Secondary Peripheral Atypical Cartilaginous Tumor / Chondrosarcoma, Grade 1

Staging is according to bone sarcoma protocols.

Unlike in secondary peripheral chondrosarcoma’s precursor osteochondroma, in which EXT1 or EXT2 is biallelically inactivated in at least a subset of the tumor cells, upon progression the cartilaginous cap of secondary peripheral chondrosarcoma becomes gradually populated by cells that retain at least one functional copy of EXT1 or EXT2. In secondary peripheral ACT/CS1, the proportion of EXT1- or EXT2-mutated alleles among all EXT alleles is about 40%, showing that EXT-mutant alleles and EXT-wildtype alleles coexist. This suggests that the wildtype cells in osteochondroma are prone to undergoing progression, and that (genetic) factors other than EXT1 or EXT2 mutations are also involved. These other factors probably involve mutations in cell-cycle regulatory genes such as CDKN2A.

Secondary peripheral ACT/CS1s show a thick (> 2 cm), lobulated cartilaginous cap (mean cap thickness: 3.9 cm). Careful gross macroscopic documentation of the thickness of the cartilaginous cap is crucial, and the cap should be measured perpendicular to the bone–cartilage interface, at its thickest portion, because the thickness is one of the most important determinants for progression in an osteochondroma.

There are no generally accepted histological criteria that indicate progression from osteochondroma towards secondary peripheral ACT/CS1. Coarse and irregular calcifications are usually prominent, and evidence of a pre-existing osteochondroma can often be seen. A lobular pattern is common, and sometimes nodules are separated from the main mass lying in the surrounding soft tissue. Binucleated cells, cystic changes (areas of cystic spaces containing mucoid material), and necrosis can be seen within the cartilaginous cap and should not be interpreted as evidence of progression, because these features can also be seen in osteochondroma. Increased vascularization can also be seen. Correlation between clinical and radiological features combined with the thickness of the cartilaginous cap is crucial to establish a diagnosis of secondary peripheral ACT/CS1. Mitoses and nuclear pleomorphism are absent. Invasion in the stalk is rare and indicative of progression.

Not clinically relevant

The clinical course can be variable and is dependent on localization and operability. The 5-year and 10-year local recurrence rates for secondary peripheral chondrosarcoma are 15.9% and 17.5%, respectively, and the 5-year and 10-year mortality rates are 1.6% and 4.8%. Local recurrences can occur and are usually related to incomplete excision in difficult locations. In the pelvis, peripheral CS1 can become very large and thereby difficult to excise completely, eventually becoming inoperable and fatal in some cases.

Not clinically relevant

Essential: location at the surface of the bone; presence of a pre-existing osteochondroma; size of the cartilaginous cap exceeds 2 cm, measured perpendicular to the bone–cartilage interface; absence of nuclear pleomorphism and mitoses.