[1785] Loss of SMARCB1/INI1 Expression in Pediatric Poorly Differentiated Chordomas

Lindsey Clark, Murat Gokden, Ali G Saad. University of Arkansas for Medical Sciences, Little Rock

Background: Chordomas are malignant neoplasms that typically arise in adults in the axial spine. However, pediatric chordomas usually display an aggressive clinical course and show unusual histological features. We noted the absence of SMARCB1/INI1 expression by immunohistochemistry in an index case of poorly differentiated chordoma of the base of the skull in a child leading us to further study SMARCB1/INI1 immunoexpression in 4 additional cases of pediatric chordomas.
Design: The files of the Department of Pathology at Arkansas Children's Hospital and University of Arkansas for Medical Sciences were searched for poorly differentiated chordomas occuring in children. Immunohistochemistry for SMARCB1/INI1 (Cell Marque; prediluted) was performed according to the manufacturer guidelines. Fluorescence in situ hybridization (FISH) was performed on paraffin-embedded tissue using the BAC clone RP11-80O7 (Bluegnome, Cambridge, UK) the target of which are 3.4 kb distal to the SMARCB1 locus at 22q11.23. Demographic and clinical data were collected from the patients' medical records.
Results: The search resulted in 5 poorly differentiated chordomas (3 males and 2 females; median age: 12.5 years; range: 9-17 years). All cases were chordomas of the base of the skull. All cases were reviewed for the accuracy of diagnosis. By immunohistochemistry, there was loss of SMARCB1/INI1 expression in all 5 cases. In all cases, INI-1 immunoexpression was retained in the endothelial cells serving as internal positive control and confirming the immun0-reactivity of the tissue (in two cases, the blocks were in storage for more than 15 years). FISH studies were performed on 2 cases and showed evidence of deletion in SMARCB1/INI1 locus on chromosome 22q. In two cases (ages 10 and 11.7 years, respectively) the tumor cells showed moderate atypia and pleomorphism as well as large eosinophilic cytoplasm and eccentric nucleus reminiscent of atypical teratoid rhabdoid tumor. In these specific two cases, the diagnosis of chordoma was confirmed by the positivity of the tumors to brachyury, a specific marker of notochordal differentiation.
Conclusions: We report 5 cases of pediatric poorly differentiated chordoma showing loss of SMARCB1/INI1 by immunohistochemistry. Awareness of this immunoprofile of poorly differentiated chordomas is important to avoid diagnostic pitfalls. This is particularly true in those cases where the cytomorphology resembles atypical teratoid rhabdoid tumor.
Category: Neuropathology

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 271, Tuesday Afternoon


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