Seminars in Diagnostic Pathology
Volume 23, Issue 2 , Pages 70-83 , May 2006

Gastrointestinal stromal tumors: Pathology and prognosis at different sites

  • Markku Miettinen, MD

      Affiliations

    • Corresponding Author InformationAddress reprint requests and correspondence: Markku Miettinen, MD, Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, 6825 16th Street, N.W., Bldg 54, Rm. G090, Washington, DC 20306-6000.
  • ,
  • Jerzy Lasota, MD

References 

  1. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–580
  2. Kindblom LG, Remotti HE, Aldenborg F, et al. Gastrointestinal pacemaker cell tumor (GIPACT) Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol. 1998;153:1259–1269
  3. Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): -Definition, occurrence, pathology, differential diagnosis and molecular genetic features. Pol J Pathol. 2003;54:3–24
  4. Lee JR, Joshi V, Griffin JW, et al. Gastrointestinal autonomic nerve tumor: immunohistochemical and molecular identity with gastrointestinal stromal tumor. Am J Surg Pathol. 2001;25:979–987
  5. Antonescu CR, Viale A, Sarran L, et al. Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site. Clin Cancer Res. 2004;10:3282–3290
  6. Subramanian S, West RB, Corless CL, et al. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene. 2004;23:7780–7790
  7. Demetri G, van Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–480
  8. Miettinen M, Sarlomo-Rikala M, Sobin LH, et al. Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol. 2000;24:211–222
  9. Kim KM, Kang DW, Moon WS, et al. Gastrointestinal stromal tumors in Koreans: its incidence and the clinical, pathologic and immunohistochemical findings. J Korean Med Sci. 2005;20:977–984
  10. Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era: a population-based study in western Sweden. Cancer. 2005;103:821–829
  11. Tryggvason G, Gislason HG, Magnusson MK, et al. Gastrointestinal stromal tumors in Iceland, 1990-2003: the Icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer. 2005;117:289–293
  12. Miettinen M, Makhlouf HR, Sobin LH, et al. Gastrointestinal stromal tumors (GISTs) of the jejunum and ileum: a clinicopathologic, immunohistochemical and molecular genetic study of 906 cases prior to imatinib with long-term follow-up. Am J Surg Pathol. 2006;30:477–489
  13. Trupiano JK, Stewart RE, Misick C, et al. Gastric stromal tumors (A clinicopathologic study of 77 cases with correlation of features with non-aggressive and aggressive behaviors). Am J Surg Pathol. 2002;26:705–714
  14. Wong NACS, Young R, Malcomson RDG, et al. Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach. Histopathology. 2003;43:118–126
  15. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic studies of 1765 cases with long-term follow-up. Am J Surg Pathol. 2005;29:52–68
  16. Abraham SC, Krasinskas AM, Hofstetter WL, et al. “Seedling” mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common in the esophagogastric region. Mod Pathol. 2006;19(suppl 1):100A
  17. Appelman HD, Helwig EB. Gastric epithelioid leiomyoma and leiomyosarcoma (leiomyoblastoma). Cancer. 1976;38:708–728
  18. Miettinen M, Kopczynski J, Maklouf HR, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas of the duodenum: a clinicopathologic, immunohisto-chemical, and molecular genetic study of 167 cases. Am J Surg Pathol. 2003;27:625–641
  19. Goldblum JR, Appelman HD. Stromal tumors of the duodenum (A histologic and immunohistochemical study of 20 cases). Am J Surg Pathol. 1995;19:71–80
  20. Daum O, Klecka J, Ferda J, et al. Gastrointestinal stromal tumors of the pancreas: case report with documentation of KIT gene mutation. Virchows Arch. 2005;446:470–472
  21. Tworek JA, Appelman HD, Singleton TP, et al. Stromal tumors of the jeujunum and ileum. Mod Pathol. 1997;10:200–209
  22. Min K-W. Small intestinal stromal tumors with skeinoid fibers (Clinicopathological, immunohistochemical, and ultrastructural investigations). Am J Surg Pathol. 1992;16:145–155
  23. Brainard JA, Goldblum JR. Stromal tumors of the jejunum and ileum: a clinicopathologic study of 39 cases. Am J Surg Pathol. 1997;21:407–416
  24. Yantiss RK, Rosenberg AE, Selig MK, et al. Gastrointestinal stromal tumors: an ultrastructural study. Int J Surg Pathol. 2002;10:101–113
  25. Tworek J, Goldblum JR, Weiss SW, et al. Stromal tumors of the abdominal colon (A clinicopathologic study of 20 cases). Am J Surg Pathol. 1999;23:937–945
  26. Miettinen M, Sarlomo-Rikala M, Sobin LH, et al. Gastrointestinal stromal tumors and leiomyosarcomas in the colon (A clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases). Am J Surg Pathol. 2000;24:1339–1352
  27. Miettinen M, Sobin LH. Gastrointestinal stromal tumors in the appendix (A clinicopathologic and immunohistochemical study of four cases). Am J Surg Pathol. 2001;25:1433–1437
  28. Yap WM, Tan HW, Goh SGN, et al. Appendiceal gastrointestinal stromal tumor (Letter to the editor). Am J Surg Pathol. 2005;29:1545–1547
  29. Tworek J, Goldblum JR, Weiss SW, et al. Stromal tumors of the anorectum (A clinicopathologic study of 22 cases). Am J Surg Pathol. 1999;23:946–954
  30. Miettinen M, Furlong M, Sarlomo-Rikala M, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus (A clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases). Am J Surg Pathol. 2001;25:1121–1133
  31. Hassan I, You N, Dozois EJ, et al. Clinical, pathologic, and immunohistochemical characteristics of gastrointestinal stromal tumors of the colon and rectum: implications for surgical management and adjuvant therapies. Dis Col Rectum. 2006;49:609–615
  32. Changchien CR, Wu MC, Tasi WS, et al. Evaluation of prognosis for malignant rectal gastrointestinal stromal tumor by clinical parameters and immunohistochemical staining. Dis Col Rectum. 2004;47:1922–1929
  33. Firoozmand E, Binder S, Thompson A, et al. A gastrointestinal stromal tumor discovered in a resected hemorrhoidal donut after stapled hemorrhoidopexy: report of a case. Am Surg. 2005;71:155–158
  34. Miettinen M, Monihan JM, Sarlomo-Rikala M, et al. Gastrointestinal stromal tumors/smooth muscle tumors/GISTs in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases. Am J Surg Pathol. 1999;23:1109–1118
  35. Reith JD, Goldblum JR, Lyles RH, et al. Extragastrointestinal (soft tissue) stromal tumors (An analysis of 48 cases with emphasis on histological predictors of outcome). Mod Pathol. 2000;13:577–585
  36. Yamamoto H, Oda Y, Kawaguchi K, et al. c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue). Am J Surg Pathol. 2004;28:479–488
  37. Agaimy A, Wunsch PH. Gastrointestinal stromal tumours: a regular origin in the muscularis propria, but an extremely diverse gross presentation (A rfeview of 200 to critically re-evaluate the concept of so-called extragastrointestinal stromal tumors). Langenbecks Arch Surg. 2006;[EPub Jan 2006]
  38. Lam MM, Corless CL, Goldblum JR, et al. Extragastrointestinal stromal tumors presenting as vulvovaginal/rectovaginal septal masses: a diagnostic pitfall. Int J Gynecol Pathol. 2006;25:288–292
  39. Lasota J, Carlson J, Miettinen M. Spindle cell tumor of urinary bladder serosa with phenotypic and genotypic features of gastrointestinal stromal tumor. Arch Pathol Lab Med. 2000;124:894–897
  40. Wingen CB, Pauwels PA, Debiec-Rychter M, et al. Uterine gastrointestinal stromal tumor. Gynecol Oncol. 2005;97:970–972
  41. Sakurai S, Hishima T, Takazawa Y, et al. Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum. Pathol Int. 2001;51:524–531
  42. Ortiz-Hidalgo C, Bojorge BL, Albores-Saavedra J. Stromal tumor of the gallbladder with phenotype of interstitial cells of Cajal (A previously unrecognized neoplasm). Am J Surg Pathol. 2000;24:1420–1423
  43. Mendoza-Marin M, Hoang MP, Albores-Saavedra J. Malignant stromal tumor of the gallbladder with interstitial cells of Cajal phenotype. Arch Pathol. 2002;126:481–483
  44. Park JK, Choi SH, Lee S, et al. Malignant gastrointestinal stromal tumor of the gallbladder. J Korean Med Sci. 2004;19:763–767
  45. Furihata M, Fujimori T, Imura J, et al. Malignant stromal tumor, so called “gastrointestinal stromal tumor”, with rhabdomyomatous differentiation occurring in the gallbladder. Pathol Res Pract. 2005;201:609–613
  46. Siddio MA, East D, Hock YL, et al. Gastrointestinal stromal tumor of the pharynx. J Laryngol Otol. 2004;118:315–316
  47. Prakash S, Sarran L, Socci N, et al. Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol. 2005;27:179–187
  48. Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature. Am J Surg Pathol. 2005;29:1373–1381
  49. Carney JA. Gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma (Carney triad): natural history, adrenocortical component, and possible familial occurrence. Mayo Clin Proc. 1999;74:543–552
  50. Takazawa Y, Sakurai S, Sakuma Y, et al. Gastrointestinal stromal tumors of neuro-fibromatosis type I (von Recklinghausen’s disease). Am J Surg Pathol. 2005;29:755–763
  51. Andersson J, Sihto H, Meis-Kindblom JM, et al. NF1-associated gastrointestinal stromal tumors have unique clinical, phenotypic, and genotypic characteristics. Am J Surg Pathol. 2005;29:1170–1176
  52. Miettinen M, Fetsch JF, Sobin LH, et al. Gastrointestinal stromal tumors in patients with neurofibromatosis 1 (A clinicopathologic study of 45 patients with long-term follow-up). Am J Surg Pathol. 2006;30:90–96
  53. Kinoshita K, Hirota S, Isozaki K, et al. Absence of c-kit gene mutations in gastrointestinal stromal tumours from neurofibromatosis type 1 patients. J Pathol. 2004;202:80–85
  54. Sarlomo-Rikala M, Kovatich A, Barusevicius A, et al. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol. 1998;11:728–734
  55. Medeiros F, Corless CL, Duensing A, et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol. 2004;28:889–894
  56. Lasota J, Dansonka-Meiszkowska A, Sobin LH, et al. A great majority of GISTs with PDGFRA mutations represent gastric tumors with low or no malignant potential. Lab Invest. 2004;84:874–883
  57. Rossi G, Valli R, Bertolini F, et al. PDGFR expression in differential diagnosis between KIT-negative gastrointestinal stromal tumours and other primary soft-tissue tumours of the gastrointestinal tract. Histopathology. 2005;46:522–531
  58. Yi ES, Strong CR, Piao Z, et al. Epithelioid gastrointestinal stromal tumor with PDGFRA activating mutation and immunoreactivity. Appl Immunohistochem Mol Morphol. 2005;13:157–161
  59. Duensing A, Joseph NE, Medeiros F, et al. Protein kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs). Cancer Res. 2004;64:5127–5131
  60. Blay P, Astudillo A, Buesa JM, et al. Protein kinase C theta is highly expressed in gastrointestinal stromal tumors but not in other mesenchymal neoplasias. Clin Cancer Res. 2004;10:4089–4095
  61. Motegi A, Sakurai S, Nakayama H, et al. PKC theta, a novel immunohistochemical marker for gastrointestinal stromal tumors (GIST), especially useful for identifying KIT-negative tumors. Pathol Int. 2005;55:106–112
  62. West RB, Corless CL, Chen X, et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol. 2004;165:107–113
  63. Pauwels P, Debiec-Rychter M, Stul M, et al. Changing phenotype of gastrointestinal stromal tumours under imatinib mesylate treatment: a potential diagnostic pitfall. Histopathology. 2005;47:41–47
  64. Torihashi S, Nishi K, Tokutomi Y, et al. Blockade of kit signaling induces transdifferentiation of interstitial cells of Cajal to a smooth muscle phenotype. Gastroenterology. 1999;117:140–148
  65. Sakurai S, Fukasawa T, Chong JM, et al. Embryonic form of smooth muscle myosin heavy chain (SMEmb/MHC-B) is gastrointestinal stromal tumor and interstitial cell of Cajal. Am J Pathol. 1999;154:23–28
  66. Miettinen M, Sarlomo-Rikala M, Kovatich AJ, et al. Calponin and h-caldesmon in soft tissue tumors: consistent h-caldesmon immunoreactivity in gastrointestinal stromal tumors indicaters traits of smooth muscle differentiation. Mod Pathol. 1999;12:756–762
  67. Tsujimura T, Makiishi-Shimobayashi C, Lundkvist J, et al. Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal. Am J Pathol. 2001;158:817–823
  68. Sarlomo-Rikala M, Tjsujimura T, Lendahl U, et al. Patterns of nestin and other intermediate filament expression distinguish between gastrointestinal stromal tumors, leiomyomas and schwannomas. APMIS. 2002;110:499–507
  69. Fletcher CD, Berman J, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002;33:459–465
  70. Gerdes J, Schwab U, Lemke H, et al. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13–20
  71. Brown DC, Gatter KC. Ki67 protein: the immaculate deception?. Histopathology. 2002;40:2–11
  72. Nakamura N, Yamamoto H, Yao T, et al. Prognostic significance of expressions of cell-cycle regulatory proteins in gastrointestinal stromal tumor and the relevance of the risk grade. Hum Pathol. 2005;36:828–837
  73. Carillo R, Candia A, Rodriguez-Peralto JL, et al. Prognostic significance of DNA ploidy and proliferative index (MIB-1) index in gastrointestinal stromal tumors. Hum Pathol. 1997;28:160–165
  74. Rudolph P, Gloeckner K, Parvaresch R, et al. Immunophenotype, proliferation. DNA ploidy, and biological behavior of gastrointestinal stromal tumors: a multivariate clinicopathologic study. 1998;29:791–800
  75. Emory TS, Derringer GA, Sobin LH, et al. Ki67 (MIB-1) immunohistochemistry as a prognostic factor in gastrointestinal smooth-muscle tumors. J Surg Pathol. 1997;2:239–242
  76. Hall PA, McCluggage WG. Assessing p53 in clinical contexts: unlearned lessons and new perspectives. J Pathol. 2006;208:1–6
  77. Al-Bozom IA. P53 overexpression in gastrointestinal stromal tumors. Pathol Int. 2001;51:519–523
  78. Feakins RM. The expression of p53 and bcl-2 in gastrointestinal stromal tumours is associated with anatomic site, and p53 expression is associated with grade and clinical outcome. Histopathology. 2005;46:270–279
  79. Panizo-Santos A, Sola I, Vega F, et al. Predicting metastatic risk of gastrointestinal stromal tumors: role of cell proliferation and cell cycle regulatory proteins. Int J Surg Pathol. 2000;8:133–144
  80. Jianhui C, Yikang J, Yuuin Z, et al. Quantitation of p53 protein expression in gastrointestinal smooth muscle tumors. Chinese Med J. 1995;108:669–673
  81. Lopez-Guerrero JA, Pellin A, Noguera R, et al. Molecular analysis of the 9p21 locus and p53 genes in Ewing family tumors. Lab Invest. 2001;81:803–814
  82. Schneider-Stock R, Boltze K, Lasota J, et al. High prognostic value of p16INK4 alterations in gastrointestinal stromal tumors. J Clin Oncol. 2003;21:1688–1697
  83. El-Rifai W, Sarlomo-Rikala M, Andersson LC, et al. DNA sequence copy number changes in gastrointestinal stromal tumors: tumor progression and prognostic significance. Cancer Res. 2000;60:3899–3903
  84. Sabah M, Cummins R, Leader M, et al. Loss of heterozygosity of chromosome 9p and loss of p16 INK4A expression are associated with malignant gastrointestinal stromal tumors. Mod Pathol. 2004;17:1364–1371
  85. Perrone F, Tamborini E, Dagrada GP, et al. 9p21 locus analysis in high-risk gastrointestinal stromal tumors characterized for c-kit and platelet-derived growth factor receptor α gene alterations. Cancer. 2005;104:159–169
  86. Schneider-Stock R, Boltze K, Lasota J, et al. Loss of p16 protein defines high-risk patients with gastrointestinal stromal tumors: a tissue microarray study. Clin Cancer Res. 2005;11:638–645
  87. Suster S, Fisher C, Moran CA. Expression of bcl-2 oncoprotein in benign and malignant spindle cell tumors of soft tissue, skin, serosal surfaces, and gastrointestinal tract. Am J Surg Pathol. 1998;22:863–872
  88. Miettinen M, Sarlomo-Rikala M, Kovatich A. Cell-type- and tumour-type-related patterns of bcl-2 reactivity in mesenchymal cells and soft tissue tumours. Virchows Arch. 1998;433:255–260
  89. Sabah M, Cummins R, Leader M, et al. Altered expression of cell cycle regulatory proteins in gastrointestinal stromal tumors markers with potential prognostic implications. Hum Pathol. 2006;37:648–655
  90. Cunningham RE, Abbondanzo SL, Chu WS, et al. Apoptosis, bcl-2 expression, and p53 expression in gastrointestinal stromal/smooth muscle tumors. Appl Immunohistochem Mol Morphol. 2001;9:19–23
  91. Montgomery E, Abraham SC, Fisher C, et al. CD44 loss in gastric stromal tumors as a prognostic marker. Am J Surg Pathol. 2004;28:168–177

 The opinions and assertions contained herein are the expressed views of the authors and are not to be construed as official or reflecting the views of the Departments of the Army or Defense.

PII: S0740-2570(06)00143-2

doi: 10.1053/j.semdp.2006.09.001

Seminars in Diagnostic Pathology
Volume 23, Issue 2 , Pages 70-83 , May 2006