BRAF Mutation Status in Inflamed Juvenile Conjunctival Nevus, Primary Acquired Melanosis and Conjunctival Common Nevus.

Background: To investigate BRAF mutation status and its associated clinicopathological features in conjunctival melanocytic lesions.

Methods: We analysed surgical specimens from 79 conjunctival melanocytic lesions, including inflamed juvenile conjunctival nevi, primary acquired melanosis (PAM) and conjunctival common nevi collected from 2013 to 2022. PAM lesions were further categorised into those without atypia and with mild, moderate or severe atypia. Conjunctival common nevi were subcategorized into junctional, subepithelial and compound nevi. BRAF V600E immunohistochemistry was performed on all specimens, with PCR-mass spectrometry used for ambiguous cases. The main outcome measures were the BRAF V600E mutation rate and related clinicopathological features.

Results: Inflamed juvenile conjunctival nevi showed a BRAF V600E mutation rate of 36.8% (7/19), while the mutation was rare in PAM (4.3%, 1/23). The mutation rate in conjunctival common nevi (67.6%, 25/37) was similar to that in cutaneous common nevi, and most BRAF V600E-mutated cases were found in the subepithelial nevus group (93.8%, 15/16). BRAF mutations were significantly associated with intralesional inflammatory stroma and subepithelial growth pattern, but not with age, lesion location, intralesional cyst and solar elastosis.

Conclusions: BRAF mutations are key driver mutations in inflamed juvenile conjunctival nevi and conjunctival common nevi. Histologically, an 'inflamed juvenile conjunctival nevus'-like inflammatory stroma correlated with BRAF mutations. In our study, solar elastosis was infrequently observed in conjunctival nevi, suggesting that the mutational signature of conjunctival melanocytic lesions resembles that of cutaneous non- or low-level cumulative solar damage type. For cases with equivocal BRAF staining, high-sensitivity sequencing is recommended to confirm mutation status.