Abstract
Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of the KIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation was confirmed by mutation analysis in peripheral blood leukocytes. However, she had no familial history of GISTs and her parents did not carry the respective germline mutation.
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References
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279:577–580
Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA (2003) PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299:708–710
Miettinen M, Lasota J (2001) Gastrointestinal stromal tumors—definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 438:1–12
Miettinen M, Fetsch JF, Sobin LH, Lasota J (2006) Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol 30:90–96
Carney JA (1999) Gastric stromal sarcoma, pulmonary chondroma and extra-adrenal paraganglioma (Carney Triad): natural history, adrenocortical component and possible familial occurence. Mayo Clin Proc 74:543–552
Hirota S, Okazaki T, Kitamura Y, O’Brien P, Kapusta L, Dardick I (2000) Cause of familial and multiple gastrointestinal autonomic tumor with hyperplasia of interstitial cells of Cajal is germline mutation of the c-kit gene. Am J Surg Pathol 24:326–327
Neuhann TM, Mansmann V, Merkelbach-Bruse S, Klink B, Hellinger A, Höffkes HG, Wardelmann E, Schildhaus HU, Tinschert S (2013) A novel germline KIT mutation (p. L576P) in a family presenting with juvenile onset of multiple gastrointestinal stromal tumors, skin hyperpigmentations, and esophageal stenosis. Am J Surg Pathol 37(6):898–905
Kang DY, Park CK, Choi JS, Jin SY, Kim HJ, Joo M, Kang MS, Moon WS, Yun KJ, Yu ES, Kang H, Kim KM (2007) Multiple gastrointestinal stromal tumors: clinicopathologic and genetic analysis of 12 patients. Am J Surg Pathol 31(2):224–232
Graham J, Debiec-Rychter M, Corless CL, Reid R, Davidson R, White JD (2007) Imatinib in the management of multiple gastrointestinal stromal tumors associated with a germline KIT K642E mutation. Arch Pathol Lab Med 131(9):1393–1396
ESMO/European Sarcoma Network Working Group (2014) Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 25(Suppl 3):iii21-6
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Vale Rodrigues, R., Santos, F., Pereira da Silva, J. et al. A case of multiple gastrointestinal stromal tumors caused by a germline KIT gene mutation (p.Leu576Pro). Familial Cancer 16, 267–270 (2017). https://doi.org/10.1007/s10689-016-9941-1
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DOI: https://doi.org/10.1007/s10689-016-9941-1