Case Reports

Recurrence of a small gastric gastrointestinal stromal tumor with high mitotic index

The Sarcoma Journal. 2019 March;3(1):17-21

References

1. Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 2011;11(12):865-878.

2. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279(5350):577-580.

3. Corless CL, Ballman KV, Antonescu CR, Kolesnikova V, Maki RG, Pisters PW, et al. Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial. J Clin Oncol. 2014;32(15):1563-1570.

4. Huang J, Zheng DL, Qin FS, Cheng N, Chen H, Wan BB, et al. Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling. J Clin Invest. 2010;120(1):223-241.

5. Joensuu H, Vehtari A, Riihimaki J, Nishida T, Steigen SE, Brabec P, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13(3):265-274.

6. Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006;130(10):1466-1478.

7. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol. 2005;29(1):52-68.

8. Patel S. Navigating risk stratification systems for the management of patients with GIST. Ann Surg Oncol. 2011;18(6):1698-1704.

9. Rossi S, Miceli R, Messerini L, Bearzi I, Mazzoleni G, Capella C, et al. Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables. Am J Surg Pathol. 2011;35(11):1646-1656.

10. National Comprehensive Cancer Network. Sarcoma. https://www.nccn.org/professionals/physician_gls/default.aspx#age. Accessed March 27, 2018.

11. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Int J Surg Pathol. 2002;10(2):81-89.

12. Huang HY, Li CF, Huang WW, Hu TH, Lin CN, Uen YH, et al. A modification of NIH consensus criteria to better distinguish the highly lethal subset of primary localized gastrointestinal stromal tumors: a subdivision of the original high-risk group on the basis of outcome. Surgery. 2007;141(6):748-756.

13. Kim MC, Yook JH, Yang HK, Lee HJ, Sohn TS, Hyung WJ, et al. Long-term surgical outcome of 1057 gastric GISTs according to 7th UICC/AJCC TNM system: multicenter observational study from Korea and Japan. Medicine (Baltimore). 2015;94(41):e1526.

14. Casali PG, Blay JY; ESMO/CONTICANET/EUROBONET Consensus Panel of experts. Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):v198-v203.

15. Joensuu H, DeMatteo RP. The management of gastrointestinal stromal tumors: a model for targeted and multidisciplinary therapy of malignancy. Annu Rev Med. 2012;63:247-258.

16. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373(9669):1097-1104.

17. Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012;307(12):1265-1272.

18. Joensuu H, Rutkowski P, Nishida T, Steigen SE, Brabec P, Plank L, et al. KIT and PDGFRA mutations and the risk of GI stromal tumor recurrence. J Clin Oncol. 2015;33(6):634-642.

19. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 2002;33(5):459-465.

20. Antonescu CR, Viale A, Sarran L, Tschernyavsky SJ, Gonen M, Segal NH, et al. Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site. Clin Cancer Res. 2004;10(10):3282-3290.

21. Arne G, Kristiansson E, Nerman O, Kindblom LG, Ahlman H, Nilsson B, et al. Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location and poor prognosis. Int J Cancer. 2011;129(5):1149-1161.

22. Bertucci F, Finetti P, Ostrowski J, Kim WK, Kim H, Pantaleo MA, et al. Genomic Grade Index predicts postoperative clinical outcome of GIST. Br J Cancer. 2012;107(8):1433-1441.

23. Koon N, Schneider-Stock R, Sarlomo-Rikala M, Lasota J, Smolkin M, Petroni G, et al. Molecular targets for tumour progression in gastrointestinal stromal tumours. Gut. 2004;53(2):235-240.

24. Lagarde P, Perot G, Kauffmann A, Brulard C, Dapremont V, Hostein I, et al. Mitotic checkpoints and chromosome instability are strong predictors of clinical outcome in gastrointestinal stromal tumors. Clin Cancer Res. 2012;18(3):826-838.

25. Skubitz KM, Geschwind K, Xu WW, Koopmeiners JS, Skubitz AP. Gene expression identifies heterogeneity of metastatic behavior among gastrointestinal stromal tumors. J Transl Med. 2016;14:51.

26. Yamaguchi U, Nakayama R, Honda K, Ichikawa H, Haseqawa T, Shitashige M, et al. Distinct gene expression-defined classes of gastrointestinal stromal tumor. J Clin Oncol. 2008;26(25):4100-4108.

27. Ylipaa A, Hunt KK, Yang J, Lazar AJ, Torres KE, Lev DC, et al. Integrative genomic characterization and a genomic staging system for gastrointestinal stromal tumors. Cancer. 2011;117(2):380-389.

28. Kawanowa K, Sakuma Y, Sakurai S, Hishima T, Iwasaki Y, Saito K, et al. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol. 2006;37(12):1527-1535.

Case Presentation and Summary

A 69-year-old man presented with periumbilical and epigastric pain of 6-month duration. His medical history was notable for hyperlipidemia, hypertension, coronary angioplasty, and spinal surgery. He had a 40 pack-year smoking history and consumed 2 to 4 alcoholic drinks per day. The results of a physical examination were unremarkable. A computed tomographic (CT) scan showed no abnormalities. An esophagogastroduodenoscopy (EGD) revealed gastric ulcers. He was treated successfully with omeprazole 20 mg by mouth daily.

A month later, a follow-up EGD revealed a 1.8 x 1.5-cm submucosal mass 3 cm from the gastroesophageal junction. The patient underwent a fundus wedge resection, and a submucosal mass 1.8 cm in greatest dimension was removed. Pathologic examination revealed a GIST, spindle cell type, with a mitotic rate of 36 mitoses per 50 hpf with negative margins. Immunohistochemistry was positive for CD117. An exon 11 deletion (KVV558-560NV) was present in KIT. The patient’s risk of recurrence was unclear, and his follow-up included CT scans of the abdomen and pelvis every 3 to 4 months for the first 2 years, then every 6 months for the next 2.5 years.

A CT scan about 3.5 years after primary resection revealed small nonspecific liver hypodensities that became more prominent during the next year. About 5 years after primary resection, magnetic resonance imaging (MRI) revealed several liver lesions, the largest of which measured 1.3 cm in greatest dimension. The patient’s liver metastases were readily identified by MRI (Figure 1) and CT imaging (Figure 2A).

Most GISTs are fluorodeoxyglucose (FDG) avid on positron-emission tomography (PET) imaging. In contrast, this patient’s liver metastases had no detectable FDG uptake (not shown). A liver biopsy revealed recurrent GIST (Figure 3).

Imatinib mesylate was begun at 400 mg per day orally. After 2 months, the liver lesions were reduced in size, with the largest lesion shrinking to 0.5 cm in greatest dimension. The liver lesions continued to decrease in size and number (Figure 2B).

At 16 months after starting imatinib, there was no sign of tumor progression.