Conventional chondrosarcoma with focal clear cell change: a clinicopathological and molecular analysis

Clear cell chondrosarcomas are known to occasionally contain areas of low-grade conventional chondrosarcoma; however, the opposite phenomenon has not yet been described. We identified five cases of conventional chondrosarcoma alongside clear cell chondrosarcoma. Here, we report on their clinicopathological and molecular characteristics, and investigate whether these hybrid lesions should be considered to be a collision tumour, conventional chondrosarcoma with clear cell change, or clear cell chondrosarcoma with extensive areas of conventional chondrosarcoma, as this has clinical implications.

Clinicohistopathological features were characterised, immunohistochemistry was performed for H3 histone family member 3B (H3F3B), histone H3 trimethylated on lysine 27 (H3K27me3), and p53, and genetic alterations of IDH1 (encoding isocitrate dehydrogenase 1), IDH2 (encoding isocitrate dehydrogenase 2), TP53 and H3F3B were evaluated. All five chondrosarcomas consisted predominantly of areas with conventional chondrosarcoma. Different grades were found [grade I (n = 1), grade II (n = 2), and grade III (n = 2)]. Up to 20% of the tumour consisted of classic features of clear cell chondrosarcoma. Gradual merging between both components was observed. Molecular analysis of conventional chondrosarcoma components revealed an IDH1 c.395G>T, p.(Arg132Leu) mutation in two cases, and an IDH1 c.394C>T, p.(Arg132Cys) mutation in one case, with identical IDH mutations in the clear cell chondrosarcoma counterpart (100%). Two cases were IDH wild-type. In all cases, none of the components harboured H3F3B mutations. High-grade tumours had an aggressive course, as three patients died of the disease.

On the basis of clinicopathological characterisation and genetic alterations, it is suggested that these lesions should be considered to be conventional chondrosarcoma, with clear cell change. Pathologists should be aware of their existence to avoid confusion with clear cell chondrosarcoma, dedifferentiated chondrosarcoma, or chondroblastic osteosarcoma.