Tuesday, September 20, 2016 Kristina Lee, MD, MPH UCLA-Olive View PGY3 Morning Report Tuesday, September 20, 2016 Kristina Lee, MD, MPH UCLA-Olive View PGY3

MKSAP Question An 82-year-old woman is evaluated for a 2-week history of left-sided headaches with pain on chewing, accompanied by achiness in the shoulders and hips. On physical examination, temperature is 38.1 °C (100.6 °F), blood pressure is 132/86 mm Hg, pulse rate is 88/min, and respiration rate is 18/min. BMI is 25. Eye examination is normal. There are tenderness and swelling over the left temporal area. Erythrocyte sedimentation rate is 85 mm/h.

Which of the following is the most appropriate immediate next step in management? A) Initiate prednisone, 15 mg/d B) Initiate prednisone, 60 mg/d C) Obtain MRI of the head D) Obtain temporal artery biopsy

CC: 49YO M presents w/ melena

Capsule Endoscopy

CT Abdomen

GIST: Gastrointestinal Stromal Tumors Typically present as subepithelial neoplasms most often located in the stomach and proximal small intestine Account for <1% of GI malignancies Approximately 4000-6000 new cases reported in the U.S. yearly More common in middle-aged and older individuals, and rarely in those under the age of 40. Although most GISTs are sporadic, familial GIST (and pediatric GIST) has been seen.

GIST: Gastrointestinal Stromal Tumors In adults, GISTs are characterized by expression of the CD117 antigen The CD117 antigen is part of the KIT transmembrane receptor tyrosine kinase that is the product of the KIT (c-kit) proto- oncogene Usually a mutation in the KIT gene leads to an abnormally activated KIT protein and enables oncogenic signaling in the cell Rarely, a subset of GISTs lack KIT mutations and instead have activating mutations in a gene encoding platelet-derived growth factor receptor alpha (PDGFRA)

GIST: Gastrointestinal Stromal Tumors Presents often with vague, nonspecific abdominal pain or discomfort Occasionally presents w/ early satiety or abdominal fullness Rarely palpable abdominal mass Malaise, fatigue, or anemia Rarely focal or widespread signs of peritonitis (with perforation)

GIST: Gastrointestinal Stromal Tumors Workup (usually of nonspecific abdominal symptoms; abdominal pain): CBC, Coags, Chem10, LFTs, amylase, lipase, T/S, albumin CT A/P w/ contrast is essential for the diagnosis and staging PET scan is increasingly used for Detection of metastatic disease Monitoring response to adjuvant therapy (imatinib)

GIST: Gastrointestinal Stromal Tumors Prognosis Tumor size Mitotic rate (in HPF) Location (small bowel vs. gastric) TNM staging system Tumor rupture Genotyping

GIST: Gastrointestinal Stromal Tumors Management Surgery is the definitive therapy Radical and complete surgical excision is the only chance for cure Imatinib mesylate (Gleevec), a tyrosine kinase inhibitor is used in GIST as: Adjuvant therapy post complete surgical resection in patients with high-risk tumors Neoadjuvant therapy prior to surgical resection Other tyrosine kinase inhibitors are used when imatinib is not tolerated or is not effective are as follows: Sunitinib: Less specific than imatinib, second line Sorafenib: Investigational Dasatinib: Investigational Nilotinib: Investigational

GIST: Gastrointestinal Stromal Tumors Demetri et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. NEJM, 2002 Aug 15;347(7):472-80.

References Rubin BP, Fletcher JA, Fletcher CD. Molecular Insights into the Histogenesis and Pathogenesis of Gastrointestinal Stromal Tumors. Int J Surg Pathol 2000; 8:5. Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001; 438:1. Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol 1999; 30:1213.Reith JD, Goldblum JR, Lyles RH, Weiss SW. Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol 2000; 13:577. Medeiros F, Corless CL, Duensing A, et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 2004; 28:889. Demetri et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. NEJM, 2002 Aug 15;347(7):472-80. Kim TW, Lee H, Kang YK, et al. Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res 2004; 10:3076. Burkill GJ, Badran M, Al-Muderis O, et al. Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread. Radiology 2003; 226:527. Demetri GD, Benjamin RS, Blanke CD, et al. NCCN task force report: optimal management of patients with gastrointestinal stromal tumor (GIST)- Update of NCCN Clinical Practice Guidelines. J Natl Comp Cancer Net 2007; 5(2 suppl):S-1.