CHERRY angiomas were significantly more prevalent and developed at a younger age in individuals with neurofibromatosis type 1 (NF1), with genetic analyses suggesting these lesions may represent a previously unrecognised vascular manifestation of the condition.
The prospective cross-sectional study included 259 participants aged 15 years or older, comprising 102 individuals with confirmed NF1 and 157 controls. The epidemiological analysis was conducted at a French national referral centre for neurofibromatoses between October 2020 and March 2021, followed by histopathological, genomic, and cell-specific molecular analyses.
Cherry angiomas were identified in 48% of individuals with NF1 compared with 18% of controls. The association remained after adjustment for age and sex and in propensity score-matched analyses.
The odds of having a cherry angioma were also higher among individuals with NF1 (odds ratio: 4.26; 95% CI: 2.44–7.56).
The researchers investigated the biological basis of the association by analysing cherry angiomas from individuals with NF1 and healthy volunteers.
Somatic NF1 loss-of-function second-hit variants were identified in 26 of 39 NF1-associated cherry angiomas (67%), while no such variants were identified in control lesions. This indicated biallelic NF1 inactivation within the NF1-associated lesions.
Genomic profiling also identified co-occurring activating variants, with GNAQ among the most frequently observed. Cell-specific sequencing indicated that NF1 second hits arose predominantly in endothelial cells and telocytes, with higher variant allele frequencies observed in endothelial cells.
Immunofluorescence analysis demonstrated increased phosphoextracellular signal-regulated kinase signalling in the vascular cell populations carrying NF1 alterations, providing further evidence of pathway activation within the lesions.
The researchers suggested that the findings extend understanding of NF1-associated manifestations beyond neural crest-derived tissues and support cherry angiomas as a potential model for NF1-related vasculopathy.
Although the study was cross-sectional, the combination of epidemiological and mechanistic findings suggests that the increased occurrence of cherry angiomas in individuals with NF1 may have a biological basis rather than representing an incidental clinical observation.
The findings could broaden the recognised spectrum of NF1-associated neoplasms and provide a model for investigating vascular disease associated with NF1 loss.
Reference
Fertitta L et al. Cherry angiomas in individuals with neurofibromatosis type. JAMA Dermayol. 2026;DOI:10.1001/jamadermatol.2026.2933.
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