A 5-year Chinese longitudinal case report on the malignant transformation of spinal Paget disease

Paget disease of bone (PDB) is a metabolic disorder typically regarded as benign, yet it carries a <1% risk of malignant transformation into osteosarcoma malignant transformation into osteosarcoma, particularly with spinal involvement. Differentiation from other aggressive spinal lesions can be challenging. In Asian populations, prognostic data on Paget sarcoma are scarce. The significance of dual SQSTM1 and ZNF687 mutations and a rapid alkaline phosphatase (ALP) surge as indicators of malignant transformation remains to be fully elucidated.

We report a case of spinal Paget sarcoma in a patient with a 5-year history of PDB. The patient presented with progressive symptoms culminating in acute neurological deterioration, including bilateral lower limb weakness and bowel/bladder dysfunction, indicating severe spinal cord compromise.

The diagnosis of malignant transformation was based on the clinical course, serial imaging showing progressive spinal involvement, a sharp rise in ALP (a hydrolase enzyme that is predominantly found in the liver and bone, and elevated serum levels of which serve as a key biomarker for hepatobiliary disorders or abnormal bone metabolism) from >800 U/L to 3100 U/L, and genetic testing confirming dual SQSTM1 and ZNF687 mutations.

The patient underwent surgical intervention, targeted therapy, and other supportive treatments. An emergency workup was performed due to rapid neurological decline.

Despite treatment, the patient experienced a rapid functional decline, with lower limb strength dropping to grade 1 by postoperative day 40, reflecting a poor prognosis associated with advanced Paget sarcoma. During the 2025 follow-up, the family was approached but declined to disclose the patient's status. The patient's survival status remains unknown as of the last follow-up.

In patients with PDB and spinal involvement, a rapid increase in ALP, especially in the context of specific genetic mutations like SQSTM1 and ZNF687, may be a critical indicator of malignancy. This case highlights the need for heightened clinical vigilance, enhanced genetic monitoring, and consideration of early biopsy to enable timely intervention and improve patient outcomes in this rare but devastating complication.