Mesenchymal Chondrosarcoma from Diagnosis to Clinical Trials

Abstract

Mesenchymal chondrosarcoma (MCS) is a rare subtype of chondrosarcoma with a poor prognosis. Although these tumors are sensitive to radiotherapy/chemotherapy, the standard treatment for localized MCS is only surgical resection, and there are no established treatment guidelines for patients with advanced and metastatic MCS. Due to the low incidence of MCS, the pathology of these tumors is still unknown, and other therapeutic options are lacking. Some studies show the potential role of the PDGF/PPI3K/AKT, PKC/RAF/MEK/ERK, and pRB pathways, and BCL2 overexpression in the pathogenesis of MCS. These findings provide an opportunity to use protein kinases and BCL2 inhibitors as potential therapy in MCS. In this review, we summarize the current knowledge about MCS diagnosis and treatment options. We show the immunological and molecular biomarkers used in the diagnosis of MCS. In addition, we discuss the known prognostic and predictive factors in MCS. Finally, we present the novel trends, including targeted therapies and ongoing clinical trials using protein kinase inhibitors and the death receptor 5 (DR5) agonist, which may be the focus of future MCS treatment studies.

Keywords: mesenchymal chondrosarcoma; prognosis; rare sarcomas; treatment.

Figure 1

X-ray images showing locally advanced high-grade mesenchymal chondrosarcoma with abundant calcification and destruction of the proximal fibula. (A) Tibia Fibula Lateral X-ray view. (B) Tibia Fibula AP X-ray view. (C) Locally advanced high-grade mesenchymal chondrosarcoma of the left fibula in a 56-year-old woman for which the patient underwent transfemoral amputation. Axial (D.1) and Coronal (D.2) CT views depicting the size of the tumor.

Figure 2

Mesenchymal chondrosarcoma. (A) Mesenchymal chondrosarcoma comprises round, undifferentiated cells and fields of cartilage tissue (asterisk) (A1). Islands of well-differentiated hyaline cartilage (A2). The round cell component could be the only finding in small biopsy material, which is challenging in diagnostics (B). Chondrocytes and the matrix may mimic osteoid disposition (asterisk). Scale bar: 100 μm (A); 20 μm (A1,A2); 50 μm (B).

Figure 3

Lumbar spinal MRI showing an intraspinal extradural L2–L3 mesenchymal chondrosarcoma in a 31-year-old female. (A) Axial T1 Turbo Spin Echo (TSE) with fat suppression. (B) Sagittal T1 TSE. (C) Coronal T1 TSE.