Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Gastrointestinal Stromal Tumors: A Clinicopathologic and Risk Stratification Study of 255 Cases from Pakistan and Review of Literature

  • Din, Nasir Ud (Department of Pathology and Microbiology, Section of Histopathology, Aga Khan University Hospital) ;
  • Ahmad, Zubair (Department of Pathology and Microbiology, Section of Histopathology, Aga Khan University Hospital) ;
  • Arshad, Huma (Department of Pathology and Microbiology, Section of Histopathology, Aga Khan University Hospital) ;
  • Idrees, Romana (Department of Pathology and Microbiology, Section of Histopathology, Aga Khan University Hospital) ;
  • Kayani, Naila (Department of Pathology and Microbiology, Section of Histopathology, Aga Khan University Hospital)
  • Published : 2015.07.13
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: To describe the clinicopathological features of gastrointestinal stromal tumors (GIST) diagnosed in our section and to perform risk stratification of our cases by assigning them to specific risk categories and groups for disease progression based on proposals by Fletcher et al and Miettinen and Lasota. Materials and Results: We retrieved 255 cases of GIST diagnosed between 2003 and 2014. Over 59% were male. The age range was 16 to 83 years with a mean of 51 years. Over 70% occurred between 40 and 70 years of age. Average diameter of tumors was 10 cms. The stomach was the most common site accounting for about 40%. EGISTs constituted about 16%. On histologic examination, spindle cell morphology was seen in almost of 85% cases. CD117 was the most useful immunohistochemical antibody, positive in 98%. Risk stratification was possible for 220 cases. Based on Fletcher's consensus proposal, 62.3 gastric, 81.8% duodenal, 68% small intestinal, 72% colorectal and 89% EGISTs were assigned to the high risk category; while based on Miettinen and Lasota's algorithm, about 48% gastric, 100% duodenal, 76% small intestinal, 100% colorectal and 100% EGISTs in our study were associated with high risk for disease progression, tumor metastasis and tumor related death. Follow up was available in 95 patients; 26 were dead and 69 alive at follow up. Most of the patients who died had high risk disease and on average death occurred just a few months to a maximum of one to two years after initial surgical resection. Conclusions: Epidemiological and morphologic findings in our study were similar to international published data. The majority of cases in our study belonged to the high risk category.

Keywords

References

  1. Agaimy A, Wunsch PH (2006). Gastrointestinal stromal tumors: a regular origin in the muscularis propria, but an extremely diverse gross presentation. A review of 200 cases to critically re-evaluate the concept of so-called extra-gastrointestinal stromal tumors. Langenbecks Arch Surg, 391, 322-9. https://doi.org/10.1007/s00423-005-0005-5
  2. Ahmad Z, Arshad H, Fatima S, et al (2013). Gastrointestinal, liver and biliary tract pathology: a histopathological and epidemiological perspective from Pakistan with review of the literature. Asian Pac J Cancer Prev, 14, 6997-7005. https://doi.org/10.7314/APJCP.2013.14.11.6997
  3. Ashraf M, Jha J, Choudhry A (2011). Neoadjuvent and adjuvant therapy with imatinib for locally advanced gastrointestinal stromal tumors in Eastern Indian patients. Asian Pac J Cancer Prev, 12, 2059-64.
  4. Blay JY, von Mehren M, Blackstein ME (2010). Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors. Cancer, 116, 5126-37. https://doi.org/10.1002/cncr.25267
  5. Cao H, Zhang Y, Wang M, et al (2010). Prognostic analysis of patients with gastrointestinal stromal tumors: a single unit experience with surgical treatment of primary disease. Chin Med J, 123, 131-6.
  6. Chen T, Liu H, Hu Y, et al (2013). Value of three risk-stratification criteria in Chinese patients with gastrointestinal stromal tumors. Nan Fang Yi Ke De Xue Xue Bao, 33, 918-22.
  7. Chiang NJ, Chen LT, Tsai CR, et al (2014). The epidemiology of gastrointestinal stromal tumors in Taiwan,1998-2008: a nationwide cancer registry based study. BMC Cancer, 18, 102.
  8. Cho MY, Sohn JM, Kim JM, et al (2010). Current trends in the epidemiological and pathological characteristics of gastrointestinal stromal tumor in Korea, 2003-2004. J Korean Med Sci, 25, 853-62. https://doi.org/10.3346/jkms.2010.25.6.853
  9. Coindre JM, Emile JF, Monges G, et al (2005). Gastrointestinal stromal tumors: definition, histological, immunohistochemical, and molecular features, and diagnostic strategy. Ann Pathol, 25, 358-85. https://doi.org/10.1016/S0242-6498(05)80145-2
  10. DeMatteo RP, Lewis JJ, Leung D, et al (2000). Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg, 231, 51-8. https://doi.org/10.1097/00000658-200001000-00008
  11. Dematteo RP, Ballman KV, Antonescu CR, et al (2009). American college of surgeons oncology group (ACOSOG) intergroup adjuvant GIST study team. adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumor: a randomised, double-blind, placebo-controlled trial. Lancet, 373, 1097-04. https://doi.org/10.1016/S0140-6736(09)60500-6
  12. Demetri GD, Reichardt P, Kang YK, et al (2013). Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib (GRID): an international, multicentric, randomised, placebo-controlled, phase 3 trial. Lancet, 381, 295-302. https://doi.org/10.1016/S0140-6736(12)61857-1
  13. Demir L, Ekinci N, Erten C (2013). Does immunohistochemistry provide additional prognostic data in gastrointestinal tumors? Asian Pac J Cancer Prev, 14, 4751-58. https://doi.org/10.7314/APJCP.2013.14.8.4751
  14. Du C, Zhou Y, Song C, et al (2014). Is there a role of surgery in patients with recurrent or metastatic gastrointestinal stromal tumors responding to imatinib: a prospective randomized trial in China. Eur J Cancer, 50, 1772-8. https://doi.org/10.1016/j.ejca.2014.03.280
  15. Emory TS, Sobin LH, Lukes L, et al (1999). Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol, 23, 82-7. https://doi.org/10.1097/00000478-199901000-00009
  16. Fletcher CD, Berman JJ, Corless C, et al (2002). Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol, 33, 459-65. https://doi.org/10.1053/hupa.2002.123545
  17. Franquemont DW (1995). Differentiation and risk assessment of gastrointestinal stromal tumors. Am J Clin Pathol, 103, 41-7. https://doi.org/10.1093/ajcp/103.1.41
  18. Heinrich MC, Rubin BP, Longley BJ, et al (2002). Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol, 33, 484-95. https://doi.org/10.1053/hupa.2002.124124
  19. Hornick JL, Fletcher CD (2004). The significance of KIT (CD117) in gastrointestinal stromal tumors. Int J Surg Pathol, 12, 93-7. https://doi.org/10.1177/106689690401200201
  20. Jacob J, Mussi C, Ronellenfitsch U, et al (2013). Gastrointestinal stromal tumors of the rectum: results of surgical and multimodality therapy in the era of Imatinib. Ann Surg Oncol, 20, 586-92. https://doi.org/10.1245/s10434-012-2647-1
  21. Joensuu H, Hohenberger P, Corless C (2013). Gastrointestinal stromal tumor. Lancet, 382, 973-83. https://doi.org/10.1016/S0140-6736(13)60106-3
  22. Kapoor R, Khosla D, Kumar P, et al (2013). Five-year follow up of patients with gastrointestinal stromal tumors: recurrence-free survival by risk group. Asian Pac J Clin Oncol, 9, 40-6. https://doi.org/10.1111/j.1743-7563.2011.01494.x
  23. Lakshmi VA, Chacko RT, Kurian S (2010). Gastrointestinal stromal tumors: a 7-year experience from a tertiary care hospital. Indian J Pathol, 53, 628-33. https://doi.org/10.4103/0377-4929.72005
  24. Li JC, Zhu HY, Chen TX, et al (2013). Roles of mTOR and p-mTOR in gastrointestinal stromal tumors. Asian Pac J Cancer Prev, 14, 5925-8. https://doi.org/10.7314/APJCP.2013.14.10.5925
  25. Li J, Gao J, Hong J, et al (2012). Efficacy and safety of sunitinib in Chinese patients with imatinib- resistant or -intolerant gastrointestinal stromal tumors. Future Oncol, 8, 617-24. https://doi.org/10.2217/fon.12.29
  26. Liegl-Atzwanger B, Fletcher JA, Fletcher CD (2010). Gastrointestinal stromal tumors. Virchows Arch, 456, 111-27. https://doi.org/10.1007/s00428-010-0891-y
  27. Mechtersheimer G, Egerer G, Hensel M, et al (2004). Gastrointestinal stromal tumors and their response to treatment with the tyrosine kinase inhibitor imatinib. Virchows Arch, 444, 108-18. https://doi.org/10.1007/s00428-003-0945-5
  28. Miettinen M, Kopczynski J, Makhlouf HR, et al (2003). Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol, 27, 625-41. https://doi.org/10.1097/00000478-200305000-00006
  29. Miettinen M, Sobin LH, Lasota J (2005). 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, 29, 52-68. https://doi.org/10.1097/01.pas.0000146010.92933.de
  30. Miettinen M, Lasota J (2006). Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol, 23, 70-83. https://doi.org/10.1053/j.semdp.2006.09.001
  31. Miettinen M, Makhlouf H, Sobin LH, et al (2006). Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol, 30, 477-89. https://doi.org/10.1097/00000478-200604000-00008
  32. Miettinen M, Wang ZF, Lasota J (2009). DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: a study of 1840 cases. Am J Surg Pathol, 33, 1401-8. https://doi.org/10.1097/PAS.0b013e3181a90e1a
  33. Miettinen M, Fletcher CDM, Kindblom LG, et al (2010). Mesenchymal tumors of the stomach. In Bosman FT, Carneiro F, Hruban RH, Theise ND eds. WHO classification of tumors of the digestive system. IARC, Lyon, France, pp. 74-9.
  34. Miettinen M, Fletcher CDM, Kindblom LG, et al (2010a). Mesenchymal tumors of the small intestine. In Bosman FT, Carneiro F, Hruban RH, Theise ND eds. WHO classification of tumors of the digestive system. IARC, Lyon, France, pp.115-16.
  35. Miettinen M, Fletcher CDM, Kindblom LG, et al (2010b). Mesenchymal tumors of the Colon and Rectum. In Bosman FT, Carneiro F, Hruban RH, Theise ND eds. WHO classification of tumors of the digestive system. IARC, Lyon, France, pp.181-2.
  36. Miettinen MM, Lasota J, Corless CL, et al (2013). Gastrointestinal stromal tumors. In Fletcher DM, Bridge JA, Hogendoorn PCW, Mertens F. WHO classification of tumors of soft tissue and bone. IARC, Lyon, France, pp.164-7.
  37. Nilsson B, Bumming P, Meis-Kindblom JM, et al (2005). Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era-a population-based study in Western Sweden. Cancer, 103, 821-9. https://doi.org/10.1002/cncr.20862
  38. Ravikumar G, Kalegowda IY, Ananthamurthy A (2011). Clinicopathologic spectrum of gastrointestinal stromal tumors-experience at a tertiary care center. Indian J Cancer, 48, 466-70. https://doi.org/10.4103/0019-509X.92281
  39. Rosai J (2003). GIST: an update. Int J Surg Pathol, 11, 177-86. https://doi.org/10.1177/106689690301100304
  40. Rubin BP, Fletcher JA, Fletcher CD (2000). Molecular insights into the histogenesis and pathogenesis of gastrointestinal Stromal Tumors. Int J Surg Pathol, 8, 5-10. https://doi.org/10.1177/106689690000800105
  41. Rubin BP (2006). Gastrointestinal stromal tumors: an update. Histopathology, 48, 83-96. https://doi.org/10.1111/j.1365-2559.2005.02291.x
  42. Selcukbiricik F, Yalcin S, Tural D, et al (2013). Gastrointestinal stromal tumors in Turkey: experience from 3 centers. Onkologie, 36, 18-24. https://doi.org/10.1159/000346673
  43. Sevinc A, Camci C, Sari I, et al (2010). Cyclooxygenase-2 expression in gastrointestinal stromal tumors. Asian Pac J Cancer Prev, 11, 849-53.
  44. Sun XV, Feng ZJ, Huang P, et al (2012). Expression of DOG1, CD117 and PDGFRA in gastrointestinal stromal tumors and correlations with clinicopathology. Asian Pac J Cancer Prev, 13, 1389-93. https://doi.org/10.7314/APJCP.2012.13.4.1389
  45. Tryggvason G, Gislason HG, Magnusson MK, et al (2005). Gastrointestinal stromal tumors in Iceland, 1990-2003: the Icelandic GIST study: a population-based incidence and pathologic risk stratification study. Int J Cancer, 117, 289-93. https://doi.org/10.1002/ijc.21167
  46. Tworek JA, Appelman HD, Singleton TP, et al (1997). Stromal tumors of the jejunum and ileum. Mod Pathol, 10, 200-9.
  47. Wang C, Ma HX, Jin MS, et al (2014). Association of matrix metalloproteinase (MMP)-2 and -9 expression with extragastrointestinal stromal tumor metastasis. Asian Pac J Cancer Prev, 15, 4187-92. https://doi.org/10.7314/APJCP.2014.15.10.4187
  48. Wang ZH, Liang XB, Wang Y, et al (2013). Epidemiology survey of gastrointestinal stromal tumors in Shanxi province in 2011. Zhoughua Yi Xue Za Zhi, 93, 2541-4.
  49. Yamamoto H, Oda Y, Kawaguchi K, et al (2004). c-kit and PDGFRA mutations in extragastrointestinal stromal tumors (gastrointestinal stromal tumors of the soft tissue). Am J Surg Pathol, 28, 479-88. https://doi.org/10.1097/00000478-200404000-00007
  50. Yoon DH, Ryu MH, Ryoo BY et al (2012). Sunitinib as a second-line therapy for advanced GISTs after failure of imatinib: relationship between efficiency and tumor genotype in Korean patients. Invest New Drugs, 30, 819-27. https://doi.org/10.1007/s10637-010-9593-1
  51. Zhang Y, Cao H, Wang M, et al (2009). Analysis of clinicopathology and prognosis in 181 patients with gastrointestinal stromal tumors. Zhonghua Wei Chang Wai Ke Za Zhi, 12, 150-4.

Cited by

  1. Interleukins 17 and 23 in patients with gastric neoplasms vol.6, pp.1, 2016, https://doi.org/10.1038/srep37451
  2. Clinicopathologic features and prognostic grouping of gastrointestinal stromal tumors (GISTs) in Pakistani patients: an institutional perspective vol.11, pp.1, 2018, https://doi.org/10.1186/s13104-018-3562-8