Angiosarcoma, also known as malignant hemangioendothelioma, is a rare and aggressive malignant vascular tumour arising from endothelial cells, which accounts for approximately 10% of soft tissue sarcomas in the head and neck. Between October 1996 and July 2008, 10 patients were diagnosed with angiosarcomas (AS) in the head and neck region, 8 of whom were included in this study (there were 7 high-grade and 1 low-grade lesions). AS were characteristically positive for vascular markers such as CD31, CD34, and factor VIII. CD31 was thought to be the most sensitive and specific marker for AS and was positive in 6 patients. Six patients were treated surgically with or without postoperative radiotherapy and/or chemotherapy. Two patients had large and extensive lesions that were considered to be inoperable, they were given palliative chemotherapy and/or radiotherapy. Of the 8 patients reviewed in this study, 5 died of local recurrence or distant metastasis with a survival time of 8–19 months, 2 patients are alive with disease and 1 patient is free of disease. The predeliction for local recurrence and distant metastasis and the high-grade characteristics of this tumour seemed to be correlated to the poor prognosis, although the small number of patients prevented statistical analysis.
Angiosarcomas (AS), also known as malignant hemangioendotheliomas, are malignant vascular tumours arising from vascular endothelial cells, which comprise 2% of soft tissue sarcomas. The most common site of involvement is the head and neck region, accounting for 52% of cases . AS predominantly occur in the elderly, the median age is 60–71 years and they have a predilection for males. AS display remarkable clinical heterogeneities and present as extremely aggressive lesions with the propensity for local recurrence and distant dissemination, leading to poor prognosis. The 5-year survival rate for AS in the head and neck region is 10–35% . Extensive surgery and postoperative wide-field radiation are considered the optimal therapy, but the effects of chemotherapy are uncertain.
The aim of this study is to determine the biological behaviour of AS in the head and neck region, and describe the morphologic and immunohistochemical features, based on a review of 8 consecutive patients treated in the authors’ department.
Materials and methods
Between October 1996 and July 2008, 10 patients were diagnosed as AS in the head and neck region at the Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine. All the pathological diagnoses were reconfirmed by the department of oral pathology at the authors’ institution. Two patients refused further treatment and were excluded from this study. The other 8 patients were treated and followed-up regularly. Clinical information was obtained from the patients’ charts regarding their sex, age, site, size, tumour features, duration of symptoms, medical history, local recurrence, metastasis, treatment, microscopic findings and immunohistochemical markers.
Hematoxylin–eosin (H–E) stained slides were reviewed. Immunohistochemical staining was also reviewed and the reaction to endothelial cell markers, such as CD31, CD34, factor VIII, and the epithelioid marker, cytokeratin, were recorded ( Table 1 ).
|No.||Age/sex||Primary site||Size (cm)||Metastasis||Recurrence||Treatment||CD31||CD34||Factor γ||Cytokeratin|
|2||81/F||Soft palate||5–10||None||Yes||S + RT||(+)||NA||NA||(+)|
|3||29/M||Nasal cavity and sinuses||5–10||Yes||Yes||RT + CT||NA||NA||NA||NA|
|4||76/M||Face||>10||Yes||Yes||S + RT + CT||(+)||(+)||(−)||(−)|
|5||55/F||Tongue base and pharynx||5–10||Yes||Yes||S + CT||(+)||(+)||(+)||(−)|
|6||80/F||Scalp||>10||None||Yes||S + RT||(+)||(−)||(+)||(−)|
There were 3 males and 5 females, aged 29–81 years (average 57.5 years). Six patients were treated with surgery, 4 of them with positive surgical margins were subsequently treated by radiotherapy and/or chemotherapy. The other 2 patients, with advanced inoperable lesions, were treated with chemotherapy and/or radiotherapy. Of the 6 patients who underwent surgery, there were 5 recurrences and 2 metastases. At the last follow up, 5 patients had died (survival times 8–19 months), 2 patients were alive with disease, and 1 patient with low-grade AS was alive and disease free.
The primary sites of the lesions included scalp and face in 4 patients, parapharyngeal region in 3 ( Fig. 1 ) and nasal sinuses in 1. The lesions were larger than 10 cm in 3 patients, 5–10 cm in 3, and less than 5 cm in 2 patients. The primary symptoms varied, 3 patients developed exudative erythematous and purpuric lesions with or without ulceration in the skin, 4 patients with deep lesions presented with symptoms of hemorrhage, edema and ulceration, 6 patients had symptomatic pain and 1 patient presented with a single subcutaneous asymptomatic nodule on the cheek.
Early diagnosis of AS was difficult and mainly depended on clinical examination, imaging and pathologic findings. The image features of AS were nonspecific although they helped to define the extent of lesions ( Fig. 2 ) and distant metastases to other organs. The exact diagnosis could only be established by microscopic manifestations and immunophenotypes.
Microscopically, the tumour margins can be well demarcated or infiltrative, but cutaneous AS often infiltrated extensively through the dermis, with microscopic involvement extending well beyond the clinically apparent boundaries. Sometimes the characteristically disseminated intralesional hemorrhage was distinct.
The histopathologic features were diverse and mainly included three patterns: irregular vascular channels; sheets of cells; and cells of undifferentiated morphology. Most lesions were made up of large, rounded epithelioid cells arranged in sheets, small nests, cords or irregular vascular channels dissecting through the dermis. The vascular channels communicated with each other, resulting in an anastomosing network that can form varied patterns. Vascular anastomosing channels were lined by atypical endothelium, which could be a single layer or several layers thick ( Fig. 3 A and B ). The morphocytology of tumour cells varied from epithelioid to pleomorphic spindled cells with the former predominating. In some cases, mitotic activity and subtle vascular lumen formation could be observed. Sometimes vacuolated tumour cells were seen in epithelioid areas of AS ( Fig. 3 C). In addition, low-grade lesions could be seen composed of irregular vascular channels lined by flattened endothelial cells, which may retain the functional and morphologic properties of normal vascular endothelium.