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Abstrakt
Extraskeletal Myxoid Chondrosarcomas are not Characterized by Loss of INI1/SMARCB1: Immunohistochemical Analysis of 16 Cases
Bharat Rekhi, Mukta Ramadwar and Jyoti Bajpai
Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, characterized by t (9; 22) translocation, including EWSR1 and NR4A3 gene rearrangements, observed in most cases. On histopathologic examination, an EMC has certain diagnostic mimics, such as myoepithelial tumors, epithelioid malignant peripheral nerve sheath tumor and epithelioid sarcomas. All these tumors are included in the category of INI1/SMARCB1- deficient tumors. Lately, few studies have shown loss of INI1 in certain EMCs. Considering there is preclinical data regarding role of EZH2 inhibitor in “INI1 deficient” tumors, it is crucial to recognize such tumors.
Objectives: To evaluate immunohistochemical features, including INI1/SMARCB1 immunostaining results in 16 prospectively diagnosed cases of EMC.
Methods: Immunohistochemical staining was performed on formalin-fixed paraffin embedded tissue sections by immunoperoxidase method using a MACH 2 Universal HRP-Polymer detection kit. Two cases were tested for EWSR1 rearrangement by fluorescent in-situ hybridization (FISH) technique.
Results: Sixteen EMCs occurred in 13 males and 3 females, most commonly in lower extremities; followed by chest wall, pelvis, including iliac fossa, shoulder and parasapinal region; in patients within age-range of 17-72 years (median=47.5). On histopathologic examination, most tumors displayed round to polygonal cells arranged in cords, trabeculae and pseudoglandular pattern in an abundant myxoid stroma. Three tumors revealed “rhabdoid” cells. By immunohistochemistry, tumor cells were positive for NSE (13/13) (100%), S100 protein (10/15) (66.6%), EMA (2/12) (16.6%), AE1/AE3 (0/9), P63 (0/2) and SMA (2/3), the latter in tumors containing rhabdoid-like cells. INI1/SMARCB1 was diffusely retained in all 16 tumors (100%). Two cases tested for EWSR1 rearrangement, were found to be positive for the same.
Conclusion: An optimal immunohistochemical panel for differentiating an EMC from its diagnostic mimics may include antibody markers, such as NSE, S100 protein, AE1/AE3, EMA and SMA. EMCs, including those containing rhabdoid cells do not seem to be in the category of INI1-deficient tumors.