Peripheral intermediate and high-grade chondrosarcoma

Peripheral chondrosarcomas grade 2 and 3 are malignant intermediate and high-grade chondrogenic neoplasms originating from the bony surface in the chondral cap of pre-existing osteochondromas as a result of malignant transformation, thus the name secondary peripheral chondrosarcoma ^1,2. Secondary peripheral low-grade chondrosarcomas are not covered in this article.

Terminology

The term ‘chondrosarcoma secondary to osteochondroma’ is discouraged ¹.

Epidemiology

Intermediate and high-grade chondrosarcomas make up for ~9-10% ³ of secondary peripheral chondrosarcomas the remainder being peripheral low-grade chondrosarcomas. Similarly to their low-grade counterparts, peripheral chondrosarcomas grades 2 and 3 are most often seen in the 3^rd and 4^th decades of life ^1,4.

Associations

Intermediate and high-grade peripheral chondrosarcomas are associated with solitary osteochondromas and hereditary multiple exostoses from which they progress ^1-3.

Diagnosis

The diagnosis of secondary peripheral chondrosarcoma is made by a combination of clinical information, the location of the tumor and typical imaging features such as the size of the cartilaginous cap ^{1, 5,6}. In addition to imaging features pointing to a high-grade tumor such as a sizable chondral cap, a diffusely thickened cap type and intraosseous extension of the chondral tumor ⁵ the presence of mitoses and nuclear pleomorphism on histology aid in establishing the correct diagnosis ⁶. However, it is important to note that tumor grade determined by preoperative biopsy seems to be inaccurate in a significant number of cases ⁷.

Diagnostic criteria

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

• cartilaginous tumor originating from a pre-existing osteochondroma or evidence of a precursor lesion stalk

• cartilaginous cap with a size exceeding 2 cm, perpendicular to the bone-cartilage interface (tidemark)

• presence of mitoses and/or nuclear pleomorphism

Clinical presentation

A longstanding mass lesion with recent enlargement and/or pain are typical symptoms. Tumor growth after puberty or skeletal maturity is suspicious ¹. Depending on the location of the tumor limited joint motion or neurological symptoms might occur ¹.

Pathology

Peripheral chondrosarcomas grades 2 and 3 are malignant intermediate and high-grade cartilaginous neoplasms evolving at the surface of bone within the cartilaginous cap of pre-existing osteochondromas ^1-3.

Etiology

Individuals with osteochondromas in particular multiple osteochondromas at risk of tumor progression with an estimated risk of ~5%.

Location 

The most common sites involved are the pelvis, trunk and proximal femur ^1,3.

Macroscopic appearance

Grossly, peripheral chondrosarcomas grades 2 and 3 are characterized by the following features ¹:

• lobular translucent blue-white tumor

• focal areas with myxoid and cystic changes

• lobular cartilaginous cap exceeding 2 cm

• possibly recognisable osteochondroma stalk

Microscopic appearance

Histomorphologically, peripheral intermediate and high-grade chondrosarcomas are identical to central intermediate and high-grade chondrosarcomas and display the following microscopical features ^1,6:

• cartilaginous matrix-producing tumor

• coarse and irregular calcifications

• lobular pattern

• presence of nuclear pleomorphism and mitoses

• sometimes evidence of endochondral ossification and a pre-existing osteochondroma

• cystic spaces with mucoid material

• binucleated cells, areas of necrosis

Immunophenotype

Immunohistochemistry stains are reactive for S100 ¹.

Genetics

Similar to central intermediate and high-grade chondrosarcomas, secondary peripheral intermediate and high-grade chondrosarcomas are associated with chromosomal instability and complex karyotypes probably due to alterations in p53 and RB1 signaling pathways. As opposed to peripheral low-grade chondrosarcomas where EXT-mutant and EXT-wildtype cells coexist, EXT-wildtype cells predominate in peripheral intermediate and high-grade chondrosarcomas ¹. Mutations in IDH1 and IDH2 are absent ¹.

Radiographic features

General radiographic signs of secondary peripheral high-grade chondrosarcoma overlap with the imaging features of other peripheral cartilaginous tumors especially low-grade peripheral chondrosarcoma and periosteal chondrosarcoma.

Plain radiograph/CT

Radiographic features of peripheral chondrosarcomas include the following ^9,10:

• enlargement of a previously non-growing osteochondroma after skeletal maturation

• irregular or indistinct lesion surface

• intralesional focal osteolytic areas

• irregular lesion calcification

• extensive erosion or destruction of the adjacent bone

• soft tissue mass with scattered or irregular chondral calcifications

MRI

The cartilage cap of peripheral chondral tumors including osteochondromas, and peripheral low-grade and high-grade chondrosarcomas is best evaluated with fat-saturated T2 weighted images ^9-12. The cut-off thickness of the chondral cap >2 cm measured from the tidemark of the subchondral bone plate has high accuracy for the differentiation towards osteochondromas ¹⁰.

Additional features indicating peripheral high-grade chondrosarcoma include the following ⁵:

• diffuse cap type (>75% of the circumference of the cartilage cap thickened)

• greater cap thickness

• intraosseous extension

Signal characteristics

• T1: low signal vs muscle

• T2/STIR: high signal intensity with punctate or curvilinear signal voids indicating matrix mineralization ^9,10

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

Nuclear medicine

Increased uptake on bone scintigraphy indicates peripheral chondrosarcoma ⁷.

Radiology report

The radiological report should include a description of the following ^5,9-12:

• tumor size and location (tubular bones of extremities, axial skeleton)

• tumor margins/surface

• intralesional calcifications with irrelugalities and/or lytic zones

• the thickness of the cartilaginous cap ⁵

  • measured from the tidemark of the subchondral bone plate: cut-off value >2 cm, but high-grade tumors tend to have thicker caps

  • estimation of the abnormally thickened cap type (focal/regional/diffuse) ⁵

• involvement of the stalk

• adjacent bone destruction

• presence of metastases

Treatment and prognosis

Surgical excision with wide margins is the treatment of choice ^1,13. Prognosis is significantly worse than for their low-grade counterparts with a mortality rate of slightly more than 20% ¹³.

Like in peripheral low-grade chondrosarcoma, recurrences are a major problem with multiple recurrences being quite common ¹³.

Complications

The main complication is local and distant tumor recurrences ¹. Peripheral high-grade chondrosarcoma might have metastases.

History and etymology

Chondrosarcomas as well as their differentiation into central and peripheral chondrosarcomas was first described by the American bone pathologists Louis Liechtenstein and Henry Lewis Jaffe in 1942 ¹⁴. The designation of secondary peripheral intermediate and high-grade chondrosarcomas as a separate entity within the WHO classification of bone tumors happened in the fourth edition ¹⁵.

Differential diagnosis

The main differential diagnoses of low-grade peripheral chondrosarcomas are ^5,9-11:

• dedifferentiated chondrosarcoma: bi-morphic histomorphology

• central intermediate and high-grade chondrosarcoma: no stalk or evidence of osteochondroma,

• low-grade peripheral chondrosarcoma: smaller cap thickness, focal or regional cap type

• osteochondroma: cap thickness <2 cm

• periosteal chondrosarcoma: no precursor osteochondroma, association with the periosteum

• periosteal chondroma: originates from periosteum or the bony surface; lesion size <3 cm ¹⁶

• periosteal osteosarcoma

See also

• chondrosarcoma

• conventional chondrosarcoma

• chondrosarcoma grading