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Poorly differentiated SMARCB1/INI1-negative chordomas
Aims:
To analyze the clinicopathological characteristics of poorly differentiated chordomas (PDCs) with SMARCB1/INI1 loss in children.
Materials:
Four cases of PDCs were included in the study.
Methods:
Immunohistochemistry was performed with respect to brachyury, Glut-1, keratin 18, keratin 19, INI1, vimentin, S-100, CK, EMA, GFAP, etc. Fluorescence in situ hybridization (FISH) was performed for SMARCB1/INI1 from 3 patients.
Results:
Histologically, contrary to typical histologic features for conventional chordomas, 4 tumors were composed of ovoid or atypical fusiform cells. Sporadic physaliphorous cells were evident. Tumor cells had large vacuoles in the cytoplasm that were even remarkable on the imprint cytology slide. By immunohistochemistry, each case revealed loss of SMARCB1/INI1 expression and nuclear expression of brachyury. Glut-1, keratin 18, keratin 19, CK, EMA, and vimentin were positive in these PDCs. Except for 1 patient who had not yet completed FISH, the other 3 cases demonstrated the loss of SMARCB1/INI1 gene by fluorescence in situ hybridization.
Conclusion:
Poorly differentiated SMARCB1/INI1-negative chordoma is a unique subset of chordoma representing a clinically, histopathologically, and molecularly distinct entity with rapid progression and poor prognosis which should not be confused with conventional chordomas. Sporadic physaliphorous cells (tumor cells with large vacuoles in the cytoplasm) provided important diagnostic clues of PDCs. Combination use of characteristic markers of notochord cells (brachyury, Glut-1, keratin 18, and keratin 19) along with INI1 were effective diagnostic tools.
Insights
Poorly differentiated chordomas with SMARCB1/INI1 loss in children are a distinct entity with aggressive behavior. Diagnostic clues include physaliphorous cells and specific immunohistochemical markers.
Area of Science:
- Pediatric oncology
- Skeletal pathology
- Molecular diagnostics
Background:
- Chordomas are rare bone tumors arising from notochordal remnants.
- Poorly differentiated chordomas (PDCs) represent an aggressive subtype with limited understanding.
- SMARCB1/INI1 loss is a key molecular event in certain pediatric tumors.
Observation:
- This study analyzed four pediatric cases of PDCs exhibiting SMARCB1/INI1 loss.
- Histological features included atypical fusiform cells and prominent cytoplasmic vacuoles (physaliphorous cells).
- Immunohistochemistry confirmed loss of SMARCB1/INI1 expression and nuclear brachyury, with positive staining for Glut-1, keratins, EMA, and vimentin.
Findings:
- All analyzed PDCs demonstrated loss of SMARCB1/INI1 expression, confirmed by immunohistochemistry and FISH in most cases.
- These tumors showed distinct histopathological features compared to conventional chordomas.
- Nuclear brachyury expression was consistently observed in these PDCs.
Implications:
- SMARCB1/INI1-negative PDCs constitute a unique and aggressive subset of chordoma in children.
- Recognizing physaliphorous cells and utilizing a panel of markers (brachyury, Glut-1, keratins, INI1) aids in diagnosis.
- Accurate classification is crucial for appropriate management and distinguishing from conventional chordomas due to differing prognoses.
