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Angiosarcoma of the Heart: Case Report and Review of the Literature

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Angiosarcoma of the Heart: Case Report and Review of the Literature ANTICANCER RESEARCH 26: 4837-4842 (2006) Angiosarcoma of the Heart: Case Report and Review of the Literature S. BATZIOS1, A. MICHALOPOULOS1, L. KAKLAMANIS2, J. STATHOPOULOS1, M. CHRISTOPOULOU1, J. KOUTANTOS1 and G.P. STATHOPOULOS1 1First Oncology Clinic, Errikos Dunant Hospital, Athens; 2Pathology Department, Onassion Hospital, Athens, Greece Abstract. Background: Primary angiosarcoma of the heart is Case report an extremely rare malignant disease. Patients and Methods: A 32-year-old female with primary angiosarcoma of the heart at A 32-year-old woman was admitted to hospital because of a an advanced stage with lung and bone metastases is presented. 10-day fever, shortness of breath and pain in the left shoulder The tumor showed extensive expression of c-erb-B2 and a which radiated to the left arm. The ECG demonstrated sinus moderate expression of c-kit. Chemotherapy (cisplatin, tachycardia with a pulse rate of 140 bpm which was persistent epirubicin and ifosfamide) was administered. Herceptin as well and not related to the high fever. She was clinically as glivec were added to the above combination. Results: There immobilized and any effort increased breathlessness. A was a good partial response and the lung deposits almost transesophageal echocardiography was performed and disappeared. The duration of response was 6 months. showed a tumor 4.6x2 cm in the right ventricle. Computed Conclusion: This case of angiosarcoma of the heart is tomography (CT) of the chest showed multiple metastatic presented because of the extreme rarity of this disease, and its nodules in both lungs and an osteolytic lesion with a soft- responsiveness to chemotherapy in combination with imatinib tissue mass attached to it, at the right first rib. A biopsy of and herceptin. this mass was performed. The histopathology showed angiosarcoma (malignant epithelioid hemangioendo- Primary tumors of the heart are rare entities with an thelioma). At that time, CT of the abdomen and brain and a autopsy-defined incidence of 0.2% (1); one quarter of these bone scan were negative with respect to the spread of the are benign tumors. The most frequent malignant cardiac disease. tumors are sarcomas, with patients having a median survival Chemotherapy (epirubicin 75 mg/m2 on day 1, cisplatin of 6 months (2). Angiosarcoma of the heart constitutes 2% 80 mg/m2 on day 1 and ifosfamide 2 gr/m2 per day on days of primary cardiac neoplasms (including benign tumors) and 1, 2 and 3, plus uromitexan 800 mg x 2 on days 1, 2 and 3) it is the most common primary malignant cardiac tumor (3). was administered. A histological specimen was examined for More often it develops in the right ventricle, especially gene expression (particularly c-kit and c-erb-B2). Both were arising from the right atrium, and less often from the expressed, but c-erb-B2 in particular, was highly expressed. pericardium (4). These tumors may be asymptomatic over a Trastuzumab (herceptin) 150 mg once weekly and imatinib long period of time and when the symptoms appear, the (glivec 400 mg tablet) were added to the treatment. disease is already advanced. The main clinical signs are pulmonary hypertension, haemopericardium, cardiac Patient follow-up. Within a short period of time, (4-6 weeks) tamponade and pulmonary embolism (5). the patient showed clinical improvement which was The present study presents a case of primary cardiac confirmed by a CT scan of the chest in the 8th week after angiosarcoma and a review of the literature. the beginning of treatment. There was a good objective partial response and a highly improved clinical benefit (quality of life). The patient no longer required the administration of oxygen; the esophageal echogram, as well as the CT scan of the chest (both examined by experienced Correspondence to: G.P. Stathopoulos, MD, Semitelou 2A, 115 28 Athens, Greece. Tel: +30 210 7752600, Fax: +30 210 7251736, e- radiologists before treatment and one month and 6 months mail: [email protected] post treatment) showed a reduction in the size of the cardiac mass and the lung metastases had almost Key Words: Angiosarcoma, heart, c-hit, c-erb-B2, herceptin, glivec. disappeared. The duration of response was 6 months; this 0250-7005/2006 $2.00+.40 4837 ANTICANCER RESEARCH 26: 4837-4842 (2006) Figure 1. Trans-esophageal ultrasound. Mass of 4.6 x 2 cm attached to the right ventricle wall. was followed by a deterioration expressed by bone pain, The aetiology of angiosarcoma is unknown. Chronic dyspnea and central nervous system symptomatology. The lymphedema is the most common pathogenic preceding patient presented with hemiparesis, headache and blurred condition. Chronic lymphedema may appear after radiation vision. The bone scan revealed multiple bone metastases. therapy in mastectomized patients (Stewart-Treves Magnetic resonance tomography (MRI) showed multiple syndrome [STS], a rare, extremely malignant and rapidly- signs of brain metastases, mainly in the right parietal lobe. progressing tumor – angiosarcoma developing in CT of the chest showed a recurrence of metastatic disease lymphostasis of an arm after radical mastectomy for cancer) with numerous nodules in the lungs. Despite supportive (6) or after radical inguinal lymphadenectomy for metastatic treatment, within a few weeks the patient failed to recover melanoma (Kettles syndrome, a lymphoma-associated and died 7 months post diagnosis. angiosarcoma which occurs in the leg of patients as a Histological and radiological images are shown in consequence of radical inguinal lymphadenectomy for Figures 1-6. metastases from malignant melanoma) (2). Chronic idiopathic or traumatic lymphedemas have also been Review of the literature. Angiosarcoma is a rare, malignant pathogenetically related (5). Other aetiological factors are neoplasm characterized by the rapid proliferation of the radiation (post radiotherapy sarcoma), the existence of a undifferentiated malignant cells which originate from the foreign body, environmental carcinogens and pre-existing vascular endothelium. The tumor is characterized by the benign conditions such as chronic osteomyelitis in cases of configuration of vessel channels. This is an aggressive angiosarcoma of the bone (2). neoplasm with a tendency for local relapse and a high rate of Angiosarcoma is classified according to the TNM metastases. There are approximately 60 new cases per year in system. The pathological classification is graded as the United States and the annual incidence is approximately moderate or low differentiation. Locally advanced 2-3 per population of 100,0000 (4). The worldwide incidence is angiosarcoma is stage IIB. The histological diagnosis of also low. This neoplasm can occur in any organ of the body angiosarcoma is often difficult and immunohistochemical but it more frequently occurs on the skin and soft tissues (5). examination for several cellular markers is often needed to 4838 Batzios et al: Angiosarcoma of the Heart Figure 2. Immunohistochemistry showing positive expression of CD34 indicating the angiogenic origin of the neoplasm. Figure 3. Histological specimen showing the extensive expression of the c-erbB2 gene. Figure 4. Histological specimen showing moderate expression of c-kit (CD117). 4839 ANTICANCER RESEARCH 26: 4837-4842 (2006) Figure 5. CT scan of the lungs showing the response of the disease a) before treatment and b) after treatment. Figure 6. MRI of the brain showing metastatic lesions. 4840 Batzios et al: Angiosarcoma of the Heart confirm the diagnosis. The detection of CD34 determines administered (15). Taxanes have also rendered satisfactory the endothelial origin of the malignant cells (7). results (17). The possibility of adding molecular Angiosarcoma belongs to the category of sarcomas with therapeutic factors (monoclonal antibodies) depends on no specific genetic alterations but several karyotype the expression or not of oncogenes in the malignant cells. detachments and the addition of chromosomal material In the past few years, emphasis has also been placed on have been described as well in osteosarcomas, malignant the important expression of vascular endothelial growth fibrous histiocytomas, non-myxoid liposarcoma and factor as a tumor marker in the serum of sarcoma patients leiomyosarcoma (7). The molecular pathogenesis of these (18). The successful administration of anti-angiogenetic genetic lesions seems to be related to pathways of factors (bevacizumab) in other tumors indicates that there deactivation of the oncosuppressive gene p53, via the may be possible therapeutic benefit in sarcomas as well molecular expression of retinoblastoma oncogenes (7). The (19). In the case of our patient presented here, the expression of MDM2 and CDK4 constitutes a frequent expression of c-erb-B2 was impressively high, while c-kit finding in the majority of soft-tissue sarcomas (6). The expression was moderate. The expression of c-kit in absence of specific mutations and the usually poor angiosarcomas appears increased and related to the stem expression of certain oncogenes, on the one hand, limit the cell factor (20). The simultaneous administration of possibility of molecular classification and, on the other herceptin and imatinib (glivec) with chemotherapy might hand, the hope of therapeutic intervention using targeting have assisted clinical improvement and tumor reduction therapy with monoclonal antibodies (8). However, a in our patient (21). frequent expression of the oncogenes EGFR and c-erb-B2 Primary angiosarcoma of the heart is a very rare and has been detected in
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