1. ¹Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC
2. ²Department of Surgery, Jagiellonian University, Krakow, Poland
3. ³Department of Pathomorphology, Jagiellonian University, Krakow, Poland
4. ⁴Department of Pathology, Otto-von-Guericke University, Magdeburg, Germany
5. ⁵Laboratory of Pathology, Turku University Hospital, Turku, Finland
6. ⁶Department of Pathology, University Hospital of Tromsoe, Norway
7. ⁷Department of Pathology, Haartman Institute of the University of Helsinki, Helsinki, Finland
8. ⁸Chair of Oncology, Medical University of Lodz, Lodz, Poland
9. ⁹Department of Molecular Pathology, Maria Sklodowska-Curie Memorial Cancer Institute, Warsaw, Poland

Correspondence: Jerzy Lasota, M.D., Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, 14th Street and Alaska Avenue, N.W., Washington, DC 20306-6000; fax: 202-782-9182; e-mail: lasota@afip.osd.mil

Accepted 15 August 2003.

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs express KIT and have KIT mutations. Majority of these mutations cluster in the 5' end of the KIT juxtamembrane domain. Little is known about the clinicopathological profile of GIST carrying internal tandem duplications in the 3' end of KIT juxtamembrane domain (ITDs in the 3' KIT-JM). In this study, 500 immunohistochemically KIT-positive GISTs were screened for this type of mutation, and 18 cases were identified (3.6%). The majority of the ITDs consisted of 1 to 18 codon duplications, with Tyr⁵⁷⁸, Asp⁵⁷⁹, and Leu⁵⁷⁶ being the most commonly duplicated codons. There were 14 gastric (78%), 2 small intestinal (11%), and 2 anal (11%) primary tumors diagnosed in 12 females and 6 males with median age of 71 years. The frequency of IDTs in gastric GISTs was 6.5% and was only 0.5% in intestinal GISTs. There was a strong female predominance (79%) among the patients with gastric tumors. Histologically, 16 GISTs were spindle cell, and 2 had epithelioid morphology. The sizes of primary tumors varied from 1 to >20 cm. Based on the combination of tumor size and mitotic activity, six tumors were classified as benign or probably benign, eight as having uncertain malignant potential, and only four as malignant. Follow-up data available in 17 patients confirmed the malignant course of disease in 3 cases. Only one of the tumors classified as potentially malignant metastasized, although the follow-up was limited in some cases. In summary, the great majority of GISTs with ITDs in the 3' KIT-JM were mitotically inactive tumors occurring predominantly in the stomach and that seemed to have a favorable course. This suggests that presence of these IDTs may define a clinicopathologically favorable subset of GISTs. The consequence of these mutations to KIT signaling should be investigated.