INI-1 Expression in Cytokeratin-Positive Tumors of Bone
R Tirabosco, AM Flanagan. Royal National Orthopaedic Hospital, London, United Kingdom; University College London, London, United Kingdom
Background: Loss of INI-1 expression by immunohistochemistry has been reported in rhabdoid tumors of kidney, soft tissue and central nervous system, and more recently in epithelioid sarcoma (ES) of classic and proximal type. ES is a rare soft tissue sarcoma showing epithelial differentiation, as detected by cytokeratin expression (CK), and is associated with an ominous prognosis. Recently, a case of ES presumably arising in bone has been described, a diagnosis strengthened by loss of INI-1 expression by immunohistochemistry and FISH. This tumor was characterised by a prominent matrix deposition with a chicken-wire pattern, resembling an osteosarcoma (OS) or a chondroblastoma, tumors on which INI-1 expression has not yet been investigated. Furthermore, CK expression has been described in various bone tumors including OS. In this study, we have assessed INI-1 expression on a large number of bone tumors which potentially may be included in the differential diagnosis of ES.
Design: Material included 447 bone tumors known to express CK to some extent, and comprise 276 OS, 126 chordomas, 21 chondroblastomas, 10 CK-positive PNET/Ewing's sarcomas, 7 CK-positive bone sarcoma NOS, 4 metastatic carcinoma of unknown primary (CUP), 1 malignant mixed tumors of bone and 2 epithelioid angiosarcoma of bone. OS, chordomas and chondroblastomas have been assessed on tissue microarrays; the remaining tumors on full sections. BAF47 antibody (clone 25) has been employed. A classic ES of soft tissue was used as control.
Results: Only 5 cases of 447 bone tumors showed complete loss of INI-1 expression, a finding that was confirmed on full tissue sections. These included 1CUP, 2OS and 2 chordomas (brachyury positive). Review of the H&E slides confirmed the diagnoses of OS and chordoma. The INI-1 negative CUP was found to represent a poorly differentiated vimentin and CK positive tumor with focal rhabdoid cytoplasm, which occured in the proximal femur of a 25 year-old-woman. Despite extensive investigations, this was the only lesion identified in this patient and on review is now considered to represent a possible primary ES of bone.
Conclusions: Having assessed the INI-1 expression in a large number of bone tumors, we found that less than 1% of OS failed to express INI-1 protein and report for the first time the loss of INI-1 immunoeractivity in 1.5% of chordomas. We report a potential new case of ES of bone previously diagnosed as CUP, which prompts the assessment of INI-1 in all poorly differentiated cancers of unknown primary, especially in young individuals.
Category: Bone & Soft Tissue
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 20, Tuesday Morning