International Journal of Colorectal Disease

, Volume 21, Issue 1, pp 84–88 | Cite as

Differential diagnosis of gastrointestinal leiomyoma versus gastrointestinal stromal tumor

  • Jens Kuhlgatz
  • Bjoern Sander
  • Mariola Monika Golas
  • Bastian Gunawan
  • Thorsten Schulze
  • Hans-Jürgen Schulten
  • Eva Wardelmann
  • László Füzesi
Case Report



Strategies for the diagnosis of tumors arising in the intestinal muscular wall are rapidly evolving. Immunoreactivity for CD117 (KIT) usually supports the diagnosis of gastrointestinal stromal tumor (GIST), but a small subset of GISTs lacks KIT expression. In these cases the differential diagnosis of KIT-negative GIST versus one of their morphological mimics is difficult and bears critical implications for therapeutic management.

Case report

Here, we report a case of a KIT-negative smooth muscle cell tumor of the colon in a 21-year-old man with the clinical appearance of GIST. Mutations of the KIT and platelet-derived growth factor receptor alpha (PDGFRA) gene could be ruled out. No chromosomal imbalances characteristic of GIST were found. However, cytogenetic analysis revealed losses at 7q, which has previously been reported in cases of uterine leiomyoma.


We discuss current approaches to the differential diagnosis of true gastrointestinal smooth muscle cell tumor versus GIST.


Gastrointestinal leiomyoma GIST CGH KIT PDGFRA 


  1. 1.
    Greenson JK (2003) Gastrointestinal stromal tumors and other mesenchymal lesions of the gut. Mod Pathol 16:366–375PubMedGoogle Scholar
  2. 2.
    Miettinen M, Lasota J (2001) Gastrointestinal stromal tumors—definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 438:1–12PubMedGoogle Scholar
  3. 3.
    Yantiss RK, Spiro IJ, Compton CC, Rosenberg AE (2000) Gastrointestinal stromal tumor versus intra-abdominal fibromatosis of the bowel wall: a clinically important differential diagnosis. Am J Surg Pathol 24:947–957PubMedGoogle Scholar
  4. 4.
    Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ et al (2002) Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 33:459–465PubMedGoogle Scholar
  5. 5.
    Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G et al (2000) KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 156:791–795PubMedGoogle Scholar
  6. 6.
    Wardelmann E, Losen I, Hans V, Neidt I, Speidel N, Bierhoff E et al (2003) Deletion of Trp-557 and Lys-558 in the juxtamembrane domain of the c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors. Int J Cancer 106:887–895PubMedGoogle Scholar
  7. 7.
    Hou YY, Tan YS, Sun MH, Wei YK, Xu JF, Lu SH et al (2004) C-kit gene mutation in human gastrointestinal stromal tumors. World J Gastroenterol 10:1310–1314PubMedGoogle Scholar
  8. 8.
    Rubin BP, Singer S, Tsao C, Duensing A, Lux ML, Ruiz R et al (2001) KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61:8118–8121PubMedGoogle Scholar
  9. 9.
    Wardelmann E, Hrychnyk A, Merkelbach-Bruse S, Pauls K, Goldstein J, Hohenberger P et al (2004) Association of platelet-derived growth factor receptor alpha mutations with gastric primary site and epithelioid or mixed cell morphology in gastrointestinal stromal tumors. J Mol Diagn 6:197–204PubMedGoogle Scholar
  10. 10.
    Gunawan B, Schulten HJ, von Heydebreck A, Schmidt B, Enders C, Hoer J et al (2004) Site-independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours. J Pathol 202:421–429PubMedGoogle Scholar
  11. 11.
    Fletcher CD (2002) Clinicopathologic correlations in gastrointestinal stromal tumors. Hum Pathol 33:455PubMedGoogle Scholar
  12. 12.
    Lasota J, Wozniak A, Sarlomo-Rikala M, Rys J, Kordek R, Nassar A, Sobin LH, Miettinen M (2000) Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases. Am J Pathol 157:1091–1095PubMedGoogle Scholar
  13. 13.
    Heinrich MC, Corless CL, Dünsing A, McGreevey L, Chen CJ, Joseph N et al (2003) PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299:708–710PubMedGoogle Scholar
  14. 14.
    El-Rifai W, Sarlomo-Rikala M, Andersson LC, Knuutila S, Miettinen M (2000) DNA sequence copy number changes in gastrointestinal stromal tumors: tumor progression and prognostic significance. Cancer Res 60:3899–3903PubMedGoogle Scholar
  15. 15.
    Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J (2000) Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases. Am J Surg Pathol 24:1339–1352PubMedGoogle Scholar
  16. 16.
    Miettinen M, Kopczynski J, Makhlouf HR, Sarlomo-Rikala M, Gyorffy H, Burke A, Sobin LH, Lasota J (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 27:625–641PubMedGoogle Scholar
  17. 17.
    Sarlomo-Rikala M, El-Rifai W, Lahtinen T, Andersson LC, Miettinen M, Knuutila S (1998) Different patterns of DNA copy number changes in gastrointestinal stromal tumors, leiomyomas, and schwannomas. Hum Pathol 29:476–481PubMedGoogle Scholar
  18. 18.
    Debiec-Rychter M, Dumez H, Judson I, Wasag B, Verweij J, Brown M et al (2004) Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 40:689–695PubMedGoogle Scholar
  19. 19.
    Andersson J, Sjogren H, Meis-Kindblom JM, Stenman G, Aman P, Kindblom LG (2002) The complexity of KIT gene mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. Am J Pathol 160:15–22PubMedGoogle Scholar
  20. 20.
    Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, Robson M et al (2003) Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res 9:3329–3337PubMedGoogle Scholar
  21. 21.
    Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H et al (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21:4342–4349PubMedGoogle Scholar
  22. 22.
    Kim TW, Lee H, Kang YK, Choe MS, Ryu MH, Chang HM et al (2004) Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res 10:3076–3081PubMedGoogle Scholar
  23. 23.
    Wasag B, Debiec-Rychter M, Pauwels P, Stul M, Vranckx H, Oosterom AV, Hagemeijer A, Sciot R (2004) Differential expression of KIT/PDGFRA mutant isoforms in epithelioid and mixed variants of gastrointestinal stromal tumors depends predominantly on the tumor site. Mod Pathol 17:889–894PubMedGoogle Scholar
  24. 24.
    Kinoshita K, Isozaki K, Hirota S, Nishida T, Chen H, Nakahara M et al (2003) C-kit gene mutation at exon 17 or 13 is very rare in sporadic gastrointestinal stromal tumors. J Gastroenterol Hepatol 18:147–151PubMedGoogle Scholar
  25. 25.
    Lasota J, Jasinski M, Sarlomo-Rikala M, Miettinen M (1999) Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol 154:53–60PubMedGoogle Scholar
  26. 26.
    Raspollini MR, Amunni G, Villanucci A, Pinzani P, Simi L, Paglierani M, Taddei GL (2004) C-Kit expression in patients with uterine leiomyosarcomas: a potential alternative therapeutic treatment. Clin Cancer Res 10:3500–3503PubMedGoogle Scholar
  27. 27.
    Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, Kitamura Y (2003) Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 125:660–667PubMedGoogle Scholar
  28. 28.
    El-Rifai W, Sarlomo-Rikala M, Andersson LC, Miettinen M, Knuutila S (1998) DNA copy number changes in gastrointestinal stromal tumors—a distinct genetic entity. Ann Chir Gynaecol 87:287–290PubMedGoogle Scholar
  29. 29.
    Levy B, Mukherjee T, Hirschhorn K (2000) Molecular cytogenetic analysis of uterine leiomyoma and leiomyosarcoma by comparative genomic hybridization. Cancer Genet Cytogenet 121:1–8PubMedGoogle Scholar
  30. 30.
    Boghosian L, Dal Cin P, Sandberg AA (1988) An interstitial deletion of chromosome 7 may characterize a subgroup of uterine leiomyoma. Cancer Genet Cytogenet 34:207–208PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Jens Kuhlgatz
    • 1
  • Bjoern Sander
    • 2
  • Mariola Monika Golas
    • 2
  • Bastian Gunawan
    • 2
  • Thorsten Schulze
    • 3
  • Hans-Jürgen Schulten
    • 2
  • Eva Wardelmann
    • 4
  • László Füzesi
    • 2
  1. 1.Department of General and Visceral SurgeryAlbert Schweitzer HospitalNortheimGermany
  2. 2.Department of PathologyUniversity of GöttingenGöttingenGermany
  3. 3.Department of RadiologyAlbert Schweitzer HospitalNortheimGermany
  4. 4.Department of PathologyUniversity of BonnBonnGermany

Personalised recommendations