ARTICLE
Angiosarcomas of the skin are rare tumours occurring spontaneously, in
areas of chronic lymphoedema or after radiotherapy. Spontaneous angiosarcomas
mostly occur in elderly people on the scalp and face [1]. Treatment of
this form is disappointing, especially in relapsing or metastasizing forms.
The good results obtained with immunotherapy in some vascular proliferative
diseases prompted us to administer recombinant human interferon alpha
treatment in two cases of metastasizing angiosarcoma of the scalp and
face.
Case report
Case 1
A 58-year-old man, without a past medical history, was referred to the
dermatology department for an extensive erythematous plaque of the left
fronto-temporal area of the scalp. Physical examination revealed a violaceous
plaque of 15 x 10 cm with a central necrotic area surrounded by a few
small nodules. The clinical examination was normal except for a left retromandibular
lymphadenopathy. Complete blood count, sedimentation rate and usual serum
biochemistry were in the normal range. Chest X-ray, computer tomography
of the thorax, abdomen and head, and bone scintigraphy results were normal.
A skin biopsy specimen showed anastomosing vascular channels in the
dermis, lined by atypical endothelial cells with foci of intraluminal
tufting and a proliferation of large polygonal cells with granular cytoplasm,
pleiomorphic nuclei and prominent eosinophilic nucleoli. The immunohistochemical
analysis showed positive reactivity with factor VIII-related-antigen and
negativity with HMB-45, S-100 protein and cytokeratin. Cutaneous angiosarcoma
was diagnosed on the basis of histological and immunohistochemical criteria.
Excision of the lymphadenopathy revealed angiosarcoma metastasis. As
the lesion was of large size and on the scalp, surgical resection was
not possible and the patient received radiotherapy on the tumor site of
the scalp (54 grays within 2 months) and on the adenopathy (46 grays within
1 month). The lesion remained unchanged and interferon alpha treatment
(18 million units intramuscularly daily) was started two months after
the end of the radiotherapy. The patient showed a rapid partial clinical
response after 1 month of treatment. Clinical tolerance was correct but
the dosage was reduced (9 million units daily) when the platelet count
dropped. One month later, the treatment was discontinued because the skin
lesions increased in size. The patient died 10 months after diagnosis.
Case 2
A 73-year-old man presented with an angiomatous nodule of the right
parieto-temporal region of the scalp. Clinical and paraclinical investigations
revealed no other tumoral localizations. Histological examination showed
a nodular proliferation in the dermis associating atypical fusiform cells
and vascular proliferation; walls were delineated by tufting endothelial
cells. Immunohistochemical analysis revealed positive staining with factor
VIII-related-antigen and vimentin and negative staining with cytokeratin,
EMA and alpha1-anti-chemotrypsin. Cutaneous angiosarcoma was diagnosed
and a large surgical excision was performed. A relapse occurred 1 year
later and the patient received radiotherapy (68 grays within 2 months)
leading to a decrease of the cutaneous lesion. Three months later, a new
relapse occurred with cutaneous (Fig.
1) and cervical node involvement. Interferon alpha therapy was
started at a dose of 9 million units three times weekly for 5 months.
The tolerance to the treatment was poor, leading to asthenia and moderate
weight loss and the tumor increased in size. Despite two treatments with
cyclophosphamide, vincristine, adriamycine and DTIC, and irradiation of
the cervical node, the patient died 30 months after diagnosis.
Discussion
Angiosarcoma of the scalp and face is a rare vascular tumor arising
in elderly people. Men are more frequently affected than women. The prognosis
is poor due to the rapid increase of the tumor and frequent plurifocal
cutaneous localizations. The evolution is characterized by lymph node
metastasis and visceral involvement, mainly in the lung, heart or bone
[1]. The overall survival as been estimated as 12% at 5 years in a large
series of 72 patients [2]. Half of the patients died 15 months after onset
of the disease. The main prognostic factor is the size of the tumor and
survival is enhanced if the lesion is less than 5 cm in diameter [3].
A combination of large surgical excision and electron beam therapy of
the scalp is proposed by some authors as the treatment of choice but this
point of view is supported only by very few cases [4]. Chemotherapy is
disappointing in cases of disseminated disease [3].
Immunotherapy could be promising. Indeed, interferon alpha is known
for its antiproliferative activity on endothelial cells [5]. It can also
inhibit the effects of vascular growth factors [6]. Moreover, in a few
clinical situations, immunotherapy has been used for the treatment of
vascular proliferation. Interferon alpha was proposed with success for
the treatment of life threatening haemangiomas in childhood [7]. Interferon
alpha also provides good results for the treatment of Kaposi's sarcoma
[8]. Other cytokines have been used for the treatment of malignant vascular
tumors: two cases of malignant haemangio-endothelioma have responded to
IL2 therapy [9-12]; intrapleural tumor infiltrating lymphocytes (TIL)
associated with intravenous IL2 was efficient in a case of metastatic
Stewart-Treves syndrome [13]. More recently, Spieth et al. [14]
reported stabilisation of a relapsing angiosarcoma of the head with a
treatment associating 13-cis-retinoic acid (0.5 mg/k/day) and interferon
alpha (6 x 106 UI, 3 times per week).
However, these good results are not constant. Interferon alpha is sometimes
inefficient in treating childhood haemangiomas [15], and failure of treatment
with this drug was reported in a case of radiation-induced angiosarcoma
[16]. To our knowledge, angiosarcomas of the scalp and face have never
been treated with interferon alpha only. Unfortunately, our two cases
do not confirm the good result obtained by Spieth et al. using
a combination of interferon and retinoids. Interferon alone appears inefficient
in angiosarcoma of the head and neck, as in radiation-induced angiosarcoma.
The poor result obtained with interferon alone could be explained by
the degree of differentiation or the rate of progression of the tumor.
Indeed, good results obtained with interferon mostly concern well differentiated
tumors or tumors with slow progression. In poorly differentiated or aggressive
tumors, interferon perhaps remains insufficient for an antiproliferative
effect. The better results obtained with the combination of interferon
and retinoids could be explained by the capability of retinoids to induce
the differentiation and the increase of interferon receptor expression
on the tumoral cells [17].
Article accepted on 27/1/00
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