The authors report a unique case in which an angiosarcoma arose from skeletal haemangiomatosis in a 72 year old man. This patient had a history of atomic bomb irradiation more than 50 years ago. Radiographically, the patient had multiple sclerotic foci of benign haemangiomas in the pelvis, the sacrum, and the left femur. The patient developed a high grade angiosarcoma in the left pubic bone. It is thought that atomic bomb irradiation played an important role in the development of the malignant lesion.
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Malignant transformation of benign haemangiomas is rare. We describe a patient with skeletal haemangiomatosis who developed a secondary angiosarcoma in the pelvis.
In March 1996, a 72 year old Japanese man presented with a five month history of left hip pain. This patient had been exposed to atomic bomb irradiation at Hiroshima near the end of the Second World War. His medical history included diabetes mellitus, liver cirrhosis, and colon polyps. The patient underwent colon polypectomy at 71 years of age. On admission, radiographs of the pelvis revealed multiple sclerotic foci in iliums, the sacrum, and left proximal femur, and an extensive osteolytic lesion in the left pubic bone (fig 1). Computed tomography showed multiple irregular osteosclerosis in the pelvis. A 99mtechnetiom scintigraphic scan showed increased uptake only in the left pubic bone. A systemic investigation failed to find other lesions. The patient subsequently underwent an open biopsy. Specimens obtained from the sclerotic area of the left ilium consisted of sclerotic bony trabeculi and cavernous haemangiomas (fig 2). Specimens obtained from the left pubic bone were composed of spindle pleomorphic cells with nuclear atypia and massive interstitial haemorrhage (fig 3). A pronounced vascular formation lined by the atypical cells was noted. Mitotic figures were common (7–8/10 high power fields). The cells were found to have positive immunoreactivity for factor VIII associated antigen (using a monoclonal antibody from Dako Japan, Kyoto, Japan). Based on the radiographic and histological findings, a diagnosis of angiosarcoma arising from benign haemangiomatosis was made. Despite intensive chemotherapy and 50 Gy of irradiation, the tumour continued to increase in size. The patient died of massive retroperitoneal bleeding in April 1997. Radiographic changes in multiple sclerotic areas concordant with haemangiomas were not seen until the patient's death.
Atomic bomb survivors are known to have a high risk of developing various malignant and benign tumours. A significant excess risk for cancers of the digestive system, breast, gastrointestinal tract, lung, skin, liver, ovary, urinary bladder, and other organs has been demonstrated.1 Sarcomas with a haematopoietic origin, such as leukaemia, lymphoma, and multiple myeloma are also frequently seen in atomic bomb survivors.2 Malignant bone tumours in these patients are less common.3 In addition, the incidence of non-cancer diseases such as liver cirrhosis and myocardial infarction is increased.4 Our patient had a medical history of liver cirrhosis and colon polyps.
Skeletal haemangiomatosis is recognised as a rare, congenital, or developmental disorder. It is defined as multiple haemangiomatous lesions that involve two or more non-contiguous osseous sites.5 Skeletal haemangiomatosis can be associated with cutaneous, soft tissue and/or visceral haemangiomas. The histological findings are identical to capillary and cavernous haemangiomas of other sites. Patients with systemic haemangiomatosis have high morbidity because of massive bleeding; however, the prognosis for patients with haemangiomatosis confined to the bone is more favourable.5 Some patients with skeletal haemangiomatosis develop local pain and deformity, but others are asymptomatic. Radiographs of skeletal haemangiomatosis show mixed osteolytic and osteoblastic to pure osteoblastic lesions in the axial and appendicular bones.5,6
Our patient had a benign haemangiomatosis confined to the bone. De novo angiosarcomatous transformation from skeletal haemangiomatosis is extremely unusual. To our knowledge, only one such case, reported by Wallis et al in 1964, has been published.6 They reported a 31 year old woman with diffuse skeletal haemangiomatosis who developed malignant lesions in the pelvis. In contrast, angiosarcomas arising from cutaneous haemangiomatosis in Maffucci and Kasabach-Merritt syndromes have occasionally been described in the literature.7,8
However, it should be remembered that there is a close association between irradiation and the occurrence of angiosarcoma. There have been some reports on secondary angiosarcomas developing from benign haemangiomas that had previously been treated by irradiation.9
Furthermore, several cutaneous angiosarcomas have occurred in patients who have been treated for malignant lesions with therapeutic irradiation. These most commonly occur in patients with uterine cervix and breast carcinomas. Secondary cutaneous angiosarcomas often arise on the skin in the anterior abdominal wall and mastectomy scars. They usually develop many years after initial radiotherapy. However, osseous angiosarcoma secondary to therapeutic irradiation has been described infrequently. The most common radiation induced sarcoma of bone is osteogenic sarcoma.10
The differential diagnosis of our present case includes epithelioid haemangioendothelioma of bone. This disease occurs in multiple osseous sites. Histologically, epithelioid haemangioendothelioma is characterised by the presence of epithelioid endothelial cells. Cytoplasmic vacuoles of various sizes are reported to be present in all cases. Signet ring cell-like structures also are identified in most epithelioid haemangioendotheliomas. These pathological findings were not found in our case.
Our patient developed a secondary angiosarcoma from a benign skeletal haemangiomatosis more than 50 years after being exposed to irradiation from the atomic bomb. Because of the patient's clinical history and the rarity of de novo malignant transformation of skeletal haemangiomatosis, we believe that the radiation played an important role in the development of the malignant lesion. A careful search of the literature revealed no similar reports.