Skip to main content
Log in

Multiple Gastric Stromal Tumors in a Child without Syndromic Association Lacks Common KIT or PDGFRα Mutations

Pediatric and Developmental Pathology

Abstract

A diagnosis of multiple gastric stromal tumors that were nonmetastatic at presentation was made in an 11-year-old girl who presented with hematemesis. Gastrointestinal stromal tumor (GIST) is a rare diagnosis in childhood and reported multiple lesions are generally seen in the context of familial disease, occasionally with syndromic associations. Although there are no reports of genetic mutation in cases of pediatric GIST, very many cases of multiple GISTs investigated on a molecular level have shown germline KIT or platelet-derived growth factor receptor-α mutation; these were familial cases. Despite the negative family history in our patient, the multiplicity of lesions in such a young patient raised concern for a genetic predisposition and prompted extensive molecular workup. Repeat evaluation of distinct aliquots of tumor tissue by polymerase chain amplification followed by sequence analysis of selected coding sequences of KIT and platelet-derived growth factor receptor-α previously shown to harbor mutations in GIST, yielded no evidence of even a somatic mutation. This clinically unique case is discussed in the context of a literature review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Li P, Wei J, West AB, et al. Epithelioid gastrointestinal stroma tumor of the stomach with liver metastases in a 12-year-old girl: aspiration cytology and molecular study. Pediatr Dev Pathol 2002;5:386–394

    Article  PubMed  Google Scholar 

  2. Lasota J, Jasinski M, Sarlomo-Rikala M, Miettinen M. Mutations in exon 11 occur preferentially in malignant versus benign gastrointestinal tumors and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol 1999;154:53–60

    PubMed  CAS  Google Scholar 

  3. Lux ML, Rubin BP, Biase TL, et al. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 2000;156:791–795

    PubMed  CAS  Google Scholar 

  4. Isozaki K, Terris B, Belghiti J, et al. Germline-activating mutation in the kinase domain of KIT gene in familial gastrointestinal stromal tumors. Am J Pathol 2000;157:1581–1585

    PubMed  CAS  Google Scholar 

  5. Taniguchi M, Nishida T, Hirota S, et al. Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res 1999;59:4297–4300

    PubMed  CAS  Google Scholar 

  6. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA Activating mutations in gastrointestinal stromal tumors. Science 2003;299:708–710

    Article  PubMed  CAS  Google Scholar 

  7. Heinrich MC, Rubin BP, Longley BJ, Fletcher JA. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 2002;33:484–495

    Article  PubMed  CAS  Google Scholar 

  8. Nishida T, Hirota S, Masahiko T, et al. Familial gastrointestinal stromal tumours with germline mutation of the KIT gene. Nat Genet 1998;19:323–324

    Article  PubMed  CAS  Google Scholar 

  9. Hirota S, Isozaki K, Moryama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577–580

    Article  PubMed  CAS  Google Scholar 

  10. Corless CL, McGreevey L, Haley A, et al. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. Am J Pathol 2002;160:1567–1572

    PubMed  CAS  Google Scholar 

  11. Chompret A, Kannengiesser C, Barrois M, et al. PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor. Gastroenterology 2004;126: 318–321

    Article  PubMed  CAS  Google Scholar 

  12. Nakahara M, Isozaki K, Hirota S, et al. A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors. Gastroenterology 1998;1215:1090–1095

    Google Scholar 

  13. Andersson J, Sjogren H, Meis-Kindblom JM, et al. The complexity of KIT mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. Am J Pathol 2002;160:15–22

    PubMed  CAS  Google Scholar 

  14. Ernst SI, Hubbs AE, Przygodzki RM, et al. KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors. Lab Invest 1998;78:1633–1636

    PubMed  CAS  Google Scholar 

  15. Moskaluk CA, Tian Q, Marshall CR, et al. Mutations of c-kit JM domain are found in a minority of human gastrointestinal stromal tumors. Oncogene 1999;18:1897–1902

    Article  PubMed  CAS  Google Scholar 

  16. Singer S, Rubin BP, Lux ML, et al. Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol 2002;20:3898–3905

    Article  PubMed  CAS  Google Scholar 

  17. Heinrich MC, Corless CL, Von Mehren M, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003;1:4342–4349

    Google Scholar 

  18. Miettinen M, El-Rifai W, Sobin HL, Lasota J. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol 2002;33:478–483.

    PubMed  Google Scholar 

  19. Kerr JZ, Hicks MJ, Nuchtern JG, et al. Gastrointestinal autonomic nerve tumors in the pediatric population: a report of four cases and a review of the literature. Cancer 1999;85:220–230

    Article  PubMed  CAS  Google Scholar 

  20. Oguzkurt P, Akcoren Z, Senocak ME, et al. A huge gastric stromal tumor in a 13-year-old girl. Turk J Pediatr 2002;44:65–68

    PubMed  Google Scholar 

  21. Wu SS, Buchmiller TL, Close P, et al. Congenital gastrointestinal pacemaker cell tumor. Arch Pathol Lab Med 1999;123:842–845

    PubMed  CAS  Google Scholar 

  22. Beghini A, Tibiletti MG, Roversi G, et al. Germline mutation in the juxtamembrane domain of the kit gene in a family with gastrointestinal stromal tumors and urticaria pigmentosa. Cancer 2001;92:657–662

    Article  PubMed  CAS  Google Scholar 

  23. Maeyama H, Hidaka E, Ota H, et al. Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene. Gastroenterology 2001;120:210–215

    Article  PubMed  CAS  Google Scholar 

  24. Papillon E, Rolachon A, Calender A, et al. A malignant gastrointestinal stromal tumour in a patient with multiple endocrine neoplasia type I. Eur J Gastroenterol Hepatol 2001;13:207–211

    Article  PubMed  CAS  Google Scholar 

  25. Lespi J, Drut R. Gastrointestinal autonomic tumor associated with von Recklinghausen’s disease [in Spanish]. Acta Gastroenterol Latinoam 1997;27:271–274

    PubMed  CAS  Google Scholar 

  26. Ishida T, Wada I, Horiuchi H, et al. Multiple small intestinal stromal tumors with skeinoid fibers in association with neurofibromatosis 1 (von Recklinghausen’s disease). Pathol Int 1996;46:689–695

    Article  PubMed  CAS  Google Scholar 

  27. Hirota S, Nishida T, Isozaki K, et al. Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene. Gastroenterology 2002;122:1493–1499

    Article  PubMed  Google Scholar 

  28. Carney JA, Stratakis CA. Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. Am J Med Genet 2002;108:132–139

    Article  PubMed  Google Scholar 

  29. Valverde K, Henderson M, Smith CR, et al. Typical and atypical Carney’s triad presenting with malignant hypertension and papilledema. J Pediatr Hematol Oncol 2001;23:519–524

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maureen J. O’Sullivan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Sullivan, M.J., McCabe, A., Gillett, P. et al. Multiple Gastric Stromal Tumors in a Child without Syndromic Association Lacks Common KIT or PDGFRα Mutations. Pediatr Dev Pathol 8, 685–689 (2005). https://doi.org/10.1007/s10024-005-0083-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10024-005-0083-y

Keywords

Navigation