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Clinical and Molecular Study of ELMO-2–Related Massive Intraosseous Vascular Malformations

Lessons Learned From 25 Years of Follow-up

Vargel, Ibrahim MD, PhD*; Calis, Mert MD*; Canter, Halil Ibrahim MD; Cil, Barbaros Erhan MD

doi: 10.1097/SAP.0000000000001786
Head and Neck Surgery

Massive intraosseous vascular malformations, a relatively rare entity in the vascular malformation spectrum, deserves attention as involving the membranous bones of the craniofacial skeleton and may lead to severe life-threatening hemorrhages and even death. The main aim of this study was to summarize the 25 years of clinical experience with these vascular malformation osseous patients, focus on the molecular and genetic aspect of the clinical entity, and to emphasize the certain challenging conditions in the treatment of these patients. All the patients appeared to be unaffected at birth, whereas initial symptoms occasionally began with painless swelling in the mandible in early childhood. The disease was progressive in behavior especially in the pubertal ages and was specifically involving the maxilla and mandible of the craniofacial skeleton in all the patients. Calvarium and cranial base were the second most common involved regions among these patients (62.5%). Clavicular (50%), costal (25%), and vertebral (25%) involvements were also a significant manifestation of the disease. Tissue samples obtained from the affected individuals and the blood samples from their families were matched, revealing a loss of function mutation in the ELMO-2 gene of chromosome 20 leading to developmental abnormality of the vascular structures via RAC1 signaling and leading to abnormally enlarged vessels in the intraosseus portion of the membranous bone. Immunohistochemical staining revealed positive CD31 and smooth muscle actin staining but negative proliferation and maturity markers such as Ki-67, desmin, h-caldesmon, and myofibroblast-like desmin. The follow-up of 3 of 5 patients ended up with mortality (60%). vascular malformation osseous is intraosseous vascular malformation with aggressive biological behavior associated with ELMO-2 gene mutation. Further studies for obtaining prenatal diagnosis and achievement of gene therapy should take place. As the disease rapidly progresses as the affected individual grows, surgical interventions should be taken into consideration before the initiation of complications.

From the *Department of Plastic Reconstructive and Aesthetic Surgery, Hacettepe University Faculty of Medicine

Department of Plastic Reconstructive and Aesthetic Surgery, Acibadem University Faculty of Medicine

Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Received August 29, 2018, and accepted for publication, after revision November 4, 2018.

B.E.C. is now with the Department of Radiology, Koc University Hospital, Istanbul, Turkey.

This study was presented at the 28th Annual Meeting of European Society of Plastic Surgeons in Pisa, Italy, May 25-27, 2017.

Conflicts of interest and sources of funding: none declared.

Reprints: Ibrahim Vargel, MD, PhD, Hacettepe Universitesi Hastaneleri, Plastik Rekonstruktif ve Estetik Cerrahi A.D., 06100 Sihhiye, Ankara, Turkey. E-mail:

Online date: March 14, 2019

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