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Pulmonary Tumor Embolism as a Presenting Feature of Cavoatrial Hepatocellular Carcinoma
Pulmonary Tumor Embolism as a Presenting Feature of Cavoatrial Hepatocellular Carcinoma* Kevin Wilson, MD; Jeffrey Guardino, MD; and Oz M. Shapira, MD, FCCP
Pulmonary tumor embolism as a presenting feature of hepatocellular carcinoma is rare. It has been reported only once previously. In that case, other signs and symptoms of liver disease were present. We report the case of a patient with cavoatrial hepatocellular carcinoma presenting with isolated pulmonary tumor embolism, without any clinical or laboratory evidence of liver disease. Hepatocellular carcinoma should be included in the differential diagnosis as a rare cause of pulmonary tumor embolism. (CHEST 2001; 119:657– 658) Key words: carcinoma, hepatocellular; embolism; liver neoplasms; pulmonary embolism; vena cava, inferior Abbreviation: IVC ⫽ inferior vena cava
presenting features of hepatocellular carciF requent noma include abdominal pain, a right-upper-quadrant
mass, weight loss, ascites, and abnormal liver function tests. Winterbauer et al1 described the only case reported in the literature of hepatocellular carcinoma presenting with pulmonary tumor embolism. In that case, there were other symptoms and laboratory findings that were suggestive of associated liver disease. We report a case of a patient with hepatocellular carcinoma presenting with pulmonary tumor emboli. In contrast to the prior case, there was no evidence of acute or chronic abdominal pathology on presentation.
Figure 1. Echocardiogram showing a 6-cm solid mass (arrows) within the intrahepatic IVC at the junction with the right atrium.
Several weeks later, he was readmitted with recurrent dyspnea. A repeat ventilation-perfusion scan showed multiple new abnormalities consistent with new pulmonary emboli. The international normalized ratio was within therapeutic range. Hematologic workup for a hypercoagulable state was normal. During this admission, he developed ascites. Contrast-enhanced CT of the abdomen demonstrated an IVC mass extending into the hepatic veins. A discrete liver mass was not seen. Angiography of the IVC confirmed the presence of a 6-cm mass extending from the level of the hepatic veins to the right atrium, with evidence of partial obstruction resulting in retrograde filling of a lumbar vein (Fig 2). Cardiac catheterization showed moderately reduced left ventricular ejection fraction, pulmonary hypertension (pulmonary artery
Case Report A 65-year-old man presented with recurrent episodes of dyspnea. He denied orthopnea, hemoptysis, cough, peripheral edema, or chest pain. His medical history was significant for coronary artery disease with recent non-Q-wave myocardial infarction and obesity. There was no history of hepatitis or alcohol intake. Admission physical examination was unremarkable. A plain chest radiograph was clear, and the laboratory profile was within normal limits. Two-dimensional Doppler echocardiogram revealed moderate to severe biventricular dysfunction and a 6-cm echogenic mass in the intrahepatic inferior vena cava (IVC) extending into the right atrium (Fig 1). A ventilation-perfusion lung scan revealed multiple unmatched perfusion defects, consistent with pulmonary embolism. The mass was assumed to be an organized thrombus, the patient was treated with heparin, followed by warfarin, and discharged home. *From the Department of Medicine, Division of Pulmonary and Critical Care Medicine (Dr. Wilson), Division of Cardiology (Dr. Guardino), and the Department of Cardiothoracic Surgery (Dr. Shapira), Boston University School of Medicine, Boston, MA. Manuscript received April 7, 2000; revision accepted July 6, 2000. Correspondence to: Oz M. Shapira, MD, FCCP, Department of Cardiothoracic Surgery, Boston Medical Center, 88 East Newton St, Boston, MA 02118; e-mail: [email protected]
Figure 2. Angiography of the IVC confirming the presence of a mass extending from the level of the hepatic veins (arrowheads) to the right atrium with evidence of partial obstruction resulting in retrograde filling of a lumbar vein (arrow). CHEST / 119 / 2 / FEBRUARY, 2001
657
pressure of 56/30 mm Hg), and coronary angiography revealed a 70% left anterior descending coronary artery stenosis. The patient underwent coronary artery bypass grafting using the left internal mammary artery to the left anterior descending coronary artery. Using deep hypothermia and circulatory arrest, the right atrium and the distal end of the IVC were explored. A 6-cm red-brown mass covered by a thin layer of fibrin was found that was almost totally occluding the IVC. After excising the IVC mass, extension of this tumor to the right hepatic vein was noted. The hepatic venous component could only be partially excised. Histologic examination (Fig 3) revealed hepatocellular carcinoma. The patient recovered uneventfully.
Discussion This case is the second reported case of tumor emboli as a presenting feature of hepatocellular carcinoma and the only reported case in which pulmonary embolism was the sole presentation without any of the typical manifestations of hepatocellular carcinoma. Hepatocellular carcinoma typically presents with some combination of abdominal pain, right-upper-quadrant mass, weight loss, or ascites. More than 70% of patients have cirrhosis, and ⬎ 80% have abnormal alkaline phosphatase, 5⬘-nucleotidase, or serum glutamic oxaloacetic transaminase (SGOT). None of these were observed in the patient described. Pulmonary manifestations of hepatocellular carcinoma vary. The most common manifestation is the appearance of “cannonball” metastases. Less common forms of pulmonary involvement include diffuse interstitial infiltration, a solitary pulmonary nodule mimicking bronchogenic carcinoma, and pleural effusion.2 Pulmonary embolization in patients with hepatocellular carcinoma may result from either tumor embolization or thromboembolization. Tumor embolization can range from small, asymptomatic microemboli detected only at autopsy to massive saddle emboli complicated by cardiovascular collapse and death. Microscopic tumor emboli are characterized by perfusion abnormalities on ventilationperfusion scan despite a normal pulmonary arteriogram.3 The association between venous thromboembolism and a subsequent diagnosis of cancer has been known for over
Figure 3. Histology of the IVC mass showing hepatocellular carcinoma adherent to the wall of the IVC. 658
a century. Sorensen et al4 confirmed this and showed that there were strong associations with certain types of cancer—in particular, cancer of the pancreas, ovary, liver, and brain. In light of the demonstrable association between venous thromboembolism and primary hepatic cancer, it is surprising that only one case of hepatocellular carcinoma presenting as pulmonary thromboembolism has previously been reported. This may be due to the low prevalence of hepatic cancer in the western world or because the diagnosis of malignancy is typically established prior to the thromboembolic event. We believe that in this case the pulmonary emboli were tumor emboli rather than thromboemboli, for several reasons. The IVC mass enlarged, and the patient had recurrent embolic events despite therapeutic anticoagulation. The tumor was covered with only a very fine fibrin layer, with the cephalad end being free of thrombus. There was no evidence of deep vein thrombosis on lower-extremity and pelvic venous ultrasound. Finally, the tumor mass at the cavoatrial junction almost completely occluded the IVC, preventing embolization from peripheral sources. The only clue to the presence of hepatocellular carcinoma in this case was the IVC mass. The differential diagnosis of an IVC mass includes an organized thrombus and primary or secondary tumors such as renal cell carcinoma. However, other rare tumors, such as hemangiosarcoma and IV leiomyomatosis, have also been described.5,6 In our case, findings of a contrast-enhanced CT scan specifically aimed at these diagnoses were negative. The surgical approach to IVC masses is difficult. Deep hypothermia and circulatory arrest have been increasingly used to afford optimal exposure and to allow complete resection of the mass.7 In summary, hepatocellular carcinoma should be included in the differential diagnosis of pulmonary tumor embolism, even in the absence of clinical or laboratory data suggestive of abdominal pathology. The diagnosis should be strongly considered in any patient with an IVC mass.
References 1 Winterbauer RH, Elfebein IB, Ball WC. Incidence and clinical significance of tumor embolization to the lungs. Am J Med 1968; 45:271–290 2 DeVita VT, Trujillo NP, Blackman AH, et al. Pulmonary manifestations of primary hepatic carcinoma. Am J Med Sci 1965; 250:428 – 436 3 Schriner RW, Ryu JH, Edwards WD. Microscopic tumor embolism causing subacute cor pulmonale. Mayo Clin Proc 1991; 66:143–148 4 Sorensen HT, Mellemkjaer L, Steffensen FH, et al. The risk of diagnosis of cancer after deep vein thrombosis or pulmonary embolism. N Engl J Med 1998; 338:1169 –1173 5 Raaf HN, Raaf JH. Sarcomas related to the heart and vasculature. Semin Surg Oncol 1994; 10:374 –382 6 Bertrand P, Amabile P, Hardwigger J, et al. Intravenous leiomyomatosis with caval involvement: report of a case with radical resection and venous replacement. Arch Surg 1998; 133:460 – 462 7 Donatelli F, Pocar M, Triggiani M, et al. Surgery of cavo-atrial renal cell carcinoma employing circulatory arrest: immediate and mid-term results. Cardiovasc Surg 1998; 6:166 –170 Selected Reports
Pulmonary tumor embolism as a presenting feature of hepatocellular carcinoma is rare. It has been reported only once previously. In that case, other signs and symptoms of liver disease were present. We report the case of a patient with cavoatrial hepatocellular carcinoma presenting with isolated pulmonary tumor embolism, without any clinical or laboratory evidence of liver disease. Hepatocellular carcinoma should be included in the differential diagnosis as a rare cause of pulmonary tumor embolism. (CHEST 2001; 119:657– 658) Key words: carcinoma, hepatocellular; embolism; liver neoplasms; pulmonary embolism; vena cava, inferior Abbreviation: IVC ⫽ inferior vena cava
presenting features of hepatocellular carciF requent noma include abdominal pain, a right-upper-quadrant
mass, weight loss, ascites, and abnormal liver function tests. Winterbauer et al1 described the only case reported in the literature of hepatocellular carcinoma presenting with pulmonary tumor embolism. In that case, there were other symptoms and laboratory findings that were suggestive of associated liver disease. We report a case of a patient with hepatocellular carcinoma presenting with pulmonary tumor emboli. In contrast to the prior case, there was no evidence of acute or chronic abdominal pathology on presentation.
Figure 1. Echocardiogram showing a 6-cm solid mass (arrows) within the intrahepatic IVC at the junction with the right atrium.
Several weeks later, he was readmitted with recurrent dyspnea. A repeat ventilation-perfusion scan showed multiple new abnormalities consistent with new pulmonary emboli. The international normalized ratio was within therapeutic range. Hematologic workup for a hypercoagulable state was normal. During this admission, he developed ascites. Contrast-enhanced CT of the abdomen demonstrated an IVC mass extending into the hepatic veins. A discrete liver mass was not seen. Angiography of the IVC confirmed the presence of a 6-cm mass extending from the level of the hepatic veins to the right atrium, with evidence of partial obstruction resulting in retrograde filling of a lumbar vein (Fig 2). Cardiac catheterization showed moderately reduced left ventricular ejection fraction, pulmonary hypertension (pulmonary artery
Case Report A 65-year-old man presented with recurrent episodes of dyspnea. He denied orthopnea, hemoptysis, cough, peripheral edema, or chest pain. His medical history was significant for coronary artery disease with recent non-Q-wave myocardial infarction and obesity. There was no history of hepatitis or alcohol intake. Admission physical examination was unremarkable. A plain chest radiograph was clear, and the laboratory profile was within normal limits. Two-dimensional Doppler echocardiogram revealed moderate to severe biventricular dysfunction and a 6-cm echogenic mass in the intrahepatic inferior vena cava (IVC) extending into the right atrium (Fig 1). A ventilation-perfusion lung scan revealed multiple unmatched perfusion defects, consistent with pulmonary embolism. The mass was assumed to be an organized thrombus, the patient was treated with heparin, followed by warfarin, and discharged home. *From the Department of Medicine, Division of Pulmonary and Critical Care Medicine (Dr. Wilson), Division of Cardiology (Dr. Guardino), and the Department of Cardiothoracic Surgery (Dr. Shapira), Boston University School of Medicine, Boston, MA. Manuscript received April 7, 2000; revision accepted July 6, 2000. Correspondence to: Oz M. Shapira, MD, FCCP, Department of Cardiothoracic Surgery, Boston Medical Center, 88 East Newton St, Boston, MA 02118; e-mail: [email protected]
Figure 2. Angiography of the IVC confirming the presence of a mass extending from the level of the hepatic veins (arrowheads) to the right atrium with evidence of partial obstruction resulting in retrograde filling of a lumbar vein (arrow). CHEST / 119 / 2 / FEBRUARY, 2001
657
pressure of 56/30 mm Hg), and coronary angiography revealed a 70% left anterior descending coronary artery stenosis. The patient underwent coronary artery bypass grafting using the left internal mammary artery to the left anterior descending coronary artery. Using deep hypothermia and circulatory arrest, the right atrium and the distal end of the IVC were explored. A 6-cm red-brown mass covered by a thin layer of fibrin was found that was almost totally occluding the IVC. After excising the IVC mass, extension of this tumor to the right hepatic vein was noted. The hepatic venous component could only be partially excised. Histologic examination (Fig 3) revealed hepatocellular carcinoma. The patient recovered uneventfully.
Discussion This case is the second reported case of tumor emboli as a presenting feature of hepatocellular carcinoma and the only reported case in which pulmonary embolism was the sole presentation without any of the typical manifestations of hepatocellular carcinoma. Hepatocellular carcinoma typically presents with some combination of abdominal pain, right-upper-quadrant mass, weight loss, or ascites. More than 70% of patients have cirrhosis, and ⬎ 80% have abnormal alkaline phosphatase, 5⬘-nucleotidase, or serum glutamic oxaloacetic transaminase (SGOT). None of these were observed in the patient described. Pulmonary manifestations of hepatocellular carcinoma vary. The most common manifestation is the appearance of “cannonball” metastases. Less common forms of pulmonary involvement include diffuse interstitial infiltration, a solitary pulmonary nodule mimicking bronchogenic carcinoma, and pleural effusion.2 Pulmonary embolization in patients with hepatocellular carcinoma may result from either tumor embolization or thromboembolization. Tumor embolization can range from small, asymptomatic microemboli detected only at autopsy to massive saddle emboli complicated by cardiovascular collapse and death. Microscopic tumor emboli are characterized by perfusion abnormalities on ventilationperfusion scan despite a normal pulmonary arteriogram.3 The association between venous thromboembolism and a subsequent diagnosis of cancer has been known for over
Figure 3. Histology of the IVC mass showing hepatocellular carcinoma adherent to the wall of the IVC. 658
a century. Sorensen et al4 confirmed this and showed that there were strong associations with certain types of cancer—in particular, cancer of the pancreas, ovary, liver, and brain. In light of the demonstrable association between venous thromboembolism and primary hepatic cancer, it is surprising that only one case of hepatocellular carcinoma presenting as pulmonary thromboembolism has previously been reported. This may be due to the low prevalence of hepatic cancer in the western world or because the diagnosis of malignancy is typically established prior to the thromboembolic event. We believe that in this case the pulmonary emboli were tumor emboli rather than thromboemboli, for several reasons. The IVC mass enlarged, and the patient had recurrent embolic events despite therapeutic anticoagulation. The tumor was covered with only a very fine fibrin layer, with the cephalad end being free of thrombus. There was no evidence of deep vein thrombosis on lower-extremity and pelvic venous ultrasound. Finally, the tumor mass at the cavoatrial junction almost completely occluded the IVC, preventing embolization from peripheral sources. The only clue to the presence of hepatocellular carcinoma in this case was the IVC mass. The differential diagnosis of an IVC mass includes an organized thrombus and primary or secondary tumors such as renal cell carcinoma. However, other rare tumors, such as hemangiosarcoma and IV leiomyomatosis, have also been described.5,6 In our case, findings of a contrast-enhanced CT scan specifically aimed at these diagnoses were negative. The surgical approach to IVC masses is difficult. Deep hypothermia and circulatory arrest have been increasingly used to afford optimal exposure and to allow complete resection of the mass.7 In summary, hepatocellular carcinoma should be included in the differential diagnosis of pulmonary tumor embolism, even in the absence of clinical or laboratory data suggestive of abdominal pathology. The diagnosis should be strongly considered in any patient with an IVC mass.
References 1 Winterbauer RH, Elfebein IB, Ball WC. Incidence and clinical significance of tumor embolization to the lungs. Am J Med 1968; 45:271–290 2 DeVita VT, Trujillo NP, Blackman AH, et al. Pulmonary manifestations of primary hepatic carcinoma. Am J Med Sci 1965; 250:428 – 436 3 Schriner RW, Ryu JH, Edwards WD. Microscopic tumor embolism causing subacute cor pulmonale. Mayo Clin Proc 1991; 66:143–148 4 Sorensen HT, Mellemkjaer L, Steffensen FH, et al. The risk of diagnosis of cancer after deep vein thrombosis or pulmonary embolism. N Engl J Med 1998; 338:1169 –1173 5 Raaf HN, Raaf JH. Sarcomas related to the heart and vasculature. Semin Surg Oncol 1994; 10:374 –382 6 Bertrand P, Amabile P, Hardwigger J, et al. Intravenous leiomyomatosis with caval involvement: report of a case with radical resection and venous replacement. Arch Surg 1998; 133:460 – 462 7 Donatelli F, Pocar M, Triggiani M, et al. Surgery of cavo-atrial renal cell carcinoma employing circulatory arrest: immediate and mid-term results. Cardiovasc Surg 1998; 6:166 –170 Selected Reports