title: KIT-negative gastrointestinal stromal tumor of the abdominal soft tissue: a clinicopathologic and genetic study of 10 cases.
abstract: Gastrointestinal stromal tumor (GIST) typically occurs in the gastrointestinal (GI) tract, and expresses KIT protein that is associated with KIT or platelet-derived growth factor receptor-α (PDGFRA) gene mutation. Extragastrointestinal stromal tumors (EGISTs) are a minor subset of GIST that occurs in the soft tissue outside the GI tract, and in very rare cases, these tumors can be KIT negative. We examined the clinicopathologic and molecular characteristics of 10 cases of KIT-negative EGIST by using immunohistochemical staining and gene mutation analysis. The tumors occurred in the omentum (n=5), mesentery (n=2), retroperitoneum (n=1), pelvic cavity (n=1), and not otherwise specified regions of the abdominal cavity (n=1). They ranged from 4 to 33 cm (median, 15 cm) in maximum diameter with relatively low mitotic counts (median, 3.5 per 50 high-power fields). Morphologically, most cases were of epithelioid cell (n=9) or mixed epithelioid and spindle cell (n=1) type, accompanied by variable amounts of myxoid stroma. By immunohistochemical staining, the tumors were positive for CD34 (80%), protein kinase C (PKC) θ (90%), and discovered on GIST-1 (DOG1) (90%), but were negative for KIT (0%). The majority of the examined cases (7 of 9 cases; 78%) had PDGFRA mutations in exon 12 (n=1) or exon 18 (n=6). One case (11%) had a mutation in KIT exon 11, and the remaining 1 had no mutation in either KIT or PDGFRA. Distant metastasis and local recurrence occurred in 1 (10%) and 2 (20%) patients, respectively, and adverse outcome was correlated with larger (>10 cm) tumor size and high mitotic counts (>5/50 high-power fields). Therefore, KIT-negative EGISTs can be characterized by preferential omental origin, epithelioid cell type, low mitotic activity, and mutation of the PDGFRA gene, and these features are similar to those of KIT-negative gastric GISTs. As KIT-negative EGISTs should be considered to be a potential abdominal soft tissue neoplasm, immunohistochemical staining panel and molecular analysis are necessary not only to confirm the diagnosis but also to determine the therapeutic strategy.
authors.affiliation: Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. hidetaka@surgpath.med.kyushu-u.ac.jp
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Aya
authors.initials: A
authors.lastname: Kojima
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nagata
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Satsuki
authors.initials: S
authors.lastname: Takahashi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D000008:Abdominal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075369:Anoctamin-1; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D018118:Chloride Channels; D004252:DNA Mutational Analysis; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000737:chemistry / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D008940:Mitotic Index; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011493:Protein Kinase C / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology* / Q000628:therapy
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D018118:Chloride Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D011493:Protein Kinase C