A 25-year-old female presented with persistent low back pain for the previous 3 months, accompanied by weakness in both lower extremities for 3 days. Physical examination revealed grade 0/5 muscle strength in both lower extremities. Magnetic resonance imaging (MRI) and computed tomography (CT) scans revealed a large lytic lesion with an extra-spinal component involving the T11 and T12 spinal segments. The tumor measured approximately 11.26 cm x 7.29 cm, compressing the spinal cord at the T11 level and invading the left erector spinae (Fig. 1).

MRI results. (A) Magnetic resonance imaging (MRI) showing a thoracic spine tumor before chemotherapy; the red arrow indicates compression of the spinal cord by the tumor. (B) Follow-up MRI after two rounds of chemotherapy shows minimal change in the tumor size compared to pre-treatment; red arrows indicate that the spinal cord remains severely squeezed. (C) Follow-up MRI 1 month after starting treatment with entrectinib shows a tumor at the 11th thoracic vertebra, with spinal cord compressed reduced and the tumor significantly shrinking. The red arrow indicates the reduced compression of the spinal cord, which gradually returns to its normal position. (D) Follow-up MRI after 2 months of continuous treatment with entrectinib shows further tumor shrinkage and continued spinal cord compression reduction. The red arrow indicates the further reduction in spinal cord compression, with visible cerebrospinal fluid

A pathological review of a percutaneous needle biopsy specimen confirmed the diagnosis of spindle cell sarcoma. Microscopically, atypical cells were observed in a fascicular or woven pattern with relatively uniform cell morphology and distribution around blood vessels. The nuclei were round or short, spindle-shaped with small visible nucleoli, and focal involvement of the striated muscle was noted.

Immunohistochemical analysis revealed positive staining for TRK, partial positivity for S-100, and positivity for CD99, GFAP (weak positivity in a small amount), H3K27Me3, and INI-1. Results were negative for Demin and SOX-10, and Ki-67 staining revealed a labeling index of 40%. Based on these findings, second-generation sequencing was recommended for further molecular analyses.

To assess the tumor’s mutational profile and identify potential therapeutic targets, extensive high-throughput sarcoma testing was performed. The testing included DNA sequencing of all exons in 706 genes, partial introns in 67 genes, RNA sequencing of all exons in 649 genes, tumor mutational burden calculation, microsatellite instability assessment, human leukocyte antigen (HLA)-I genotyping, germline pathogenic variant screening of 65 genes, analysis of gene variant interactions, and variants of unknown significance (VUS) in both DNA and RNA sequencing.

The results revealed 20 potentially clinically significant variants and 10 VUS in DNA sequencing; in contrast, RNA sequencing identified one clinically significant rearrangement and no VUS rearrangements. No harmful germline variants were detected. HLA-I genotyping revealed a heterozygous profile.

Genetic analysis, based on clinical guidelines for soft tissue sarcoma diagnosis, identified an NTRK3 gene rearrangement, specifically a SPECC1L exon6-NTRK3 exon14 fusion, with a mutation abundance of 52%. Fluorescence in situ hybridization confirmed a break in the NTRK gene (Fig. 2), suggesting the tumor was an NTRK rearranged spindle cell tumor. These findings indicated that the patient might benefit from targeted therapies such as entrectinib and larotrectinib (Table 1).

Gene molecular diagnostic report. (A) The test sample contained 100 tumor cells, more than 15% of which showed isolated signals, interpreted as positive. The patient tested positive for NTRK gene fusions. (B) Positive control experiment

The patient received two cycles of doxorubicin/ifosfamide combination chemotherapy while awaiting NGS results. MRI scan after chemotherapy showed no significant changes compared with prior scans, suggesting the tumor did not respond well to chemotherapy. After discussions at multidisciplinary team meetings, the patient was advised to undergo targeted therapy with entrectinib (600 mg QD PO).

One month after starting entrectinib treatment, the patient experienced sensory recovery in both lower extremities and a gradual improvement in muscle strength. Overall, muscle strength in the lower extremities was approximately 2–3 out of 5. MRI and CT scans revealed considerable tumor shrinkage, and en bloc resection became feasible (Fig. 1).

The patient underwent total en bloc spondylectomy, which involved completely removing the three vertebral bodies invaded by the tumor, along with the surrounding soft tissues and ribs, through a posterior approach. The resection area was reconstructed using 3D-printed artificial vertebral bodies (Fig. 3). The procedure lasted approximately 9 h and 3 min, with intraoperative blood loss of 2500 ml. Postoperative pathological results were consistent with pre-surgical findings, showing tumor necrosis of approximately 70% and a tumor-free surgical margin. Microscopic examination revealed invasion of the striated muscle and adipose tissue (Fig. 4).

Tumor specimens and intraoperative X-ray fluoroscopy. (A) Front view of the specimen. (B) Rear view of the specimen. (C) Intraoperative fluoroscopy of the specimen, upper and lower views. (D) Intraoperative fluoroscopy of the specimen, anteroposterior view

Histopathological features. (A) Specimen after block resection of the thoracic tumor. Yellow arrows indicate staining boundaries. (B) Tumor cells invade adipose and striated muscle tissue under low magnification. (C) Tumor cells invade adipose and striated muscle tissue under medium magnification. (D) Tumor cells invade adipose and striated muscle tissue under high magnification

The patient was discharged without complications 1 month postoperatively. Prior to discharge, the patient was able to sit upright independently and did not require any external assistance. Muscle strength in the lower extremities had improved to approximately 2–3 out of 5.