The Expanding Role of Genetic Testing in Orbital Vascular Malformations
Author: Gregory Griepentrog
Base Hospital / Institution: Mayo Clinic, USA
ePoster presentation
Abstract ID: 25-106
Purpose
Orbital vascular anomalies are a heterogenous group of disorders (tumors and malformations) that comprise one of the most common classes of space-occupying orbital lesions in children. As a subset of this broader category, vascular malformations form due to errors in vascular morphogenesis, often early in embryonic life. Arising from somatic (acquired) mutations, direct tissue biopsy is the only means to obtain genetic material for analysis. Currently, genetic testing is considered a key component of the comprehensive care for patients with vascular anomalies. Accurate identification of a genetic variant can aid in definitive diagnosis and directly impact management. Due to the relatively high risks of periorbital vascular tissue biopsy, obtaining tissue for genetic analysis has not become standard. Herein, we present 2 cases of patients requiring surgical vascular malformation debulking, at which time, somatic mutation testing was obtained. The implications of the genetic analysis are discussed.
Methods
Case series of two patients undergoing vascular malformation debulking with somatic mutation analysis.
Results
Case 1: A 17-year-old female presented with a long-standing history of a full-thickness vascular lesion at the right upper eyelid lash line extending into the palpebral conjunctiva, causing mechanical ptosis. She had failed previous topical timolol, along with bleomycin sclerotherapy, elsewhere. An orbital MRI revealed an enhancing well-circumscribed T2 hyperintense nodule consistent with a venous malformation. Surgical debulking was performed along with genetic testing. A TEK c.2690A>G (p.Tyr897Cys) variant confirmed the diagnosis of venous malformation. She has had minimal regrowth since surgery. Based on the underlying genetics, a PI3K-AKT-mTOR inhibitor, will be utilized in the future with significant regrowth.
Case 2: A 4-month-old male whom, due to rapid expansion, underwent debulking of a presumed isolated venous malformation involving the right superolateral preseptal tissues. Genetic testing of the lesion revealed a TEK c.2689T>A (p.Tyr897Asn) variant consistent with venous malformation. He subsequently underwent additional debulking at ages 8-months and 32-months.
Conclusion
In cases of surgical debulking of vascular malformation, somatic tissue analysis should be strongly considered to assist in both diagnosis and potential targeted therapy. In both cases presented, a vascular malformation arose due to gain-of-function somatic pathogenic variant within the PI3K-ARK-mTOR pathway, crucial for cellular processes including cell cycle regulation, proliferation, and migration. Specifically, these TEK-related vascular malformations may be targeted with the mTOR inhibitor sirolimus, or more recently, the PI3K inhibitor, alpelisib.
Additional Authors
| First name | Last name | Base Hospital / Institution |
|---|---|---|
| SAM | Chisholm | Medical College of Wisconsin, USA |
| Yasaman | Ataei | Medical College of Wisconsin, USA |
