Path. Res. Pract. 186, 296-299 (1990)
Teaching Cases
Primary Leiomyosarcoma of the Truncus Pulmonalis Report of a Case with Typical Features and Unusual Metastases A. Nerlich, w. Permanetter, B. LUdwig 1 and K. Remberger
Institute of Pathology, University of Munich, FRG, and Medizinische Klinik, Klinikum GroBhadern 1, Munich, FRG
SUMMARY
We present the fatal case of a patient with a primary leiomyosarcoma of the pulmonary trunk. During the patient's clinical course of 2 months, the pulmonary valve and the proximal segment of the truncus pulmonalis had to be removed surgically. At autopsy, we found an extensive local tumour recurrence with an almost complete obliteration of the right ventricular outflow. The right pulmonary artery was subtotally obliterated by a tumour thrombus, and the lungs and both adrenal glands showed extensive tumour metastases. A solitary tumour metastasis within the lumen of the right vena iliaca communis obviously was associated with diagnostic manipulations in the course of heart catheterization.
Introduction Primary neoplasms of the truncus pulmonalis or the pulmonary arteries are extremely rare. Wright et a1. 10 collected a series of 67 cases from the literature and added one case from their own files. All but 15 cases thereof had not been diagnosed before autopsy. In the recent literature other cases have been presented 1,2,4,7 with an increasing proportion of tumours being detected before death. We observed a case of primary leiomyosarcoma of the truncus pulmonalis, which was treated by resection of the proximal part of the pulmonary trunk, and implantation of a pulmonary valve bioprosthesis.
Case Report
Clinical History The 47 year old patient had a history of three months' duration of dyspnoea. Additionally he presented typical signs of progressive congestive heart failure, especially pulmonary edema with pleural effusion and enlargement of liver and spleen. There was no history of a previous 0344-0338/90/0186-0296$3.50/0
serious illness. Because of the progressive character of his complaints, he was admitted to hospital two months prior to his death. In two-dimensional echocardiography, a marked dilatation of the right ventricle along with a polypoid mass in the truncus pulmonalis, shortly distal and adjacent to the pulmonary valve, could be demonstrated. A chest radiograph demonstrated only signs of pulmonary congestion and pleural effusion, pulmonary infarction could not be detected. The heart was radiographically enlarged, the pulmonary out-flow tract was unremarkable. A heart catheterization, performed through the right common iliac vein, disclosed a large polypoid mass adjacent to the pulmonary valve. During the following surgical intervention the pulmonary valve was replaced by a bioprosthesis, and the proximal part of the truncus pulmonalis (2.5 cm in length) was resected and replaced by a prosthetic implant. The immediate post-operative course was uneventful. Echocardiographic and radiological re-examination of the patient four weeks later demonstrated new tumour masses in the right ventricle close to the implanted valve prosthesis. In the periphery of both lungs a total of 7 localized round, radiodense areas could be demonstrated, © 1990 by Gustav Fischer Verlag, Stuttgart
Primary Leiomyosarcoma of Truncus Pulmonalis . 297
which were presumed to represent tumour metastases. The patient developed progressive cardiac difficulties and died of cardiac failure.
Histological Findings (Fig. 1) Already during the surgical intervention, by frozen sections; the sarcomatous nature of the tumour could be confirmed. The tumour specimen, removed by the cardiac surgeon, microscopically consisted of interlacing bundles of cells with blunt-ended nuclei. Occasionally areas with marked hyperchromatic and bizarre nuclei were recognised; rarely a few giant cells could be found. The tumour cells in the interwoven bundles mostly had ovoid nuclei, which were sometimes arranged in a palisading pattern. There was a large number of atypical mitoses (more than 10 per high power field 40x) and the van Gieson stain showed that there was only sparse collagenous material between the elongated tumour cells. Parts of the tumour showed myxoid and occasionally fibrous degeneration. All the morphologic characteristics of the tumour could be summarized in the diagnosis of a leiomyosarcoma. Immunohistochemical staining was negative for S-100 protein, neuron specific enolase, alpha 1 anti-chymotrypsin, myoglobin and epithelial markers. There was only a positive reaction with an antibody against desmin filaments (Fig. 1b).
In the resected segment of the truncus pulmonalis, the whole diameter of the vessel wall was replaced by the tumour mass. Only focal areas showed intact residuals of the vessel. Forming polypoid masses, the tumour extremely narrowed the lumen and destroyed the pulmonary valve. The morphological appearance of the tumour in the surgical specimen was completely preserved in the metastases at autopsy.
Autopsy Findings Postmortem examination showed an extensive tumour infiltration of the whole base of the heart, forming a compact (12 x 10 x 10 em) tumour mass. Proximal vessel segments, including the ascending aorta and the truncus pulmonalis, which had been replaced in part by a dacron implant, were surrounded and infiltrated by the tumour. Similarly, the interatrial septum was thickened and filled with tumour masses. The anterior wall of the left cardiac ventricle was surrounded by a rigid tumour mass, extensively infiltrating the epicardial fat and protruding into the myocardium in a finger-like pattern. Most remarkable were the multiple small tumour nodules (up to 1 em in diameter) lying in the subendocardium of the right ventricular outflow, which was almost completely obliterated (Fig. 2). Small subendocardial tumour metastases were
Fig. 1a. Histological aspect of tumour tissue showing cells in an interwoven pattern of bundles with markedly hyperchromatic and often bizarre nuclei (H & E; Original magn. x 100, inset x 400). - b. Histological slide of the tumor with demonstration of desmin filaments by immunohistological staining (indirect immunoperoxidase method, monoclonal antibody against desmin from Boehringer Mannheim Biochemica, magn. X 200).
298 . A. Nerlich et al.
Fig. 2. Macroscopic feature of the right ventricular outflow at autopsy showing polypoid tumour masses (white arrow) with subtotal obliteration of the lumen of the valve prothesis (black arrow), which is in the pulmonary valve position.
Fig. 3. Small solitary tumour nodule (white arrow) within the lumen of the right V. iliaca communis.
Discussion seen adjacent to the suture material in the right ventricle. The right pulmonary artery was extensively infiltrated and the lumen was sub-totally obliterated by central tumour thrombus material adherent to the vessel wall (8 cm long). In both lungs multiple tumour metastases in central and peripheral areas could be found (up to 1 cm in diameter); histologically there was evidence for multiple small tumour emboli. The sternum was infiltrated by a continuous growth from the heart into the bone. In the pleural cavity of the right lung, two subpleural metastases (up to 2 cm in diameter) were noted. Lymph nodes of both pulmonary hili as well as paratracheal and para-aortal lymph nodes were free of tumour cells, although the connective tissue areas surrounding hilar lymph nodes showed extensive continuous tumour infiltration. Both adrenal glands showed metastases and were nearly completely destroyed by the tumour (4 X 6 cm). The most unusual finding was a solitary mass within the lumen of the right common iliac vein (1 x 1.5 cm in diameter), without any evidence for tumour infiltration in any other peripheral blood vessel (Fig. 3). A further autopsy finding was a small leiomyoma in the mucosa of the jejunum with no evidence of malignant transformation. In addition to hypertrophy of both cardiac ventricles (500 g), the myocardium showed, besides the continuous tumour infiltration, a moderate interstitial and perivascular fibrosis in the areas free of tumour. A remarkable sclerosis of coronary arteries could not be seen.
Primary malignant tumours of the pulmonary arteries are rare 3,5,7-9. In a recent report 67 cases have been collected lo . In a review of the available literature we were able to find four additional cases l ,2,4,7. All but 15 cases reviewed by Wright et al. IO had not been diagnosed before autopsy. The application of non-invasive diagnostic methods, such as sonography and computerized tomography, however, increases the number of cases which have been diagnosed during life. With progression in cardiac surgery, pathologists have to be aware of primary malignant tumours of the pulmonary vessels in biopsy material and intra-operative frozen sections. Primary sarcomas of the pulmonary arteries occur more often in females than in males (approx. 65% women)6. Most patients are in their sixth decade (maximum 50-55 years)3, although Wright et al. lo observed a patient of only 21 years of age. All the tumours reported in the literature were localized in the pulmonary trunk3 . The pulmonary valve was involved in 57%. All tumours had a polypoid appearance, with a more or less pronounced obliteration of the vessel lumen. There is a predominance of leiomyosarcomas; 50% of the tumours are classified as undifferentiated sarcomas. On critical review, however, about half of the latter cases may represent leiomyosarcomas6. The prognosis of patients with primary sarcoma of the pulmonary arteries is rather poor. In Bleisch's series3 only 6 patients out of 60 lived for more than one year after diagnosis. In 15 patients surgical resection was attempted, but there were 5 reports
Primary Leiomyosarcoma of Truncus Pulmonalis . 299
of tumour recurrence in those cases. The presented cases showed an extremely rapid growth of the tumor with early fatal out-come, so that the interval between diagnosis and death was not longer than two months. This fact may be due to the delay or even the inability to set up the clinical diagnosis as early as possible. Modern, non-invasive techniques such as echocardiography to or computerized tomography4 offer a new way for early diagnosis, which may enable proper surgical removal of the tumour. Thus Wright et al. tO reported that their patient was still alive 16 months after initial diagnosis, which had been established by echocardiography at an early date. This, however, may in most cases be hampered by the missing differential diagnostic consideration of a primary tumour of the pulmonary arteries. Thus in the present case the symptoms of dyspnea and progressive heart failure associated with presumed arterial occlusion of the pulmonary trunk did not immediately lead to the diagnostic application of sonography or computerized tomography. Although in the series of Bleisch et al. 3 metastases could be found in all patients, they state that only during the last period of life true pulmonary metastases occurred radiographically in their cases, while tumour emboli before may have been resolved by the host. This may be essential for the prognosis of the patients. In our case, we similarly observed multiple pulmonary metastases which were noted only four weeks before death. Additionally, we found bilateral adrenal metastases which were the only haematogenic metastases. There are two other reports of adrenal metastases 3 with no apparent predominance of metastases in those organs. The selective affection of the adrenal glands in our case remains unexplained. Finally, a very interesting aspect in the reported case was the small intraluminal metastasis in the right iliacal vein,
most obviously associated with a lesion of the vessel in the course of heart catheterization. Therefore one has to be aware of the danger of implantation metastases due to diagnostic manipulations.
References t Abrams HL, McLoud TC (1985) Case records of the Massachusetts General Hospital. New Engl J Med 312:
1242-1252
2 Balduin R, Origo R, Schiraldi C, Carraro R (1986) Ante mortem diagnosis of primary leiomyosarcoma of the pulmonary artery. Respiration 49: 307-310 3Bleisch VR, Kraus FT (1980) Polypoid sarcoma of the pulmonary trunk: analysis of the literature and report of a case with leptomeric organelles and ultrastructural features of rhabdomyosarcoma. Cancer 46: 314-324 4 Fitzgerald PM (1983) Primary sarcoma of the pulmonary trunk: CT findings. J Comp Ass Tomogr 7: 521-523 5 Hayes WL, Farha SJ, Brown RL (1974) Primary leiomyosarcoma of the pulmonary artery. Am J Cardiol 34: 615-617 6 McAllister HA, Fenoglio JJ (1978) Tumours of the cardiovascular system. Atlas of Tumor Pathology, second series, Fasicle 15, Armed Forces Institute of Pathology, Washington 7 Schoenfeld Y, Avidor I, Libau E, Levy MJ, PinkhasJ (1981) Primary leiomyosarcoma of the pulmonary artery. Respiration
41: 208-213
8 Sethi GK, SlavenJE, KepesJJ (1972) Primary sarcoma of the pulmonary artery. J Thorac Cardiovasc Surg 63: 587-593 9 Wackers FJ, Van der SchootJB, HampeJF (1969) Sarcoma of the pulmonary trunk associated with hemorrhagic tendency. Cancer 23: 339-351 10 Wright EC, Wellons HA, Martin RP (1983) Primary pulmonary artery sarcoma diagnosed non-invasively by twodimensional echocardiography. Circulation 67: 459-462
Received April 7, 1988 . Accepted in revised form October 6, 1989
Key Words: Pulmonary leiomyosarcoma - Truncus pulmonalis - Valve bioprothesis Dr. A. Nerlich, Pathologisches Institut der Universitat Munchen, Thalkirchnerstr. 36, 0-8000 Munchen 2, FRG
Teaching Cases
Primary Leiomyosarcoma of the Truncus Pulmonalis Report of a Case with Typical Features and Unusual Metastases A. Nerlich, w. Permanetter, B. LUdwig 1 and K. Remberger
Institute of Pathology, University of Munich, FRG, and Medizinische Klinik, Klinikum GroBhadern 1, Munich, FRG
SUMMARY
We present the fatal case of a patient with a primary leiomyosarcoma of the pulmonary trunk. During the patient's clinical course of 2 months, the pulmonary valve and the proximal segment of the truncus pulmonalis had to be removed surgically. At autopsy, we found an extensive local tumour recurrence with an almost complete obliteration of the right ventricular outflow. The right pulmonary artery was subtotally obliterated by a tumour thrombus, and the lungs and both adrenal glands showed extensive tumour metastases. A solitary tumour metastasis within the lumen of the right vena iliaca communis obviously was associated with diagnostic manipulations in the course of heart catheterization.
Introduction Primary neoplasms of the truncus pulmonalis or the pulmonary arteries are extremely rare. Wright et a1. 10 collected a series of 67 cases from the literature and added one case from their own files. All but 15 cases thereof had not been diagnosed before autopsy. In the recent literature other cases have been presented 1,2,4,7 with an increasing proportion of tumours being detected before death. We observed a case of primary leiomyosarcoma of the truncus pulmonalis, which was treated by resection of the proximal part of the pulmonary trunk, and implantation of a pulmonary valve bioprosthesis.
Case Report
Clinical History The 47 year old patient had a history of three months' duration of dyspnoea. Additionally he presented typical signs of progressive congestive heart failure, especially pulmonary edema with pleural effusion and enlargement of liver and spleen. There was no history of a previous 0344-0338/90/0186-0296$3.50/0
serious illness. Because of the progressive character of his complaints, he was admitted to hospital two months prior to his death. In two-dimensional echocardiography, a marked dilatation of the right ventricle along with a polypoid mass in the truncus pulmonalis, shortly distal and adjacent to the pulmonary valve, could be demonstrated. A chest radiograph demonstrated only signs of pulmonary congestion and pleural effusion, pulmonary infarction could not be detected. The heart was radiographically enlarged, the pulmonary out-flow tract was unremarkable. A heart catheterization, performed through the right common iliac vein, disclosed a large polypoid mass adjacent to the pulmonary valve. During the following surgical intervention the pulmonary valve was replaced by a bioprosthesis, and the proximal part of the truncus pulmonalis (2.5 cm in length) was resected and replaced by a prosthetic implant. The immediate post-operative course was uneventful. Echocardiographic and radiological re-examination of the patient four weeks later demonstrated new tumour masses in the right ventricle close to the implanted valve prosthesis. In the periphery of both lungs a total of 7 localized round, radiodense areas could be demonstrated, © 1990 by Gustav Fischer Verlag, Stuttgart
Primary Leiomyosarcoma of Truncus Pulmonalis . 297
which were presumed to represent tumour metastases. The patient developed progressive cardiac difficulties and died of cardiac failure.
Histological Findings (Fig. 1) Already during the surgical intervention, by frozen sections; the sarcomatous nature of the tumour could be confirmed. The tumour specimen, removed by the cardiac surgeon, microscopically consisted of interlacing bundles of cells with blunt-ended nuclei. Occasionally areas with marked hyperchromatic and bizarre nuclei were recognised; rarely a few giant cells could be found. The tumour cells in the interwoven bundles mostly had ovoid nuclei, which were sometimes arranged in a palisading pattern. There was a large number of atypical mitoses (more than 10 per high power field 40x) and the van Gieson stain showed that there was only sparse collagenous material between the elongated tumour cells. Parts of the tumour showed myxoid and occasionally fibrous degeneration. All the morphologic characteristics of the tumour could be summarized in the diagnosis of a leiomyosarcoma. Immunohistochemical staining was negative for S-100 protein, neuron specific enolase, alpha 1 anti-chymotrypsin, myoglobin and epithelial markers. There was only a positive reaction with an antibody against desmin filaments (Fig. 1b).
In the resected segment of the truncus pulmonalis, the whole diameter of the vessel wall was replaced by the tumour mass. Only focal areas showed intact residuals of the vessel. Forming polypoid masses, the tumour extremely narrowed the lumen and destroyed the pulmonary valve. The morphological appearance of the tumour in the surgical specimen was completely preserved in the metastases at autopsy.
Autopsy Findings Postmortem examination showed an extensive tumour infiltration of the whole base of the heart, forming a compact (12 x 10 x 10 em) tumour mass. Proximal vessel segments, including the ascending aorta and the truncus pulmonalis, which had been replaced in part by a dacron implant, were surrounded and infiltrated by the tumour. Similarly, the interatrial septum was thickened and filled with tumour masses. The anterior wall of the left cardiac ventricle was surrounded by a rigid tumour mass, extensively infiltrating the epicardial fat and protruding into the myocardium in a finger-like pattern. Most remarkable were the multiple small tumour nodules (up to 1 em in diameter) lying in the subendocardium of the right ventricular outflow, which was almost completely obliterated (Fig. 2). Small subendocardial tumour metastases were
Fig. 1a. Histological aspect of tumour tissue showing cells in an interwoven pattern of bundles with markedly hyperchromatic and often bizarre nuclei (H & E; Original magn. x 100, inset x 400). - b. Histological slide of the tumor with demonstration of desmin filaments by immunohistological staining (indirect immunoperoxidase method, monoclonal antibody against desmin from Boehringer Mannheim Biochemica, magn. X 200).
298 . A. Nerlich et al.
Fig. 2. Macroscopic feature of the right ventricular outflow at autopsy showing polypoid tumour masses (white arrow) with subtotal obliteration of the lumen of the valve prothesis (black arrow), which is in the pulmonary valve position.
Fig. 3. Small solitary tumour nodule (white arrow) within the lumen of the right V. iliaca communis.
Discussion seen adjacent to the suture material in the right ventricle. The right pulmonary artery was extensively infiltrated and the lumen was sub-totally obliterated by central tumour thrombus material adherent to the vessel wall (8 cm long). In both lungs multiple tumour metastases in central and peripheral areas could be found (up to 1 cm in diameter); histologically there was evidence for multiple small tumour emboli. The sternum was infiltrated by a continuous growth from the heart into the bone. In the pleural cavity of the right lung, two subpleural metastases (up to 2 cm in diameter) were noted. Lymph nodes of both pulmonary hili as well as paratracheal and para-aortal lymph nodes were free of tumour cells, although the connective tissue areas surrounding hilar lymph nodes showed extensive continuous tumour infiltration. Both adrenal glands showed metastases and were nearly completely destroyed by the tumour (4 X 6 cm). The most unusual finding was a solitary mass within the lumen of the right common iliac vein (1 x 1.5 cm in diameter), without any evidence for tumour infiltration in any other peripheral blood vessel (Fig. 3). A further autopsy finding was a small leiomyoma in the mucosa of the jejunum with no evidence of malignant transformation. In addition to hypertrophy of both cardiac ventricles (500 g), the myocardium showed, besides the continuous tumour infiltration, a moderate interstitial and perivascular fibrosis in the areas free of tumour. A remarkable sclerosis of coronary arteries could not be seen.
Primary malignant tumours of the pulmonary arteries are rare 3,5,7-9. In a recent report 67 cases have been collected lo . In a review of the available literature we were able to find four additional cases l ,2,4,7. All but 15 cases reviewed by Wright et al. IO had not been diagnosed before autopsy. The application of non-invasive diagnostic methods, such as sonography and computerized tomography, however, increases the number of cases which have been diagnosed during life. With progression in cardiac surgery, pathologists have to be aware of primary malignant tumours of the pulmonary vessels in biopsy material and intra-operative frozen sections. Primary sarcomas of the pulmonary arteries occur more often in females than in males (approx. 65% women)6. Most patients are in their sixth decade (maximum 50-55 years)3, although Wright et al. lo observed a patient of only 21 years of age. All the tumours reported in the literature were localized in the pulmonary trunk3 . The pulmonary valve was involved in 57%. All tumours had a polypoid appearance, with a more or less pronounced obliteration of the vessel lumen. There is a predominance of leiomyosarcomas; 50% of the tumours are classified as undifferentiated sarcomas. On critical review, however, about half of the latter cases may represent leiomyosarcomas6. The prognosis of patients with primary sarcoma of the pulmonary arteries is rather poor. In Bleisch's series3 only 6 patients out of 60 lived for more than one year after diagnosis. In 15 patients surgical resection was attempted, but there were 5 reports
Primary Leiomyosarcoma of Truncus Pulmonalis . 299
of tumour recurrence in those cases. The presented cases showed an extremely rapid growth of the tumor with early fatal out-come, so that the interval between diagnosis and death was not longer than two months. This fact may be due to the delay or even the inability to set up the clinical diagnosis as early as possible. Modern, non-invasive techniques such as echocardiography to or computerized tomography4 offer a new way for early diagnosis, which may enable proper surgical removal of the tumour. Thus Wright et al. tO reported that their patient was still alive 16 months after initial diagnosis, which had been established by echocardiography at an early date. This, however, may in most cases be hampered by the missing differential diagnostic consideration of a primary tumour of the pulmonary arteries. Thus in the present case the symptoms of dyspnea and progressive heart failure associated with presumed arterial occlusion of the pulmonary trunk did not immediately lead to the diagnostic application of sonography or computerized tomography. Although in the series of Bleisch et al. 3 metastases could be found in all patients, they state that only during the last period of life true pulmonary metastases occurred radiographically in their cases, while tumour emboli before may have been resolved by the host. This may be essential for the prognosis of the patients. In our case, we similarly observed multiple pulmonary metastases which were noted only four weeks before death. Additionally, we found bilateral adrenal metastases which were the only haematogenic metastases. There are two other reports of adrenal metastases 3 with no apparent predominance of metastases in those organs. The selective affection of the adrenal glands in our case remains unexplained. Finally, a very interesting aspect in the reported case was the small intraluminal metastasis in the right iliacal vein,
most obviously associated with a lesion of the vessel in the course of heart catheterization. Therefore one has to be aware of the danger of implantation metastases due to diagnostic manipulations.
References t Abrams HL, McLoud TC (1985) Case records of the Massachusetts General Hospital. New Engl J Med 312:
1242-1252
2 Balduin R, Origo R, Schiraldi C, Carraro R (1986) Ante mortem diagnosis of primary leiomyosarcoma of the pulmonary artery. Respiration 49: 307-310 3Bleisch VR, Kraus FT (1980) Polypoid sarcoma of the pulmonary trunk: analysis of the literature and report of a case with leptomeric organelles and ultrastructural features of rhabdomyosarcoma. Cancer 46: 314-324 4 Fitzgerald PM (1983) Primary sarcoma of the pulmonary trunk: CT findings. J Comp Ass Tomogr 7: 521-523 5 Hayes WL, Farha SJ, Brown RL (1974) Primary leiomyosarcoma of the pulmonary artery. Am J Cardiol 34: 615-617 6 McAllister HA, Fenoglio JJ (1978) Tumours of the cardiovascular system. Atlas of Tumor Pathology, second series, Fasicle 15, Armed Forces Institute of Pathology, Washington 7 Schoenfeld Y, Avidor I, Libau E, Levy MJ, PinkhasJ (1981) Primary leiomyosarcoma of the pulmonary artery. Respiration
41: 208-213
8 Sethi GK, SlavenJE, KepesJJ (1972) Primary sarcoma of the pulmonary artery. J Thorac Cardiovasc Surg 63: 587-593 9 Wackers FJ, Van der SchootJB, HampeJF (1969) Sarcoma of the pulmonary trunk associated with hemorrhagic tendency. Cancer 23: 339-351 10 Wright EC, Wellons HA, Martin RP (1983) Primary pulmonary artery sarcoma diagnosed non-invasively by twodimensional echocardiography. Circulation 67: 459-462
Received April 7, 1988 . Accepted in revised form October 6, 1989
Key Words: Pulmonary leiomyosarcoma - Truncus pulmonalis - Valve bioprothesis Dr. A. Nerlich, Pathologisches Institut der Universitat Munchen, Thalkirchnerstr. 36, 0-8000 Munchen 2, FRG
