title: Sarcomatous transformation of EGFR and TP53 mutation-positive metastatic adenocarcinoma of the lungs, masquerading as a primary pleomorphic sarcoma of the proximal femur.
abstract: 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.
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 Japan ; Department of Orthopaedic Surgery, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Toda-Ishii
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 Japan ; Department of Orthopaedic Surgery, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Akaike
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Kurisaki-Arakawa
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 Japan ; Department of Orthopaedic Surgery, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Mukaihara
authors.affiliation: Department of Orthopaedic Surgery, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suehara
authors.affiliation: Department of Orthopaedic Surgery, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takagi
authors.affiliation: Department of Orthopaedic Surgery, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421 Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D003937:Diagnosis, Differential; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012509:Sarcoma / Q000235:genetics / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; Lung adenocarcinoma; TP53; metastasis