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Pulmonary Embolus Presenting as the Initial Manifestation of Renal Cell Carcinoma
Pulmonarv Embolus Presenting as the ~nitial Manifestation of Renal Cell Carcinoma James D. Daughtry, M.D., Bruce H. Stewart, M.D., Leonard A. R. Golding, M.D., a n d Laurence K. Groves, M.D.
ABSTRACT Recent literature suggests that pulmonary embolus secondary to renal cell carcinoma may be more common than previously suspected. Renal tumors are known for their ability to metastasize early, often before the primary lesion is apparent. A patient with renal cell carcinoma and having massive pulmonary tumor embolus is presented. Attention was called to the occult tumor by the identification of clear cell carcinoma in the pulmonary embolic material. Pulmonary embolectomy and surgical extirpation of the primary tumor resulted in longterm survival.
showed a pH of 7.27, PCQ of 140 mm Hg, and carbon dioxide content of 14. Chest roentgenogram revealed only mild linear atelectasis of both bases. Cyanosis persisted, and pulmonary angiograms were done to evaluate the possibility of pulmonary embolus. This study showed obstruction of the right main pulmonary artery and left lower lobe pulmonary artery (Fig 1). Because of the patient’s dependence upon vasopressors to maintain an adequate blood pressure, an emergency embolectomy was performed. Marked distention of the right heart and pulRenal cell carcinoma with pulmonary embolus monary arteries were noted at operation. On may be more common than previously sup- total cardiopulmonary bypass the main pulmoposed. We report the history of a patient in nary artery was opened, and a mass, totally whom renal cell carcinoma was initially man- occluding the right pulmonary artery, was enifested by a massive pulmonary embolus which countered. Aided by manual compression of the occluded the main right pulmonary artery and right and left lungs, both right and left pulmothe lower division of the left pulmonary artery. nary arteries were cleared of embolic material. Emergency pulmonary embolectomy followed The material removed was unusual in appearby subsequent radical nephrectomy has resulted ance and was submitted for frozen-section exin a 2% year survival to date. amination, which revealed clear cell carcinoma compatible with renal origin (Fig 2). A 68-year-old white man was admitted to the Hemodynamically, the patient had a prompt emergency room following a sudden collapse and satisfactory recovery, but on reacting from outside the hospital after visiting a relative. He anesthesia he manifested aphasia and was found to be unarousable, cyanotic, hemianopia, which gradually improved. After hypotensive, and incontinent of urine and had a cardiovascular recovery, an excretory urogram, head laceration and weak peripheral pulse. Be- renal and carotid angiograms, and inferior cause of hypotension, he was immediately cavogram were performed. The left kidney, uregiven vasopressors, and his systolic pressure ter, and urinary bladder were normal, but derose to 90 mm Hg. The electrocardiogram dem- layed visualization of a few separated calyces in onstrated a small-voltage QRS complex with S-T the right kidney was noted. The angiographic depression in the precordial leads and a right pattern was compatible with renal cell carbundle-branch block. Blood gas determinations cinoma with invasion and replacement of most of the parenchyma of the right kidney. The right From the Departments of Urology and Cardiovascular renal vein was involved, and renal function was Surgery, Cleveland Clinic Foundation, Cleveland, OH. markedly diminished. Inferior cavogram reAccepted for publication Feb 3, 1977. vealed a large filling defect approximately 4 cm Address reprint requests to Dr. Daughtry, Cleveland Clinic, The Clinic Center, 9500 Euclid Ave, Cleveland, OH 44106. in diameter in the vena cava at the level of the 178
179 Case Report: Daughtry et al: Pulmonary Embolus from Renal Cell Carcinoma
A
Fig 2 . Photomicrograph of hemorrhagic pulmonary embolic material diagnostic of clear cell carcinoma. (HDE; X40.)
B
Fig 1 . ( A )Pulmonary angiogram shows massive pulmonary embolus obstructing the right main pulmonary artery with decreased blood flow into the entire right lung field. (B)Pulmonary angiogram shows pulmonary emboli obstructing the left lower lobe pulmonary artery with cutoff of the vascularity in the left rnidlung field.
right renal vein, compatible with tumor thrombus. Bone scan was normal, with no suspicious areas of increased radioactivity to suggest an osteoblastic metastasis. A carotid angiogram performed because of the neurological deficit demonstrated complete occlusion of the left internal carotid artery at its origin; the right common carotid artery appeared to be normal. The carotid obstruction was consistent with cerebral atherosclerosis and thrombosis secondary to the patient’s hypotension rather than to metastatic neoplasm. Computer tomography of the brain performed during this acute neurological problem showed increased uptake over the left cerebral area compatible with an acute stroke, but a metastatic tumor could not be ruled out. Approximately two weeks following pulmonary embolectomy, the patient experienced considerable gross hematuria, colicky right flank pain, and general abdominal discomfort. Cystoscopy was performed, and a large number of
180 The Annals of Thoracic Surgery Vol 24 No 2 August 1977
well-formed clots were noted within the bladder. There appeared to be no gross bladder lesion, and multiple urine specimens showed no tumor cells. Right radical nephrectomy and inferior vena cavotomy were then performed. A large tumor was found in the lower two-thirds of the kidney, and multiple satellite nodules were scattered throughout the kidney parenchyma. Renal veins, particularly those draining the area of the tumor mass, showed intravascular presence of neoplasm, and tumor involved the main renal vein to the cava. The diagnosis of renal cell carcinoma of the clear cell type involving the lower pole of the right kidney was confirmed histologically (Fig 3 ) . The patient had an uneventful recovery from his nephrectomy, and a few days postoperatively he was able to void satisfactorily. Serum creatinine stabilized at 1.5 mgllOO ml; hemoglobin, complete blood count, and SMA-12 were also within normal limits. Chest roentgenogram showed no obvious metastasis; pulmonary Fig3. Photomicrograph of right kidney neoplasm demonstrating renal cell carcinoma of clear cell type. ( H b E ; X160.)
function was normal. There was some improvement in aphasia, with no other neurological findings. The patient’s general health is stable. He had no symptoms of metastasis 30 months postoperatively. Comment Renal cell carcinoma may manifest itself in a bizarre fashion, in this case as a massive pulmonary embolus. Recent literature suggests that pulmonary embolus secondary to renal cell carcinoma may be more common than was formerly suspected [121. These tumors are known for their ability to metastasize early in their course, often before the primary lesion is apparent. The classic triad of flank pain, hematuria, and abdominal mass is present in only approximately 15% of cases [8, 101. About 25% of patients with renal cell carcinoma will have evidence of metastatic disease upon initial examination [5, 71. Metastatic renal cell carcinoma may simulate other tumors in its presentation, and the unusual signs and symptoms make diagnosis extremely difficult. Creevy [ 3 ] and others have stated that malignant renal tumors should be classified with syphilis and tuberculosis among the great mimickers encountered in medicine. In our patient attention was called to the occult tumor by the identification of a clear cell carcinoma in a massive pulmonary embolus. The gross appearance of the operative specimen was atypical for a pure thrombus; therefore, frozen-section examination was performed. Vena cava and renal vein involvement by renal cell carcinoma has been reported by Arkless [l],Coman [21, and Svane [ l l l . The incidence of renal cell carcinoma involving the vena cava or renal vein has varied from 9.5% in Svane’s report to 54% in that of McDonald and Priestley [41. The presence of renal vein involvement increases the possibility of pulmonary emboli. Tumor emboli and pulmonary involvement seem to be common phenomena. Winterbauer and associates [12] and Arkless [l] found that 25% of the pulmonary lesions in this disease were secondary to tumor emboli. Renal cell carcinoma extending into the vena cava ar well as to the renal vein carries a poor progno? ’
181 Case Report: Daughtry et al: Pulmonary Embolus from Renal Cell Carcinoma
McDonald and Priestley [4] noted that 38% of their patients with vascular involvement were dead within one year, compared to 18% of those without extension. Richie and associates [9] reported a 72% mortality over three years following nephrectomy for those with vascular involvement, compared to 51% mortality for those without vascular involvement. Myers and colleagues [61 also reported a poor prognosis for those with vascular involvement, ie, 55% three-year mortality with vascular involvement compared to 29% without. Pulmonary tumor emboli usually occur due to spontaneous release from the primary neoplasm; occasionally they may result from manipulation of the renal vein at the time of nephrectomy. Chemotherapy and irradiation are also believed to predispose the patient to tumor embolization 1131. Recent studies indicate that tumor emboli do not necessarily develop into pulmonary metastases. Some may be destroyed intraluminally or remain latent without parenchymal invasion [12]. Woo-Ming and co-workers [13]reported on a calcified tumor thrombus in the left pulmonary artery of a patient who had undergone radical nephrectomy for renal cell carcinoma 11 years previously. Renal vein extension of the tumor had been noted at the time of nephrectomy, and the patient was asymptomatic without signs of recurrence. Signs of either vena cava obstruction or pulmonary emboli should alert the clinician to the possibility of renal cell carcinoma with invasion of the vena cava. Large intracardiac thrombi secondary to renal cell carcinoma may cause considerable mechanical embarrassment of the tricuspid valve. Anuria, secondary to bilateral renal vein involvement, is also possible and may accompany total occlusion of the inferior vena cava. Sudden death due to tricuspid valve obstruction or massive pulmonary tumor em-
boli can occur. Since these tumor emboli may be destroyed intraluminally, or remain latent without parenchymal invasion, surgical extirpation of the primary tumor can theoretically result in a cure and should be done if the patient’s general condition permits.
References 1. Arkless R: Renal carcinoma: how it metastasizes. Radiology 84: 496, 1965 2. Coman RD: Mechanisms responsible for the origin and distribution of blood-borne tumor metastases. Cancer Res 13:397, 1953 3. Creevy CD: Confusing clinical manifestations of malignant renal neoplasms. Arch Intern Med 553395, 1935 4. McDonald JR, Priestley JT: Malignant tumor of the kidneys, surgical and prognostic significance of tumor thrombosis of the renal vein. Surg Gyneco.1 Obstet 77:245, 1943 5. Middleton RG: Surgery for metastatic renal cell carcinoma. J Urol 97:975, 1967 6. Myers GH, Fehrenbaker LG, Kelalis PP: Prognostic significance of renal vein invasion by hypernephroma. J Urol 100:420, 1968 7. Ochsner MG: Renal cell carcinoma: five year follow-up study of 70 cases. J Urol 93:361, 1965 8. Ochsner MG, Braman W: Renal cell carcinoma: review of 26 years of experience at the Ochsner Clinic. J Urol 110:643, 1973 9. Richie EW, Griffiths IH, Thackray AC: New growths of kidney and ureter. Br J Urol 23:297, 1951 10. Silverberg SG, Evans RH, Koehler AL: Clinical and pathologic features of initial metastatic presentations of renal cell carcinoma. Cancer 23: 1126, 1969 11. Svane S: Tumor thrombus of the inferior vena cava resulting from renal carcinoma. Scand J Urol Nephrol3:245, 1969 12. Winterbauer RH, Elfenbeins IB, Ball WC: Incidence and clinical significance of tumor embolization to the lung. Am J Med 45:271, 1968 13. Woo-Ming M, Murray M, Bateson S: Calcified tumor-thrombus of the left pulmonary artery due to metastatic renal carcinoma. Br J Radio1 39:267, 1966
ABSTRACT Recent literature suggests that pulmonary embolus secondary to renal cell carcinoma may be more common than previously suspected. Renal tumors are known for their ability to metastasize early, often before the primary lesion is apparent. A patient with renal cell carcinoma and having massive pulmonary tumor embolus is presented. Attention was called to the occult tumor by the identification of clear cell carcinoma in the pulmonary embolic material. Pulmonary embolectomy and surgical extirpation of the primary tumor resulted in longterm survival.
showed a pH of 7.27, PCQ of 140 mm Hg, and carbon dioxide content of 14. Chest roentgenogram revealed only mild linear atelectasis of both bases. Cyanosis persisted, and pulmonary angiograms were done to evaluate the possibility of pulmonary embolus. This study showed obstruction of the right main pulmonary artery and left lower lobe pulmonary artery (Fig 1). Because of the patient’s dependence upon vasopressors to maintain an adequate blood pressure, an emergency embolectomy was performed. Marked distention of the right heart and pulRenal cell carcinoma with pulmonary embolus monary arteries were noted at operation. On may be more common than previously sup- total cardiopulmonary bypass the main pulmoposed. We report the history of a patient in nary artery was opened, and a mass, totally whom renal cell carcinoma was initially man- occluding the right pulmonary artery, was enifested by a massive pulmonary embolus which countered. Aided by manual compression of the occluded the main right pulmonary artery and right and left lungs, both right and left pulmothe lower division of the left pulmonary artery. nary arteries were cleared of embolic material. Emergency pulmonary embolectomy followed The material removed was unusual in appearby subsequent radical nephrectomy has resulted ance and was submitted for frozen-section exin a 2% year survival to date. amination, which revealed clear cell carcinoma compatible with renal origin (Fig 2). A 68-year-old white man was admitted to the Hemodynamically, the patient had a prompt emergency room following a sudden collapse and satisfactory recovery, but on reacting from outside the hospital after visiting a relative. He anesthesia he manifested aphasia and was found to be unarousable, cyanotic, hemianopia, which gradually improved. After hypotensive, and incontinent of urine and had a cardiovascular recovery, an excretory urogram, head laceration and weak peripheral pulse. Be- renal and carotid angiograms, and inferior cause of hypotension, he was immediately cavogram were performed. The left kidney, uregiven vasopressors, and his systolic pressure ter, and urinary bladder were normal, but derose to 90 mm Hg. The electrocardiogram dem- layed visualization of a few separated calyces in onstrated a small-voltage QRS complex with S-T the right kidney was noted. The angiographic depression in the precordial leads and a right pattern was compatible with renal cell carbundle-branch block. Blood gas determinations cinoma with invasion and replacement of most of the parenchyma of the right kidney. The right From the Departments of Urology and Cardiovascular renal vein was involved, and renal function was Surgery, Cleveland Clinic Foundation, Cleveland, OH. markedly diminished. Inferior cavogram reAccepted for publication Feb 3, 1977. vealed a large filling defect approximately 4 cm Address reprint requests to Dr. Daughtry, Cleveland Clinic, The Clinic Center, 9500 Euclid Ave, Cleveland, OH 44106. in diameter in the vena cava at the level of the 178
179 Case Report: Daughtry et al: Pulmonary Embolus from Renal Cell Carcinoma
A
Fig 2 . Photomicrograph of hemorrhagic pulmonary embolic material diagnostic of clear cell carcinoma. (HDE; X40.)
B
Fig 1 . ( A )Pulmonary angiogram shows massive pulmonary embolus obstructing the right main pulmonary artery with decreased blood flow into the entire right lung field. (B)Pulmonary angiogram shows pulmonary emboli obstructing the left lower lobe pulmonary artery with cutoff of the vascularity in the left rnidlung field.
right renal vein, compatible with tumor thrombus. Bone scan was normal, with no suspicious areas of increased radioactivity to suggest an osteoblastic metastasis. A carotid angiogram performed because of the neurological deficit demonstrated complete occlusion of the left internal carotid artery at its origin; the right common carotid artery appeared to be normal. The carotid obstruction was consistent with cerebral atherosclerosis and thrombosis secondary to the patient’s hypotension rather than to metastatic neoplasm. Computer tomography of the brain performed during this acute neurological problem showed increased uptake over the left cerebral area compatible with an acute stroke, but a metastatic tumor could not be ruled out. Approximately two weeks following pulmonary embolectomy, the patient experienced considerable gross hematuria, colicky right flank pain, and general abdominal discomfort. Cystoscopy was performed, and a large number of
180 The Annals of Thoracic Surgery Vol 24 No 2 August 1977
well-formed clots were noted within the bladder. There appeared to be no gross bladder lesion, and multiple urine specimens showed no tumor cells. Right radical nephrectomy and inferior vena cavotomy were then performed. A large tumor was found in the lower two-thirds of the kidney, and multiple satellite nodules were scattered throughout the kidney parenchyma. Renal veins, particularly those draining the area of the tumor mass, showed intravascular presence of neoplasm, and tumor involved the main renal vein to the cava. The diagnosis of renal cell carcinoma of the clear cell type involving the lower pole of the right kidney was confirmed histologically (Fig 3 ) . The patient had an uneventful recovery from his nephrectomy, and a few days postoperatively he was able to void satisfactorily. Serum creatinine stabilized at 1.5 mgllOO ml; hemoglobin, complete blood count, and SMA-12 were also within normal limits. Chest roentgenogram showed no obvious metastasis; pulmonary Fig3. Photomicrograph of right kidney neoplasm demonstrating renal cell carcinoma of clear cell type. ( H b E ; X160.)
function was normal. There was some improvement in aphasia, with no other neurological findings. The patient’s general health is stable. He had no symptoms of metastasis 30 months postoperatively. Comment Renal cell carcinoma may manifest itself in a bizarre fashion, in this case as a massive pulmonary embolus. Recent literature suggests that pulmonary embolus secondary to renal cell carcinoma may be more common than was formerly suspected [121. These tumors are known for their ability to metastasize early in their course, often before the primary lesion is apparent. The classic triad of flank pain, hematuria, and abdominal mass is present in only approximately 15% of cases [8, 101. About 25% of patients with renal cell carcinoma will have evidence of metastatic disease upon initial examination [5, 71. Metastatic renal cell carcinoma may simulate other tumors in its presentation, and the unusual signs and symptoms make diagnosis extremely difficult. Creevy [ 3 ] and others have stated that malignant renal tumors should be classified with syphilis and tuberculosis among the great mimickers encountered in medicine. In our patient attention was called to the occult tumor by the identification of a clear cell carcinoma in a massive pulmonary embolus. The gross appearance of the operative specimen was atypical for a pure thrombus; therefore, frozen-section examination was performed. Vena cava and renal vein involvement by renal cell carcinoma has been reported by Arkless [l],Coman [21, and Svane [ l l l . The incidence of renal cell carcinoma involving the vena cava or renal vein has varied from 9.5% in Svane’s report to 54% in that of McDonald and Priestley [41. The presence of renal vein involvement increases the possibility of pulmonary emboli. Tumor emboli and pulmonary involvement seem to be common phenomena. Winterbauer and associates [12] and Arkless [l] found that 25% of the pulmonary lesions in this disease were secondary to tumor emboli. Renal cell carcinoma extending into the vena cava ar well as to the renal vein carries a poor progno? ’
181 Case Report: Daughtry et al: Pulmonary Embolus from Renal Cell Carcinoma
McDonald and Priestley [4] noted that 38% of their patients with vascular involvement were dead within one year, compared to 18% of those without extension. Richie and associates [9] reported a 72% mortality over three years following nephrectomy for those with vascular involvement, compared to 51% mortality for those without vascular involvement. Myers and colleagues [61 also reported a poor prognosis for those with vascular involvement, ie, 55% three-year mortality with vascular involvement compared to 29% without. Pulmonary tumor emboli usually occur due to spontaneous release from the primary neoplasm; occasionally they may result from manipulation of the renal vein at the time of nephrectomy. Chemotherapy and irradiation are also believed to predispose the patient to tumor embolization 1131. Recent studies indicate that tumor emboli do not necessarily develop into pulmonary metastases. Some may be destroyed intraluminally or remain latent without parenchymal invasion [12]. Woo-Ming and co-workers [13]reported on a calcified tumor thrombus in the left pulmonary artery of a patient who had undergone radical nephrectomy for renal cell carcinoma 11 years previously. Renal vein extension of the tumor had been noted at the time of nephrectomy, and the patient was asymptomatic without signs of recurrence. Signs of either vena cava obstruction or pulmonary emboli should alert the clinician to the possibility of renal cell carcinoma with invasion of the vena cava. Large intracardiac thrombi secondary to renal cell carcinoma may cause considerable mechanical embarrassment of the tricuspid valve. Anuria, secondary to bilateral renal vein involvement, is also possible and may accompany total occlusion of the inferior vena cava. Sudden death due to tricuspid valve obstruction or massive pulmonary tumor em-
boli can occur. Since these tumor emboli may be destroyed intraluminally, or remain latent without parenchymal invasion, surgical extirpation of the primary tumor can theoretically result in a cure and should be done if the patient’s general condition permits.
References 1. Arkless R: Renal carcinoma: how it metastasizes. Radiology 84: 496, 1965 2. Coman RD: Mechanisms responsible for the origin and distribution of blood-borne tumor metastases. Cancer Res 13:397, 1953 3. Creevy CD: Confusing clinical manifestations of malignant renal neoplasms. Arch Intern Med 553395, 1935 4. McDonald JR, Priestley JT: Malignant tumor of the kidneys, surgical and prognostic significance of tumor thrombosis of the renal vein. Surg Gyneco.1 Obstet 77:245, 1943 5. Middleton RG: Surgery for metastatic renal cell carcinoma. J Urol 97:975, 1967 6. Myers GH, Fehrenbaker LG, Kelalis PP: Prognostic significance of renal vein invasion by hypernephroma. J Urol 100:420, 1968 7. Ochsner MG: Renal cell carcinoma: five year follow-up study of 70 cases. J Urol 93:361, 1965 8. Ochsner MG, Braman W: Renal cell carcinoma: review of 26 years of experience at the Ochsner Clinic. J Urol 110:643, 1973 9. Richie EW, Griffiths IH, Thackray AC: New growths of kidney and ureter. Br J Urol 23:297, 1951 10. Silverberg SG, Evans RH, Koehler AL: Clinical and pathologic features of initial metastatic presentations of renal cell carcinoma. Cancer 23: 1126, 1969 11. Svane S: Tumor thrombus of the inferior vena cava resulting from renal carcinoma. Scand J Urol Nephrol3:245, 1969 12. Winterbauer RH, Elfenbeins IB, Ball WC: Incidence and clinical significance of tumor embolization to the lung. Am J Med 45:271, 1968 13. Woo-Ming M, Murray M, Bateson S: Calcified tumor-thrombus of the left pulmonary artery due to metastatic renal carcinoma. Br J Radio1 39:267, 1966