1. 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

2. 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 ( °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.

3. 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

4. CC: 49YO M presents w/ melena

5. Capsule Endoscopy

7. CT Abdomen

8. 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 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.

9. 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)

10. 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)

11. 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)

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

13. 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

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

15. 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, Aug 15;347(7):
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.