Angiosarcoma arising on rhinophyma

ARTICLE

Cutaneous angiosarcoma is a rare tumor with three main types: angiosarcoma of the face and scalp in the elderly (Wilson-Jones angiosarcoma); angiosarcoma secondary to chronic, persistent lymphedema; and angiosarcoma on areas treated previously with radiotherapy [1-3]. We report the interesting case of an elderly man with rhinophyma upon which an angiosarcoma developed, and discuss the possible pathogenetic role of the prior process and the diagnostic bases for this tumor.

Case report

An 82-year-old man was referred to our clinic having developed a tumor on the right nasal wing over the previous year. It was 2 cm in diameter, reddish, and had an edematous appearance with dilated pores (Fig. 1). The remainder of the distal extremity of the nose showed marked diffuse cutaneous enlargement. For years the patient had suffered repeated episodes of inflammation and supuration on the central part of the face, which had been treated with only partial improvement with several cycles of tetracycline, and his nose had gradually increased in size (Fig. 2).

Histological examination of the lesion showed the existence of marked sebaceous hyperplasia and abundant dilated lymph vessels in the upper dermis, with absence of appreciable inflammatory reaction (Fig. 3). Beside these was a dense proliferation of atypical cells with some solid areas and other angiomatous areas. The histopathological diagnosis was difficult due to the coexistence of fusiform and epithelioid cells, vascular channels, and extravasated erythrocytes (Fig. 4). Reticulin stain revealed fine layers surrounding the cells which, after immunohistological study, were positive for CD31, thus demonstrating their endothelial origin (Fig. 5). Other studies proved positive for vimentin and negative for actin, cytokeratins, CD68, and S-100. Ultrastructurally, there was a vascular pattern with vessels showing basal lamina, and cells with pinocytotic vesicles, filaments, cytoplasmic vacuoles, but no Weibel-Palade bodies can be seen (Fig. 6). No enlarged regional lymph nodes were noted and radiological studies ruled out the presence of extracutaneous illness.

The process was treated with radiotherapy. Three months later a 2 cm, painless, rolling nodular subcutaneous lesion was noted on the left mandibular branch. The patient initially refused both fine needle aspiration for cytological study and computerised tomography (CT), but two months later, when he presented to the Emergency Department with a painful, warm, erythematous mass in the same area, fine needle aspiration of the lymph node was positive for neoplastic cells, and CT was suggestive of necrotized adenopathy. The patient was again referred for radiotherapy, receiving selective radiation of the lymph node with a linear accelerator. At the present time, ten months later, the patient is asymptomatic.

Discussion

Although angiosarcoma on the head and neck of elderly people was first described by Caro and Stubenrauch in 1954 [4], it was Wilson Jones who defined in detail the clinical and histopathological features of this variant of cutaneous angiosarcoma in 1964 [5]. The tumor is slightly more common in men than in women and its clinical presentation is usually confusing, sometimes having a benign appearance resembling other cutaneous disorders, such as cellulitis or erysipelas, thereby making early diagnosis difficult [6, 7]. They appear more often on the central and upper parts of the face and the scalp, their size varying from just a few centimetres to more than 15 cm in diameter [8]. The lesions can be flat, raised, or nodular with a bluish, red or purple colour, and the larger lesions especially are sometimes accompanied by areas of ulceration, haemorrhage, or secondary infection, whereas the smaller, initial lesions are commonly asymptomatic [9]. Their local extension is often underestimated as they extend beyond what is clinically apparent, as well as the fact that they can also present multiple lesions, making it even more difficult to determine their extension [10]. This type of neoplasm grows gradually in a centrifugal pattern over a relatively short period of time, and in advanced cases can even involve a large part of the scalp, face, neck, and upper area of the trunk [11]. From the dermis, where it envelops and destroys the adnexal, neural, and vascular structures, it gradually infiltrates the soft tissues respecting the bone and the epidermis and spreading to the lymph vessels of the neck. It can metastasise to the liver, spleen, kidneys, bone, myocardium, but mainly the lungs [12]. Sudden onset thrombocytopenia has been reported in patients with angiosarcoma of the head and scalp, associated with rapid growth of the primary tumor and metastatic lesions. Although no anti-platelet antibodies or platelet associated IgG have been described, serum levels of beta-thromboglobulin and platelet factor 4 have been found to be raised [13], suggesting that the platelets are destroyed and consumed within the vascular bed of the tumor.

Histologically, there are very variable degrees of differentiation from one lesion to the next, and even within different areas of the same tumor [14, 15]. In well-differentiated lesions there are dilated, irregular vascular channels lined with flat endothelial cells which dissect the dermis, interconnecting to form a network. Some endothelial cells can be large, hyperchromatic, and pleomorphic, protruding into the vascular lumen and producing small, papillary formations. They present numerous erythrocytes, either in the vascular lumina or extravasated. Poorly differentiated angiosarcomas can appear as solid proliferations of polygonal or spindle-shaped endothelial cells with marked mitotic activity and poorly formed vascular spaces, with cytoplasmic vacuoles in the neoplastic cells and few, if any, erythrocytes in the vascular channels [16]. There is usually a patchy inflammatory infiltrate. Reticulin stain demonstrates vascular lumina not seen with usual stains.

As in our case, the diagnosis needs immunohistological and ultrastructural studies. The factor VIII related antigen [17, 18] and Ulex europaeus lectin type I can be positive for neoplastic cells, although an important percentage of these lesions are negative for both markers [19]. Thrombomodulin, a factor VIII related antigen antagonist, is positive in most angiosarcomas, although it is also positive in other non-vascular neoplasia [20]. CD34 antigen has been suggested by some in order to discriminate between malignant and benign tumors, since only benign lesions are positive [21], although it can also be detected in non-vascular sarcomas [22]. CD31, an antibody against adhesion molecules in the endothelium, seems to be a highly sensitive and specific marker for endothelial differentiation, although not all angiosarcomas express this membrane antigen [24]. In the well-differentiated areas, electron microscopic examination shows the basal lamina, intermediate connections, pinocytotic vesicles, cytoplasmic filaments, cytoplasmic vacuoles, and occasionally Weibel-Palade bodies [25]. Poorly differentiated tumors may present these characteristics only rudimentarily or not at all.

Differential diagnosis of these tumors should include benign vascular proliferations, Kaposi's sarcoma, from which it is distinguished by the more marked polymorphism of this latter lesion, malignant melanoma, and metastases from adenocarcinomas and high grade fibrosarcomas, in which cases the presence of cytoplasmic vacuoles within the neoplastic cells is of great diagnostic value.

With regards to prognosis, it should be remembered that angiosarcomas of the face and scalp are aggressive and proliferate easily, having a low survival rate and a five-year mortality higher than 70% [26]. They can disseminate locally, recur, or metastasise to the viscera via the lymph vessels or the blood stream, with pulmonary metastases being the most common and the leading cause of death in these patients [12], followed in frequency by metastases to the lymph nodes, soft tissue, bone, and liver. It is important to remember that a sudden onset of marked thrombocytopenia may suggest the rapid growth of the primary tumor or herald the development of metastatic disease. Prognosis bears no relation with sex, localisation, histological variety, or mitotic activity, although those lesions of less than 5 cm diameter and those with a prominent lymphocytic infiltrate seem to have a more favourable prognosis. Early diagnosis resulting from clinical suspicion and confirmed by biopsy is of great value. The case reported herein highlights the importance of the histological study of any erythematous enlargement of the skin on the nose, especially when it adopts tumorous characteristics.

Although not a recognised predisposing factor, we believe that the chronic lymphedema in the nose of our patient as a consequence of repeated inflammatory episodes of rosacea leading to the rhinophyma could have been relevant. However it is impossible to establish that with complete assurance. This tumor originates in the vessels, and although it is uncertain whether they are blood or lymph, the possibility exists of developing angiosarcomas on lymphedematous extremities [27, 28], after mastectomy and axillary lymph node resection [29], in congenital lymphedemas or those arising from other surgical or traumatic inflammatory mechanisms [30, 31].

The treatment of choice is wide, local surgical removal [32], although this is only possible in small tumors, combined with electron accelerator radiotherapy. High doses and wide fields are required, as the degree of microscopic invasion of the tumor always spreads beyond what is clinically apparent and recurrences at the periphery of the treated zone are common. Some authors have suggested the possibility of local control of the tumor margins by means of multiple peripheral biopsies or with Mohs' technique, but always followed by electron beam and radiotherapy [33]. These considerations make an early diagnosis all the more important in order to improve the poor survival rate of these patients.

Article accepted on 19/7/00

REFERENCES

1. Cadwell JB, Ryan MT Benson PM, James WD. Cutaneous angiosarcoma arising in the radiation site of a congenital hemangioma. J Am Acad Dermatol 1995; 33: 865-70.

2.. Goette EK, Detlefs RL. Postirradiation angiosarcoma. J Am Acad Dermatol 1985; 12: 922-6.

3. Sessions SC, Smenk RD. Cutaneous angiosarcoma of the breast after segmental mastectomy and radiation therapy. Arch Surg 1992; 127: 1362-3.

4. Caro MR, Stubenrauch CH Jr. Hemangioendothelioma of the skin. Arch Dermatol Syph 1945; 51: 295-304.

5. Wilson Jones E. Malignant angioendothelioma of the skin. Br J Dermatol 1964; 76: 21-39.

6. Diaz-Cascajo C, De La Vega M, Rey-Lopez A. Superinfected cutaneous angiosarcoma: a highly malignant neoplasm simulating an inflammatory process. J Cutan Patol 1997; 24: 56-60.

7. Hodgkinson DJ, Soule EH, Woods JE. Cutaneous angiosarcoma of the head and neck. Cancer 1979; 44: 1106-13.

8. Mark RJ, Sercarz J Fu YS, et al. Angiosarcoma of the head and neck. Arch Otolaryngol Head Neck Surg 1993; 119 : 973-8.

9. Sánchez-Pérez J, Fraga J, Aragües M, Garcia-Díez A. Angiosarcoma de cara y cuero cabelludo. Actas Dermosifiliogr 1989; 80: 299-303.

10. Villalva A, Chantres MT, Sánchez Yus E, Robledo A, Olmos L. Angiosarcoma de la cara y cuero cabelludo de Wilson Jones. Med Cutan Ibero Lat Am 1989; 17: 15-8.

11. Hierro S, Frias G, Erazo A. Tumor difuso de región frontal y cuero cabelludo: angiosarcoma clásico de Wilson Jones. Piel 1997; 12: 43-4.

12. Repiso B, Pérez-Gil A, Argueta O, Rios JJ, Sotillo I, Camacho F. Angiosarcoma de cara y cuero cabelludo. A propósito de un caso. Actas Dermosifiliogr 1999; 90: 104-8.

13. Satoh T, Takahashi Y, Yokozeki H, Katayama I, Nishioka K. Cutaneous angiosarcoma with thrombocytopenia. J Am Acad Dermatol 1999; 40 (5 Pt 2): 872-6.

14. Requena L, Sangüeza 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: 143-78.

15. Ackerman AB, Gou Y, Vitale P, Vossaert K. Clues to diagnosis in dermatopathology III. Chicago: ASCP Press. 1993: 357-60.

16. Bhutto AM, Uehara K, Takamiyagi A,Hagiwara K, Nonaka S. Cutaneous malignant hemangioendothelioma: clinical and histopathological observations of nine patients and a review of the literature. J Dermatol 1995; 22: 253-61.

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

18. Burgdorf WHC, Mukai K, Rosai J. Immunohistochemical identification of factor VIII related antigen in endothelial cells of cutaneous lesions of alleged vascular nature. Am J Clin Pathol 1981; 75: 167-71.

19. Swanson PE, Wick MR. Immunohistochemical evaluation of vascular neoplasms. Clin Dermatol 1991; 9: 243-53.

20. Yonezawa S, Marayuma I, Tanaka S, et al. Thrombomodulin as a marker for vascular tumors: comparative study with factor VIII and Ulex europeaus, lecitin. Am J Clin Pathol 1987; 88: 405-11.

21. Suster S, Wong TY. On the discriminatory value of anti-HPCA-1 (CD-34) in the differential diagnosis of benign and malignant cutaneous vascular proliferations. Am J Dermatopathol 1994; 16: 355-63.

22. Traweek ST, Kanalaft PL, Metha P, Battifora H. The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia. Am J Clin Pathol 1992; 96: 25-31.

23. DeYoung BR, Swanson PE, Argenyi ZB, et al. CD31 immunoreactivity in mesenchymal neoplasms of the skin and subcutis: report of 145 cases and review of putative immunohistologic markers of endothelial differentiation. J Cutan Patol 1995; 22: 215-22.

24. DeYoung BR, Wick MR, Fitzgibbon JF, et al. CD31: an immunospecific marker for endothelial differentiation in human neoplasms. Appl Immunohistochem 1993; 1: 97-103.

25. Mackay B, Ordoñez NG, Huang WL. Ultrastructural and immunocytochemical observations on angiosarcoma. Ultrastruct Pathol 1989; 13: 97-106.

26. Holden CA, Spittle MF, Wilson Jones E. Angiosarcoma of the face and scalp, prognosis and treatment. Cancer 1987; 59: 1046-57.

27. Herrmann JB. Lymphangiosarcoma of the clinically edematous extremity. Surg Gynecol Obset 1965; 121: 1107-15.

28. Capo V, Ozello L, Fenoglio CM, et al. Angiosarcomas arising in edematous extremities. Hum Pathol 1985; 16: 144-50.

29. Stewart FW, Treves N. Lymphangiosarcoma in postmastectomy lymphedema. Cancer 1984; 1: 64-81.

30. Chen KTK, Bauer V, Flam MS. Angiosarcoma in postsurgical lymphedema: an unusual occurrence in a man. Am J Dermatopathol 1991; 13: 488-92.

31. Alessi E, Sala F, Berti E. Angiosarcomas in lymphedematous limbs. Am J Dermatopathol 1986; 8: 371-8.

32. Morrison WH, Byers RM Garden AS, Evans HL, Kian Ang K, Peters LJ. Cutaneous angiosarcoma of the head and neck. A therapeutic dilemma. Cancer 1995; 76: 319-27.

33. Bullen R, Larson PO, Landeck AE, Nychay S, Snow SN, Hazen P, Kinsella T, Lamond J. 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.