Sarcomatous transformation of EGFR and TP53 mutation-positive metastatic adenocarcinoma of the lungs, masquerading as a primary pleomorphic sarcoma of the proximal femur.

We investigated a case of metastatic adenocarcinoma of the lungs at the left proximal femur, masquerading as a primary pleomorphic sarcoma. A 72-year-old woman presented with pain in her left thigh in conjunction with a mass that had been gradually growing over a few months. She was being treated with gefitinib for lung adenocarcinoma positive for the epidermal growth factor receptor (EGFR) mutation L858R, and had multiple bone metastases. The lung adenocarcinoma and metastases had stabilized with the treatment. The metastatic lesions in the bone had also received radiation; however, a tumor in the proximal femur kept growing despite treatment. A biopsy specimen from the proximal femur revealed the proliferation of spindle-shaped cells without an epithelial glandular component. The patient underwent en bloc resection of the proximal femur that was replaced by prosthesis. Histologically, the resected tumor was entirely composed of pleomorphic cells and tumor giant cells exhibiting no apparent glandular structures. Tumor cells were diffusely positive for p53 and focally positive for epithelial markers and EGFR, but were negative for thyroid transcription factor-1, suggesting an initial diagnosis of primary pleomorphic sarcoma. Genetic examination revealed mutations in EGFR and p53 that were of the same type as the lung tumor, leading to the final diagnosis of the femoral mass as a sarcomatous transformation of metastatic lung adenocarcinoma. However, secondary genetic alterations that might explain the acquired resistance to gefitinib could not be found in the proximal femoral tumor. The patient remains alive and the remaining lesions are well controlled.