Peggy McGuire* was out working in her yard, doing some light pruning, when a tree branch struck her left upper eyelid. The run-in left her with a bruise. A month later, the 70-year-old visited her ophthalmologist. At that time, the area of ecchymosis appeared to be resolving. Her visual acuity was 20/20 in her right eye and 20/25 in her left; exophthalmometry was normal (16 millimeters and 15 mm, with a base of 95 mm); and the slit-lamp and dilated fundus examinations were normal. Her history included breast cancer, hypercholesterolemia and hypertension, and she was taking tamoxifen (Nolvadex), simvastatin (Zocor) and losartan (Cozaar), respectively, for these conditions.
Three months after the initial injury, Mrs. McGuire returned to her ophthalmologist. The bruised area was larger; it now involved both the upper and lower eyelids of the left eye. In addition, she complained of a burning sensation in her temporal eyelid.
The ophthalmologist ordered a complete blood count and prothrombin time (PT) and partial thromboplastin time (PTT) tests; the results were within normal limits. A month later, she returned for a follow-up visit. Even though she had been off aspirin in the interim, there was no improvement in the ecchymosis. She was then referred to an oculoplastic surgeon.
Caption: The bruise extended onto the nose and lower lid (Fig. 1). Microscopic
|Fig. 1||Fig. 2|
examination revealed vascular channels lined in many areas by multiple
layers of atypical endothelial cells with mitotic figures (Fig. 2).Initial Considerations
The initial evaluation of recurrent ecchymosis should include investigation of the patient’s hematologic indices. If these are unremarkable, then malignancies and vasculitis should be considered.
In this case, the normal PT indicated normal function of the extrinsic coagulation pathway, effectively ruling out deficiencies of factor VII. Similarly, the normal PTT value indicated normal function of the intrinsic coagulation factors (factors VIII, IX, XI and XII). The bleeding time was not measured; however, Mrs. McGuire’s blood counts and chemistry panels were normal. (A prolonged bleeding time would be indicative of an acquired platelet dysfunction secondary to myeloproliferative disorders, dysproteinemia, uremia or medication side effects.)
One esoteric possibility to be considered would be amyloidosis. Patients with systemic amyloidosis may have waxy ecchymotic eyelid papules in association with vitreous veils and opacities as well as pupillary abnormalities. Another consideration for the ophthalmologist when evaluating periorbital ecchymosis in the geriatric population is recurrent trauma secondary to abuse. What Turned Up
On examination, the oculoplastic surgeon found the area of ecchymosis to extend onto the nose and lower lid (Fig. 1), along with a 1 centimeter x 1 cm fluctuant area in the temporal portion of the upper eyelid. This area was felt to represent an enlarged vascular space.
The surgeon performed an excisional biopsy of the lesion. At the time of biopsy, he found the lesion to be predominantly vascular and remarked that the dermis overlying the vascular lesion simply “peeled off like tissue paper.”
The differential diagnosis of vascular lesions includes hemangioma, venous malformation, hemangiopericytoma, sarcoma, mesothelioma, Kaposi’s sarcoma and intravascular papillary endothelial hyperplasia.
On microscopic examination, the lesion was characterized by a proliferation of arborizing, dissecting vascular channels lined in many areas by multiple layers of atypical endothelial cells with mitotic figures (Fig. 2). Due to the malignant potential of this proliferation, the slides were sent to Brigham and Women’s Hospital in Boston for an outside consultation. The pathologist there classified the lesion as a morphologically low-grade cutaneous angiosarcoma.Uncommon and Aggressive
Angiosarcomas are uncommon neoplasms, accounting for 1 percent of all soft tissue sarcomas. The cutaneous form occurs most commonly on the scalp or upper face of patients in their 70s and 80s. Because the tumor often presents after relatively minor trauma and because of its low incidence, it takes an average of 18 months to establish an accurate diagnosis, resulting in an unfavorable prognosis.
Cutaneous angiosarcoma usually arises from the small blood vessels of the skin or the lymphatic system, or both. Well-differentiated (low-grade) lesions are composed of a single layer of flat endothelial cells that form distinct, often irregular, anastomosing vascular channels. These vascular channels create their own tissue planes by dissecting through dermal collagen. In Mrs. McGuire’s case, this is why the dermis simply peeled off of the underlying lesion at the time of biopsy.
In poorly differentiated (high-grade) tumors, large pleomorphic cells form solid sheets and may resemble carcinoma. Holden et al. determined that the distinction between well-differentiated and poorly differentiated cutaneous angiosarcomas did not correlate reliably with outcome. Holden et al. analyzed patients with small tumors (< 5 cm diameter), medium-sized tumors (between 5 and 10 cm) and large tumors (> 10 cm) and demonstrated that only the tumor size has a substantial effect on survival rates.1
Cutaneous angiosarcoma is difficult to excise completely, because the tumor tends to infiltrate horizontally with multifocal lesions before metastasizing, most commonly to the cervical lymph nodes, lung and liver. Nearly all of the surgical margins on Mrs. McGuire were positive for angiosarcoma, despite a wide-field excision.Treatment and Survival
Due to the diffuse and multifocal nature of the tumor, standard treatment employs a combination of wide surgical excision and radiotherapy. High doses of radiation—from 3,000 to 7,000 centigrays, in daily fractions of 180 to 300 cGy—are recommended.2
Recently, small studies documenting clinical resolution of cutaneous angiosarcomas have been reported with liposomal doxorubicin (Adriamycin, Doxil) followed by radiotherapy3
and with paclitaxel as single-agent chemotherapy.4
Historically, the overall survival has been poor, with roughly half of patients dying within 15 months of presentation.1
In one study, the five-year survival rate was 8 percent for patients treated by surgery, 14 percent for those treated with radiotherapy and chemotherapy and 67 percent in patients treated with a combination of surgery, radiotherapy and chemotherapy.2
Even though Mrs. McGuire’s lesion was characterized as low grade, she underwent an orbital exenteration with wide local excision of the tumor. Three weeks after the exenteration, she began wide-field radiation therapy and both liposomal doxorubicin and paclitaxel.
In summary, cutaneous angiosarcoma of the face and scalp is an uncommon, aggressive neoplasm. Ecchymosis frequently presents after relatively minor trauma, resulting in a delayed diagnosis. Because early diagnosis and aggressive treatment are essential, the ophthalmologist should consider cutaneous angiosarcoma in the differential diagnosis of a persistent periorbital ecchymosis in an elderly patient.
2 Mark, R. J. Arch Otolaryngol Head Neck Surg
3 Wollina, U. et al. J Cancer Res Clin Oncol
4 Fata, F. et al. Cancer
______________________________Dr. Carolan is finishing his ophthalmology residency and Dr. Berris is clinical professor of ophthalmology; both are at the University of California, Davis.
_____________________________* Patient name is fictitious.