S2922 A Imatinib-Resistant Metastatic GIST Tumor Manifests as Diffuse Pruritus

Abstract

INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the prevalent nonepithelial tumors of the GI tract. GIST can manifest with a plethora of symptoms including early satiety, dysphagia, abdominal pain, bleeding and obstruction from mass effect. The main stay for medical therapy has been Imatinib, a tyrosine kinase inhibitor shutting down the oncogenic signal promoting tumor growth. Most GIST respond to Imatinib, while 10–15% will show disease progression or imatinib resistance. The following case highlights a genetic mutation conferring Imatinib resistance in a metastatic GIST. CASE DESCRIPTION/METHODS: A 64-year-old Nigerian man presented with acute exacerbation and generalized pruritis which was localized and mild for over 10 years. His physical exam only revealed diffuse excoriations on upper extremities, face and back. Labs showed a mixed hepatocellular and cholestatic pattern of transaminases. Hepatitis serology showed previously cleared infection with hepatitis B. Due to concomitant abdominal discomfort he was admitted and underwent colonoscopy and upper endoscopy which were negative. CT of abdomen with intravenous contrast showed numerous and diffusely distributed hypo-attenuated masses with the largest measuring 12.9 × 8 × 8 cm (Figure 1). Interventional radiology guided biopsy of the liver mass was performed with pathology consistent with oval and spindled shaped tumor cells with very rare mitosis. Immunostains of tumor cells were strongly and diffusely positive for GIST-1, weakly positive for KIT(CD117) (Figure 2). Given the liver masses on imaging and convincing pathology findings, he was diagnosed with metastatic GISTs with unknown primary and discharged to outpatient oncology for initiation of Imatinib mesylate. Within a couple weeks of treatment, he was hospitalized due to increased vascularity and hemorrhage within the tumor. Further genetic test was positive for D842V platelet derived growth factor receptor-alpha (PDGFRA) mutation which has been shown to confer resistance to Imatinib. He was then switched to second line agent- Sunitinib considering minimal improvement in lesion size on ultrasound with 3 months treatment with Imatinib. DISCUSSION: Most of the patients who have imatinib-resistance show KIT exon 9 or PDGFRA exon 18 D842V mutations. For patients imatinib-resistant GIST, sunitinib is a second-line drug treatment. This case highlights the need for further precise and targeted research on the various mechanisms of imatinib resistance in those presenting with metastatic GIST.Figure 1.: Core needle Biopsy of liver Panel A: H&E, objective x20; Panel B: H&E, objective x40; Panel C: immunohistochemistry of DOG1, x20 objective. Microscopic description: The entire liver core needle biopsy shows diffuse sheet of tumor cells (Panel A) with oval and spindled cytologic feature (Panel B) with very rare mitosis. Immunohistochemistry shows the tumor cells are strongly and diffusely positive for DOG1(Panel C), weakly positive for CD117 (not shown). It was diagnosed metastatic gastrointestinal stromal tumor to the liver. Molecular study (Quest diagnostics, Chantilly) on core biopsy specimen detected D842V mutant in the PDGFRA gene Exon 18.Figure 2.: Axial cut (left) and coronal cut (right) of a CT of the patient described showing a large liver lesion.