title: Glandular differentiation in dedifferentiated chondrosarcoma: molecular evidence of a rare phenomenon.
abstract: Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not been described. Our patient was a 64-year-old man with a history of prostate cancer status post-radiation and hormonal therapy. On screening bone scan, he was found to have increased uptake in his right femoral shaft. Biopsy revealed intermediate-grade conventional chondrosarcoma. Subsequent femoral resection was remarkable for an intermediate-grade chondrosarcomatous component juxtaposed to an area composed of anastomosing nests and cords of malignant epithelial cells showing nuclear atypia and increased mitotic activity. A fibroblastic-appearing spindle cell population was intimately associated with the epithelial cells. The epithelial cells labeled with 34bE12, AE1/AE3, EMA, and Vimentin (both spindled and epithelial components) while being negative for prostate-specific antigen, prostate specific acid phosphatase, cytokeratin 20, thyroid transcription factor-1, and CDX2. The patient developed local recurrence 9 months after the initial resection but has had no metastatic disease and consistently undetectable prostate-specific antigen levels. Deep parallel sequencing of the dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene at codon R132 leading to a substitution of arginine, with serine confirming glandular differentiation in dedifferentiated chondrosarcoma.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065. Electronic address: jourg@mskcc.org.
authors.forename: George
authors.initials: G
authors.lastname: Jour
authors.affiliation: Cytogenetics and Genomics Laboratory, Department of Pathology, University of Washington Medical Center, University of Washington School of Medicine, Seattle, WA, 98105.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anatomic Pathology, University of Washington Medical Center, Seattle, WA, 98105.
authors.forename: Robert
authors.initials: R
authors.lastname: Ricciotti
authors.affiliation: Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, 98105; Department of Genome Sciences, University of Washington, Seattle, WA, 98105.
authors.forename: Colin
authors.initials: C
authors.lastname: Pritchard
authors.affiliation: Department of Anatomic Pathology, University of Washington Medical Center, Seattle, WA, 98105.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Hoch
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D054337:Cell Dedifferentiation; D002813:Chondrosarcoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D004252:DNA Mutational Analysis; D005091:Exons; D005266:Femoral Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D010027:Osteotomy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: Cytogenomic microarray; Dedifferentiated chondrosarcoma; Epithelial glandular differentiation; Mesenchymal epithelial transition; Metastasis; Next generation sequencing