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Angiosarcoma of the eyelid is a rare potentially life threatening tumour arising from the vascular endothelium. Through the presentation of a case, the clinicopathological features and management of this condition are described.
A 69 year old white man presented with multifocal red-blue maculopapular lesions located in his right cheek and eyelids (Fig 1A). The patient had first noticed the lesions 9 months previously. An incisional biopsy from the upper eyelid was performed. In subsequent staging investigations no metastases were found. The patient was otherwise in good health and was HIV negative. He underwent surgical resection of all clinically detectable lesions followed by adjuvant radiotherapy (total dose 45 Gy). After 34 months of follow up there was no evidence of local recurrence or distant metastases.
Histopathologically, the specimens consisted of skin and subcutaneous tissue. The lesions proved to be well differentiated angiosarcoma characterised by interlacing blood vessels lined by plump endothelial cells with hyperchromatic nuclei. Using Ki-67, the proliferation rate was assessed as 5%–7% (Fig 1B). Immunohistochemically, the tumour cells showed a positive reaction for vimentin, CD34 (human haemopoietic progenitor cell antigen) and FVIII-RA. They were consistently negative for S100 and HMB45 (results not shown).
Cutaneous angiosarcoma is a distinct subgroup of angiosarcomas most commonly seen in the skin and superficial soft tissues in patients over 55 years.1 The majority of these tumours arise in the head and neck area, particularly the scalp. They are aggressive and tend to recur locally and disseminate widely with a 5 year survival of approximately 12%–29%.1,2 To our knowledge, there are only seven well documented cases involving the eyelid.3–8 Clinically, the lesions in our patient resembled those previously reported in view of the purple coloured maculopapular lesions, suggesting a vascular origin.1,3–8 In 50% of cases the lesions are multifocal.1 Often the lesions are poorly defined and the true extent of disease may be difficult to determine clinically.1,2,5,7,8 The differential diagnosis includes ecchymoses, capillary haemangioma, melanoma, and Kaposi's sarcoma. Advanced lesions may ulcerate and atypical cases simulating, cellulitis, rosacea and xanthelasma have also been reported.3,5–8 Owing to lack of clinical awareness and the varied presentation, diagnosis is often delayed.1
Histologically, angiosarcomas display a spectrum from well to poorly differentiated varieties. The present case was consistent with a well differentiated angiosarcoma with characteristic interlacing channels lined by atypical endothelial cells and expression of immunohistochemical markers of vascular differentiation (CD34 and FVIII-RA).9 Often tumours display both vasoformative and undifferentiated areas.9 The present case was noteworthy, in that the entire tumour appeared to be well differentiated. The proliferation rate was low to moderate compared to the reported rate for angiosarcoma (>10% in 72% of cases assessed by Ki-67).10 Mitotic index has been observed as an independent histological prognostic marker for cutaneous angiosarcoma although other histological makers remain poorly defined.11 In the present case low proliferation index and well differentiated histological features may have contributed to a better outcome.
The most important clinical prognostic factor is lesion size, with tumours <5 cm in diameter having a better prognosis.11 This underlies the importance of early diagnosis and appropriate management. The mainstay of treatment for cutaneous angiosarcoma includes surgery and/or radiotherapy although, due to the rarity of this condition, there are no standard guidelines.2,12 As illustrated by our case, the primary lesions were contained within the anterior lamella of the lids and it was possible to surgically encompass the primary lesions avoiding exenteration and without compromising prognosis. In such cases, the surgical aim is to resect all clinically identifiable disease. In areas of doubt, microscopic control of surgical margins may have a role in guiding the extent of resection. Angiosarcomas usually respond to radiotherapy to some degree and most authors suggest that combined surgery and radiotherapy offers the best chance for long term control.2 In one series of 28 head and neck angiosarcomas, Mark et al12 have reported better survival after 32 months (median) with combined surgery and radiotherapy compared with surgery alone. In cases unsuited to surgery, radiotherapy alone may be considered, however usually only partial responses are achieved.2,12 The role of chemotherapy remains undefined.
In summary, cutaneous angiosarcoma should be included in the differential diagnosis of vascular or atypical eyelid lesions as early recognition is critical to optimise outcome. Classification of the mitotic index and degree of histopathological differentiation may be useful criteria in predicting the biological behaviour. Treatment needs to be individualised to the patient and in selected cases complete excision of clinically evident disease may be appropriate. Adjuvant radiotherapy is recommended due to the aggressive natural history of angiosarcoma.
The excellent technical assistance of Carmen Hofmann-Rummelt is acknowleged. The study was supported in part by the Alexander von Humboldt Foundation, Bonn, Germany (RMC), The Deutsche Forschungsgemeinschaft, Bonn, Germany (TH), Allergan Australia in conjunction with The Royal Australian and New Zealand College of Ophthalmologists and Sydney Eye Hospital (RMC).