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Review Article Spinal Chondrosarcoma: a Review

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Review Article Spinal Chondrosarcoma: a Review Hindawi Publishing Corporation Sarcoma Volume 2011, Article ID 378957, 10 pages doi:10.1155/2011/378957 Review Article Spinal Chondrosarcoma: A Review Pavlos Katonis,1 Kalliopi Alpantaki,1 Konstantinos Michail,1 Stratos Lianoudakis,1 Zaharias Christoforakis,1 George Tzanakakis,2 and Apostolos Karantanas3 1 University Hospital, University of Crete, Heraklion 711 10, Greece 2 Department of Histology, Medical School, University of Crete, Heraklion 710 03, Greece 3 Department of Radiology, University Hospital, University of Crete, Heraklion 711 10, Greece Correspondence should be addressed to Pavlos Katonis, [email protected] Received 6 September 2010; Accepted 3 January 2011 Academic Editor: Peter Houghton Copyright © 2011 Pavlos Katonis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chondrosarcoma is the third most common primary malignant bone tumor. Yet the spine represents the primary location in only 2% to 12% of these tumors. Almost all patients present with pain and a palpable mass. About 50% of patients present with neurologic symptoms. Chemotherapy and radiotherapy are generally unsuccessful while surgical resection is the treatment of choice. Early diagnosis and careful surgical staging are important to achieve adequate management. This paper provides an overview of the histopathological classification, clinical presentation, and diagnostic procedures regarding spinal chondrosarcoma. We highlight specific treatment modalities and discuss which is truly the most suitable approach for these tumors. Abstracts and original articles in English investigating these tumors were searched and analyzed with the use of the PubMed and Scopus databases with “chondrosarcoma and spine” as keywords. 1. Introduction differentiation is related to the presence of a “rings and arcs” pattern of calcification into the tumor matrix. The According to the World Health Organization, chondrosarco- differential diagnosis depends on the presence of calcifica- mas represent a heterogenous group of tumors characterized tions. If present, then the main consideration is enchon- by their ability of cartilage formation [1]. Chondrosarcoma is droma. If absent, many lesions should be also considered the third most common primary malignant bone tumor after such as metastases, malignant fibrous histiocytoma, and osteosarcoma and Ewing’s sarcoma. However, the incidence fibrosarcoma. The following criteria favor a diagnosis of of spinal chondrosarcomas is estimated to be from 2% to chondrosarcoma: deep endosteal scalloping (>2/3 of cortical 12% in various series [2].Thethoracicspineisthemost frequent localization, followed by the cervical and lumbar thickness), cortical disruption, periosteal reaction, soft tissue region [3]. Unlike most other malignant spinal tumors, the mass, and intense radionuclide uptake. Associated soft tissue lesions may arise in the vertebral body (5%), the posterior mass is a common finding, and, thus, CT or MRI are elements (40%), or both (45%), since there are three growth important to fully appreciate the extraosseous extension [5]. centers in each vertebra from which the tumor originates [4]. The histologic grading is just one indicator that can pre- The most common presenting symptom in chondrosarcoma dict the tumor’s biological behavior. Prognosis is also related is pain. Other complaints include a palpable mass and to management. The clinical challenge is to prevent recur- neurologic deficits in half of the patients [3]. rence and to optimize treatment options. Chondrosarcomas The radiological features of chondrosarcomas vary sig- are typically resistant to known protocols of radiotherapy nificantly depending upon the histologic grade. The spec- and chemotherapy; therefore, surgical removal is essential, trum of findings starts with lysis, which is difficult to and the outcome is based on the margins achieved [6, 7]. This discriminate form enchondromas. High-grade tumors are review focuses on the most relevant issues relating to clas- demonstrated radiographically with a moth-eaten destruc- sification, diagnostic work-up, and surgical management of tion and interrupted periosteal reaction. Higher grade of spinal chondrosarcomas. The principles of surgical excision 2 Sarcoma and reconstruction as well as novel treatment options like that inactivation of EXT1 and EXT2 encourages osteochon- radiofrequency ablation and cryosurgery are also discussed. droma development, the exact molecular trigger causing its malignant transformation is unclear [16]. It is evident that several growth-signaling pathways which are normally 2. Histopathological Classification activated during skeletal growth such as the Indian hedgehog of Chondrosarcoma (IHH)/parathyroid hormone-like hormone (PTHLH) factor, wingless type (Wnt) protein, and transforming growth Chondrosarcoma has been classified into conventional and factor (TGF) signaling pathways are deprived in secondary variant types. The variant types of chondrosarcoma include chondrosarcoma. The IHH signaling and the Wnt signaling the least aggressive clear cell type and the high-grade mes- are downregulated while the TGF signaling and the PTHLH enchymal and dedifferentiated tumors associated with poor signaling, which is downstream of the IHH and it is prognosis. Conventional chondrosarcoma, which constitutes responsible for chondrocyte proliferation, are up regulated approximately 85% of all chondrosarcomas, is further clas- and increased with increasing histological grade [13, 16]. sified into primary (85%) and secondary (15%) [8]. The On the contrary, EXT genes are not involved in the primary chondrosarcoma arises de novo within the bone development of primary chondrosarcoma, and, in this case, and can extend through the cortex with a large soft-tissue the initiate event remains unidentified [17]. These tumors mass. A secondary chondrosarcoma develops on the surface are usually aneuploid, with complex karyotypes, and 96% of of the bone mostly as a result of malignant transformation them contain alterations at some level in the pRb pathway within the cartilage cap of a pre-existing benign tumor [18]. such as osteochondroma [1, 9]. It has been reported that secondary chondrosarcomas tend to be of a lower grade 3. Rare Chondrosarcoma Subtypes exhibiting a better prognosis than primary tumors [10]. In general, primary and secondary chondrosarcomas are In addition to conventional chondrosarcoma, several variant histologically similar, and, for both, three different grades subtypes of chondrosarcoma are recognized which are are recognized, which is one of the most reliable predictors extremely rare especially when they originate in the spine of clinical behavior [11]. These histological grades are [19]. directly connected with prognosis and the risk of metastases. Clear cell chondrosarcoma is a rare variant chondrosar- Grade I tumors are characterized by low cellularity and coma with relatively good prognosis. It is described as a lack of pleomorphism; they contain a rich hyaline cartilage “round cell” neoplasm with clear, empty cytoplasms. Benign matrix and rarely metastasize [12]. In contrast, grade III giant cells may be present, which is the reason that it chondrosarcomas are extremely cellular with pleomorphism might erroneously be diagnosed as a chondroblastoma. and mitotic figures. Mucomyxoid matrix areas are frequent Vascularity is a common feature in this tumor. Although it in grade III tumors and metastases occur in 70% of patients. has a reasonably benign biological behavior, clear cell chon- Grade II chondrosarcoma hold some of the characteristics of drosarcoma needs to be treated as a malignancy. Metastases both grade I and grade III [11]. In addition, to histological are rare, but may occur up to 20 years following initial grade of the lesion, the prognosis depends on the possibility diagnosis; consequently, long-term followup is required [20]. of performing en bloc excision with proper oncologic On the molecular level, recent studies have shown that margins. Because of the difficulties associated with en bloc there is evidence of extra copies of chromosome 20 and surgery in the spine, tumors of the vertebral column have had loss or rearrangements of 9p. Also, expression of PTHLH, a deprived prognosis independent of the histological grade PDGFIHH, Runt-related transcription factor 2, and matrix [9]. metalloproteinase 2 [21, 22]werefound. It seems that chondrosarcomas may be biologically Mesenchymal chondrosarcoma is another rare variant of dynamic, since up to 13% of recurrent tumors display chondrosarcoma, which is highly malignant. The prognosis a higher grade of malignancy or even dedifferentiation of this tumor is extremely poor. It can involve both the compared to the initial neoplasm, with a severe adverse bone and soft tissues. Huvos et al. classified mesenchymal prognosis. Alterations in TP53 as well as the CDKN2A (p16) chondrosarcoma into hemangiopericytoma-like and small tumor suppressor gene are thought to be important for the dark round cell type. The same team reported that this tumor progression of low-grade towards high-grade chondrosar- occurs in relatively young patients (mean age of presentation coma. [13, 14]. 26 years) [23]. Histopathologically, it is characterized by Although primary and secondary chondrosarcomas varying amounts of differentiated cartilage admixed with show similarity in histopathologic features, they
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