title: Non-rhabdoid pediatric SMARCB1-deficient tumors: overlap between chordomas and malignant rhabdoid tumors?
abstract: Somatic alterations in the tumor suppressor gene SMARCB1 were first described in the malignant rhabdoid tumor (MRT) of infancy. Since then, SMARCB1 alterations have been found in other tumors, forming a varied group of SMARCB1-deficient tumors, which sometimes shares overlapping immunohistochemical and histological findings. Thus, the diagnosis is challenging. We report two cases of pediatric SMARCB1-deficient tumors from the clivus that illustrate the diagnostic difficulties. Both cases were strongly positive for epithelial markers associated with loss of BAF47 (INI1) expression, and were negative for S100 and CD34. Molecular analyses of the SMARCB1 gene found a deletion of all nine exons in both cases. In the first case, a 5-year-old girl presented with a thoracic metastasis of a clival tumor, which was diagnosed as MRT and treated accordingly. The morphological findings and the expression of brachyury would favor the diagnosis of a poorly differentiated chordoma. The second case was a quickly fatal clival tumor in a 2-year-old boy: This tumor was morphologically undifferentiated and raises the problem of differential diagnosis between an MRT, a malignant myoepithelial tumor, or an undifferentiated chordoma due to the location and the expression of brachyury. Studies of biological signatures, such as transcriptome profiling, could help to understand the apparent overlap between these tumors.
authors: Department of Biopathology, Centre Léon Bérard, Lyon, France. Electronic address: carenard@free.fr.
authors: Caroline
authors: C
authors: Renard
authors: Department of Biopathology, Centre Léon Bérard, Lyon, France.
authors: Daniel
authors: D
authors: Pissaloux
authors: Department of Biopathology, Centre Léon Bérard, Lyon, France.
authors: Anne Valérie
authors: AV
authors: Decouvelaere
authors: Department of Pediatric Oncology & INSERM U830, Institut Curie, Paris, France; INSERM U830, Laboratory of Genetics and Cancer Biology, Institut Curie, Paris, France; SIRIC, Translational Research in Pediatric Oncology, Institut Curie, Paris, France.
authors: Franck
authors: F
authors: Bourdeaut
authors: Department of Biopathology, Centre Léon Bérard, Lyon, France.
authors: Dominique
authors: D
authors: Ranchère
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D002675:Child, Preschool; D002817:Chordoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics*; D003388:Cranial Fossa, Posterior / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008297:Male; D018335:Rhabdoid Tumor / Q000235:genetics / Q000473:pathology*; D009418:S100 Proteins / Q000096:biosynthesis; D000071796:SMARCB1 Protein; D019292:Skull Base Neoplasms / Q000235:genetics / Q000473:pathology*; D020825:T-Box Domain Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000098908:Brachyury Protein
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D009418:S100 Proteins; D000071796:SMARCB1 Protein; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C513266:SMARCB1 protein, human
keywords: INI1 (BAF47); Rhabdoid tumor; brachyury; chordoma; clivus