Angiosarcoma of the proximal humerus: a case report and review of the literature
© Yamashita et al.; licensee BioMed Central Ltd. 2012
Received: 26 July 2012
Accepted: 12 September 2012
Published: 10 October 2012
Angiosarcoma of bone is an uncommon primary bone neoplasm that is composed of tumor cells that show endothelial differentiation. This is an aggressive malignancy characterized by frequent local recurrence and distant metastases. The majority of patients die within one year of diagnosis, and this shows that angiosarcoma of bone is an aggressive high-grade tumor.
We present the case of a 65-year-old Japanese woman who had primary angiosarcoma of the proximal humerus with a pathological fracture. An open biopsy confirmed a diagnosis of primary angiosarcoma of bone. Our patient was treated with neoadjuvant chemotherapy and wide resection. One month after surgery, she developed multifocal distant metastasis to her liver and spleen.
Angiosarcoma of the humerus is extremely rare. Radiographically, there is no specific finding associated with angiosarcoma of bone as opposed to other malignant bone tumors. The cornerstone of treatment is en bloc resection followed by as much adjuvant radiation therapy as possible. However, the role of chemotherapy remains undefined, and better systemic agents are clearly needed.
KeywordsAngiosarcoma Proximal humerus Chemotherapy Surgery
Malignant vascular tumors of bone are very rare and account for less than 1% of primary malignant bone tumors. Angiosarcoma is an uncommon neoplasm characterized by rapidly proliferating and extensively infiltrating anaplastic cells derived from vessels and lining irregular blood-filled spaces. Skeletal angiosarcoma generally affects young adults and elderly individuals, and age distribution shows a wide range with a nearly equal distribution from the second to the eighth decade of life. Angiosarcomas tend to affect long tubular bones of the extremities and the axial skeleton, mainly the spine. The bones of the lower limb, particularly the femur and the tibia, are most commonly involved, followed by the pelvis, vertebral column, and the bones of the upper limbs[3, 4]. We describe an extremely rare case of a woman with angiosarcoma of the humerus who underwent chemotherapy and wide resection.
Our patient was treated with three cycles of pre-operative chemotherapy composed of mesna, doxorubicin, ifosfamide, and dacarbazine, which is the MAID protocol. During the three cycles of pre-operative chemotherapy, the size of the mass did not change, but her spontaneous pain decreased.
Reported cases of angiosarcoma of the humerus
Hasegawa et al.
A multilocular osteolytic lesion with undefined margins and destroyed cortical and medullary bone
Amputation of the arm at the level of the scapula
Fukuroku et al.
Severe bone destruction of diaphysis of humerus by tumor invasion
Voggenreiter et al.
Expansile lytic lesion involving the entire diaphysis of the humerus with a fracture in the distal portion of the lesion
Disarticulation of the shoulder
Mittal et al.
Erosion of medial cortex with lytic areas at upper end of humerus
Wide resection and adjuvant chemotherapy
Radiographically, there is no specific finding associated with angiosarcoma of bone as opposed to other malignant bone tumors. Lesions are usually highly destructive and may grow too fast to invoke a periosteal reaction. They may be eccentric and may have a purely lytic or mixed lytic sclerotic pattern. More aggressive features include osseous expansion, cortical permeation, and an associated soft tissue mass. CT and magnetic resonance imaging characteristics of angiosarcoma may also be non-specific. In general, pathological fractures of high-grade primary bone sarcomas occur either spontaneously or after minimal trauma. The incidence of pathological fracture at diagnosis in patients with angiosarcoma of bone is unknown.
Pathologically, these tumors may contain either hemangiomatous or lymphangiomatous cellular elements, which are often difficult or impossible to distinguish histologically, particularly with higher degrees of anaplasia. Identification of vascular channels allows diagnosis; thus, the term angiosarcoma is preferable to hemangiosarcoma or lymphangiosarcoma for these malignant vascular neoplasms. Verbeke et al. recently reported that primary angiosarcoma of bone exhibiting more than three mitoses per 10 high-powered fields (HPFs), a prominent nucleolus, and fewer than five eosinophilic granulocytes per 10 HPFs has a more aggressive course and worse outcome, indicating that these histological criteria have prognostic value.
In angiosarcoma, local recurrence is frequent, prognosis is notoriously poor, and early metastases develop. Metastases to the lungs and other parenchymal organs are found in about 66% of cases. It is reported that the majority of patients die within one year of diagnosis, and this shows that angiosarcoma of bone is an aggressive high-grade tumor. In our case, one month after surgery, multiple distant metastases were observed, despite three cycles of pre-operative chemotherapy (MAID).
The treatment of angiosarcoma is often quite challenging. The cornerstone of treatment is en bloc resection followed by as much adjuvant radiation therapy as possible. Surgery combined with immediate post-operative radiation therapy could be an optimal treatment method, even if complete resection is possible. In our patient, adjuvant radiotherapy was not performed, because she refused.
The role of chemotherapy remains undefined. Several anticancer drug combinations, including cisplatin with doxorubicin, cisplatin plus paclitaxel, and cisplatin plus doxorubicin plus paclitaxel, have been investigated. Abraham et al. reported that doxorubicin-based chemotherapy regimens, which are commonly used for other sarcoma subtypes, have also been used for angiosarcomas. Patients were generally treated with doxorubicin-based regimens or vinorelbine, and 64% of patients had at least a partial response to at least one regimen. Given these data, a combination of mesna, doxorubicin, ifosfamide, and dacarbazine – that is, the MAID protocol – was administered to our patient before and after surgery. However, post-operative CT scans revealed distant metastases in her liver and spleen. Prolonged responses were uncommon, and better systemic agents are clearly needed.
Recently, a novel t (1; 14) (p21; q24) translocation was described in angiosarcoma of bone. To the best of our knowledge, this is the first cytogenic aberration reported in angiosarcoma of bone. However, small series have shown the involvement of tumor-suppressor genes such as p53 and p16, mainly in angiosarcoma of soft tissue, suggesting a possible role in tumorigenesis in a subset of angiosarcomas. It is still unclear whether primary angiosarcoma of bone is a true separate entity or is similar to primary angiosarcoma of deep soft tissues. Further molecular studies might be required in order to investigate the different therapeutic targets.
We present an extremely rare case of angiosarcoma of bone with a pathological fracture. Our case adds to the limited literature on angiosarcoma of the humerus. The cornerstone of treatment is en bloc resection followed by as much adjuvant radiation therapy as possible. However, the role of chemotherapy remains undefined, and better systemic agents are clearly needed.
Written informed consent was obtained from the patient for publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Mesna, doxorubicin, ifosfamide, and dacarbazine.
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