• 1

    Phillips BS. Tumors of the intestinal tract. In:Withrow SJ, MacEwen EF, ed.Small animal clinical oncology. 3rd ed.Philadelphia: WB Saunders Co, 2001;335346.

    • Search Google Scholar
    • Export Citation
  • 2

    Chen HC, Parris LS, Parris RG. Duodenal leiomyosarcoma with multiple hepatic metastases in a dog. J Am Anim Hosp Assoc 1986;22:533537.

  • 3

    Bruecker KA, Withrow SJ. Intestinal leiomysarcoma in six dogs. J Am Anim Hosp Assoc 1988;24:281284.

  • 4

    Kapatkin AS, Mullen HS, Mathiesen DT, et al. Leiomyosarcoma in dogs: 44 cases (1983–1988). J Am Vet Med Assoc 1992;201:10771079.

  • 5

    Patnaik AK, Hurvitz AI, Johnson GF. Nonlymphoid intestinal neoplasia in 32 dogs and 14 cats. Vet Pathol 1977;14:547555.

  • 6

    Cohen M, Post GS. Nephrogenic diabetes insipidus in a dog with intestinal leiomyosarcoma. J Am Vet Med Assoc 1999;215:18181820.

  • 7

    Sircar K, Hewlett BR, Huizinga JD. Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol 1999;23:377389.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Nishida T, Hirota S. Biological and clinical review of stromal tumors in the gastrointestinal tract. Histol Histopathol 2000;15:12931301.

    • Search Google Scholar
    • Export Citation
  • 9

    Miettinen M, Lasota J. Gastrointestinal stromal tumors—definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001;438:112.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577580.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Kitamura Y, Hirota S, Nishida T. Molecular pathology of c-kit proto-oncogene and development of gastrointestinal stromal tumors. Ann Chir Gynaecol 1998;87:282286.

    • Search Google Scholar
    • Export Citation
  • 12

    Kindblom LG, Remotti HE, Aldenborg F, et al. Gastrointestinal pacemaker cell tumor (GI-PACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998;152:12591269.

    • Search Google Scholar
    • Export Citation
  • 13

    Lasota J, Jasinkski M, Sarlomo-Rikala M, et al. C-kit mutations occur preferentially in malignant versus benign GISTs and do not occur in leiomyomas and leiomyosarcomas. Am J Pathol 1999;154:5360.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Lasota J, Wozniak A, Sarlomo-Rikala M, et al. Mutations in exon 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases. Am J Pathol 2000;157:10911095.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Lux ML, Rubin BP, Biase TL, et al. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 2000;156:791795.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Taniguchi M, Nishida T, Hirota S, et al. Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res 1999;154:16431647.

    • Search Google Scholar
    • Export Citation
  • 17

    Del Piero F, Summers BA, Cummings JF, et al. Gastrointestinal stromal tumors in equids. Vet Pathol 2001;38:689697.

  • 18

    Hafner S, Harmon BG, King T. Gastrointestinal stromal tumors of the equine cecum. Vet Pathol 2001;38:242246.

  • 19

    Banjerjee M, Lowenstine LJ, Munn RJ. Gastric stromal tumors in two Rhesus macaques (Macaca mulatta). Vet Pathol 1991;28:3036.

  • 20

    Frost D, Lasota J, Miettinen M. Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic, immunohistochemical, and molecular genetic study of 50 cases. Vet Pathol 2003;40:4254.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Bettini G, Morini M, Marcato PS. Gastrointestinal spindle cell tumours of the dog: histological and immunohistochemical study. J Comp Pathol 2003;129:283293.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Kumagai K, Uchida K, Miyamoto T, et al. Three cases of canine gastrointestinal stromal tumors with multiple differentiations and c-kit-expression. J Vet Med Sci 2003;65:11191122.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    LaRock RG, Ginn PE. Immunohistochemical staining characteristic of canine gastrointestinal stromal tumors. Vet Pathol 1997;34:303311.

  • 24

    Epperson A, Hatton WJ, Callaghan B, et al. Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol Cell Physiol 2000;279:C529C539.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Demetri GD. Targeting the molecular pathophysiology of gastrointestinal stromal tumors with imatinib. Mechanisms, successes, and challenges to rational drug development. Hematol Oncol Clin North Am 2002;16:11151124.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472480.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Cohen MH, Williams G, Johnson JR, et al. Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res 2002;8:935942.

    • Search Google Scholar
    • Export Citation
  • 28

    Druker BJ, Lydon NB. Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 2000;105:37.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    London C. Kinase inhibitors in cancer therapy. Vet Comp Oncol 2004;2:177193.

  • 30

    Birchard SJ, Couto CG, Johnson S. Nonlymphoid intestinal neoplasia in 32 dogs and 14 cats. J Am Anim Hosp Assoc 1986;22:533537.

  • 31

    Crawshaw J, Berg J, Sardinas JC, et al. Prognosis for dogs with nonlymphomatous, small intestinal tumors treated by surgical excision. J Am Anim Hosp Assoc 1998;34:451456.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Cohen M, Post GS, Wright JC. Gastrointestinal leiomyosarcoma in 14 dogs. J Vet Intern Med 2003;17:107110.

Advertisement

Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990–2003)

Kelli N. Russell VMD1, Stephen J. Mehler DVM, DACVS2, Katherine A. Skorupski DVM, DACVIM3, Jennifer L. Baez VMD, DACVIM4, Frances S. Shofer PhD5, and Michael H. Goldschmidt MSc, BVMS, DACVP6
View More View Less
  • 1 Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
  • | 2 Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
  • | 3 Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
  • | 4 Center for Animal Referral and Emergency Services, 2010 Cabot Blvd W, Ste D, Langhorne, PA 19047
  • | 5 Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
  • | 6 Matthew J. Ryan Veterinary Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104

Abstract

Objective—To reexamine (via immunohistochemical techniques) canine tissue samples that had been previously classified as gastrointestinal leiomyosarcomas (GILMSs), identify and differentiate gastrointestinal stromal tumors (GISTs) from GILMSs, and compare the biological behavior and clinical course of GISTs and GILMSs in dogs.

Design—Retrospective case series.

Animals—42 dogs.

Procedures—Medical records of 42 dogs for which a histologic diagnosis of GILMS was confirmed were reviewed for signalment, clinical signs, physical examination findings, results of initial diagnostic tests, surgical findings, adjunctive treatment, location of the tumor, completeness of resection, and outcome after surgery. Archived tumor tissue specimens from each dog were restained via immunohistochemical techniques to differentiate tumor types. Long-term follow-up information was obtained from the medical record or through telephone interviews with owners and referring veterinarians.

Results—On the basis of immunohistochemical findings, 28 of 42 tumors were reclassified as GISTs and 4 were reclassified as undifferentiated sarcomas; 10 tumors were GILMSs. In dogs, GISTs developed more frequently in the cecum and large intestine and GILMSs developed more frequently in the stomach and small intestine. Median survival times for dogs with GISTs and GILMSs were 11.6 and 7.8 months, respectively; if only dogs surviving the perioperative period were considered, median survival times were 37.4 and 7.8 months, respectively. These differences, however, were not significant.

Conclusions and Clinical Relevance—In dogs, many previously diagnosed GILMSs should be reclassified as GISTs on the basis of results of immunohistochemical staining. The biological behavior of these tumors appears to be different.

Abstract

Objective—To reexamine (via immunohistochemical techniques) canine tissue samples that had been previously classified as gastrointestinal leiomyosarcomas (GILMSs), identify and differentiate gastrointestinal stromal tumors (GISTs) from GILMSs, and compare the biological behavior and clinical course of GISTs and GILMSs in dogs.

Design—Retrospective case series.

Animals—42 dogs.

Procedures—Medical records of 42 dogs for which a histologic diagnosis of GILMS was confirmed were reviewed for signalment, clinical signs, physical examination findings, results of initial diagnostic tests, surgical findings, adjunctive treatment, location of the tumor, completeness of resection, and outcome after surgery. Archived tumor tissue specimens from each dog were restained via immunohistochemical techniques to differentiate tumor types. Long-term follow-up information was obtained from the medical record or through telephone interviews with owners and referring veterinarians.

Results—On the basis of immunohistochemical findings, 28 of 42 tumors were reclassified as GISTs and 4 were reclassified as undifferentiated sarcomas; 10 tumors were GILMSs. In dogs, GISTs developed more frequently in the cecum and large intestine and GILMSs developed more frequently in the stomach and small intestine. Median survival times for dogs with GISTs and GILMSs were 11.6 and 7.8 months, respectively; if only dogs surviving the perioperative period were considered, median survival times were 37.4 and 7.8 months, respectively. These differences, however, were not significant.

Conclusions and Clinical Relevance—In dogs, many previously diagnosed GILMSs should be reclassified as GISTs on the basis of results of immunohistochemical staining. The biological behavior of these tumors appears to be different.

Contributor Notes

Dr. Mehler's present address is the College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Dr. Skorupski's present address is the Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616.

Presented as an abstract at the 24th Annual Meeting of the Veterinary Cancer Society, Kansas City, Mo, November 2004.

Address correspondence to Dr. Russell.