Sporadic hypertrophic and nodular port-wine stain: a study of 27 cases with emphasis on histological features and novel mutation type.

Aims: To investigate the clinicopathological features and molecular characteristics of sporadic hypertrophic and nodular port-wine stains (PWS).

Methods: We analysed the clinicopathological and molecular characteristics of 27 sporadic hypertrophic and nodular PWS retrieved from our pathology database from 2013 to 2023 and reviewed the relevant literature.

Results: There were 13 men and 14 women who ranged in age from 10 to 66 years. The main sites were the head and neck (23/27, 85%), which showed irregular thickening and darkening of purplish-red patches on the skin surface and the development of nodularity. Histologically, immature venule-like channels with irregular dilation are arranged in clusters or honeycombs, which are widely distributed primarily in the papillary layer and deep dermis and partly extend into the subcutaneous fat layer and other deep tissues. Dilated vessels with irregular shapes often exhibit fibrous thickening and an increased number of large vessels without vascular endothelial cell proliferation. All vessels showed similar characteristics, with positive staining for CD34, ERG and GNAQ in the endothelial cells, and negative staining for elastic fibres. Nine patients had somatic GNAQ mutations (9/11, 82%), including exon four mutations (6 cases, p.R183Q), exon five mutations (2 cases, p.Q209R) and exon two mutations (one case, p.G48V). Two patients had somatic BCL6 corepressor-like 1 (BCORL1) gene mutations (2/11, 18%), including exon 3 mutations (p.T1111M) and exon 7 mutations (p.G1391R).

Conclusions: Sporadic hypertrophic and nodular PWS are mostly related to somatic GNAQ mutations. This is the first study to identify the Rare GNAQ G48V and somatic BCORL1 mutations.