Clinicopathological, Immunohistochemical, Ultrastructural and Molecular Analysis of Clear Cell Sarcoma (CCS)-Like Tumor of the GI Tract.
David L Stockman, Marrku Miettinen, Dominic Spagnolo, Hugo Dominguez, Volkan Adsay, Pauline Chou, Peter vanTuinen, Benhur Amanuel, Saul Suster, Eduardo V Zambrano. Medical College of Wisconsin, Milwaukee; Armed Forces Institute of Pathology, Washington, DC; QEII Medical Centre, Nedlands, Western Australia, Australia; Cancer Institute of Mexico, Mexico City, Mexico; Emory University Hospital, Atlanta, GA; Children's Memorial Hospital, Chicago, IL
Background: CCS of soft parts is a rare soft tissue tumor, defined by S100 positivity, melanocytic markers, ultrastructural melanosomes and specific chromosomal abnormalities. A GI tumor, possessing the same chromosomal abnormalities, but with different morphologic, immunophenotypic, ultrastructural and behavioral characteristics, has been described and designated CCS of GI tract (CCS-GI).
Design: 15 cases of CCS-GI were analyzed for the clinical, histopathological, immunohistochemical and molecular features.
Results: 8 female and 7 male patients (mean age: 43; range: 17–77); all de novo neoplasms involving small intestine(10), stomach(3), and colon(2), with solid, nested, trabecular/ribbon-like, pseudoalveolar, pseudoglandular, pseudopapillary, and fascicular patterns featuring predominantly epithelioid cytologic features, ranging from small to fusiform. Nucleoli were prominent. Mitotic activity was high. Osteoclast-like giant cells were identified in most cases. All cases showed vimentin, S100, and SOX10 expression. Synaptophysin was detected in 7/13, CD56 in 4/7, NSE in 4/8. All cases were negative for GIST (DOG1, CD117, CD34) and melanocytic (HMB45, MelanA, Tyrosinase) markers. MiTF showed focal (<1%) weak positivity in 2 cases. AE1/AE3, SMA and desmin were negative in all cases. Ultrastructural analysis of 5 cases yielded synapse-like structures, primitive gap junctions, dense core granules and no identifiable melanosomes or premelanosomes. Ewing sarcoma breakpoint region 1 (EWSR1), CREB1 and ATF1, were studied by break-apart FISH in 10 cases showing EWSR1-ATF1 t(12;22) (6), EWSR1-CREB1 t(2;22) (1), extra EWSR1 copies(1), and EWSR1-? t(?;22) (2). Follow-up data showed death 3-108 months (mean: 37) after initial surgery(7), alive with disease(2), and no evidence of disease(1).
Conclusions: This study shows that CCS-GI follows a neuroectodermal line of differentiation, displaying S100, SOX10, Synaptophysin, and NSE positivity, with synapse-like structures and dense core granules at the ultrastructural level, for which we propose the term gastrointestinal neuroectodermal tumor (GNET).
Category: Bone & Soft Tissue
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 8, Monday Morning