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Journal of Clinical Oncology, Vol 25, No 23 (August 10), 2007: pp. 3547-3549 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.12.3562
Intracardiac Metastasis of Germ Cell Tumor Complicated by Pulmonary Hypertension and ThrombocytopeniaUniversity of California San Diego Moores Cancer Center, La Jolla, CA A 51-year-old man presented to the emergency department in October 2005 with progressive dyspnea and pleuritic chest pain of 5-day duration. Over the prior 3 to 4 weeks, he complained of increasing fatigue and night sweats. In addition, he experienced a 10-pound weight loss over 3 months. Physical examination was remarkable for cervical and axillary adenopathy and a holosystolic murmur. CBC demonstrated WBC 10,900/mL with a normal differential, hemoglobin 12.8 g/dL, and platelets 44,000/mL. Comprehensive chemistry panel, prothrombin time, partial thromboplastin time, and troponins were all within the normal range. ECG was also normal. A chest radiograph showed a small pleural effusion on the right and helical computed tomography (CT) demonstrated a saddle embolus in the main and right pulmonary arteries, and a thrombus in the right ventricle. Marked enlargement of lymph nodes in the retrotracheal, subcarinal, left cervical, supraclavicular and axillary areas was noted. Enoxaparin 1 mg/kg twice daily was initiated and the patient was admitted to the hospital. Additional work-up included a genital exam, which identified a varicocele on the left and normal testes. Further laboratory tests showed ß-human chorionic gonadotropin (ß-HCG) 39,600 mU/mL, lactate dehydrogenase 693 U/mL, and alfa-fetoprotein 8 ng/mL. Subsequent CT of the abdomen and pelvis identified a left retroperitoneal mass measuring 5.1 cm. An axillary node biopsy confirmed the diagnosis of a mixed germ cell tumor predominantly choriocarcinoma and embryonal carcinoma with focal areas of teratomatous differentiation (Fig 1). Two hypoechoic nodules in the right testicle and a varicocele on the left were identified on ultrasonography. The patient was thus diagnosed with high-risk, stage III nonseminomatous germ cell tumor (NSGCT) with pulmonary emboli.
To avoid pulmonary toxic agents, full-dose etoposide, ifosfamide, and cisplatin (VIP) was initiated. His platelet count declined to 11,000/mL on day 5 of cycle 1. The patient had no new complaints and his clinical examination was unchanged. Renal function was normal. There was no clinical evidence of bleeding and his hemoglobin was stable in the 9 to 10 g/dL range. Coagulation work-up included: PTT 36.6 seconds, PT 11.1 seconds, D-dimer 2,355 ng/mL, fibrinogen 200 mg/dL, and positive plasma protamine paracoagulation test. Peripheral smear (Fig 2) was remarkable for schistocytes and a low platelet count. He was considered to have chronic low-grade disseminated intravascular coagulation. Enoxaparin was held, and argatroban was started until a negative heparin platelet factor IV antibody assay ruled out heparin-induced thrombocytopenia 4 days later. Enoxaparin was then restarted. Supportive platelet transfusions were given to maintain a count more than 50,000/mL. His fibrinogen level was stable in the 200 to 300 mg/dL range without transfusions of plasma products. To further evaluate the holosystolic murmur and the right ventricular thrombus, an echocardiogram was performed and identified a large mobile mass fixed to the tricuspid valve and right atrium extending into the right ventricle and pulmonary arteries bilaterally. The pulmonary artery pressure was 41 mmHg.
By day 21 of cycle 1 of chemotherapy, his adenopathy had decreased and ß-HCG had declined. He continued on enoxaparin and a second cycle of VIP was administered. Weekly echocardiograms were performed in order to monitor the cardiac mass and pulmonary artery pressures. ß-HCG levels steadily declined to 65 mU/mL on day 14 of cycle 2. By day 19 of chemotherapy cycle 2, his pulmonary artery pressures had steadily increased from 41 mmHg to 73 mmHg without change in the size of right ventricular mass; raising the concern of ongoing tumor microemboli to the pulmonary vessels. He also continued to require twice per week platelet support. Elective resection of the intracardiac tumor was undertaken on day 21 of cycle 2. His platelet count was 69,000/mL after platelet transfusion and hemoglobin was 8.8 g/dL preoperatively. Enoxaparin was discontinued on the day before surgery. Under cardiopulmonary bypass the tumor was removed from the superior vena cava, right atrium, tricuspid valve, right ventricle, and an endarterectomy of both right and left pulmonary arteries was performed (Fig 3). Approximately 8 hours postoperatively, his platelet count rose to 168,000/mL and remained normal thereafter (Fig 4); hemoglobin remained stable at 12.0 g/dL after receiving two units of packed RBCs postoperatively. The operative specimen contained teratoma and fibrosis; no active tumor was identified. The patient was discharged on postoperative day 3 with complete resolution of his dyspnea, a platelet count of 270,000/mL, and hemoglobin 11.5 g/dL. He subsequently completed two additional cycles of VIP without complications and underwent surgical debulking of residual disease in the neck, axilla, chest, and abdomen. A right orchiectomy was also performed. Histology from all sites was consistent with the cardiac specimen, showing only teratoma and fibrosis. The patient was last seen in February 2007, 17 months from initial presentation to the emergency department, with a normal performance status and clinically free of disease.
Involvement of the inferior vena cava, superior vena cava, cardiac endothelium, and valvular surfaces by NSGCT is a rare occurrence. In an autopsy series of 78 patients with NSGCT, metastasis was identified intracardiac in 3.8% and involving the pericardium in 3.8%.1 A second autopsy series found no intracardiac metastasis in 154 patients, but identified pericardial involvement in 1.3%.2 Of 13 reported cases of metastatic NSGCT involving the right atrium, 11 of these cases had a caval provenance, suggesting that hematogenous spread via the inferior vena cava is likely the most common source of intracardiac metastasis.3-13 Consistent with this, one recent review suggested that involvement of the right atrium and ventricle (14 cases) is more common than involvement of the left atrium and ventricle (six cases).14 Of 25 reported cases of NSGCT involving the heart, 16 underwent surgical resection after chemotherapy 3-9,13,15-22 for removal of residual teratoma. Two underwent surgical resection because of arterial emboli15 or thrombocytopenia.19 To our knowledge, the patient described here represents the first case, in which progressive pulmonary hypertension secondary to tumor emboli and persistent thrombocytopenia prompted surgical resection of the intracardiac tumor. Inclusive of our case, three patients presented with hemolytic anemia and thrombocytopenia.3,19 One patient improved with effective chemotherapy and two patients underwent surgical resection for persistent anemia or thrombocytopenia. The proposed mechanism of hemolysis is similar to that caused by prosthetic heart valves.23,24 The destruction of RBCs occurs as the result of mechanical trauma by contacting a foreign material, or structural damages under high shear stress associated with turbulent blood flow. Activation and destruction of platelets under high shear stress is also well-documented in the literature.25 It has been demonstrated that shear stress can induce von Willebrand factor–mediated platelet aggregation by enhanced von Willebrand factor binding to GpIb/IX/V complex and GpIIb-IIIa.26,27 In our patient, although chronic disseminated intravascular coagulation caused by metastatic NSGCT may lower platelet counts, platelet aggregation, and consumption caused by high shear stress associated with turbulent blood flow in the area of tumor involved cardiac valves and blood vessels is likely the primary mechanism of the acute decline in his platelet counts. Consistent with the proposed mechanism, his blood counts improved within hours after removal of the tumor. In conclusion, the current case demonstrates the necessity for surgical excision of tumor thrombus associated with progressive pulmonary hypertension and persistent thrombocytopenia despite clinical response to chemotherapy. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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