Dermatology Online Journal

Papillary intralymphatic angioendothelioma of the thigh: A case report and review of the literature
Katherine A Ward BA, Phillip M Ecker MD, Rebekah R White CNP, Tanya E Melnik MD, Evin H Gulbahce MD, Mark S Wilke MD, Omar P Sangueza MD
Dermatology Online Journal 16 (4): 4

University of Minnesota

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Abstract

The term angiosarcoma, encompasses several neoplasms, all of which exhibit a malignant process derived from endothelial cells of the vessels. The most common form of angiosarcoma is highly aggressive, often fatal, and usually affects the head and neck region of elderly white men. Other low-grade forms of angiosarcoma, including papillary intralymphatic angioendothelioma, also known as Dabska tumor, are less invasive, affect a wider age range, and offer a better prognosis. There are several predisposing factors that increase the risk of angiosarcoma and include chronic lymphedema of the extremities, preexisting vascular lesions, and prior radiation, often as therapy for other malignancies. We report an unusual case of a very small, low-grade angiosarcoma on the thigh of an adult female with no known predisposing risk factors.

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Introduction

Angiosarcoma is a rare vascular-derived malignancy that accounts for approximately 1.6 percent of soft tissue sarcomas [1]. The classical presentation of angiosarcoma is an erythematous or bruise-like lesion of the skin [2, 3, 4]. The majority of angiosarcoma cases occurs in the elderly, with a median age of 75 years [5]. Men are 2 to 3 times more likely than women to present with angiosarcoma [3, 6, 7]. There are several predisposing factors that increase the risk of angiosarcoma and include chronic lymphedema of the extremities, preexisting vascular lesions, and prior radiation, often as therapy for other malignancies [6, 7, 8]. The vast majority of cutaneous angiosarcomas involve the head or neck [5, 6]. Fewer than 10 reported cases of angiosarcoma have arisen in the lower extremities in the absence of predisposing factors [6]. We report an unusual case of a very small, low-grade angiosarcoma, also known as papillary intralymphatic angioendothelioma, on the thigh of an adult female with no known predisposing risk factors.

Case report

In May 2009, a 58-year-old female presented with a 3-month history of a dark pink, papule on the left thigh. She had no history of skin cancer but past medical history revealed eczema. The remainder of her medical history was unremarkable.

Figure 1	Figure 2
Figure 1. Papillary intralymphatic angioendothelioma of the left anterior lateral thigh Figure 2A. Most of the dermis is involved with tumor (H&E, x4) Figure 2B. Capillary sized vessels with cuboidal endothelial cells (H&E, x40) Figure 2C. Other vessels had endothelial cell proliferation forming glomerulus-like structures (H&E, x40)

Figure 3
Figure 3. Immunohistochemical staining for CD-31 revealed positivity of the tumor cells (x20)

Physical examination revealed a 5 x 8 mm erythematous papule on the left anterior lateral thigh (Figure 1). The differential diagnosis for the lesion on the thigh at the time of visit included dermatofibroma, basal cell carcinoma, and inflamed nevus. The lesion was biopsied to confirm the diagnosis.

Dermatopathologic examination revealed an atypical vascular proliferation of the dermis composed of irregular vessels with slightly pleomorphic endothelial cells, prominent papillary projections into vascular spaces, and occasional mitotic figures (Figure 2). Immunohistochemical staining revealed positivity for CD-31 (Figure 3). The pathologic diagnosis was low-grade angiosarcoma, otherwise known as papillary intralymphatic angioendothelioma or Dabska tumor.

The patient was scheduled for immediate wide local excision of the angiosarcoma. An elliptical excision to fascia measuring 70 x 23 mm achieved negative margins. No inguinal lymphadenopathy was appreciated. The patient returned after 14 days for suture removal and revealed a well-healing wound. The patient was referred to an oncologist who obtained a CT scan of the lungs, which revealed several pulmonary nodules that were felt to be most likely unrelated to the angiosarcoma. No additional treatments were undertaken given the patient’s otherwise excellent health. A follow-up CT scan in October 2009 revealed unchanged nodules since June 2009. On the patient’s last follow-up visit in December 2009, the patient was doing well, with no evidence of recurrence of the lesion or metastasis. The patient was instructed to return for routine skin exams every 3 months for the next 3 years.

Discussion

The term angiosarcoma encompasses several neoplasms, all of which exhibit a malignant process derived from endothelial cells of the vessels [9, 10]. The spectrum of angiosarcoma is wide and has varying degrees of severity. The most common form of angiosarcoma is highly aggressive and occurs in the skin and superficial tissues of the elderly [5, 11]. Approximately 60 percent of angiosarcomas are of this cutaneous form and roughly 50 percent occur in the head and neck [4, 5, 6, 12]. These high-grade angiosarcomas exhibit significant endothelial cell atypia and a tendency for extensive extravascular expansion [12]. This invasive form of tumor is often fatal soon after diagnosis because of local recurrences and metastases, most often to the lung, followed by the lymph nodes [14]. Meis-Kindblom et al. reported 53 percent mortality at a median interval of 11 months [14]. The 5-year survival rate of cutaneous angiosarcoma is approximately 34 percent [5].

Other low-grade forms of angiosarcoma, such as Dabska tumor, more commonly known today as papillary intralymphatic angioendothelioma, present differently. Papillary intralymphatic angioendothelioma was first described in 1969 by Dabska et al. as malignant endovascular papillary angioendothelioma of the skin in childhood [15]. Since then, approximately 30 cases of papillary intralymphatic angioendothelioma have been reported in the literature, 12 of which were in adults [16]. It appears that papillary intralymphatic angioendothelioma may affect a wider age range than originally described. In a study of 12 cases, Fanburg-Smith et al. reported that the mean age of patients with papillary intralymphatic angioendothelioma was 30 years [13]. The age range for all reported cases is from birth to 83 years [16]. However, the finding of papillary intralymphatic angioendothelioma in an aged patient is still considered to be a rare event [17].

Papillary intralymphatic angioendothelioma is deemed by most sources to be a low-grade angiosarcoma that most often occurs in the skin and subcutis [16]. Unlike most high-grade angiosarcomas that typically occur in the head and neck regions, papillary intralymphatic angioendothelioma does not show a preference for a specific anatomic site. Reported cases of papillary intralymphatic angioendothelioma have arisen in the dermis or subcutis of the thigh, buttocks, abdomen, hand, heel, and tongue, as well as deeper locations including the testis, muscle, spleen, and bone [13, 18-23]. Cases of reported papillary intralymphatic angioendotheliomas have ranged in size from 1 to 40 cm [13]. The prognosis for patients diagnosed with the tumor has been shown to be fairly good. At long-term follow-up, Dabska et al. reported only one case of metastatic disease to the axillary lymph nodes out of the original six cases described in 1969 [15]. Fanburg-Smith et al. demonstrated no evidence of disease in the majority of the 12 cases in that study at follow-up [13]. As a result of the low metastatic potential, papillary intralymphatic angioendothelioma has been classified as a low-grade malignancy [15].

The diagnosis of papillary intralymphatic angioendothelioma should be reserved for low-grade angiosarcomas with characteristic features, including irregular vascular channels lined by endothelial cells with a “hobnail” appearance, papillary projections with a central hyaline core, and scarce mitotic figures [16, 24]. Immunohistochemical staining has been used to aid in diagnosing papillary intralymphatic angioendotheliomas and includes positivity for D2-40, CD-31, and VEGFR3 [16, 25, 26]. These markers are strongly expressed in normal lymphatic endothelium and point to a lymphatic origin of papillary intralymphatic angioendotheliomas [16, 25, 26].

Diagnosing angiosarcoma is often difficult and delayed as a result of the rarity of this type of malignancy and confounding histologic assessment [27]. The differential diagnosis for angiosarcoma often includes a wide spectrum of lesions depending on the degree of differentiation of the tumor. High-grade angiosarcomas must be differentiated from hemangiomas, Kaposi sarcomas, malignant melanomas, metastases, and vascular venous malformations [3]. The differential diagnosis for low-grade angiosarcomas includes papillary intralymphatic angioendothelioma, spindle cell, epithelioid, or retiform hemangioendothelioma, and Masson’s papillary intravascular endothelial cell hyperplasia [13]. There is no staging system for angiosarcoma [6].

Treatment of angiosarcoma differs greatly depending on the grade of the tumor. High-grade angiosarcomas present a systemic problem with high risk of metastases and are therefore often treated with wide local excision, followed by radiation or chemotherapy [3]. Low-grade angiosarcomas, like papillary intralymphatic angioendothelioma, have little morbidity after surgical excision and thus no additional treatment may be necessary [13]. However, the optimal treatment of angiosarcoma remains uncertain and further studies to investigate this are warranted.

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