(P 76) GENETIC EVIDENCE OF METACHRONOUS DEDIFFERENTIATION OF CHONDROSARCOMA AT A DISTANT SITE

Objective: Dedifferentiated chondrosarcoma is a subtype of chondrosarcoma with a bimorphic histological appearance of a chondrosarcoma component with a transition to a high-grade, noncartilaginous sarcoma. It is particularly difficult to confirm the diagnosis when a sarcoma with no cartilaginous component occurs at a distant location from the primary lesion. We report a new emerging phenomenon of chondrosarcoma: metachronous dedifferentiation at a distant site with genetic evidence.

Methods: The patient was a 72-year-old woman with multiple lesions in the pelvis, lungs, and liver 18 months after resection of grade 2 central chondrosarcoma in the sternum. Imaging showed no cartilage component at any location. Although a needle biopsy from the pelvic region confirmed the diagnosis as high-grade sarcoma without a cartilage component, it was difficult to distinguish between a secondary sarcoma and metachronous metastatic lesions derived from dedifferentiated chondrosarcoma. Therfore, we compared the genomic alterations of the initial chondrosarcoma and the subsequent noncartilaginous sarcoma by whole exome sequencing (WES).

Results: Forty-three (30 nonsynonymous, 11 synonymous, one splicing junction, and one indel) and 57 (39 nonsynonymous, 13 synonymous, and 5 indel) somatic mutations were identified in the sternal resection specimen and the pelvic sarcoma specimen. Nineteen (14 nonsynonymous, 4 synonymous, and 1 indel) mutations were commonly found. In addition, the copy number analysis revealed highly similar aneuploidy between the two specimens, showing a wide range of chromosomal losses. Whole-chromosomal loss of heterozygosity (LOH) was commonly observed in 14 autosomes excluding Chr 2, 5, 7, 15, 16, 19, 20, and 21 in both samples. Multiple common somatic mutations and chromosomal losses indicated that sternal chondrosarcoma and pelvic noncartilaginous sarcoma were clonally related and that the pelvic tumor should represent a dedifferentiated chondrosarcoma arising from sternal grade 2 chondrosarcoma.

Conclusion: We evaluated the WES of central chondrosarcoma and metachronous dedifferentiated lesions. The possibility of metachronous dedifferentiation should be considered when a secondary sarcoma develops after central chondrosarcoma surgery, even if it arises in a different location from the primary tumor.