Gastrointestinal Stromal Tumors with Intracranial Metastasis: Treatment Strategy and Review of the Literature

Introduction

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms that arise from precursors of the gastrointestinal tract connective tissue. Approximately 70% of GISTs are located in the stomach, 20% in the small bowel, and 5% in the rectum ( ). Stromal tumors belong to the leiomyosarcoma or leiomyoma group. GISTs arise from precursors of the intestinal cells of Cajal ( ). Clinically, GISTs are usually diagnosed based on KIT (CD117) expression using immunohistochemical analysis ( ). The gain-of-function of c-kit or platelet-derived growth factor receptor alpha ( PDGFRA ) plays a critical oncogenic role in GISTs ( ). Approximately 70% of mutations in c-kit are detected in exon 11, particularly in the 5′ end ( Fig. 15.1 ). The mutational status of c-kit is often predictive of the clinical response to imatinib mesylate ( ). Imatinib mesylate is a competitive inhibitor of multiple tyrosine kinases, including KIT and PDGFRA , and its clinical effectiveness for advanced GISTs has been documented ( ).

Most metastases occur in the liver and peritoneum as a result of hematogenous spread and peritoneal seeding. Metastatic GISTs to the central nervous system (CNS) are very rare. Most intracranial metastases are treated surgically with or without additional radiotherapy. Imatinib mesylate is believed to be ineffective for brain metastases because it cannot pass through the blood–brain-barrier (BBB) and does not achieve adequate levels in the brain when administered in lower concentrations ( ). Therefore, current clinical practice guidelines recommend surgical resection as a first priority. Adjuvant therapy is considered an option for patients with a substantial risk of relapse ( ).

According to a PubMed database and literature search, 15 cases of brain metastases from primary GISTs have been reported to date. The list of GISTs in the CNS and their clinical features are given in Table 15.1 . Here, we summarize and review the relevant literature regarding intracranial metastasis of GISTs.

Clinical Features of GISTs

Neuroradiological Findings

Common radiological features of GIST metastases include a round mass located in the subcortex, which is occasionally accompanied by perifocal edema, which resembles meningioma. Typical magnetic resonance imaging shows an isointense T1-weighted and iso- and low intense T2-weighted lesion and homogenous enhancement after gadolinium injection ( Fig. 15.2 ). Rarely, ring enhancement of gadolinium or intratumoral hemorrhages has been noted in intracranial metastatic GISTs ( ).