Cherry hemangioma is the most common hemangioma in adult life. Neoplastic and non-neoplastic theories had both been proposed for its pathogenesis, but its nature is still poorly understood. We noted a significant subset of anastomosing hemangiomas and congenital hemangiomas harbored a population of small capillaries surrounded by a perivascular hyaline layer, reminiscent of the vessels seen in cherry hemangioma. Both anastomosing hemangioma and congenital hemangioma harbor recurrent mutations in exon 5 of GNAQ and its paralogues. In this study, we analyzed 68 cherry hemangiomas and 17 cherry hemangioma-like hemangiomas exhibiting additional non-classical features including markedly dilated, cavernous vessels, and/or a deep component extending to the deep dermis. By Sanger sequencing, GNAQ, GNA11, and GNA14 exon 5 mutations were identified in 12, 4, and 32 cherry hemangiomas, respectively, and 5, 3, and 3 cherry hemangioma-like hemangiomas, respectively. MassARRAY analysis detected mutations (including exon 2 GNAQG48V mutations) in additional 8 cherry hemangiomas and 3 cherry hemangioma-like hemangiomas. Overall, the cherry hemangiomas and cherry hemangioma-like hemangiomas had equal GNA mutation rates (82%), and GNA14 and GNAQ mutations were present in approximately half of cherry hemangiomas and cherry hemangioma-like hemangiomas, respectively. All mutations were mutually exclusive. KRASG12V mutation was also detected in one cherry hemangioma-like hemangioma without GNA mutations. In summary, our study demonstrated recurrent GNA14/GNAQ/GNA11 mutations were present in the majority of this very common hemangioma and established its neoplastic nature. Our results also expanded the morphological spectrum of GNA-mutated hemangiomas to include tumors composed of cavernous-like vessels and indicated GNA14 was the most commonly mutated gene in vascular tumors.
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This work was in part supported by the research fund from the Ministry of Science and Technology, Taiwan (MOST 107-2320-B-002-048-) and 108-S4200 from National Taiwan University Hospital to Jau-Yu Liau.
Conflict of interest
The authors declare that they have no conflict of interest.
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