Chondrosarcoma of bone: diagnosis and therapy

Conventional chondrosarcoma (grades I–III)

The conventional chondrosarcoma is the most common chondrosarcoma with an estimated annual incidence of 3–4/100,000.

The majority of these are central tumors that arise from within the intramedullary channel of the bones. Subperiosteal and extraosseous chondrosarcoma are rarities. The main tumor site is the pelvic bone, the femur, and the shoulder girdle (proximal humerus/scapula) [ , ]. Most of the tumors appear around the sixth decade of life.

The radiological appearance of these tumors is heterogeneous. They present as osteolytic lesions that can represent all grades of the Lodwick classification [ , ]. Signs of malignancy are a cortical destruction and/or an extraosseous tumor component ( Fig. 50.1A–C ). Further, in the plain radiograph the scalloping phenomenon is one characteristic sign seen in most of the tumors. However, it is most common in low-grade tumors and less often present in fast-growing high-grade chondrosarcomas. In the CT scan small, amorphous spots of matrix calcification are characteristic for high-grade chondrosarcoma as is a predominance of osteolytic bone destruction. In contrast, low-grade chondrosarcomas present regularly a so-called “rings and arcs” sign which is based on the slow tumor growth and the adaptation of the surrounding bone.

In the MRI there is no general pattern for all chondrosarcomas also. In low-grade chondrosarcomas the imaging presents a more or less homogeneous signal in the T1 sequences and a signal uptake in T2 which is based on the high percentage of water and the small number of tumor cells in the tumor matrix. In contrast, high-grade chondrosarcomas commonly present larger parts of tumor necrosis, a higher portion of fibrous tissue, a higher cell density, less chondroid matrix and therefore present more inhomogeneous [ ].

The dignity of chondrosarcomas is generally based on histopathological findings. However, in literature several different grading systems are used over the years. Most of them are based on the cells morphology, the nucleus size and morphology, the prominence of the nucleoles, the chromatin structure, and the mitotic activity of the tumor chondrocytes. Other criteria are the tumor cell number or the rate of necrosis which both are associated with the tumor grading. According to these aspects in most of the grading systems the tumors are classified into three grades of malignancy [ ]. Up to 60% of conventional chondrosarcomas as well as dedifferentiated chondrosarcoma (ddCS) present IDH1 R132 and IDH2 R172 mutations. This valuable biomarker can be used to distinguish conventional chondrosarcoma from chondroblastic osteosarcoma, chondromyxoid fibroma, or chondroblastoma as this marker has not been found in one of these lesions [ ].

Dedifferentiated chondrosarcoma

The ddCS is a special subtype in the group of the malignant cartilage tumors. It is commonly classified as a grade IV chondrosarcoma due to its biological aggressiveness. The long bones of the extremities and the pelvis are the predominate sites. The mean age at diagnosis ranges from 65 to 75 years and is slightly older than in patients with a conventional chondrosarcoma [ ]. Characterized is this entity by its typical bimorphic histological appearance with areas of low-grade chondrosarcoma adjacent to small parts of high-grade sarcoma components. The high-grade component can either be osteosarcoma, malignant fibrous histiozytoma, fibrosarcoma, or anaplastic spindle cell sarcoma [ ].

In the imaging the ddCS is characterized mainly by the low-grade component with a scalopping sign and a homogenous appearance in most parts of the tumor. The high-grade component is commonly associated with an aggressive osteolytic tumor growth with cortical destruction, tumor necrosis, and frequently an extraosseous tumor formation ( Fig. 50.2A and B ). Besides the plain radiograph the MRI is usually the best method to illustrate the bimorphic composition of the tumor to confirm the diagnosis ( Fig. 50.2B ).

Mesenchymal chondrosarcoma

The mesenchymal chondrosarcoma is a rare subentity. In contrast to the dedifferentiated and the conventional chondrosarcoma this tumor appears mainly in younger patients. The main age at diagnosis is the second and third decade of life. Further, the most common tumor site is the axial skeleton and the extraskeletal soft tissue unlike to other chondrosarcoma [ ]. In terms of its histological appearance it presents as a tumor with small spindle cell–like tumor cells besides smaller parts of normal cartilage. Especially because of the small cell component the differentiation from a Ewing's sarcoma or synovial sarcoma can be difficult. Proof of the HEY1 - NCOA2 fusion transcript in the tumor cells is highly specific for this entity and allows an accurate diagnosis in difficult cases [ ]. The mesenchymal chondrosarcoma has to be classified as a high-grade malignancy in terms of its clinical course and its therapy.

Clear-cell chondrosarcoma

This rare type of chondrosarcoma is almost always located at the epiphyseal part of the long bones of the extremities. Its histological appearance is characterized, like the ddCS, by its bimorphic composition. These tumors present parts of classic malignant chondrocytes besides parts of swollen chondrocytic cells with a clear cytoplasm that allows the pathologist to separate them easily from other chondrosarcoma [ ]. Because of its relatively low proliferation rate and the slow tumor growth this tumor appears in the plain radiograph typically as a sharp edging osteolytic lesion with a sclerotic border ( Fig. 50.3 ).

Regarding to its clinical behavior, its prognosis, and therapy, it is graduated as an intermediate-grade chondrosarcoma [ ].

Secondary chondrosarcoma

Secondary chondrosarcomas typically arise from preexisting benign cartilage lesions like enchondroma or osteochondroma, especially if they are associated with syndromes such as hereditary multiple exostosis (HME), Ollier's disease, or Maffucci's syndrome.

HME is a monogenetic, autosomal dominant disorder, mainly caused by loss-of-function mutations in exotoxin-1 (EXT-1) and exotoxin-2 (EXT-2) [ , ]. Chondrosarcomas arising from osteochondroma are almost solely low-grade chondrosarcomas with less than 8% high-grade variants [ , ]. The clinical aspect of this secondary malignancy is a new proliferative growth of preexisting benign lesions in adults and/or newly diagnosed clinical symptoms like pain. In these cases we routinely recommend a further MRI diagnostic with specific cartilage sequences (D3W,FL2D) to judge the cartilage cap of the osteochondroma. Cartilage cap thickness of more than 2–3 cm and an inhomogeneous appearance are strong hints for a malignant transformation and indicate an open biopsy. The risk of secondary malignancy is about 1%–5% in case of multifocal lesions over the spam of life [ , ].

Secondary chondrosarcomas arising from benign enchondroma or in patients with Maffucci syndrome or Ollier's disease have a risk of being high grade in more than 30% [ ]. The rate of malignant transfer of a benign lesion is less than 1% if there is a single lesion and about 10% in case of multifocal manifestation or a syndrome association [ ]. In patients with known preexisting lesions particularly in combination with a diagnosed syndrome we attach strong importance on the clinical course. If these patients report on newly occurred pain and clinical symptoms an advanced diagnostic up to an open biopsy is recommended. Routinely whole body MRI (e.g., every 3–6 months) might be useful in early detection of malignant changes in patients with multiple enchondromas [ ].