The first case of mesenchymal chondrosarcoma (MCS) was described by Lichtenstein and Bernstein in 1959 [5
]. Approximately 10% occur in the head and neck region, being the maxillomandibulofacial skeleton the site in the head and neck where mesenchymal chondrosarcomas are most commonly encountered. Less commonly encountered sites in the head and neck include the sinonasal tract, orbit, and thyroid gland [1
]. Our case is one of the approximately 30 cases already reported with localization in the orbit. This tumor tends to affect patients in their second or third decades of life, with a female preponderance [1
], something important to notice given that the patient herein described is a 52-year-old male, in contrast with the typical sex and age of onset.
Clinically, these tumors tend to present with compression of the ocular globe resulting in progressive proptosis and/or visual abnormalities, such as diplopia or reduction in visual acuity. The radiological examination is relevant to help establish the diagnosis. CT scans usually reveal presence of foci of calcification in the lesion. MRI scans are helpful to delimitate the lesion margins [7
]. Our patient presented these clinical and radiological findings, in accordance with previous reports in the literature.
Histologically, this tumour exhibits a biomorphic appearance of undifferentiated mesenchymal cells with islands of mature hyaline cartilage [8
]. Immunohistochemical analysis often reveals positivity for vimentin, S100 protein and CD99; meanwhile, actin, cytokeratin, and EMA are typically negative [9
]. The differential diagnosis of orbital MCS includes hemangiopericytoma, myxochondrosarcoma, osteogenic sarcoma, and osteochondroma as primary tumors and lymphoma, neuroblastoma, synovial cell sarcoma, and chondrosarcoma as tumors affecting the orbit secondarily (direct invasion or metastasis) [11
]. This case presented no difficulty in the histopathological diagnosis since it showed a characteristic morphological pattern composed of round cells with an abrupt transition to well-differentiated hyaline cartilage and a hemangiopericytoma-like vascular pattern. The immunohistochemical analysis was positive for S100 protein and negative for cytokeratin and actin, which are some of the immunohistochemical characteristics often described for this type of tumors. In this case, hemangiopericytoma was considered the principal differential diagnosis.
Surgical resection with wide margins is known as the most effective treatment modality for chondrosarcoma [3
]. Zakkak et al. reviewed various treatment modalities in the maxilla and mandible and found that the best outcome was after radical surgery [12
]. The overall low incidence of regional metastasis may suggest that neck dissection is not indicated.
Radiotherapy might play a role when accompanied by surgery although some believe MCS to be a radioresistant tumor [3
]. Some authors report the use of preoperative radiation therapy to reduce tumor bulk prior to radical resection, with the hope of reducing extension in continuity or by micrometastasis, but it does not change the preoperative approach. Postoperative radiotherapy does not show a statistically significant proof of better prognosis even when there is evidence that demonstrates trend toward increased survival [14
Chemotherapy has a limited role in chondrosarcoma and should be used as an adjuvant therapy in cases with aggressive behavior with potential metastasis, rapid local recurrence, and high-grade lesions [2
]. This patient was advised the same chemotherapy regimen as used for Ewing's sarcoma. The standard neoadjuvant/adjuvant chemotherapy backbone consists of vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACD). Since then, a number of studies have sought to improve on that standard, using chemotherapy with VACD either alone or alternating with ifosfamide and etoposide (VACD-IE), the latter significantly improved 5-year disease-free survival (DFS) (69% versus 54%, P
= .005), and mesenchymal chondrosarcoma could be treated as per Ewing's sarcoma [15
There are numerous active signaling pathways that have been described in human chondrosarcoma, trying to suggest potential molecular targets for directed chemotherapy. One of these is a pathway dependent on phosphoinositide-3 kinase and MEK-extracellular signal-regulated kinase (ERK) signaling. Additionally, chondrosarcoma cell proliferation and degradation is dependent on peroxisome proliferator-activated receptor-gamma (PPAR-c) activity, with a loss of PPAR-c expression and associated apoptosis in high-grade tumors. Targeting these pathways may improve control of cranial chondrosarcoma and decrease the need of recurrent operations [16
The prognosis of patients with MCS is extremely variable, ranging from complete tumor response and long-term survival, to rapid local tumor progression with widespread metastasis. The mesenchymal histology alone carries a nearly 10-fold increase in 5-year mortality. The overall 5- and 10-year survival for patients with mesenchymal chondrosarcoma, when considering all sites, is 55% and 27%, respectively. It has been postulated that earlier detection and diagnosis of lesions in the head and neck may in part account for improved survival for mesenchymal chondrosarcoma located in the head and neck [1