Dedifferentiated peripheral chondrosarcoma: a clinicopathologic, immunohistochemical, and molecular analysis of four cases

Abstract

Peripheral dedifferentiated chondrosarcoma (DCS) is an exceedingly rare aggressive surface bone neoplasm in which a high-grade sarcoma arises within an osteochondroma. Four such examples were identified in our files, representing 11.1% of all DCS treated at our hospital in the years 1995-2010, and were the object of the present study. The patients were two men and two women ranging in age between 30 and 64 years, with tumors located in the pelvis (n 0 2), in the scapula (n 0 1), and the tibia (n 0 1). Radiologically, there was evidence of a preexisting osteochondroma associated with aggressive osteolytic areas at the base and periphery of the exostosis, extending to the bone segment of origin and to the soft tissues. Immunohistochemical analysis of cell cycle regulators showed consistent loss in the expression of p16 and overexpression of cyclin D1, and to a lesser extent of RB and p53, in the anaplastic compartments of peripheral DCS in comparison with the well-differentiated cartilaginous components, while no significant expression of MDM2 was observed in any of the cases studied. Moreover, PDGFR! was absent in both tumor components, and PDGF-R" was strongly and diffusely positive in all the cases. Finally, no mutations were identified in exons 4-9 of the TP53 gene in both cases, showing positivity for p53 in the anaplastic component. In conclusion, our study shows that alterations of genes implicated in the regulation of the G1 to the S phase cell cycle checkpoint contribute to the process of dedifferentiation in peripheral secondary chondrosarcoma (CS), although the molecular mechanisms seem at least in part to differ from those involved in the process of dedifferentiation of central CS. PDGFR" could represent a potential target for treatments with receptor tyrosine kinase inhibitors in peripheral DCS.

Targeted Next-Generation Sequencing Identifies Molecular and Genetic Events in Dedifferentiated Chondrosarcoma

“…Prior studies have identified TP53 mutation and/or protein overexpression in DDCS, although only in a few tumors and without separate study of both components. 10,15,16,31,32 The current study confirms that inactivating mutations in TP53 are common in DDCS and, in a subset of cases, the TP53 mutation is restricted to the dedifferentiated nonchondrogenic component. In the subset of cases in which TP53 mutations were present in both components, the alteration was subclonal in the chondrogenic components relative to the IDH1/2 alteration.…”

Dedifferentiated Peripheral Chondrosarcoma: A Review of Radiologic Characteristics

“…This finding diverges from the largest reports of central dedifferentiated chondrosarcoma where MFH-like features comprised from 4% to 22% of the total cases, and osteosarcoma-like characteristics usually dominate [2, 3, 16, 28]. Other reports have documented a rate of MFH-like histologic subtypes greater than 50% in the peripheral form of dedifferentiated chondrosarcoma, indicating that the peripheral form may have a predilection for this morphology [7, 12, 15]. …”

Secondary Peripheral Dedifferentiated Chondrosarcoma

“…We reviewed previous reports about peripheral dedifferentiated CS, excluding additional reports from the same institution (Table I) [5][6][7][8][9][10][11][12] . Overall, 28 cases appeared in the English literature.…”