Cutaneous angiosarcoma of the head and neck: a case presentation and review of the literature.

Abstract

Cutaneous angiosarcoma of the head and neck is a ram vascular neoplasm. When it does occur, it is most common in elderly white men. Early diagnosis and treatment are essential for local control of this aggressive tumor, but recognition can be delayed because of its rarity or because of difficulty in making a pathologic diagnosis. A combined-modality treatment approach is most often advocated. We report the case of a 77-year-old black man who presented with a 1-month history of two painless, violaceous, sub-centimeter nodules of the upper lip. After a diagnosis of low-grade angiosarcoma was definitively established, the lesions were locally excised with good cosmetic and functional results. The patient subsequently was found to have probable metastatic disease, but he declined further intervention. We review the literature on cutaneous angiosarcoma, and we discuss its epidemiology, presentation, tissue diagnosis, treatment, and prognosis in an effort to increase awareness of this rare malignancy.

Introduction

Angiosarcoma is a rare malignancy of the head and neck. It is usually seen in the elderly, and the prognosis is dismal. Diagnosis can be delayed as a result of the entity's rarity or confounding tissue histology. Early detection and treatment are essential to control this highly malignant soft-tissue cancer.

Case report

A77-year-old black man presented to another subspecialty clinic with a 1-month history of two painless, violaceous, subcentimeter nodules of the upper lip. Initial histologic findings suggested that these lesions were pyogenic granulomas. After a few months, similar nodules developed on the skin of the midface; they were biopsied and diagnosed as low-grade angiosarcomas. The initial pathologic specimens were reviewed and considered to be epithelioid hemangioendotheliomas. The patient was referred to our clinic for evaluation and management.

On clinical examination, the patient was generally fit and in no distress. Several nontender, violaceous, smooth, fleshy, nonblanching, pedunculated lesions measuring less than 1 cm each were scattered around the upper lip and nose (figure 1, A). No cervical lymphadenopathy was found. Findings on the remainder of his head and neck examination were unremarkable.

[FIGURE 1 OMITTED]

A metastatic workup was initiated. Results of the basic metabolic profile and liver function tests were within normal ranges. The complete blood count revealed normocytic anemia. A finding on chest plain film was suspicious for an ascending aortic aneurysm. Computed tomography of the chest and abdomen demonstrated a large, low-density left retroperitoneal mass with enhancing peripheral nodules and two similar masses in the right hepatic lobe. These lesions were radiologically consistent with metastasis of the angiosarcoma.

The patient refused further diagnostic procedures for the abdominal masses, but he did undergo local excision of the facial lesions. The postoperative cosmetic and functional results were good (figure 1, B).

Pathologic examination revealed an angiosarcoma of varied differentiation. The specimen was made up of pleomorphic spindle cells with an indistinct luminal formation (figure 2). These findings were in contrast with those of the patient's previous biopsy specimens, which lacked nuclear pleomorphism.

[FIGURE 2 OMITTED]

Discussion

Epidemiology/presentation. In the United States, soft-tissue sarcomas account for less than 1% of all malignancies; 5 to 15% of these tumors occur in the head and neck. (1) The most common soft-tissue sarcomas encountered in otolaryngology practice are rhabdomyosarcomas and malignant fibrous histiocytomas; angiosarcomas represent less than 0.1% of all head and neck malignancies? One-third to one-half of all cases of cutaneous angiosarcoma present in the head and neck. (2,3) The most common subsites are the scalp and upper face. (4-6) Angiosarcoma is seldom seen in the lower face. Large series reviews have demonstrated that angiosarcomas most often present in men in the seventh and eighth decades of life. (3,4,6-8) Among the studies in which race was reported, the overwhelming majority of patients were white. (4,7)

Although the cause of angiosarcoma is unknown, sun exposure has been proposed as a risk factor in light of the low incidence of this tumor in dark-skinned individuals. However, some authors discount sun exposure as a risk factor because affected patients have a low rate of skin carcinomas. (7) A history of trauma has also been associated with the diagnosis of angiosarcoma; in one series, (8) trauma was involved in 27% of cases, although this relationship may be spurious. (3,5) The most commonly demonstrable risk factor for head and neck angiosarcoma is a history of irradiation. (6,7,9) Risk factors for developing angiosarcoma in other anatomic subsites--such as exposure to vinyl chloride, pyothorax, and thorium oxide and the presence of lymphedema--have not been clearly implicated in head and neck lesions.

Delays in diagnosis are common and may be attributable to a lack of clinical awareness and difficulty in making a histologic assessment. (5,6) Angiosarcoma may also be difficult to diagnose because of its protean clinical nature. Case reports of unusual presentations have described presenting signs that resembled alopecia, rhinophyma, and rosacea. Other initial presentations of angiosarcoma may be an asymptomatic bruise-like lesion, violaceous nodules or plaques, chronic edema, cellulite, or skin ulceration; the latter was the most common presentation in one series. (7) Angiosarcoma may also present as multifocal disease, whether it is clinically obvious or not; Mark et al reported multifocal disease in 9 of 28 patients (32.1%). (6)

Cervical metastasis is generally uncommon at presentation. (6,7) In a series of 18 patients, Lydiatt et al found no case of distant metastasis at presentation, although one-third of these patients did eventually develop metastasis, most often to the lung. (7) In contrast, Naka et al reported that 7 patients in a series of 29 (24.1%) had a metastasis at the initial examination; all 29 patients eventually developed distant disease. (3) Naka et al stressed the difficult nature of identifying early pulmonary metastasis.

Pathology. Angiosarcoma is a difficult diagnosis to make, even for experienced pathologists, because of its rarity and complex histology. (3) Cutaneous angiosarcomas may be grouped on the basis of gross or histologic features. Grossly, a lesion may be nodular, ulcerative, or macular. (8,10) Histologically, tumors contain a proliferation of ramifying and anastomosing vascular channels that "dissect" through surrounding structures. Increased numbers of plump endothelial cells line the vascular channels; these cells may be spindled, epithelioid, or polygonal. Tumors are classified as low-grade or high-grade, depending on their cellularity, pleomorphism, and mitotic activity. Necrosis is a common finding. (10) Although no immunohistochemical stain is pathognomonic, the diagnosis may be aided by a finding of positivity for factor-VIII-related antigen, Ulex europaeus, laminin, CD31, and CD34, (3,10,11) although a finding of factor-VIII-related antigen positivity may not be reliable. (6) Electron microscopy will occasionally reveal rod-shaped, microtubulated Weibel-Palade bodies, (10) but again, this finding may not be particularly reliable, as only 1 of 13 specimens demonstrated this structure in one series. (11)

Treatment/prognosis. The optimal treatment has not been completely established. For advanced disease, radical excision has historically been advocated. Surgery alone or radiation with or without chemotherapy may yield similarly dismal results. Mark et al reported that only 2 of 19 patients (10.5%) who received a single-modality treatment were alive at the time of their review, and all 19 had a component of local failure. (6)

Surgical control is quite often poor because of the multifocality of angiosarcoma and the lack of clinical correlation with pathologic margins. In a small series, Bullen et al achieved good local control with Mohs' surgery and punch-biopsy tumor mapping followed by electron-beam radiation. (12)

The failure of radiotherapy can often be attributed to an underestimation of the peripheral extension of disease. Therefore, some authors advocate total scalp irradiation. (4,6) Surgeons at the M.D. Anderson Cancer Center in Houston reported using limited surgical resection followed by wide-field irradiation for focal disease, and they were able to treat patients with advanced disease who would have otherwise required radical excision plus radiation with or without chemotherapy. (4) Although their overall results were poor, they did see a statistically significant difference in 5-year locoregional control rates above the clavicles when gross tumor resection was possible prior to radiation therapy (40 vs. 24%). (4) Therefore, many authors advocate postoperative radiation therapy despite negative surgical margins. (4,6)

Definite advances in systemic therapy have been slow to develop. Because of the low incidence of cervical metastasis, elective treatment of the cervical lymph nodes is not recommended. (7) Paclitaxel as a single agent appears to be useful for scalp and facial angiosarcomas. (13) Sasaki et al recommended curative radiation therapy combined with recombinant interleukin-2 (rIL-2) immunotherapy for nodular lesions smaller than 5 cm, in part because high-dose rIL-2 administration may suppress the development of distant metastasis. (8) The current consensus is to use a combined-modality approach, including excision of disease with negative margins if possible with adjuvant radiotherapy with or without chemotherapy.

A clear correlation exists between the prognosis and the size or initial stage of an angiosarcoma. (2,5,6) The importance of early capture cannot be understated. Bleeding, pain, and lesion size greater than 5 cm are predictors of a poor outcome. (2,7) Lydiatt et al reported that all patients in their series whose initial tumor was surgically unresectable and/or larger than 10 cm died of disease. (7) The results of most series have indicated that neither the tumor's clinical pattern nor its grade is predictive of local recurrence or survival. (5,7) However, one study indicated that long-term survival might be positively correlated with gross nodular morphology, while an endophytic presentation was uniformly fatal within 2 years. (8) Recurrent disease also confers a dismal prognosis. (6,8)

References

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(2.) Maddox JC, Evans HL. Angiosarcoma of skin and soft tissue: A study of forty-four cases. Cancer 1981 ;48:1907-21.

(3.) Naka N, Ohsawa M, Tomita Y, et al. Angiosarcoma in Japan. A review of 99 cases. Cancer 1995;75:989-96.

(4.) Morrison WH, Byers RM, Garden AS, et al. Cutaneous angiosarcoma of the head and neck. A therapeutic dilemma. Cancer 1995;76: 319-27.

(5.) Holden CA. Spittle MF, Jones EW. Angiosarcoma of the face and scalp, prognosis and treatment. Cancer 1987;59:1046-57.

(6.) Mark RJ, Tran LM, Sercarz J, et al. Angiosarcoma of the head and neck. The UCLA experience 1955 through 1990. Arch Otolaryngol Head Neck Surg 1993; 119:973-8.

(7.) Lydiatt WM, Shaha AR, Shah JR Angiosarcoma of the head and neck. Am J Surg 1994;168:451-4.

(8.) Sasaki R, Soejima T, Kishi K, et al. Angiosarcoma treated with radiotherapy: Impact of tumor type and size on outcome. Int J Radiat Oncol Biol Phys 2002;52:1032-40.

(9.) Chen KT, Hoffman KD, Hendricks EJ. Angiosarcoma following therapeutic irradiation. Cancer 1979;44:2044-8.

(10.) Wenig BM. Atlas of Head and Neck Pathology. Philadelphia: W.B. Saunders; 1993:88-9.

(11.) Holden CA, Spaull J, Das AK, et al. The histogenesis of angiosarcoma of the face and scalp: An immunohistochemical and ultrastructural study. Histopathology 1987;11:37-51.

(12.) Bullen R. Larson PO, Landeck AE, et al. Angiosarcoma of the head and neck managed by a combination of multiple biopsies to determine tumor margin and radiation therapy. Report of three cases and review of the literature. Dermatol Surg 1998;24:1105-10.

(13.)Fata F, O'Reilly E, Ilson D, et al. Paclitaxel in the treatment of patients with angiosarcoma of the scalp or face. Cancer 1999;86:2034-7.

Jonathan Glickstein, MD; Merry E. Sebelik, MD; Qing Lu, MD

From the Department of Otolaryngology, University of Tennessee, Memphis, Health Science Center (Dr. Glickstein and Dr. Sebelik), and the Department of Pathology, Veterans Administration Hospital, Memphis (Dr. Lu).

Reprint requests: Jonathan Glickstein, MD, Department of Otolaryngology, Health Science Center, 956 Court Ave., Suite B226, Memphis, TN 38163. Phone: [phone]; fax: [phone]; e-mail: [e-mail]