Paget’s sarcoma with sarcoma-specific TP53 mutation arising from a Japanese patient

A 71-year-old woman visited our hospital with a feeling of dullness in her left hip joint in March 2012. A plain radiography of her left femur showed irregularly increased density with interspersed radiolucent areas at the left proximal femur. The cortex of the left femur was enlarged. The patient was diagnosed with Paget’s disease. She was treated with bisphosphonates (35 mg/week alendronic acid), and the level of alkaline phosphatase (ALP) in her serum gradually improved to within normal levels. A malignant tumor arising from Paget’s disease was suspected in September 2014; an increase in serum ALP levels coincided with the malignant transformation. A biopsy of the left distal femur revealed Paget’s osteosarcoma. After chemotherapy, the patient underwent a total resection of the left femur; it was replaced with an artificial femur. The surgical specimen was composed of pleomorphic tumor cells with tumor osteoid in the background of the Pagetic bone. Focal tumor necrosis was observed. After surgery, serum ALP levels returned to within normal levels. Furthermore, the patient underwent partial lobectomies for 4 metastatic lung lesions that had been gradually increasing in size over the 9 months following the total femoral replacement. Because of its rarity in Japan, the contribution of SQSTM1 mutations to Paget’s disease in Japanese patients remains unclear. Molecular testing revealed that this case did not contain a somatic SQSTM1 mutation, but there was a sarcoma component-restricted TP53 mutation, suggesting a significant role for TP53 in the malignant transformation of Paget’s disease.