Poorly Differentiated Chordomas. Diagnostic Utility of Immunohistochemistry for Brachyury and SMARCB1/INI1.
Hannes Vogel, Jesse K McKenney, Charles D Bangs, Michael SB Edwards, Paul G Fisher, Katherine Callahan, Murat Gokden, Bret C Mobley. Stanford University, Palo Alto, CA; University of Arkansas, Little Rock
Background: Chordomas in pediatric patients are more likely to display unusual histological features and aggressive behavior. We noted the absence of SMARCB1/INI1 expression by immunohistochemistry while retaining brachyury expression, a marker of notochordal differentiation, in a poorly differentiated chordoma of the sacrum in an 11 year old female.
Design: We examined 3 additional poorly differentiated chordomas of the clivus, 10 typical chordomas, and 8 atypical teratoid/rhabdoid tumors (AT/RTs) by immunohistochemistry for brachyury and SMARCB1/INI1 in order to test the utility of this immunophenotype in identifying poorly differentiated chordomas. Fluorescence in situ hybridization for markers on 22p was performed in all cases.
Results: The three additional cases were of a 7 year old male, 22 month old female, and 3 year old female. The index case, 7, and 3 year old patients were dead of disease within 12 months of diagnosis. The 22 month old female was alive with recurrent disease 12 months postoperatively. Poorly differentiated chordomas were composed of mitotically active epithelioid cells with moderately pleomorphic nuclei and prominent nucleoli. Foci of necrosis were evident for each case. Vacuolated cells were generally unapparent. All chordomas including the poorly differentiated examples were brachyury immunopositive, while all eight AT/RTs were negative for the marker; among the chordomas, only the poorly differentiated examples were SMARCB1/INI1 immunonegative, as were all of the AT/RTs. The poorly differentiated chordomas showed diffuse cytoplasmic pankeratin reactivity. Nuclear and cytoplasmic S-100 staining was observed focally in three cases and was negative in the fourth. FISH analysis using markers to chromosome 22p distal to the SMARCB1/INI1 locus indicated heterozygous deletions in three of the cases.
Conclusions: Poorly differentiated chordomas retain brachyury expression but commonly show absent SMARCB1/INI1 expression, thus can be distinguished from AT/RTs and other neoplasms by the identification of nuclear brachyury expression. Our findings suggest the loss of SMARCB1/INI1 in the subset of chordomas with aggressive features.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 2:15 PM
Platform Session: Section E, Tuesday Afternoon