GISTs were previously thought to be smooth muscle neoplasms, and most were classified as LMS. With the advent of immunohistochemistry and electron microscopy, it has become apparent that GISTs may have myogenic features, neural attributes, and characteristics of both muscle and nerve or may lack differentiation [3]. Sarlomo-Rikala et al. [4] pointed out that the c-kit antibody is a useful marker for diagnosing GISTs and for distinguishing them from true leiomyomas and neurogenic tumors. c-kit over expression because of activating mutations appears to drive the neoplastic growth of GISTs [5–7]. GISTs most commonly occur in the stomach (52%), small intestine (25%), esophagus (5%), and large bowel (11%) [8]. The most intriguing findings in the current study were the observation of a lesion that was located outside the gastrointestinal tract, primarily the mesentery, omentum, and retroperitoneum [1, 2], but fulfilled the histologic and immunohistochemical criteria for classification as GIST. EGIST is positive for c-kit expression, with histological appearance similar to GIST.
It is recognized that GIST cells exhibit characteristics similar to those of the interstitial cells of Cajal (ICC), the pacemaker cells of the gastrointestinal tract [9, 10]. Presence of an ICC system was reported in extragastrointestinal locations, guinea pig urinary bladder [11], guinea pig mesenteric arteries [12], sheep mesenteric lymphatic vessels [13], and fetal endothelial cells [14]. Bolton et al. identified non-contractile cells closely resembling ICC in the wall of the portal vein and mesenteric artery using immunohistochemical approaches in combination with confocal imaging [15]. Povstyan et al reported that two layers of ICC were detected by c-kit and methylene blue staining in the media of the rabbit portal vein in sub-endothelial intramuscular and deeper intramuscular positions [16]. As per these reports, c-kit-positive stromal tumors can occur in extragastrointestinal anatomic sites, particularly in those that are embryologically linked to mesenchymal cells, similar to the vessels. In our resected specimen, immunohistochemical staining could not demonstrate the normal media wall of the IVC to be positive for c-kit expression. However, it was confirmed that there was a vascular tumor of ICC origin. EGIST of the IVC is a very rare kind of tumor, and there are no reports of EGIST arising from the IVC till date.
Tumors of the IVC are uncommon malignancies with a tendency for both local recurrence and systemic dissemination. Surgical resection remains the therapeutic gold standard for GISTs and LMS, and tumor resectability is an important prognostic factor. However, LMS arising in the intima has poorer prognosis than mural sarcomas because intimal origin is a source of widespread metastases. Additionally, seeding of the tumor to distant sites occurs earlier. In our case, adjuvant therapy was not administered because there was no evidence of metastases and recurrences and the tumor was originating from the media of the vessel wall. Although distinction between GIST and LMS is important, GIST might be effectively treated with tyrosine kinase inhibitors, such as imatinib mesylate [17, 18]. There is the possibility that GIST occurred in the present case, which was initially reported as LMS of the IVC because those were histologically classified together as LMS owing to their similarities as determined via light microscopy. The potential occurrence of GIST-like tumors outside the gastrointestinal tract should be recognized in the differential diagnosis of tumors of the great vessels.
