Mesenchymal Chondrosarcoma: A Rare Aggressive Variant of Chondrosarcoma

A 15-year-old boy reported a 2-month history of severe left thigh pain Physical examination revealed left thigh swelling measuring 6x5 cm. X-ray of the region showed mixed lytic and sclerotic lesion involving the femoral head and neck. A Computed Tomography scan showed mixed lytic and sclerotic lesion involving the femoral head and neck with cortical irregularity and mild periosteal reaction with associated soft tissue in the anterior aspect.  Magnetic resonance imaging demonstrated heterogeneous signal intensity lesion with areas of sclerosis involving the femoral head and neck. The large associated soft tissue in the anterior aspect appears predominantly hyperintense on T2W images. On post-contrast axial and sagittal images, heterogeneous enhancement with areas of necrosis involving soft tissue was seen. A presumptive radiological differential diagnosis of Ewing Sarcoma and Osteosarcoma was made. However, on histopathology, it was a case of mesenchymal chondrosarcoma.

Mesenchymal Chondrosarcoma (MCS), first described by Lichtenstein and Bernstein 1 in 1959 is a rare tumor representing less than 4% of all chondrosarcomas. [2][3][4][5] Mesenchymal chondrosarcoma is a poorly understood entity and the only consistently described features of MCS are the unique, biphasic histology and the poor prognosis, despite variable lengths of disease-free survival. 4 The rarity of this tumor leads to substantial diagnostic, prognostic, and management challenges. In this case report, we present the characteristic clinical, radiographic, and histopathologic features of MCS seen in a 15 years old patient.

CASE REPORT
A 15 years-male patient presented in March 2014 with a complaint of a painful left hip joint and upper thigh for the past 2 months. On examination, a firm vertically hemi-ellipsoid swelling in the upper left thigh involving the left hip was observed. There was no regional lymphadenopathy or neurovascular deficit. Complete blood count and routine biochemical analysis were normal. X-ray of the region showed mixed lytic and sclerotic lesion involving the femoral head and neck ( fig.1A). A Computed Tomography (CT) scan showed mixed lytic and sclerotic lesion involving the femoral head and neck with cortical irregularity and mild periosteal reaction with associated soft tissue in the anterior aspect    The patient underwent surgical excision. Multiple bits of pale white to dark white tissue altogether measuring 4.5 cm was received for histopathology. On microscopic examination of Hematoxylin and Eosin stained slides, a tumor was observed composed of islands of cartilage containing malignant chondrocytes and juxtaposed with a small round to oval tumor cells arranged in sheets. Tumor cells were small and had mild to moderate pleomorphism, a scant amount of cytoplasm, and round to oval hyperchromatic nuclei. Hemangiopericytoma-like vascular proliferation was seen admixed with tumor cells. The chondroid islands were also noted with multinucleated tumor giant cells, occasional areas of osteoid matrix, and calcification. A histopathological diagnosis of MCS was given. After the histopathological diagnosis was given, the patient underwent chemotherapy and radiotherapy. Though the patient had pulmonary metastasis three years back for which the patient underwent surgical excision, the patient is doing well as of October 2020.

DISCUSSION
Classical Chondrosarcoma (CC) is the second most common sarcoma of bone. 2 It includes a heterogeneous group of neoplasms characterized by the production of a cartilage matrix. Chondrosarcoma has a classic intramedullary origin, however extra skeletal origin is not uncommon.MCS differs from CC as to its rarity, age distribution, aggressiveness, and a higher percentage of extraskeletal tumors. The MCS is a rare tumor and accounts for only 2% to 4% of all chondrosarcomas. [2][3][4][5] MCS classically occurs in young adults i.e in second and third decades of life, 4 whereas most CC patients are>50 years old. MCS has a 10-year survival rate far below 50%, [3][4][5][6][7][8] while most CC has a more favorable prognosis. About 1/3 of MCS occur in soft tissues, whereas extraosseous CC account for <1% of all CC. [9][10][11] In the case series by Nakashima Y. et al. of 111 cases of MCS 72(64.86%) tumors were in bone, 38(34.23%) in nonskeletal tissues, and 1(0.01%) in both bone and soft tissue. Amongst the skeletal sites most common site for MCS is pelvic bones followed by femur, humerus, vertebra, mandible, and skull. 4 The radiographic appearance is largely not specific and is, at times, variable. Lesions are characteristically osteolytic and locally destructive, with soft tissue extension and finely stippled calcification. 3 The radiological findings of this case showed similar features.
The histology of MCS shows a paradoxical histological picture of highly cellular zones composed of anaplastic small cells along with islands of relatively hypocellular chondroid areas. These islands may be calcified or even ossified. The cellular areas with anaplastic small cells may show vascular proliferation with a hemangiopericytoma-like pattern. The diagnosis is more readily apparent if both components are present. The current case showed the classical findings of both the components. The absence of cartilage in the biopsy sample can cause this tumor to be confused with other small, round, blue-cell tumors Furthermore, the cartilage can be the predominant pattern with small malignant cells between the lobules leading to an erroneous diagnosis of conventional chondrosarcoma. A differential diagnosis of small cell osteosarcoma can be made erroneously if the chondroid islands have undergone ossification however, the very characteristic low-grade appearing cartilaginous foci and typical nuclear morphology should suggest MCS. The other histologic differential diagnosis for MCS includes Ewing sarcoma, lymphoma, neuroblastoma, desmoplastic small round cell tumo rand small cell osteosarcoma. 6,12,13

Prognosis and grading
Although there are typically no tumor necrosis and the mitotic count is relatively low, MCS is classified as grade 3 in the grading systems of the French Federation of Cancer Centers Sarcoma Group (FNCLCC) and the National Cancer Institute.14 This classification is based on its highly malignant clinical behavior, and frequent but late local and metastatic recurrences leading to poor long-term outcomes. Much of the current knowledge about the clinical course of MCS was gained from the largest retrospective series published in 1986, which included information on the treatment of 78 patients with adequate followup. Thirty-seven of these patients had been treated with radiation, chemotherapy, or both after the initial surgery. 4

CONCLUSIONS
The current case report highlights that MCS is an entity to be considered in young patients presenting with tumors mimicking chondrosarcoma or osteosarcoma as MCS has a worse prognosis compared to both.