Mesenchymal chondrosarcoma

Mesenchymal chondrosarcomas (MCS) are rare highly malignant chondrosarcomas with a biphasic morphology of a primitive mesenchymal tumour and a well-differentiated cartilaginous component.

Epidemiology

Mesenchymal chondrosarcomas are rare tumours and make up for ~2-4% of all chondrosarcomas ¹. They occur in a wide age range and peak in the second and third decades of life ^1-3. They are slightly more common in men ^1,3.

Diagnosis

The diagnosis of mesenchymal chondrosarcomas is established by histology and molecular pathology ¹.

Diagnostic criteria

Diagnostic criteria according to the WHO classification of soft tissue and bone tumours (5th edition) ¹:

• undifferentiated tumour cells with a high nuclear-cytoplasm ratio

• islands of cartilage

The following criteria are desirable ¹:  

• presence of a staghorn vascular pattern

• HEY-NCOA2 fusion

Pathology

Mesenchymal chondrosarcomas are highly malignant neoplasms of bone and soft tissues with a biphasic histomorphology of a small round cell sarcoma with islands of hyaline cartilage ^1-6. They are thought to arise from chondroblasts ¹.

Aetiology

At the time of writing, the aetiology of mesenchymal chondrosarcomas is unknown ¹.

Location 

Mesenchymal chondrosarcomas feature a widespread anatomical distribution and are found in the bone as well as extraskeletal sites including the somatic soft tissues and intracranial sites ¹.

The most common skeletal sites involve the following ^1,4:

• craniofacial bones: ~50%

• ribs and chest wall: ~20-25%

• spine and sacrum: ~15-20%

• lower extremity: ~10-15%

Extraskeletal sites include the somatic soft tissues, the meninges and orbits ^1,5. Other sites include the uterus and nasal cavity. Visceral locations are uncommon and include the kidney ¹.

Macroscopic appearance

Grossly, mesenchymal chondrosarcomas are lobulated firm to soft masses with a variable colour ranging from tannish-white to grey or pink ^1,4,5 with foci of haemorrhage and necrosis as well as calcified deposits ¹.

Microscopic appearance

Histologically, mesenchymal chondrosarcomas are characterised by a biphasic histomorphology with the following features ^1-5:

• undifferentiated small to medium-sized round or spindled cells with a high nuclear-cytoplasmic ratio

• haemangiopericytoma-like staghorn vascular pattern

• various islands of well-differentiated hyaline cartilage

• possible appearance or mimic of osteoid formation

Immunophenotype

Immunohistochemistry stains might be positive for S100, CD99, SOX9 and vimentin ^1,4. Smooth muscle actin, GFAP and keratins are typically negative ¹.

The tumour is also negative for FLI-1, which can be helpful in the differentiation from Ewing sarcoma ^1,5. Expression of SMARCB1 (INI-1) is retained which can be helpful for the differentiation from other soft tissue tumours including extraskeletal myxoid chondrosarcoma, epithelioid sarcoma and myoepithelial carcinoma ^1,5.

Genetics

Mesenchymal chondrosarcomas are characterised by HEY1-NCOA2 rearrangements ^1,6.

Radiographic features

Plain radiograph/CT

Radiographic features of mesenchymal chondrosarcomas include the following ^4,6,7:

• eccentric osteolytic lesions

• intralesional ring-and-arc or irregular calcifications

• permeative or moth-eaten bone destruction

• cortical destruction or breakthrough

• extraosseous extension

MRI

Imaging features include the following ⁶:

• chondroid calcifications (in the majority of cases ~80%)

• biphasic appearance (in about 1/3 of cases): separated calcified and non-calcified zones

• hyperintense lobules on T2 weighted images (in about 1/3 of cases)

Signal characteristics

• T1: low to intermediate signal (vs muscle)

• T2: hyperintense lobules in about one-third of the lesions 6

• T1 C+ (Gd): septal and peripheral enhancement

Nuclear medicine

PET-CT shows increased uptake of FDG ⁶.

Radiology report

The radiological report should include a description of the following ^6-8:

• tumour size and location (metaphysis, diaphysis)

• tumour margins/surface

• intralesional calcifications

• cortical erosion/destruction

• soft tissue mass

• pathological fracture

• presence of metastases

Treatment and prognosis

Mesenchymal chondrosarcomas are aggressive neoplasms with 5-year and 10-year survival rates ranging around ~60% and ~40% ^1,9. Management includes complete resection combined with chemotherapy or radiotherapy ^1,3-5.

Young adults and children tend to have better outcomes as well as a craniofacial origin, whereas an axial origin and distant metastases at initial presentation are associated with a poorer prognosis ¹.

Complications

Complications include local recurrences and distant metastases, the latter can occur as late as >20 years after an initial presentation ¹.

History and etymology

Mesenchymal chondrosarcomas were first described by the American pathologists Louis Lichtenstein and Donald Bernstein in 1959 ^4,10.

Differential diagnosis

The differential diagnoses of mesenchymal chondrosarcoma are highly dependent on the location of the tumour, within the bone it includes the following:

• dedifferentiated chondrosarcoma

• central intermediate and high-grade chondrosarcoma

• secondary peripheral chondrosarcoma

• periosteal chondrosarcoma

• Ewing sarcoma

See also

• extraskeletal chondrosarcoma