Gastrointestinal Stromal Tumor Metastatic to Bone: Clinicopathological and Molecular Features of 29 Cases, Including 8 Previously Unreported Cases
Kemal Kosemehmetoglu, Gulsah Kaygusuz, Karen Fritchie, Ovgu Aydin, Ozlem Yapicier, Oznur Coskun, Ersin Karatayli, Gulnur Guler, Isinsu Kuzu, Sergulen Dervisoglu. Hacettepe University, Ankara, Turkey; Ankara University, Ankara, Turkey; Mayo Clinic, Rochester, MN; Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey; Anadolu Medical Center, Kocaeli, Turkey; Yildirim Beyazit University Ankara Education and Research Hospital, Ankara, Turkey
Background: Gastrointestinal stromal tumor (GIST) with metastases to bone are extremely rare, comprising less than 5% of cases, and pathologists rarely encounter such lesions in bone biopsy specimens.
Design: The available clinical, morphologic and immunohistochemical features of 29 cases of GIST with bony metastases were analyzed. 8 cases were culled from archives of 5 different institutions and 21 cases were gathered from literature review. The immunoprofile of these tumors, including KIT and DOG1 status, was investigated, and RT-PCR for KIT and PDGFRA, was performed.
Results: Male:female ratio was 18:11 with a median age of 61 years(range, 40-92 years). The most common primaries were located in stomach(24%), small intestine(24%), and extragastrointestinal sites(24%). Bone metastases were solitary in 16 cases(55%) and multiple in 13 cases(45%). Vertebrae(12), pelvis(9), ribs(9), humerus(6), femur(6), skull(4), scapula(1), clavicle(1), and mandible(1) were involved. Radiologically, all lesions were lytic with some having a sclerotic rim and adjacent soft tissue involvement. The tumors were composed of intersecting fascicles of spindle cells in 11/17(65%) cases and epithelioid cells in 2/17(12%) cases; both components were present in 4/17 cases(23%). Prominent vascular network(5/17), hyalinization(4/17), myxoid degeneration(3/17), cellular atypia(3/17), neoplastic or non-neoplastic giant cells(2/17) were encountered. In cases in which immunohistochemistry was performed, 14/17(82%) were c-kit positive, 11/14(79%) were CD34 positive, 6/8(75%) were DOG1 positive, 2/9(22%) were smooth or pan-muscle actin positive. S100(10), pancytokeratin(7), and desmin(6) were negative. KIT Exon 11 mutation was seen in 8/10 cases, one of which showed a concommitent KIT Exon 13 mutation.
Conclusions: Bone metastases from GISTs are usually seen in patients with advanced disease and are characterized by solitary or multiple lytic masses in the axial skeleton with occasional soft tissue involvement. KIT Exon 11 mutation was the most prevalent molecular alteration. Even though rare, pathologists should be aware that bony metastasis from GISTs may occur as the morphologic appearance may be quite variable.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 30, Tuesday Afternoon