Retroperitoneal Chondrosarcoma Presenting with Pleural Effusion: A Case Report O.A. Oyemade, MD, and L. Riddick, MD Ibadan, Nigeria, and Washington, DC
An adolescent male patient presented with pleural effusion of undetermined etiology which was unresponsive to antituberculous therapy. He died suddenly a few months later and was found at autopsy to have suffered from acute catastrophic pulmonary occlusion, secondary to embolization from retroperitoneal chondrosarcoma which had invaded and occluded the pulmonary arteries via the inferior vena cava. The rarity of this phenomenon in children prompted this report. Chondrosarcoma, a malignant cartilaginous tumor arising either de novo in bone, or secondary to a preexisting benign cartilaginous neoplasm, is the second most common primary malignant bone tumor.1 2 It is usually found in adulthood and old age, and is very rare in childhood and adolescence. 1-7
Case Report A 16-year-old black male patient was admitted to Howard University Hospital with a two-day history of nonproductive cough and severe left-sided anterior chest pain aggravated by lying in the supine position. There was no history of fever, hemoptysis, weight loss, or vomiting. Exposure to tuberculosis was denied, although the patient reported night sweating and diminished appetite since the onset of his illness. The patient's past medical history was noncontributory and there was no significant family history. Physical examination revealed an asthenic, afebrile young man in mild respiratory distress (respiratory rate 28/min). His blood pressure was 124/50 mmHg; his weight, 140 lbs. Significant findings were limited to
From the Department of Pediatrics, Howard University Hospital, and the Office of the Chief Medical Examiner, Washington, DC. Requests for reprints should be addressed to Dr. O.A. Oyemade, Department of Pediatrics, University College Hospital, Ibadan, Nigeria.
the chest, where examination revealed left-sided inspiratory guarding. There were no palpable masses, nor was there any area of localized tenderness. Percussion dullness and diminished breath sounds were elicited over the left lung base. No abdominal masses were palpable. Because an initial roentgenogram of the chest revealed an ill-defined infiltrate in the left lower lobe, a presumptive diagnosis of left lower lobe pneumonia was made and the patient was given oral penicillin. Over the next ten days, however, the patient's symptoms progressed in spite of penicillin therapy and subsequent chest roentgenograms revealed increasing accumulation of pleural fluid, mainly on the left side. Laboratory results of pleural fluid obtained by thoracentesis are documented in Table 1. Other laboratory data included a hematocrit level of 37.8 percent and a white blood cell count of 8,800 cells per mm3 with 70 segmented cells and 30 lymphocytes. Corrected sedimentation rates were 52 mm/hr and 49 mm/hr. Various skin tests (including the Tine test, PPD, histoplasmin, coccidioidin, Kansasi IY, IIG, IIB, Battey IVF, and mumps) were all negative. Faced with the situatidn of a patient with persistent pleural effusion and lung infiltrate unresponsive to antibiotic therapy, a working diagnosis of pulmonary tuberculosis was made, in spite of negative skin tests, and the patient was started on antituberculous therapy on the twenty-sixth hospital
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 12, 1979
day. Further diagnostic work-up included a negative bronchoscopy and bronchial washings revealed no organisms on culture. A pleural biopsy showed a nonspecific pleuritis, and no malignant cells were seen on cytologic examination. The patient was discharged from the hospital on the 28th day. He was placed on antituberculous therapy pending final results of all the above tests. However, he did not return for reevaluation and, three months after discharge, died suddenly at home after a
cardio-respiratory collapse.
Autopsy Findings An autopsy revealed the body of a normal, well-nourished black male. No masses were visible or palpable on either the shoulders, pelvis, or extremities. The positive findings were in the lungs, pelvic veins, and the retroperitoneum around the first sacral vertebra. The left thoracic cavity was almost completely obliterated by dense fibrous adhesions. There were no pleural effusions. The main pulmonary artery as well as the left, right, and segmental arteries were totally occluded by a massive tumor embolus composed of yellow-grey, glistening, semitranslucent, small oval lobules measuring from 3.0 to 5.0 cm in diameter (Figure 1). The cut surface of the tumor was smooth and chondroid; calcification was not present. On section of the lungs, three whitish-yellow firm lesions 3.0 to 5.0 cm in diameter were located in the subpleural region of the left upper lobe, while a 5 cm well-defined region of hyperemia was identified in the right upper lobe. The remainder of the parenchyma was congested, edematous, and of firm rubbery consistency. Tumor emboli were identifiable in most of the small arteries. 1181
Table 1. Results of Pleural Fluid Examination
8th Day
Color Volume (ml) RBC WBC Lymphocytes (percent) Polysegmented (percent) LDH (units) SGOT (units) Cytology Culture for Acid-Fast Bacilli Amylase LE preparation Glucose (mg/100ml) Total Protein (gm/100ml)
13th Day
Straw 750 2,000 2,600 60 40
Straw 750 1,600 800 95 5 7,617 7,323 Negative for malignant cells Negative Negative 35 Negative 115 5.4
27th Day
Pale orange-brown 600 200 1,800 76 14
Negative
necrosis noted and organizing or acute edema fluid was present in other portions of the lungs.
-AF
Discussion
S M w Ef
f.r: ~ ~ .'¢. ~~~~~~~~~~~~~~~~
....
Figure 1. Lung showing massive tumor embolism in the pulmonary artery and branches
Examination of the abdominal and pelvic veins revealed tumor extensions of tissue similar to the pulmonary embolus. This tissue extended into the left common iliac vein from a branch of the left internal iliac vein draining the retroperitoneal region around the fifth lumbar and sacral vertebrae (Figure 2). No large tumor mass was identified in this region, however, and a postmortem x-ray of the pelvis revealed no characteristic tumor. Histologically, the tumor extensions and emboli were composed of a homogeneous, pale-staining, eosinophilic matrix in which there were large clear cells with well-defined, regular nuclei, 1182
suggesting the picture of a well-differentiated chondrosarcoma (Figure 3). Sections from the soft tissues around the first sacral vertebra showed well-organized tumor implants adherent to the vascular walls. The tumor emboli in the small pulmonary arteries were also well organized and appeared to be growing within the lumen. Sections from the lesions in the left upper lobe revealed increased fibrous tissue obliterating the alveolar spaces interspersed with small foci of chondrosarcoma. The hyperemic right upper lobe was found to be due to intra-alveolar hemorrhage with increased fibrous tissue. There was no JOURNAL OF THE NATIONAL
The majority of chondrosarcomas involve the pelvic bones. Other sites include the rib, femur, humerus, spine, scapula, tibia, fibula, sacrum, and sternum, in that order. 1,2,3 In this patient, no obvious primary tumor mass was identifiable, but the origin of spread appeared to be in the lumbo-sacral region of the spine. The pathologic findings correlated with the clinical picture, and confirmed the typical course that chondrosarcoma usually takes, that is, invasion of regional veins with gradual extension to the heart and pulmonary arteries by intravascular growth or embolization.f14 However, the clinical picture of cor pulmonale secondary to pulmonary vascular occlusion was not observed in the patient; rather, a marked feature of pulmonary involvement was recurrent pleural effusion. No major series in the literature on chondrosarcomas describes this rare complication.2'4'8'15 The reaction of the pulmonary parenchyma in the left upper lobe supplied by the occluded arteries presumably produced the effusions. No infarct occurred because the embolization process by tumor masses only partially compromised the pulmonary vascularization. Instead, the chronic hypoxia led to hyperemic edematous changes most noted in the right upper lobe where the reactive pleural effusion originated. This reactive process was also probably responsible for the fact that analysis of the pleural fluid as well as the pleural biopsy specimens yielded MEDICAL
ASSOCIATION,
VOL. 71, NO. 12, 1979
no clues as to the cause of the recurrent pleural effusion. This patient therefore experienced several recurrent showers of emboli which produced his respiratory symptoms. The acute terminal event, however, occurred when the large, intravascular tumor which extended well into the inferior vena cava, broke loose and became lodged in the artery, occluding both the right and left pulmonary arteries and leading to cardiopulmonary failure. Occlusion of the main vessels is a rather unusual feature, since tumor emboli are usually quite small, and do not invade the arterial wall.367'16 This case demonstrates the extensive tumor embolic, vascular invasions of an otherwise slowly growing malignant tumor which remained clinically impossible to diagnose and which was eventually fatal to the patient because of acute pulmonary embolization of a large tumor mass. The management of this tumor is very difficult, as early diagnosis is so elusive as to make surgical excision ineffective, while no reports are available on the medical management with drugs or radiotherapy. In conclusion, no major series on chondrosarcomas discusses the unusual features of this case: (1) reactive pleural effusion, (2) marked invasion of the pulmonary by showers of tumor emboli, and (3) blockage of the artery by a breakaway large mass of tumor embolus with resultant cardiopulmonary failure. Thus, although chondrosarcoma is rare in childhood and adolescence, it should be added to the long list of causes of massive pulmonary tumor embolism.
'isit'Z. . p4(A
,,
Figure 2. Tumor in the left internal and F~~~~V~dq
common iliac veins
#f'.')~
AL
1y~~~~~~~~~~~~'
*OX~~~~~~~~4
Figure 3. Photomicrograph showing well differentiated chondrosarcoma
Acknowledgement The authors wish to acknowledge Dr. Melvin Jenkins, Chairman, Department of Pediatrics, Howard University Hospital, Washington, DC, who gave invaluable advice in the writing of this paper.
Literature Cited 1. Dahlin DC: Chondrosarcoma. In Bone Tumors, ed 2. Springfield, Ill, Charles C Thomas, 1967, pp 138-155 2. Spjut HJ, Dorfman HD, Fechner RE, et al: Fasciles. In Tumors of Bone and Cartilage, Atlas of Tumor Pathology, 2nd series, Washington, DC, Armed Forces Institute of Pathology, 1971 3. Schwarz MI, Goldman AL, Roycroft DW, et al: Vascular invasion by chondrosarcoma
simulating pulmonary emboli. Am Rev Respir Dis 106:109-113, 1972 4. Barnes R, Catto M: Chondrosarcoma of bone. J Bone Joint Surg 48(B):729-764, 1966 5. Copeland MM: Cartilagenous Tumors of Bone, course lecture. Am Acad Orthoped Surg lnst, Vol 7, 1-17, 1950 6. Warren S: Chondrosarcoma with intravascular growth and tumor emboli to lungs. Am J Pathol 7:161-167, 1931 7. Weber 0: Zur Geschichte des Enchondroms nametlich in Bezug auf dessen hereditares Vorkommen und secundare Verbreitung in inneren Organen durch Embolie. Virchows Arch 35:501-553, 1866 8. Lichtenstein L, Jaffe ML: Chondrosarcoma of bone. Am J Pathol 19:553-589, 1943 9. Case records of the Massachusetts General Hospital (Case 42361). N EngI J Med 255:477-482, 1956 10. Rudusky BM: Chondrosarcoma: Report
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 12, 1979
of a case with extensive arterial occlusion. Vasc Dis 2:352-356, 1965 11. Fry JB, Shattuck CE: Sarcomatous permeation of the inferior vena cava and right side of the heart. Br J Surg 14:337-342, 1926 12. Talerman A, Golding JSR, Kirkpatrick D: Bone tumors in Jamaica. J Bone Joint Surg 49(B)802-805, 1967 13. Rechlinghausen F von: Uber die Venose Embolie und den retrograden Transport in den Venen und in den Lymphgefassen. Virchows Arch 100:503-539, 1885 14. Winterbauer RH, Elfenbein IB, Ball WC: Incidence and significance of tumor embolization to the lungs. Am J Med 45:271-290, 1968 15. Henderson ED, Dahlin DC: Chondrosarcoma of bone-a study of two hundred and eighty-eight cases. J Bone Joint Surg 45 (A :1450-1458, 1963 16. Phemister DB: Chondrosarcoma of bone. Surg Gynecol Obstet 50:216-233, 1930 1183
An adolescent male patient presented with pleural effusion of undetermined etiology which was unresponsive to antituberculous therapy. He died suddenly a few months later and was found at autopsy to have suffered from acute catastrophic pulmonary occlusion, secondary to embolization from retroperitoneal chondrosarcoma which had invaded and occluded the pulmonary arteries via the inferior vena cava. The rarity of this phenomenon in children prompted this report. Chondrosarcoma, a malignant cartilaginous tumor arising either de novo in bone, or secondary to a preexisting benign cartilaginous neoplasm, is the second most common primary malignant bone tumor.1 2 It is usually found in adulthood and old age, and is very rare in childhood and adolescence. 1-7
Case Report A 16-year-old black male patient was admitted to Howard University Hospital with a two-day history of nonproductive cough and severe left-sided anterior chest pain aggravated by lying in the supine position. There was no history of fever, hemoptysis, weight loss, or vomiting. Exposure to tuberculosis was denied, although the patient reported night sweating and diminished appetite since the onset of his illness. The patient's past medical history was noncontributory and there was no significant family history. Physical examination revealed an asthenic, afebrile young man in mild respiratory distress (respiratory rate 28/min). His blood pressure was 124/50 mmHg; his weight, 140 lbs. Significant findings were limited to
From the Department of Pediatrics, Howard University Hospital, and the Office of the Chief Medical Examiner, Washington, DC. Requests for reprints should be addressed to Dr. O.A. Oyemade, Department of Pediatrics, University College Hospital, Ibadan, Nigeria.
the chest, where examination revealed left-sided inspiratory guarding. There were no palpable masses, nor was there any area of localized tenderness. Percussion dullness and diminished breath sounds were elicited over the left lung base. No abdominal masses were palpable. Because an initial roentgenogram of the chest revealed an ill-defined infiltrate in the left lower lobe, a presumptive diagnosis of left lower lobe pneumonia was made and the patient was given oral penicillin. Over the next ten days, however, the patient's symptoms progressed in spite of penicillin therapy and subsequent chest roentgenograms revealed increasing accumulation of pleural fluid, mainly on the left side. Laboratory results of pleural fluid obtained by thoracentesis are documented in Table 1. Other laboratory data included a hematocrit level of 37.8 percent and a white blood cell count of 8,800 cells per mm3 with 70 segmented cells and 30 lymphocytes. Corrected sedimentation rates were 52 mm/hr and 49 mm/hr. Various skin tests (including the Tine test, PPD, histoplasmin, coccidioidin, Kansasi IY, IIG, IIB, Battey IVF, and mumps) were all negative. Faced with the situatidn of a patient with persistent pleural effusion and lung infiltrate unresponsive to antibiotic therapy, a working diagnosis of pulmonary tuberculosis was made, in spite of negative skin tests, and the patient was started on antituberculous therapy on the twenty-sixth hospital
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 12, 1979
day. Further diagnostic work-up included a negative bronchoscopy and bronchial washings revealed no organisms on culture. A pleural biopsy showed a nonspecific pleuritis, and no malignant cells were seen on cytologic examination. The patient was discharged from the hospital on the 28th day. He was placed on antituberculous therapy pending final results of all the above tests. However, he did not return for reevaluation and, three months after discharge, died suddenly at home after a
cardio-respiratory collapse.
Autopsy Findings An autopsy revealed the body of a normal, well-nourished black male. No masses were visible or palpable on either the shoulders, pelvis, or extremities. The positive findings were in the lungs, pelvic veins, and the retroperitoneum around the first sacral vertebra. The left thoracic cavity was almost completely obliterated by dense fibrous adhesions. There were no pleural effusions. The main pulmonary artery as well as the left, right, and segmental arteries were totally occluded by a massive tumor embolus composed of yellow-grey, glistening, semitranslucent, small oval lobules measuring from 3.0 to 5.0 cm in diameter (Figure 1). The cut surface of the tumor was smooth and chondroid; calcification was not present. On section of the lungs, three whitish-yellow firm lesions 3.0 to 5.0 cm in diameter were located in the subpleural region of the left upper lobe, while a 5 cm well-defined region of hyperemia was identified in the right upper lobe. The remainder of the parenchyma was congested, edematous, and of firm rubbery consistency. Tumor emboli were identifiable in most of the small arteries. 1181
Table 1. Results of Pleural Fluid Examination
8th Day
Color Volume (ml) RBC WBC Lymphocytes (percent) Polysegmented (percent) LDH (units) SGOT (units) Cytology Culture for Acid-Fast Bacilli Amylase LE preparation Glucose (mg/100ml) Total Protein (gm/100ml)
13th Day
Straw 750 2,000 2,600 60 40
Straw 750 1,600 800 95 5 7,617 7,323 Negative for malignant cells Negative Negative 35 Negative 115 5.4
27th Day
Pale orange-brown 600 200 1,800 76 14
Negative
necrosis noted and organizing or acute edema fluid was present in other portions of the lungs.
-AF
Discussion
S M w Ef
f.r: ~ ~ .'¢. ~~~~~~~~~~~~~~~~
....
Figure 1. Lung showing massive tumor embolism in the pulmonary artery and branches
Examination of the abdominal and pelvic veins revealed tumor extensions of tissue similar to the pulmonary embolus. This tissue extended into the left common iliac vein from a branch of the left internal iliac vein draining the retroperitoneal region around the fifth lumbar and sacral vertebrae (Figure 2). No large tumor mass was identified in this region, however, and a postmortem x-ray of the pelvis revealed no characteristic tumor. Histologically, the tumor extensions and emboli were composed of a homogeneous, pale-staining, eosinophilic matrix in which there were large clear cells with well-defined, regular nuclei, 1182
suggesting the picture of a well-differentiated chondrosarcoma (Figure 3). Sections from the soft tissues around the first sacral vertebra showed well-organized tumor implants adherent to the vascular walls. The tumor emboli in the small pulmonary arteries were also well organized and appeared to be growing within the lumen. Sections from the lesions in the left upper lobe revealed increased fibrous tissue obliterating the alveolar spaces interspersed with small foci of chondrosarcoma. The hyperemic right upper lobe was found to be due to intra-alveolar hemorrhage with increased fibrous tissue. There was no JOURNAL OF THE NATIONAL
The majority of chondrosarcomas involve the pelvic bones. Other sites include the rib, femur, humerus, spine, scapula, tibia, fibula, sacrum, and sternum, in that order. 1,2,3 In this patient, no obvious primary tumor mass was identifiable, but the origin of spread appeared to be in the lumbo-sacral region of the spine. The pathologic findings correlated with the clinical picture, and confirmed the typical course that chondrosarcoma usually takes, that is, invasion of regional veins with gradual extension to the heart and pulmonary arteries by intravascular growth or embolization.f14 However, the clinical picture of cor pulmonale secondary to pulmonary vascular occlusion was not observed in the patient; rather, a marked feature of pulmonary involvement was recurrent pleural effusion. No major series in the literature on chondrosarcomas describes this rare complication.2'4'8'15 The reaction of the pulmonary parenchyma in the left upper lobe supplied by the occluded arteries presumably produced the effusions. No infarct occurred because the embolization process by tumor masses only partially compromised the pulmonary vascularization. Instead, the chronic hypoxia led to hyperemic edematous changes most noted in the right upper lobe where the reactive pleural effusion originated. This reactive process was also probably responsible for the fact that analysis of the pleural fluid as well as the pleural biopsy specimens yielded MEDICAL
ASSOCIATION,
VOL. 71, NO. 12, 1979
no clues as to the cause of the recurrent pleural effusion. This patient therefore experienced several recurrent showers of emboli which produced his respiratory symptoms. The acute terminal event, however, occurred when the large, intravascular tumor which extended well into the inferior vena cava, broke loose and became lodged in the artery, occluding both the right and left pulmonary arteries and leading to cardiopulmonary failure. Occlusion of the main vessels is a rather unusual feature, since tumor emboli are usually quite small, and do not invade the arterial wall.367'16 This case demonstrates the extensive tumor embolic, vascular invasions of an otherwise slowly growing malignant tumor which remained clinically impossible to diagnose and which was eventually fatal to the patient because of acute pulmonary embolization of a large tumor mass. The management of this tumor is very difficult, as early diagnosis is so elusive as to make surgical excision ineffective, while no reports are available on the medical management with drugs or radiotherapy. In conclusion, no major series on chondrosarcomas discusses the unusual features of this case: (1) reactive pleural effusion, (2) marked invasion of the pulmonary by showers of tumor emboli, and (3) blockage of the artery by a breakaway large mass of tumor embolus with resultant cardiopulmonary failure. Thus, although chondrosarcoma is rare in childhood and adolescence, it should be added to the long list of causes of massive pulmonary tumor embolism.
'isit'Z. . p4(A
,,
Figure 2. Tumor in the left internal and F~~~~V~dq
common iliac veins
#f'.')~
AL
1y~~~~~~~~~~~~'
*OX~~~~~~~~4
Figure 3. Photomicrograph showing well differentiated chondrosarcoma
Acknowledgement The authors wish to acknowledge Dr. Melvin Jenkins, Chairman, Department of Pediatrics, Howard University Hospital, Washington, DC, who gave invaluable advice in the writing of this paper.
Literature Cited 1. Dahlin DC: Chondrosarcoma. In Bone Tumors, ed 2. Springfield, Ill, Charles C Thomas, 1967, pp 138-155 2. Spjut HJ, Dorfman HD, Fechner RE, et al: Fasciles. In Tumors of Bone and Cartilage, Atlas of Tumor Pathology, 2nd series, Washington, DC, Armed Forces Institute of Pathology, 1971 3. Schwarz MI, Goldman AL, Roycroft DW, et al: Vascular invasion by chondrosarcoma
simulating pulmonary emboli. Am Rev Respir Dis 106:109-113, 1972 4. Barnes R, Catto M: Chondrosarcoma of bone. J Bone Joint Surg 48(B):729-764, 1966 5. Copeland MM: Cartilagenous Tumors of Bone, course lecture. Am Acad Orthoped Surg lnst, Vol 7, 1-17, 1950 6. Warren S: Chondrosarcoma with intravascular growth and tumor emboli to lungs. Am J Pathol 7:161-167, 1931 7. Weber 0: Zur Geschichte des Enchondroms nametlich in Bezug auf dessen hereditares Vorkommen und secundare Verbreitung in inneren Organen durch Embolie. Virchows Arch 35:501-553, 1866 8. Lichtenstein L, Jaffe ML: Chondrosarcoma of bone. Am J Pathol 19:553-589, 1943 9. Case records of the Massachusetts General Hospital (Case 42361). N EngI J Med 255:477-482, 1956 10. Rudusky BM: Chondrosarcoma: Report
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 12, 1979
of a case with extensive arterial occlusion. Vasc Dis 2:352-356, 1965 11. Fry JB, Shattuck CE: Sarcomatous permeation of the inferior vena cava and right side of the heart. Br J Surg 14:337-342, 1926 12. Talerman A, Golding JSR, Kirkpatrick D: Bone tumors in Jamaica. J Bone Joint Surg 49(B)802-805, 1967 13. Rechlinghausen F von: Uber die Venose Embolie und den retrograden Transport in den Venen und in den Lymphgefassen. Virchows Arch 100:503-539, 1885 14. Winterbauer RH, Elfenbein IB, Ball WC: Incidence and significance of tumor embolization to the lungs. Am J Med 45:271-290, 1968 15. Henderson ED, Dahlin DC: Chondrosarcoma of bone-a study of two hundred and eighty-eight cases. J Bone Joint Surg 45 (A :1450-1458, 1963 16. Phemister DB: Chondrosarcoma of bone. Surg Gynecol Obstet 50:216-233, 1930 1183
