of GA in TERTp, CDKN2A, TP53 and PTEN to be significantly lower in the HPMel cases than in LPMel.
• The study identified a higher rate of GA in CTNNB1, APC, PRKAR1A and KIT in the HPMel cohort compared with LPMel.

This study quantified the failure rates of melanoma samples for PD-L1 testing due to high melanin pigmentation. It illustrated the usefulness of CGP in identifying biomarkers that can guide treatment decisions for HPMel patients. 

These results indicate that HPMel is frequent at 13% of melanoma samples and generally emerges molecularly less developed, with a lower TMB and less frequent secondary GA of melanoma progression.

Source: Huang RSP, Tse JY, Harries L, et al. Variable genomic landscapes of advanced melanomas with heavy pigmentation. Oncologist. 2022;27(8):655-62.