Eyelid Angiosarcoma: A Case Report and Review of the Literature

Abstract

A 77-year-old woman presented with a 3-month history of a lesion on her left lower eyelid. External examination showed a tan-colored nodule with an overlying crust-covered ulcer on the left lower eyelid, nasally. The ulcer measured 12 mm × 7 mm. Complete surgical excision with a frozen section margin control was performed. Histopathological examination showed islands and sheets of spindle and epithelioid cells with little intervening stroma. The cells had copious amounts of either rounded or tapered eosinophilic cytoplasm with occasional intracytoplasmic lumina and large vesicular nuclei with prominent nucleoli. There was intense immunoreactivity for CD34, CD31, factor VIII, and Ki-67. The diagnosis was eyelid angiosarcoma. The patient refused any further therapy. At 1-year follow-up, there was no recurrence or development of metastasis. In conclusion, tan-colored eyelid nodules with overlying ulcer are usually a basal cell carcinoma; however, rarely it can be an eyelid angiosarcoma.

INTRODUCTION

Cutaneous soft-tissue sarcomas represent <1% of malignant cutaneous tumors. A review of 12, 114 cutaneous soft-tissue sarcomas showed that 2% of cases were cutaneous angiosarcomas. Cutaneous angiosarcoma mostly involves the head and neck region in 59% of cases, followed by the trunk in 25%, lower extremity in 9% and upper extremity in 5%.¹ The majority of cutaneous angiosarcoma cases were Caucasian and male.¹ The incidence of angiosarcoma increased exponentially with age from 0.1/1,000,000 person-years at the age of 45 years to 4/1,000,000 person-years at the age of 90 years.¹ Cutaneous angiosarcoma rarely involves periocular tissue. In a review of 269 patients with non-basal cell and non-squamous cell malignant eyelid tumors, Margo and Mulla² reported that none of the patients had angiosarcoma. We report a 77-year-old woman who presented with an eyelid mass, simulating basal cell carcinoma on clinical examination that proved to be angiosarcoma on histopathologic examination.

CASE REPORT

A 77-year-old otherwise healthy woman noted a lesion on the left lower eyelid about 3 months prior to presentation. The lesion grew and developed a central ulcer over the 3 months. The patient had no history of skin cancer.

External examination showed a tan-colored nodule with overlying crust-covered ulcer on the nasal aspect of the left lower eyelid, measuring 12 mm × 7 mm [Figure 1]. Complete surgical excision with a frozen section margin control was performed. Histopathologic examination showed vasoformative architecture with islands and sheets of spindle and epithelioid cells and little intervening stroma [Figure 2a]. The cells showed copious amounts of either rounded or tapered eosinophilic cytoplasm with occasional intracytoplasmic lumina and contained large vesicular nuclei with prominent nucleoli [Figure 2b]. The tumor cells showed intense positive immunoreactivity for CD34, CD31, Factor VIII, and Ki-67 [Figure 2c-f]. The mitotic count was 17/10 high-power fields. The tumor was diagnosed as eyelid angiosarcoma. The patient refused any further treatment including radiotherapy or chemotherapy. After 1 year follow-up, there has been no recurrence or development of metastasis.

Figure 1.

A tan-colored nodule with overlying crust-covered ulcer on the left lower eyelid nasally

Figure 2.

Histopathological examination showed islands/sheets of spindle and epithelioid cells with little stroma. The cells had copious amounts of rounded or tapered eosinophilic cytoplasm and large vesicular nuclei with prominent nucleoli. (b) Immunoreactivity was intense for CD31 (c), CD34 (d), Factor VIII (e) and Ki-67. (f) (A. H and E, original magnification ×10, B. H and E, original magnification ×100, C. Immunohistochemistry for CD31, CD34, factor VIII and Ki-67 original magnification ×25)

Comment

The presentation of cutaneous angiosarcoma can vary widely, mimicking various benign and malignant pathologies. A review of 47 cutaneous angiosarcoma cases revealed that rapidly expanding erythematous-to-violaceous mass was the most common presentation in half of the patients, followed by solitary blue-to-violaceous nodules suggestive of lymphoma (20%), keratotic flesh-toned papule consistent with squamous or basal cell carcinoma (20%), multicentric grouped nodules reminiscent of metastases (10%), and well-circumscribed vascular lesion such as pyogenic granuloma (5%).³ Similarly, eyelid angiosarcoma most commonly presented with erythematous nodule (38%), followed by erythematous-to-violaceous maculopapular lesion (25%), red-to-violaceous plaque or infiltrative lesion (13%), yellow plaque or infiltrative lesion (13%), and yellow nodule (13%) [Table 1]. Multifocal eyelid lesions or associated diffuse eyelid involvement in the form of eyelid swelling were seen in about half of the cases [Table 1]. The differential diagnosis of angiosarcoma includes capillary hemangioma, epithelioid hemangioma, Kaposi's sarcoma, epithelioid hemangioblastoma, hemangiopericytoma. Clinical history and examination findings are helpful in differential diagnosis, but the diagnosis of angiosarcoma is based on the histopathological evaluation.

Table 1.

Clinical Findings in 22 published cases with primary eyelid angiosarcoma

Histopathologically, angiosarcomas show vasoformative architecture, and range from well-differentiated to poorly-differentiated lesions.⁴ Abnormal; pleomorphic malignant endothelial cells are the hallmark of angiosarcoma. Low-grade, well-differentiated lesions are composed of vascular channels that grew in an infiltrative fashion and had plump endothelial cells with hyperchromic nuclei and infrequent mitoses.⁴ High-grade, poorly-differentiated lesions are densely cellular tumors with focal vascular channels. The neoplastic cells in high-grade, poorly-differentiated lesions range from spindle to epithelioid cells with large irregular nuclei with coarse chromatin and eosinophilic cytoplasm.⁴ By immunohistochemistry, tumor cells on angiosarcoma stain positive for factor VIII-related antigen, and CD31, markers for endothelial lineage of neoplasms, and CD 34, marker for hematopoietic cells, endothelial progenitor cells, and endothelial cells of blood vessels.

Surgical excision, followed by external beam radiotherapy (EBRT) has been the treatment of choice for angiosarcoma. Complete resection could be difficult because of invasive and often multifocal nature of angiosarcomas, tumor location, and its relation to other anatomical structures.⁴ Neoadjuvant chemotherapy and antiangiogenic molecules have been used in the treatment of cutaneous angiosarcoma.⁴ Lack of randomized trials and data based on few retrospective studies make it difficult to have specific management guidelines. In a review of 21 patients with cutaneous angiosarcoma of face with periorbital involvement, DeMartelaere et al.,⁵ reported that 71% of cases were treated with neoadjuvant chemotherapy and 29% underwent surgery followed by adjuvant chemotherapy or radiotherapy. Following neoadjuvant chemotherapy, 93% of the patients showed complete clinical response and 60% of them did not require surgical resection. However, 60% of them had recurrences. In the patients who underwent surgical excision followed by adjuvant therapy, 83% showed a complete clinical response, and 40% had recurrences. A review of eyelid angiosarcoma cases in the literature showed that 31% of the patients were treated with chemotherapy alone in 23% of the patients, excisional biopsy followed by EBRT or plaque radiotherapy in 18%, excisional biopsy alone in 23%, excisional biopsy followed by EBRT and chemotherapy in 9%, excisional biopsy followed by chemotherapy in 9%, EBRT alone in 9% and observation in 5% [Table 1]. Cutaneous angiosarcoma has a poor prognosis with 40% to 50% of the 5-year local regional control rate, and 20% to 40% of 5-year distant metastasis-free survival rate.⁶ On their review of the literature, Papalas et al.⁷ reported that patients with isolated, nodular eyelid involvement had a survival rate of 100% at a mean follow-up of 3 years although the patients with diffuse disease had a survival rate of 57% at a mean follow-up of 3 years. This is contrary to the poorly-differentiated histopathologic features and bad systemic prognosis in angiosarcomas of face and scalp with isolated, nodular tumors. A review of eyelid angiosarcoma cases in the literature showed 45% of cases were alive without recurrence after a mean follow-up of 45 months, 23% of cases died of systemic metastasis after a mean follow-up of 28 months, and 14% of cases died of natural causes [Table 1]. The better prognosis of eyelid angiosarcomas could be related to the finding that more of the eyelid angiosarcomas being isolated, nodular tumors rather than facial angiosarcomas (51% in eyelid angiosarcomas vs. 30% in facial angiosarcomas). Careful long-term follow-up is necessary considering the high recurrence and low local control rates at 5-years follow-up.