Ulcerated cutaneous epithelioid hemangioendothelioma

ARTICLE

Epithelioid hemangioendothelioma (EHE) is a rare soft tissue vascular tumor described first by Weiss and Enzinger in 1982, that is considered to have an intermediate malignancy between a hemangioma and an angiosarcoma [1]. Cutaneous isolated presentations are exceptional [2-7]. We report an atypical case of EHE confined to the skin, which presented clinically as a persistent ulceration.

Case report

A 52-year-old previously healthy woman presented with a six-month history of a painful small ulceration of her left ear. On physical examination, the ulceration involved the lower part of the concha (Fig. 1). The rest of the auricle was clinically unaffected. A punch biopsy was obtained from this ulcerating lesion and examination of hematoxylin-eosin-stained sections showed under an ulcerated epidermis a tumoral proliferation in a myxoid stroma composed of nests and cords of epithelioid cells diffusely occupying the dermis (Figs. 2 and 3). No large distinct vascular channels were seen. The tumor cells had intracytoplasmic lumina, compressing the nucleus peripherally. In some parts, erythrocytes were seen in the lumina (Fig. 4). Significant nuclear atypia such as nuclear hyperchromatism and poïkilocarynosis were seen but no mitotic figures were observed. Vascular immunohistochemical stainings showed positivity for CD31, CD34 (Fig. 5) and for factor VIII-related antigen. Immunohistochemical stainings showed a slight positivity for KL 1 and a negativity for S100 protein and EMA. X-rays and tomodensitometry of the skull were normal.

Conservative surgical excision with one centimeter margins all around the ulceration was undertaken but was not in sano. On histopathological examination, the tumor was ill defined; the cartilage was unaffected and no sinusoidal and interstitial growth pattern was seen on peripheral areas. Amputation of the right ear was decided and excision was at that time in sano. On clinical examination, there has been no recurrence or evidence of metastases at 1-year follow-up.

Discussion

EHE, first described in soft tissue by Weiss and Enzinger in 1982 as a borderline or low-grade malignant neoplasm is a rare vascular tumor that is considered to be histologically and biologically intermediate between a hemangioma and an angiosarcoma [1]. EHE affects men and women about equally at almost any age but rarely in childhood. No predisposing factors have been yet identified. Usually it appears as a solitary, slightly painful soft-tissue tumor which can occur at almost any anatomical location but more frequently on extremities, trunk, head and neck. In parenchymal organs, the main locations are lung, liver and bone, where the tumor tends to be multifocal [2]. Sometimes, EHE involve several sites simultaneously [8]. In Enzinger and Weiss's original series of 41 patients, the tumor seemed to arise from a medium-sized or large vein in the majority of cases. Mentzel et al. suggest that the origin of EHE from a vessel and angiocentric growth is common but it is not a consistent diagnostic criterion [5]. In Mentzel's series of 30 patients, on histopathological examination, lesions of EHE with infiltrative margins seem to be more common than well circumscribed lesions [5]. Typically, the tumor is composed of nests, cords and short strands of epithelioid, round to slightly fusiform tumor cells with abundant eosinophilic cytoplasm and round nuclei in a myxoid or sclerotic stroma. In some areas, tumor cells form small intracellular lumina containing occasional erythrocytes and in others areas, mostly peri-pherally, they form large distinct vascular channels [9, 10]. In most cases, slight cellular pleomorphism and no mitotic activity is seen. In about 25% of cases, significant atypia, mitotic activity and necrosis is seen and the prognosis of this tumor seems to be correlate essentially with these histological features [5]. Endothelial differentiation of EHE is confirmed by vascular endothelial markers, such as CD31, CD34, ulex europaeus I-lectin, and Factor VIII-related-factors which are not all always positive either. Sometimes, the tumor may show positive staining for cytokeratin and alpha-smooth muscle actin [5]. The diagnosis of EHE is extremely difficult to affirm and some have dismissed the concept of borderline vascular neoplasms and consider EHE as a low-grade epithelioid angiosarcoma [11]. Nevertheless, epithelioid angiosarcoma display more nuclear atypia and mitotic activity, more necrosis than EHE and an interstitial or sinusoidal growth pattern in its peripheral areas.

In a review of the literature, cutaneous EHE appears to be limited to a few reports [5, 6]. Numerous EHE arising in the skin have developed in association with underlying bone tumor [12-16] but in 16 well documented cutaneous cases, this rare neoplasm is isolated [2-7] (Table I). Zelger et al. report an association of cutaneous EHE, epithelioid cell histiocytoma and Spitz nevus in a young lady over a period of 9 years, which raises the question of "an underlying epithelioid disease" [4].

In this series of 16 cases, the sex incidence is about equal and the average age is 47 years. All of these cases presented as dome-shaped nodules which are sometimes painful and can have a multifocal distribution [6]. The main locations are the extremities (25% on the palms), the head and the trunk.

Histologically, cutaneous EHE are quite similar to soft-tissue lesions. An unusual histopathological feature is that the majority of cases did not arise from a medium-sized or large vein [6].

Despite classification uncertainties of EHE in the spectrum of vascular tumors, it is clear that EHE has malignant potential and its prognosis remains uncertain. Nevertheless, the prognosis of isolated cutaneous EHE after simple complete surgical excision seems good compared with systemic EHE or with cutaneous EHE with underlying bone tumor [14]. Only 2 cases of local recurrence were observed in the literature [5, 7]. The specific interest of our case is the clinical presentation. Indeed, the spontaneous ulcerative character to our knowledge has never been reported.

REFERENCES

1. Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma. A vascular tumor often mistaken for a carcinoma. Cancer 1982; 50: 970-82.

2. Resnik KS, Kantor GR, Spielvogel RL, Ryan E. Cutaneous epithelioid hemangioendothelioma without systemic involvment. Am J Dermatopathol 1993; 15: 272-6.

3. Polk P, Webb JM. Isolated cutaneous epithelioid hemangioendothelioma. J Am Acad Dermatol 1997; 36: 1026-8.

4. Zelger BG, Wambacher B, Steiner H, Zelger B. Cutaneous epithelioid hemangioendothelioma, epithelioid cell histiocytoma and Spitz nevus. J Cutan Pathol 1997; 24: 641-7.

5. Mentzel T, Beham A, Calonje E, Katenkamp D, Fletcher CDM. Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases. Am J Surg Pathol 1997; 21: 363-74.

6. Quante M, Patel NK, Hill S, Merchant W, Courtauld E, Newman P, McKee PH. Epithelioid hemangioendothelioma presenting in the Skin. A clinicopathologic study of eight cases. Am J Dermatol 1998; 20: 541-6.

7. Fitzpatrick JE, Golitz LE, Lowe L, LeBoit PE, White WL, Little WP. Self assessment-1993 (Case 4: Epithelioid hemangioendothelioma). J Cutan Pathol 1994; 21: 564.

8. Bollinger BK, Laskin WB, Knight CB. Epithelioid hemangioendothelioma with multiple site involvment. Literature review and observations. Cancer 1994; 73: 610-5.

9. Enzinger FM, Weiss SW. Hemangioendothelioma: vascular tumors of intermediate malignancy. In: Enzinger FM, Weiss SW, eds. Soft tissue tumors. 3Rd ed. St. Louis: CV Mosby; 1995: 627-40.

10. Requena L, Sangueza OP. Cutaneous vascular proliferations. Part III. Malignant neoplasms, other cutaneous neoplasms with significant vascular component, and disorders erroneously considered as vascular neoplasms.
J Am Acad Dermatol 1998; 38: 143-75.

11. Marrogi AJ, Hunt SJ, Santa Cruz DJ. Cutaneous epithelioid angiosarcoma. Am J Dermatopathol 1990; 12: 350-6.

12. Tyring S, Guest P, Lee P, Little W, Jaffe K, Pritchett R. Epithelioid hemangioendothelioma of the skin and femur. J Am Acad Dermatol 1989; 20: 362-6.

13. Vignon-Pennamen MD, Varroud-Vial C, Janssen F, Degott C, Verola O, Cottenot F. Métastases cutanées d'un hémangioendothéliome épithélioïde hépatique. Ann. Dermatol Venereol 1989; 116: 864-6.

14. Malane SL, Sau P, Benson PM. Epithelioid hemangioendothelioma associated with reflex sympathetic dystrophy. J Am Acad Dermatol 1992; 26: 325-8.

15. Ansaï S, Goto S, Aoki T, Hozumi Y, Aso K. A case of malignant hemangioendothelioma treated with recombinant interleukin-2. Clin Exp Dermatol 1993; 18: 470-5.

16. Roudier-Pujol C. Enjolras O, Lacronique J, Guillemette J, Herbreteau D, Leibowitch M, Escande JP. Hémangioendothéliome épithélioïde multifocal en rémission partielle sous traitement par interféron alpha2a. Ann Dermatol Venereol 1994; 121: 898-904.