Gastrointestinal Stromal Tumor (GIST) with Chondroid-Myxoid-Chordoid Features Mimicking Extraskeletal Myxoid Chondrosarcoma

Sonia Brar, Christian Tvetenstrand, Jagmohan Sidhu

Department of Medicine, UHS Hospitals, Johnson City, USA.
Department of Pathology and Laboratory Medicine, UHS Hospitals, Johnson City, USA.
Department of Surgery, UHS Hospitals, Johnson City, USA.

DOI: 10.4236/ojpathology.2012.23016                

Abstract

Epithelioid gastrointesinal tumors (GISTs) are less likely to have c-kit gene mutations (and express CD117) than spindle cell GISTs. CD117 negative/c-kit negative GISTs can have platelet-derived growth factor alpha (PDGFRα) gene mutations, overexpress PDGFRα protein and respond to imatinib mesylate. Many cases of CD117-negative/CD117-weakly positive, c-kit mutation negative and PDGFRα mutation positive myxoid epithelioid GISTs and one case of CD117-positive GIST with chondro-myxoid features mimicking chondrosarcoma have been reported. We report a case of myxoid epithelioid GIST with predominance of chondroid and chordoid areas resembling an extraskeletal myxoid chondrosarcoma that was strongly positive for CD117, PDGFRα and DOG1 (Discovered on GIST 1) by immunohistochemistry, but lacked c-kit and PDGFRα gene mutations. It is possible that CD117 is strongly positive if a myxoid epithelioid GIST has chondroid/chordoid appearance, but a larger study is needed to confirm this association. CD117 expression in GISTs is important, because GISTs showing CD117 positivity respond to imatinib. No comment can be made about the prognostic significance of chondroid/chordoid appearance in the GISTs.

Keywords

Gastrointestinal Stromal Tumor; GIST; PDGFRα; CD117; c-kit; Extraskeletal Myxoid Chondrosarcoma

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	M. Meittinen, M. Sarlomo-Rikala and J. Lasota, “Gastrointestinal Stromal Tumors,” Annales Chirurgiae et Gynaecologiae Fenniae, Vol. 87, No. 4, 1998, pp. 278-281.
[2]	S. R. Hamilton and L. A. Aaltonen, “World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of the Digestive System,” IARC Press, Lyon, 2000.
[3]	L. G. Kindblom, H. E. Remotti, F. Aldenborg and J. M. Meis-Kindblom, “Gastrointestinal Pacemaker Cell Tumor (GIPACT): Gastrointestinal Stromal Tumors Show Phenotypic Characteristics of the Interstitial Cells of Cajal,” American Journal of Pathology, Vol. 152, No. 5, 1998, pp. 1259-1269.
[4]	C. D. Fletcher, J. J. Berman, C. Corless, et al., “Diagnosis of Gastrointestinal Stromal Tumors: A Consensus Approach,” Human Pathology, Vol, 33, No. 5, 2002, pp. 459-465. doi:10.1053/hupa.2002.123545
[5]	E. Wardelmann, I. Neidt, E. Bierhoff, et al., “c-kit Mutations in Gastrointestinal Stromal Tumors Occur Preferentially in the Spindle Rather than in the Epitheiloid Cell Variant,” Modern Pathology, Vol. 15, No. 2, 2002, pp. 125-136. doi:10.1038/modpathol.3880504
[6]	S. Suster, D. Sorace and A. Moran, “Gastrointestinal Stromal Tumours with Prominent Myxoid Matrix. Clinicopathologic, Immunohistochemical and Ultrastructural Study of Nine Cases of a Distinctive Morphologic Variant of Myogenic Stromal Tumor,” American Journal of Surgical Pathology, Vol. 19, No. 1, 1995, pp. 59-70. doi:10.1097/00000478-199501000-00008
[7]	S. Sakurai, T. Hasegawa, Y. Sakuma, et al., “Myxoid Epithelioid Gastrointestinal Stromal Tumor (GIST) with Mast Cell Infiltrations: A Subtype of GIST with Mutations of Platelet-Derived Growth Factor Receptor Alpha Gene,” Human Pathology, Vol. 35, No. 10, 2004, pp. 1223-1230. doi:10.1016/j.humpath.2004.07.008
[8]	A. Rajput, C. Levea, M. Intengan, J. Kane and J. F. Gibbs, “Gastrointestinal Stromal Tumor: Chondro-Myxoid Variant Mimicking Chondrosarcoma,” Sarcoma, Vol. 91, No. 1-2, 2005, pp. 25-28. doi:10.1080/13577140500043708
[9]	T. Hasegawa, Y. Matsuno, T. Shimoda, et al., “Gastrointestinal Stromal Tumor: Consistent CD117 Immunostaining for Diagnosis, and Prognostic Classification Based on Tumor Size and MIB-1 Grade,” Human Pathology, Vol. 33, No. 6, 2002, pp. 669-676. doi:10.1053/hupa.2002.124116
[10]	M. R. Peterson, Z. Piao, N. Weidner and E. S. Yi, “Strong PDGFRA Positivity Is Seen in GISTs but Not in Other Intrabdominal Mesenchymal Tumors: Immunohistochemical and Mutational Analyses,” Applied Immunohistochemistry & Molecular Morphology, Vol. 14, No, 4, 2006, pp. 390-396. doi:10.1097/01.pai.0000203038.33414.a3
[11]	M. C. Heinrich, C. L. Corles, A. Duensing, et al., “PDGFRA Activating Mutations in Gastrointestinal Stromal Tumors,” Science, Vol. 299, No. 5607, 2003, pp. 708-710. doi:10.1126/science.1079666
[12]	S. Hirota, A. Obashi, T. Nishida, et al., “Gain-of-Function Mutations of Platelet-Derived Growth Factor Receptor Alpha Gene in Gastrointestinal Stromal Tumors,” Gastroenterology, Vol. 125, No. 3, 2003, pp. 660-667. doi:10.1016/S0016-5085(03)01046-1
[13]	M. C. Heinrich, C. L. Corless, G. D. Demetri, et al., “Kinase Mutations and Imatinib Response in Patients with Metastatic Gastrointestinal Stromal Tumor,” Journal of Clinical Oncology, Vol. 21, No. 23, 2003, pp. 4342- 4349. doi:10.1200/JCO.2003.04.190
[14]	G. H. Kang, A. Srivastava, Y. E. Kim, et al., “DOG1 and PKC? Are Useful in the Diagnosis of KIT-Negative Gastrointestinal Stromal Tumors,” Modern Pathology, in Press.
[15]	M. Novelli, S. Rossi, M. Rodriguez-Justo, et al., “DOG1 and CD117 Are the Antibodies of Choice in the Diagnosis of Gastrointestinal Stromal Tumors,” Histopathology, Vol. 57, No. 2, 2010, pp. 259-270. doi:10.1111/j.1365-2559.2010.03624.x
[16]	Y. Jiang, L. Ming, A. J. Montero, E. Kimchi, M. Nikfarjam and K. F. Staveley-O’Carroll, “Optimizing Imatinib Mesylate Treatment in Gastrointestinal Stroma Tumors,” Gastrointestinal Cancer Research, Vol. 2, No. 5, 2008, pp. 245-250.
[17]	Y. Koh, H. Kim, H. Lee, D. Oh, J. Kim, S. Im, et al., “KIT and PDGFRA Mutation Status and Their Immunohistochemical (IHC) Expression Profile of Gastrointestinal Stromal Tumor (GIST) Patients with Imatinib (IMT): Seven-Year Single-Center Experience,” Journal of Clinical Oncology, Vol. 27, No. 15, 2009, p. 27.
[18]	V. B. Shidham, M. Chivukula, D. Gupta, R. N. Rao and R. Komorowski, “Immunohistochemical Comparison of Gastrointestinal Stromal Tumor and Solitary Fibrous Tumor,” Archives of Pathology & Laboratory Medicine, Vol. 126, No. 10, 2002, pp. 1189-1192.