LAUSR

Simple Summary Primary malignant bone tumors are infrequent cancers. More than 90% of these neoplasms are classified as osteosarcomas, Ewing sarcomas or chondrosarcomas, and their clinical presentation, diagnosis, and treatment principles are well-established. The entities described in this article, are ultra-rare varieties of bone sarcomas, and there clinical and histological characteristics are not well known. Therefore, they are very difficult to be diagnosed and there is a lot of uncertainty on their treatment. Because of their rarity, it is also extremely difficult to perform clinical research on these cancers. This article creates more awareness of these very rare bone tumors. It explains how to recognize and diagnose each entity and it summarizes the medical scientific literature that is available on these cancers. Increasing awareness and clinical research for these cancers are key elements to improve the prognosis for patients with these diseases in the long term. Abstract Rare primary malignant bone sarcomas (RPMBS), other than osteosarcoma, chondrosarcoma, chordoma, and Ewing sarcoma, account for about 5–10% of primary bone tumors and represent a major diagnostic challenge. These tumors include spindle cell and round cell sarcoma entities, hemangiopericytoma-like and vascular tumors. Additionally, several histotypes, traditionally described in the soft tissues, such as myxofibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor of bone, have been reported in patients with primary bone tumors. While wide surgical resection is the mainstay of local treatment, systemic therapy of these rare entities is controversial. Patients with undifferentiated spindle cell or pleomorphic high-grade tumors of bone, are usually treated with osteosarcoma-like chemotherapy, while patients with round cell and undifferentiated round cell tumors (URCTs), may respond to sarcoma treatment regimens for Ewing sarcoma patients. Studies on analogies and differences among these ultra-rare tumors have seldom been reported. This review describes relevance, clinical aspects, diagnostic procedures, staging, treatment recommendations, and current research in this composite tumor group.