Poorly differentiated chordoma (PDC) is an aggressive subtype of chordoma characterized by SMARCB1 (INI1) loss and a dismal prognosis. It typically involves the axial skeleton, most commonly the skull base and the cervical spine. To our knowledge, only 5 cases of extraaxial PDC (EAPDC) have been reported, and the natural history of these tumors is not fully understood. We studied 6 cases of EAPDC, with the goal of better understanding these exceptionally rare tumors. The tumors occurred in 4 women and 2 men, ranging from 37 to 68 years of age (median, 57.5 years) and involved or originated in the left knee joint (3 cases), right knee joint (2 cases), and right wrist (1 case). Grossly, all were solid and lobulated, with areas of necrosis. Histologically, the tumors were identical to axial PDC, with sheets and lobules of overtly malignant-appearing epithelioid-to-rhabdoid cells with prominent nucleoli. Mitotic activity and necrosis were present. By immunohistochemistry, all cases expressed keratins and brachyury and were SMARCB1 deficient. Molecular genetic analysis identified SMARCB1 loss-of-function alterations in 4 of the tested cases, including mutations (2 cases) and copy number loss (2 cases). DNA methylation profiling of 4 cases of EAPDC showed clustering with axial PDC. Clinical follow-up (6 patients
median, 11.5 months
range, 1-26 months) showed 4 patients to have received transfemoral amputation and 1 extraarticular resection. None received neoadjuvant radiotherapy
1 received neoadjuvant chemotherapy and 1 adjuvant chemotherapy/immunotherapy. Local recurrences were seen in 2 patients at 7 and 8 months
3 patients developed metastases 7-11 months after surgery. Two patients were alive with metastatic disease (at 7 and 13 months), 1 died of disease (20 months), and 3 were disease free (1-26 months). We conclude that EAPDC are aggressive malignancies with an unusual predilection for the knee joint and unknown pathogenesis.