C-KIT Expression in Orbital Cavernous Venous Hemangiomas

Abstract

Orbital (slow flow) cavernous venous hemangiomas (OCVH) are the most common benign orbital tumors in adults. The c-KIT is a tyrosine kinase receptor, which is expressed on several types of cells, is thought to play a key role in tumor pathogenesis. The purpose of this study was to evaluate the presence of the receptor c-KIT in OCVH. Our retrospective study examined 16 orbital cavernous venous hemangiomas from 16 cases operated on between 2006–2016 at Emek Medical Center. The mean tumor size was 18.4 mm. Symptoms appeared between 6 months and 22 years before operation. All specimens were analyzed for the c-KIT receptor through immunohistochemistry. The c-KIT was expressed by the endothelium in all 16 preparates. Staining was strong in two cases, moderate in six, and weak in eight cases, with no statistically significant correlation between staining and tumor size (p = 0.69) or the symptom duration (p = 0.15). We conclude that c-KIT may play an important role in the pathogenesis of OCVH. This pilot study is significant in that tumor-targeted therapy such as Imatinib Mesylate and Sunitinib may have a role in treating surgically complicated cases located in the orbital apex. A large multicenter collaborative study is necessary to examine the role of c-KIT in OCVH.

Biological identity of orbital cavernous venous malformations

“…Among vascular malformations, involvement of genetic changes in their pathogenesis was first identified in venous malformations. In 1996, the presence of mutations in the TEK gene in blood samples from patients with familial mucocutaneous venous malformations was identified (93) , which was also seen in subsequent studies of other types of venous malformations (94)(95)(96)(97)(98)(99)(100) .…”

“…In the periorbital region, mutations are observed in genes that play an important role in pathways involved in angiogenesis, vascular cell growth, apoptosis, and proliferation, mainly in the RAS/mitogen-activated protein kinase pathway/extracellular signal-regulated kinase (RAS/Raf/MEK) and the p53/mTOR pathway. Mutations in genes that are possibly involved in these pathways, such as MC4R, c-Kit, and GJA4, have been found in cavernous lesions in the orbital region (94,(99)(100) . Table 2 summarizes the main genetic mutations related to cavernous vascular lesions.…”