Novel CSF1R-positive tenosynovial giant cell tumor cell lines and their pexidartinib (PLX3397) and sotuletinib (BLZ945)-induced apoptosis.

Tenosynovial giant cell tumor (TGCT) is a mesenchymal tumor derived from the synovium of the tendon sheath and joints, most frequently in the large joints. The standard of care for TGCTs is surgical resection. A new targeting approach for treating TGCTs has emerged from studies on the role of the CSF1/CSF1 receptor (CSF1R) in controlling cell survival and proliferation during the pathogenesis of TGCTs. We established four novel cell lines isolated from the primary tumor tissues of patients with TGCTs. The cell lines were designated Si-TGCT-1, Si-TGCT-2, Si-TGCT-3, and Si-TGCT-4, and the TGCT cells were characterized by CSF1R and CD68. These TGCT cells were then checked for cell proliferation using an MTT assay and three-dimensional spheroid. The responses to pexidartinib (PLX3397) and sotuletinib (BLZ945) were evaluated by two-dimensional MTT assays. All cells were positive for α­smooth muscle actin (α­SMA), fibroblast activation protein (FAP), CSF1R, and CD68. Except for Si-TGCT-4, all TGCT cells had high CSF1R expressions. The cells exhibited continuous growth as three-dimensional spheroids formed. Treatment with pexidartinib and sotuletinib inhibited TGCT cell growth and induced cell apoptosis correlated with the CSF1R level. Only Si-TGCT-4 cells demonstrated resistance to the drugs. In addition, the BAX/BCL-2 ratio increased in cells treated with pexidartinib and sotuletinib. With the four novel TGCT cell lines, we have an excellent model for further in vitro and in vivo studies.

Pigmented epithelioid melanocytoma (PEM) of the spine with compression fracture: case report.

BACKGROUND: Pigmented epithelioid melanocytoma (PEM) is a sporadic type of pigmented melanocytic tumor with uncertain malignant potential. PEM arises as a solitary neoplasm that predominantly occurs spontaneously in otherwise healthy patients. Due to its rarity, a gold standard treatment regimen does not exist; however, symptomatic cases should be managed with radiotherapy and surgery. CASE PRESENTATION: A 28-year-old Thai female presented with a sudden onset of back pain and weakness of the lower extremities during the postpartum period. Magnetic resonance imaging demonstrated abnormal soft tissue formation from T4 to T7; it extended to the vertebral bodies, left neural foramina, and posterior columns of T6 and T7. The patient underwent complete tumor debulking, decompressive laminectomy from T4 to T8, and posterior instrumentation from T3 to T10. The histopathology and immunohistochemistry suggested PEM. The patient fully resolved back pain after surgery. Nevertheless, as the patient re-presented with a neurological deficit a few months after the operative intervention, it was decided to perform a surgical resection via an en bloc vertebrectomy. At the one-year follow-up, although the patient reported continued improvement of her back pain, there was no motor power improvement. CONCLUSIONS: Spinal cord compression due to PEM is uncommon, especially in adults. Early diagnosis and treatment provide a good prognosis and help to regain lost neurological functions. Complete tumor removal and decompression of the spinal cord must be considered as a treatment strategy. Perioperative radiotherapy and chemotherapy have also been highlighted as treatment modalities for spinal tumors. With our reported case, early operative intervention coupled with radiotherapy produced satisfying outcomes.