Objectives: To review cytomorphologic characteristics of osteoblastic osteosarcoma (OOS), a variant of osteosarcoma, on fine-needle aspiration (FNA) and correlate them with histopathologic features and clinical outcomes. Study design: A retrospective review of the cytopathology archives of The Johns Hopkins Hospital revealed 22 cases of OOS on FNA in 20 patients (16 primary, 5 recurrent and 1 metastatic OOS). Results: There were 11 males and 9 females (male:female ratio 4:3) aged from 5 to 48 years (mean 17.1). Anatomic locations were: femur (7), humerus (3), tibia (4), fibula (1), iliac crest (1), pubis (1), sacrum (1), mandible (1) and soft tissue of the thigh (3). All except 1 presented with progressive pain and/or swelling. Sizes of the lesions ranged from 2.3 to 34 cm (mean 9.2). Initial FNA diagnoses were high-grade malignant neoplasm (5), osteosarcoma, non-conventional osteosarcoma (12) and OOS (5). Cytomorphologic characteristics were: moderate-high cellularity, discohesive/single cells, small tissue fragments, immature osteoid, bi-/multinucleated giant cells, plasmacytoid cells with basophilic, vacuolated cytoplasm, round to oval nuclei and macronucleoli. Cases with high-grade histology displayed pleomorphism and mitoses. Conclusions: OOS has a better prognosis than other osteosarcoma variants. The differential diagnosis of OOS includes reactive bone lesions, osteoblastoma, malignant sarcoma with an osteoid component and other osteosarcoma variants. A definitive diagnosis can be made on FNA with clinical and radiological correlation, thus facilitating immediate therapy.

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