Abstract
AimsClear 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.Methods and resultsClinicohistopathological 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.ConclusionOn 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.
Highlights
Chondrosarcomas constitute a group of malignant cartilaginous matrix-producing tumours
Molecular and immunohistochemical analyses were performed to investigate whether these hybrid tumours should be considered to be part of a collision tumour, a conventional chondrosarcoma with clear cell change, or clear cell chondrosarcoma with extensive areas of conventional chondrosarcoma
Clear cell chondrosarcoma was first described by Unni et al in 1976,1 and it has been noticed that these tumours may contain areas of conventional low-grade chondrosarcoma
Summary
All conventional chondrosarcomas with clear cell chondrosarcoma features were encountered in a subspecialty consultation practice. After antigen retrieval with Tris-EDTA (pH 9.0) at 97°C for 30 min, representative slides containing both components were stained for H3F3B K36M (RM193, 1:2000; Sanbio, Uden, The Netherlands), histone H3 trimethylated on lysine 27 (H3K27me3) (C36B11, 1:10; Cell Signaling, Danvers, MA, USA) and p53 (DO-7, 1:2000; Dako, Glostrup, Denmark) with the Omnis autostainer (Dako) and use of the Envision FLEX + detection kit (Dako). Areas composed of either conventional chondrosarcoma or clear cell chondrosarcoma features were selected. Areas where both components merged were avoided. If an IDH1 or an IDH2 mutation in the conventional chondrosarcoma component was present, further analysis of the clear cell counterpart was performed
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