Case 28-2006 — A 59-Year-Old Man with Masses in Both Kidneys
http://www.100md.com
《新英格兰医药杂志》
Presentation of Case
Dr. Donald S. Kaufman (Division of Medical Oncology): A 59-year-old man was admitted to this hospital for evaluation of bilateral renal masses. Approximately 6 months before this admission, abdominal ultrasonography was performed to evaluate fullness in the right upper quadrant found during a routine physical examination. This study revealed masses in the upper poles of both kidneys, 4.4 cm in diameter on the right and 3.1 cm in diameter on the left. A mass, 2 by 5 cm, filled most of the lumen of the suprarenal inferior vena cava. A Doppler study showed residual flow around the mass. The liver, gallbladder, common bile duct, pancreas, and spleen were normal. Two weeks later, computed tomography (CT) of the abdomen showed bilateral renal masses, each approximately 3 by 4 cm; the one in the right kidney involved the vena cava, with suspected thrombosis. A radiograph of the chest showed no abnormalities.
One month after the ultrasonographic examination, the patient was seen at this hospital for an outpatient urologic evaluation. There was a history of renal calculi, but he had not had recent hematuria, urinary symptoms, flank pain, weight loss, a change in appetite, fevers, or fatigue. He had a history of hypertension, diabetes mellitus, obesity, and polio in childhood that had required surgical correction for shortening of the left leg. Medications were enalapril, glyburide, verapamil, furosemide, and allopurinol. He was married and worked in the printing business. He had no known allergies, drank alcohol socially, and did not use tobacco. One of his parents had died from a stroke, and the other had died from a myocardial infarct; a sibling had hypertension and diabetes. His children were well.
On examination, the blood pressure was 210/80 mm Hg; the other vital signs were normal. The abdomen was obese with no palpable masses. The remainder of the examination was normal. Results of urinalysis were normal, and cytologic examination of the urine revealed renal tubular cells and casts and atypical transitional cells including clusters of transitional cells. A complete blood count, serum electrolyte levels, and liver-function tests were normal; the urea nitrogen level was 15 mg per deciliter (5.4 mmol per liter), and the creatinine level was 0.8 mg per deciliter (70.7 μmol per liter).
Three days later, the patient was seen by a nephrologist. Radioangiography of the kidneys showed symmetric renal function. CT of the thorax showed calcified hilar lymph nodes. A bone scan revealed a single focus of increased activity in the posterior T11 vertebral body, most consistent with the presence of degenerative joint disease; this finding was confirmed by radiographs of the thoracic spine. Fine-needle aspiration guided by CT was used to obtain a sample of a low-attenuation area in the left kidney; pathological examination of the specimen revealed low-grade renal-cell carcinoma. The following week, venacavography revealed a large thrombus in the inferior vena cava at the origin of the right hepatic veins. The right renal vein could not be catheterized.
Two months after the renal biopsy, the patient was admitted to this hospital, and a right nephrectomy and thrombectomy of the mass in the vena cava were performed. Intraoperative transesophageal echocardiography revealed an echodense mass extending up the inferior vena cava to a level 5.5 cm below the right atrium. Histopathological examination of the resected specimen of the kidney revealed a clear-cell renal-cell carcinoma, 7 cm in diameter, nuclear grade 3 according to the Fuhrman grading system (on a scale from 1 to 4, with grade 1 indicating the best prognosis and grade 4 the worst), invading the renal vein and the perirenal fat. The surgical margins were free of tumor. The patient's postoperative recovery was uneventful.
Two months later, repeated CT of the abdomen and pelvis revealed a mass, 5.0 by 4.5 cm, in the upper pole of the left kidney. There was no evidence of tumor recurrence in the right renal bed and no distant metastases. CT of the thorax revealed a stable pericardial lymph node 5 mm in diameter and bilateral calcified hilar lymph nodes.
Three weeks later, the patient was readmitted for resection of the tumor in the left kidney. The urea nitrogen level was 27 mg per deciliter (9.6 mmol per liter), and the creatinine level was 1.6 mg per deciliter (141 μmol per liter). At operation, the tumor was found to be centrally located and adherent to the tail of the pancreas, and the operation was terminated without resection.
Differential Diagnosis
Dr. Kaufman: May we see the CT scan?
Dr. Peter R. Mueller: An axial image obtained 6 months before admission (Figure 1A) shows a solid mass, approximately 4 cm in diameter, in the midpole of the right kidney; medially, there is bulging in the renal vein. This image correlates with the inferior venacavogram, which shows a large thrombus extending from the renal vein up to the level of the diaphragm (Figure 1B). At this time, a smaller mass, approximately 3 to 3.5 cm, was noted in the midpole of the left kidney (Figure 1C).
Figure 1. Imaging Studies at Initial Presentation 6 Months before Admission.
CT of the abdomen reveals a solid mass, approximately 4 cm in diameter, in the right kidney, extending into the collecting system (Panel A, long arrow) and into the vena cava (short arrow). An inferior venacavogram (Panel B) reveals a thrombus (arrows) extending from the right renal vein into the vena cava to the level of the diaphragm. CT of the left kidney (Panel C) reveals a tumor, approximately 3.0 to 3.5 cm in diameter, in the upper pole of the left kidney (arrow).
Dr. W. Scott McDougal: A biopsy of the left kidney was performed because, if the lesion were a benign one, such as an oncocytoma, that finding would affect the choice of therapy and provide latitude in the operative approach and subsequent course. The lesion proved to be a renal-cell carcinoma. Renal-cell carcinoma accounts for approximately 3% of all malignant tumors in adults. One half of all renal-cell carcinomas are discovered incidentally when imaging studies are obtained for symptoms not related to the kidney, as in this case. Although hematuria, flank pain, and a flank mass are considered pathognomonic for the diagnosis of this disease, this triad of symptoms and physical findings is rarely present in the modern era. The most common finding related to the cancer is painless hematuria.
Renal-cell carcinomas are staged according to the size and local extent of the disease: stage 1, 7 cm or less confined to the kidney; stage 2, greater than 7 cm confined to the kidney; stage 3, perinephric involvement; and stage 3b, tumor involving the vena cava below the diaphragm. The stage of this patient's right renal tumor was 3b, and that of the left renal tumor 1. Renal-cell carcinoma involves both kidneys in approximately 2 to 4% of patients, either synchronously or metachronously. The most important prognostic factor is the pathological stage of each tumor. For disease confined to the kidney that is classified as stage 1, as was this patient's left-sided tumor, and that can be totally resected by partial nephrectomy, the 5-year survival rate is approximately 95%.
The right kidney had a tumor thrombus extending into the vena cava. In patients with tumors that involve or extend into the vena cava, the most important prognostic indicators for survival are invasion of the wall of the vena cava and lymph-node involvement. In the experience at this hospital, when either invasion of the wall of the vena cava or lymph-node involvement is present, the 3-year survival rate approaches 0%. However, without these features, the 5-year survival rate is 75%. Since metastatic spread to regional lymph nodes or invasion of the wall of the vena cava by tumor are both such poor prognostic signs, the right kidney was approached first. In this way, had either of these findings been present, there would have been no need to address the tumor in the left kidney, because the prognosis based on the cancer on the right side would have been poor.
A right radical nephrectomy with thrombectomy of the venacaval tumor was performed. This procedure did not require cardiopulmonary bypass, because we used a cross-clamp on the vena cava below the hepatic-vein outflow. Had cardiopulmonary bypass been necessary, we would probably have used moderate hypothermia without circulatory arrest. Another technique of cardiopulmonary bypass in this situation is deep hypothermia with circulatory arrest, which renders the technical removal of the tumor bloodless and therefore less cumbersome. However, this technique results in an increased risk of postoperative renal and hepatic failure, which can be avoided by using moderate hypothermia without circulatory arrest.1
Pathological Discussion
Dr. Kristina Braaten: The specimens obtained on fine-needle aspiration (Figure 2A) and core biopsy (Figure 2B) of the lesion in the left kidney revealed grade 1 clear-cell renal-cell carcinoma. The specimen obtained from the right radical nephrectomy contained a mass, 7 by 5 cm, which bulged beneath the capsule in the superior pole of the kidney. The mass was yellow–tan with areas of hemorrhage. The renal vein contained a tumor thrombus, 2 cm in diameter, that protruded 5 cm beyond the vascular margin (Figure 3A). No lymph nodes were identified. On microscopical examination, the tumor was composed of solid nests and blood-filled tubules containing polygonal cells with abundant clear cytoplasm, typical of clear-cell renal-cell carcinoma. There was invasion of the renal hilar fat. Most of the tumor had nuclear features corresponding to Fuhrman grade 2 (Figure 3B); however, focally, the tumor was grade 3 (Figure 3C). Heterogeneity of grade within renal-cell carcinoma is a well-recognized phenomenon, and it is generally recommended that the tumor be assigned the worst grade. Grade is the second most important prognostic feature after stage, with 10-year disease-specific survival rates of 88%, 75%, and 40% for grades 1, 2, and 3, respectively, and a 5-year survival rate of 31% for grade 4.2 In summary, the patient had bilateral clear-cell renal-cell carcinoma, grade 1, clinical tumor stage 1 on the left side, and grade 3, pathological tumor stage 3b on the right side.
Figure 2. Biopsy Specimens of the Left Kidney.
In the specimen obtained by fine-needle aspiration (Panel A), clusters of carcinoma cells are present with abundant pale cytoplasm delineated by a delicate cell membrane (arrow) (Papanicolau's stain). In the core-biopsy specimen (Panel B), sheets of polygonal cells with abundant clear cytoplasm and small round nuclei are present, associated with a delicate vascular network (hematoxylin and eosin). These features are typical of renal-cell carcinoma, Fuhrman grade 1.
Figure 3. The Specimen Obtained on Right Radical Nephrectomy (Hematoxylin and Eosin).
At low magnification (Panel A), tumor is seen within the lumen of the vein and adherent to the wall of the vein (arrow). At higher magnification (Panel B), the tumor cells have nuclei that are slightly larger than those of the left renal tumor and nucleoli are evident on a high-power view. These features are consistent with Fuhrman grade 2. Areas of tumor with larger, more irregular nuclei and prominent nucleoli were also seen (Panel C), fulfilling criteria for renal-cell carcinoma, Fuhrman grade 3.
Discussion of Management
Dr. McDougal: In this case, the prognosis based on the tumor stage of the right renal cancer was good, and therefore the tumor in the contralateral kidney needed to be addressed. The survival rate among patients with contralateral disease is dependent on the stage of the tumor in each kidney. In this case, a tumor less than 4 cm in diameter confined to the kidney (stage 1) would carry an excellent prognosis (5-year survival rate of 70 to 90%). However, this patient's contralateral tumor was centrally located, and he had diabetes and the creatinine level was 1.6 mg per deciliter (141 μmol per liter) after the right nephrectomy. In a patient with diabetes and diabetic nephropathy, reducing the nephron function by removing the bulk of the remaining renal tissue would increase the risk of the development of renal failure. In preparation for the surgery, the patient was seen by a nephrologist for a thorough discussion of dialysis and its consequences.
Dr. Nina E. Tolkoff-Rubin: This patient had already undergone a right radical nephrectomy, and further surgery on the left kidney would most probably have led to chronic renal failure requiring renal-replacement therapy. Among patients receiving dialysis, the mortality rate is 20 to 25% per year, with cardiovascular disease the primary cause of death, and among patients with obesity and diabetes who are receiving dialysis, the outcome can be poor. If the patient's renal function was already impaired as a result of the removal of the right kidney, then deterioration to end-stage renal failure might be rapid (several months) if three quarters of the left kidney were also removed. Because of this patient's cancer, he would not be a candidate for transplantation for at least 2 years, and then only if there were no evidence of metastatic disease.
The patient explicitly wanted to avoid hemodialysis, which would be required three times a week and would require vascular access, restrictions in terms of dietary and fluid intake, and generalized changes in the quality of his life. Peritoneal dialysis as a home-based therapy might offer more independence but would require four to five exchanges daily, 7 days a week. For this reason, the patient wanted options for alternative treatment of his renal-cell carcinoma.
Dr. McDougal: We performed surgical exploration, intending to remove part of the left kidney, if we could do so without jeopardizing the function of the remaining kidney. On exploration, it became clear that removal of the tumor would have resulted in removal of such a large portion of the kidney that the patient would have been at high risk for progressive renal failure. In addition, because of a marked inflammatory response around the kidney as a result of prior pancreatitis and because of the tumor's central location, it appeared that an attempted partial resection would place the patient at high risk for losing the kidney altogether. In view of these findings, we decided not to remove the kidney. At this hospital, we have had experience with radiofrequency ablation, and the patient was referred to Dr. Mueller.
Dr. Mueller: Radiofrequency ablation is one of several methods of thermal ablation of tissue that has been described during the past 10 years.3,4,5,6,7 In radiofrequency ablation, alternating current is applied within the radiofrequency range through a needle through which an electrode is advanced.8 The electrical current from the electrode produces ion agitation, causing friction and heating of the tissue. Coagulative necrosis is produced in a controlled area, which is defined by the type of needle used as the probe.
Generally, the best results have been achieved in tumors less than 5 cm in greatest dimension. The standard indications for the use of radiofrequency ablation in renal-cell carcinoma are coexisting diseases that prevent patients from being good candidates for surgery, a life expectancy of less than 10 years, the presence of a solitary kidney, and von Hippel–Lindau disease.
In a series of 100 renal-cell tumors treated with radiofrequency ablation at this hospital,6,7 all tumors that were less than 4 cm in diameter were completely ablated. Tumors that were centrally located and larger, such as those described in this case, were more difficult to ablate completely. Because this procedure is relatively new, data on long-term survival are limited. However, in 16 patients followed for 4 or more years,9 there was no evidence of recurrence of completely treated tumors or of death related to tumor. The rate of complications from this procedure has been relatively low, with admission for bleeding required for only 2 of 100 patients and ureteral injury resulting from the ablation occurring in 2 patients.4
The patient under discussion was a candidate for radiofrequency ablation of the tumor in the left kidney because of the coexistence of diabetes, the presence of a single kidney, and his desire to avoid dialysis. At the initial treatment, 4 months after the right nephrectomy, a second area along the anterior middle renal parenchyma suggestive of carcinoma was identified on CT. We treated the upper-pole lesion using a single electrode for 12 minutes (Figure 4A); a biopsy specimen of the second lesion was then obtained through another puncture site, and a 12-minute radiofrequency treatment was applied to that lesion. During the next 9 months, three additional treatments were required to ablate completely the enhancing upper-pole lesion.
Figure 4. Radiofrequency Ablation and Follow-up Images.
A CT scan (Panel A) obtained with the patient in the prone position shows a single probe in the left kidney that was used for the administration of radiofrequency. On follow-up CT (Panel B) two years after the treatment for recurrent tumor at the site of the cancer in the left upper pole of the kidney, a large area of low-density material is present, suggesting a large area of tumor necrosis (arrow).
Dr. Kaufman: The patient did well for more than 3 years. As part of his regular follow-up examination at that time, CT of the chest showed a mass in the upper lobe of the left lung, which almost certainly represented metastatic disease. There were no other sites of metastatic disease on other studies, and a needle biopsy was performed.
Dr. Braaten: A fine-needle aspiration of the lesion in the left upper lobe revealed clusters of tumor cells with features consistent with metastatic renal-cell carcinoma.
Dr. Kaufman: Dr. Michaelson, this patient feels very well and has metastatic disease in a single lung nodule. What are the management considerations at this point?
Dr. M. Dror Michaelson: Numerous studies have examined the outcome of patients with a solitary metastasis of renal-cell carcinoma, treated with resection. A recent large series suggested that up to 50% of patients with a solitary pulmonary metastasis who undergo resection have disease-free survival of up to 5 years.10 In this case, where careful staging has shown no other evidence of metastases, I would recommend complete surgical removal of the solitary metastasis, if possible.
Dr. Braaten: A left upper lobectomy performed 3.5 years after the right nephrectomy confirmed the presence of a parenchymal nodule of metastatic renal-cell carcinoma, 1.7 cm in largest dimension.
Dr. Kaufman: About 14 months after the lobectomy, almost 5 years after the nephrectomy, abdominal CT showed an enhancing tumor, 4.5 cm in diameter, at the site of the cancer in the left upper pole.
Dr. Mueller: The recurrent tumor was treated with radiofrequency ablation four times during a single procedure, with needles in different positions. Two years later, there has been no recurrence of tumor within the kidney (Figure 4B).
Anatomical Diagnosis
Renal-cell carcinoma, clear-cell type, involving both kidneys, with solitary metastasis to the right lung.
No potential conflict of interest relevant to this article was reported.
Source Information
From the Departments of Urology (W.S.M.), Medicine (M.D.M.), Radiology (P.R.M.), and Pathology (K.B.) and the Division of Nephrology (N.E.T.-R.), Massachusetts General Hospital; and the Departments of Urology (W.S.M.), Medicine (N.E.T.-R., M.D.M.), Radiology (P.R.M.), and Pathology (K.B.), Harvard Medical School.
References
Stewart JR, Carey JA, McDougal WS, Merrill WH, Koch MO, Bender HW Jr. Cavoatrial tumor thrombectomy using cardiopulmonary bypass without circulatory arrest. Ann Thorac Surg 1991;51:717-722.
Ficarra V, Righetti R, Martignoni G, et al. Prognostic value of renal cell carcinoma nuclear grading: multivariate analysis of 333 cases. Urol Int 2001;67:130-134.
Farrell MA, Charboneau WJ, DiMarco DS. Image-guided radiofrequency ablation of solid renal tumors. AJR Am J Roentgenol 2003;180:1509-1513.
Gervais DA, McGovern FJ, Arellano RS, McGovern WS, Mueller PR. Radiofrequency ablation of renal cell carcinoma. I. Indications, results, and role in patient management over a 6-year period and ablation of 100 tumors. AJR Am J Roentgenol 2005;185:64-71.
Mayo-Smith WW, Dupuy DE, Parikh PM, Pezzullo JA, Cronan JJ. Imaging-guided percutaneous radiofrequency ablation of solid renal masses: techniques and outcomes of 38 treatment sessions in 32 consecutive patients. AJR Am J Roentgenol 2003;180:1503-1508.
McGovern FJ, Wood BJ, Goldberg SN, Mueller PR. Radiofrequency ablation of renal cell carcinoma via image guided needle electrodes. J Urol 1999;161:599-600.
Zagoria RJ, Hawkins AD, Clark PE, et al. Percutaneous CT-guided radiofrequency ablation of renal neoplasms: factors influencing success. AJR Am J Roentgenol 2004;183:201-207.
McDougal WS, Gervais DA, McGovern FJ, Mueller PR. Long-term follow up of patients with renal cell carcinoma treated by radiofrequency ablation with curative intent. J Urol 2005;174:61-63.
Dupuy DE, Goldberg SN. Image-guided radiofrequency tumor ablation: challenges and opportunities. J Vasc Interv Radiol 2001;12:1135-1148.
Hofmann HS, Neef H, Krohe K, Andreev P, Silber RE. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol 2005;48:77-81.(W. Scott McDougal, M.D., )
Dr. Donald S. Kaufman (Division of Medical Oncology): A 59-year-old man was admitted to this hospital for evaluation of bilateral renal masses. Approximately 6 months before this admission, abdominal ultrasonography was performed to evaluate fullness in the right upper quadrant found during a routine physical examination. This study revealed masses in the upper poles of both kidneys, 4.4 cm in diameter on the right and 3.1 cm in diameter on the left. A mass, 2 by 5 cm, filled most of the lumen of the suprarenal inferior vena cava. A Doppler study showed residual flow around the mass. The liver, gallbladder, common bile duct, pancreas, and spleen were normal. Two weeks later, computed tomography (CT) of the abdomen showed bilateral renal masses, each approximately 3 by 4 cm; the one in the right kidney involved the vena cava, with suspected thrombosis. A radiograph of the chest showed no abnormalities.
One month after the ultrasonographic examination, the patient was seen at this hospital for an outpatient urologic evaluation. There was a history of renal calculi, but he had not had recent hematuria, urinary symptoms, flank pain, weight loss, a change in appetite, fevers, or fatigue. He had a history of hypertension, diabetes mellitus, obesity, and polio in childhood that had required surgical correction for shortening of the left leg. Medications were enalapril, glyburide, verapamil, furosemide, and allopurinol. He was married and worked in the printing business. He had no known allergies, drank alcohol socially, and did not use tobacco. One of his parents had died from a stroke, and the other had died from a myocardial infarct; a sibling had hypertension and diabetes. His children were well.
On examination, the blood pressure was 210/80 mm Hg; the other vital signs were normal. The abdomen was obese with no palpable masses. The remainder of the examination was normal. Results of urinalysis were normal, and cytologic examination of the urine revealed renal tubular cells and casts and atypical transitional cells including clusters of transitional cells. A complete blood count, serum electrolyte levels, and liver-function tests were normal; the urea nitrogen level was 15 mg per deciliter (5.4 mmol per liter), and the creatinine level was 0.8 mg per deciliter (70.7 μmol per liter).
Three days later, the patient was seen by a nephrologist. Radioangiography of the kidneys showed symmetric renal function. CT of the thorax showed calcified hilar lymph nodes. A bone scan revealed a single focus of increased activity in the posterior T11 vertebral body, most consistent with the presence of degenerative joint disease; this finding was confirmed by radiographs of the thoracic spine. Fine-needle aspiration guided by CT was used to obtain a sample of a low-attenuation area in the left kidney; pathological examination of the specimen revealed low-grade renal-cell carcinoma. The following week, venacavography revealed a large thrombus in the inferior vena cava at the origin of the right hepatic veins. The right renal vein could not be catheterized.
Two months after the renal biopsy, the patient was admitted to this hospital, and a right nephrectomy and thrombectomy of the mass in the vena cava were performed. Intraoperative transesophageal echocardiography revealed an echodense mass extending up the inferior vena cava to a level 5.5 cm below the right atrium. Histopathological examination of the resected specimen of the kidney revealed a clear-cell renal-cell carcinoma, 7 cm in diameter, nuclear grade 3 according to the Fuhrman grading system (on a scale from 1 to 4, with grade 1 indicating the best prognosis and grade 4 the worst), invading the renal vein and the perirenal fat. The surgical margins were free of tumor. The patient's postoperative recovery was uneventful.
Two months later, repeated CT of the abdomen and pelvis revealed a mass, 5.0 by 4.5 cm, in the upper pole of the left kidney. There was no evidence of tumor recurrence in the right renal bed and no distant metastases. CT of the thorax revealed a stable pericardial lymph node 5 mm in diameter and bilateral calcified hilar lymph nodes.
Three weeks later, the patient was readmitted for resection of the tumor in the left kidney. The urea nitrogen level was 27 mg per deciliter (9.6 mmol per liter), and the creatinine level was 1.6 mg per deciliter (141 μmol per liter). At operation, the tumor was found to be centrally located and adherent to the tail of the pancreas, and the operation was terminated without resection.
Differential Diagnosis
Dr. Kaufman: May we see the CT scan?
Dr. Peter R. Mueller: An axial image obtained 6 months before admission (Figure 1A) shows a solid mass, approximately 4 cm in diameter, in the midpole of the right kidney; medially, there is bulging in the renal vein. This image correlates with the inferior venacavogram, which shows a large thrombus extending from the renal vein up to the level of the diaphragm (Figure 1B). At this time, a smaller mass, approximately 3 to 3.5 cm, was noted in the midpole of the left kidney (Figure 1C).
Figure 1. Imaging Studies at Initial Presentation 6 Months before Admission.
CT of the abdomen reveals a solid mass, approximately 4 cm in diameter, in the right kidney, extending into the collecting system (Panel A, long arrow) and into the vena cava (short arrow). An inferior venacavogram (Panel B) reveals a thrombus (arrows) extending from the right renal vein into the vena cava to the level of the diaphragm. CT of the left kidney (Panel C) reveals a tumor, approximately 3.0 to 3.5 cm in diameter, in the upper pole of the left kidney (arrow).
Dr. W. Scott McDougal: A biopsy of the left kidney was performed because, if the lesion were a benign one, such as an oncocytoma, that finding would affect the choice of therapy and provide latitude in the operative approach and subsequent course. The lesion proved to be a renal-cell carcinoma. Renal-cell carcinoma accounts for approximately 3% of all malignant tumors in adults. One half of all renal-cell carcinomas are discovered incidentally when imaging studies are obtained for symptoms not related to the kidney, as in this case. Although hematuria, flank pain, and a flank mass are considered pathognomonic for the diagnosis of this disease, this triad of symptoms and physical findings is rarely present in the modern era. The most common finding related to the cancer is painless hematuria.
Renal-cell carcinomas are staged according to the size and local extent of the disease: stage 1, 7 cm or less confined to the kidney; stage 2, greater than 7 cm confined to the kidney; stage 3, perinephric involvement; and stage 3b, tumor involving the vena cava below the diaphragm. The stage of this patient's right renal tumor was 3b, and that of the left renal tumor 1. Renal-cell carcinoma involves both kidneys in approximately 2 to 4% of patients, either synchronously or metachronously. The most important prognostic factor is the pathological stage of each tumor. For disease confined to the kidney that is classified as stage 1, as was this patient's left-sided tumor, and that can be totally resected by partial nephrectomy, the 5-year survival rate is approximately 95%.
The right kidney had a tumor thrombus extending into the vena cava. In patients with tumors that involve or extend into the vena cava, the most important prognostic indicators for survival are invasion of the wall of the vena cava and lymph-node involvement. In the experience at this hospital, when either invasion of the wall of the vena cava or lymph-node involvement is present, the 3-year survival rate approaches 0%. However, without these features, the 5-year survival rate is 75%. Since metastatic spread to regional lymph nodes or invasion of the wall of the vena cava by tumor are both such poor prognostic signs, the right kidney was approached first. In this way, had either of these findings been present, there would have been no need to address the tumor in the left kidney, because the prognosis based on the cancer on the right side would have been poor.
A right radical nephrectomy with thrombectomy of the venacaval tumor was performed. This procedure did not require cardiopulmonary bypass, because we used a cross-clamp on the vena cava below the hepatic-vein outflow. Had cardiopulmonary bypass been necessary, we would probably have used moderate hypothermia without circulatory arrest. Another technique of cardiopulmonary bypass in this situation is deep hypothermia with circulatory arrest, which renders the technical removal of the tumor bloodless and therefore less cumbersome. However, this technique results in an increased risk of postoperative renal and hepatic failure, which can be avoided by using moderate hypothermia without circulatory arrest.1
Pathological Discussion
Dr. Kristina Braaten: The specimens obtained on fine-needle aspiration (Figure 2A) and core biopsy (Figure 2B) of the lesion in the left kidney revealed grade 1 clear-cell renal-cell carcinoma. The specimen obtained from the right radical nephrectomy contained a mass, 7 by 5 cm, which bulged beneath the capsule in the superior pole of the kidney. The mass was yellow–tan with areas of hemorrhage. The renal vein contained a tumor thrombus, 2 cm in diameter, that protruded 5 cm beyond the vascular margin (Figure 3A). No lymph nodes were identified. On microscopical examination, the tumor was composed of solid nests and blood-filled tubules containing polygonal cells with abundant clear cytoplasm, typical of clear-cell renal-cell carcinoma. There was invasion of the renal hilar fat. Most of the tumor had nuclear features corresponding to Fuhrman grade 2 (Figure 3B); however, focally, the tumor was grade 3 (Figure 3C). Heterogeneity of grade within renal-cell carcinoma is a well-recognized phenomenon, and it is generally recommended that the tumor be assigned the worst grade. Grade is the second most important prognostic feature after stage, with 10-year disease-specific survival rates of 88%, 75%, and 40% for grades 1, 2, and 3, respectively, and a 5-year survival rate of 31% for grade 4.2 In summary, the patient had bilateral clear-cell renal-cell carcinoma, grade 1, clinical tumor stage 1 on the left side, and grade 3, pathological tumor stage 3b on the right side.
Figure 2. Biopsy Specimens of the Left Kidney.
In the specimen obtained by fine-needle aspiration (Panel A), clusters of carcinoma cells are present with abundant pale cytoplasm delineated by a delicate cell membrane (arrow) (Papanicolau's stain). In the core-biopsy specimen (Panel B), sheets of polygonal cells with abundant clear cytoplasm and small round nuclei are present, associated with a delicate vascular network (hematoxylin and eosin). These features are typical of renal-cell carcinoma, Fuhrman grade 1.
Figure 3. The Specimen Obtained on Right Radical Nephrectomy (Hematoxylin and Eosin).
At low magnification (Panel A), tumor is seen within the lumen of the vein and adherent to the wall of the vein (arrow). At higher magnification (Panel B), the tumor cells have nuclei that are slightly larger than those of the left renal tumor and nucleoli are evident on a high-power view. These features are consistent with Fuhrman grade 2. Areas of tumor with larger, more irregular nuclei and prominent nucleoli were also seen (Panel C), fulfilling criteria for renal-cell carcinoma, Fuhrman grade 3.
Discussion of Management
Dr. McDougal: In this case, the prognosis based on the tumor stage of the right renal cancer was good, and therefore the tumor in the contralateral kidney needed to be addressed. The survival rate among patients with contralateral disease is dependent on the stage of the tumor in each kidney. In this case, a tumor less than 4 cm in diameter confined to the kidney (stage 1) would carry an excellent prognosis (5-year survival rate of 70 to 90%). However, this patient's contralateral tumor was centrally located, and he had diabetes and the creatinine level was 1.6 mg per deciliter (141 μmol per liter) after the right nephrectomy. In a patient with diabetes and diabetic nephropathy, reducing the nephron function by removing the bulk of the remaining renal tissue would increase the risk of the development of renal failure. In preparation for the surgery, the patient was seen by a nephrologist for a thorough discussion of dialysis and its consequences.
Dr. Nina E. Tolkoff-Rubin: This patient had already undergone a right radical nephrectomy, and further surgery on the left kidney would most probably have led to chronic renal failure requiring renal-replacement therapy. Among patients receiving dialysis, the mortality rate is 20 to 25% per year, with cardiovascular disease the primary cause of death, and among patients with obesity and diabetes who are receiving dialysis, the outcome can be poor. If the patient's renal function was already impaired as a result of the removal of the right kidney, then deterioration to end-stage renal failure might be rapid (several months) if three quarters of the left kidney were also removed. Because of this patient's cancer, he would not be a candidate for transplantation for at least 2 years, and then only if there were no evidence of metastatic disease.
The patient explicitly wanted to avoid hemodialysis, which would be required three times a week and would require vascular access, restrictions in terms of dietary and fluid intake, and generalized changes in the quality of his life. Peritoneal dialysis as a home-based therapy might offer more independence but would require four to five exchanges daily, 7 days a week. For this reason, the patient wanted options for alternative treatment of his renal-cell carcinoma.
Dr. McDougal: We performed surgical exploration, intending to remove part of the left kidney, if we could do so without jeopardizing the function of the remaining kidney. On exploration, it became clear that removal of the tumor would have resulted in removal of such a large portion of the kidney that the patient would have been at high risk for progressive renal failure. In addition, because of a marked inflammatory response around the kidney as a result of prior pancreatitis and because of the tumor's central location, it appeared that an attempted partial resection would place the patient at high risk for losing the kidney altogether. In view of these findings, we decided not to remove the kidney. At this hospital, we have had experience with radiofrequency ablation, and the patient was referred to Dr. Mueller.
Dr. Mueller: Radiofrequency ablation is one of several methods of thermal ablation of tissue that has been described during the past 10 years.3,4,5,6,7 In radiofrequency ablation, alternating current is applied within the radiofrequency range through a needle through which an electrode is advanced.8 The electrical current from the electrode produces ion agitation, causing friction and heating of the tissue. Coagulative necrosis is produced in a controlled area, which is defined by the type of needle used as the probe.
Generally, the best results have been achieved in tumors less than 5 cm in greatest dimension. The standard indications for the use of radiofrequency ablation in renal-cell carcinoma are coexisting diseases that prevent patients from being good candidates for surgery, a life expectancy of less than 10 years, the presence of a solitary kidney, and von Hippel–Lindau disease.
In a series of 100 renal-cell tumors treated with radiofrequency ablation at this hospital,6,7 all tumors that were less than 4 cm in diameter were completely ablated. Tumors that were centrally located and larger, such as those described in this case, were more difficult to ablate completely. Because this procedure is relatively new, data on long-term survival are limited. However, in 16 patients followed for 4 or more years,9 there was no evidence of recurrence of completely treated tumors or of death related to tumor. The rate of complications from this procedure has been relatively low, with admission for bleeding required for only 2 of 100 patients and ureteral injury resulting from the ablation occurring in 2 patients.4
The patient under discussion was a candidate for radiofrequency ablation of the tumor in the left kidney because of the coexistence of diabetes, the presence of a single kidney, and his desire to avoid dialysis. At the initial treatment, 4 months after the right nephrectomy, a second area along the anterior middle renal parenchyma suggestive of carcinoma was identified on CT. We treated the upper-pole lesion using a single electrode for 12 minutes (Figure 4A); a biopsy specimen of the second lesion was then obtained through another puncture site, and a 12-minute radiofrequency treatment was applied to that lesion. During the next 9 months, three additional treatments were required to ablate completely the enhancing upper-pole lesion.
Figure 4. Radiofrequency Ablation and Follow-up Images.
A CT scan (Panel A) obtained with the patient in the prone position shows a single probe in the left kidney that was used for the administration of radiofrequency. On follow-up CT (Panel B) two years after the treatment for recurrent tumor at the site of the cancer in the left upper pole of the kidney, a large area of low-density material is present, suggesting a large area of tumor necrosis (arrow).
Dr. Kaufman: The patient did well for more than 3 years. As part of his regular follow-up examination at that time, CT of the chest showed a mass in the upper lobe of the left lung, which almost certainly represented metastatic disease. There were no other sites of metastatic disease on other studies, and a needle biopsy was performed.
Dr. Braaten: A fine-needle aspiration of the lesion in the left upper lobe revealed clusters of tumor cells with features consistent with metastatic renal-cell carcinoma.
Dr. Kaufman: Dr. Michaelson, this patient feels very well and has metastatic disease in a single lung nodule. What are the management considerations at this point?
Dr. M. Dror Michaelson: Numerous studies have examined the outcome of patients with a solitary metastasis of renal-cell carcinoma, treated with resection. A recent large series suggested that up to 50% of patients with a solitary pulmonary metastasis who undergo resection have disease-free survival of up to 5 years.10 In this case, where careful staging has shown no other evidence of metastases, I would recommend complete surgical removal of the solitary metastasis, if possible.
Dr. Braaten: A left upper lobectomy performed 3.5 years after the right nephrectomy confirmed the presence of a parenchymal nodule of metastatic renal-cell carcinoma, 1.7 cm in largest dimension.
Dr. Kaufman: About 14 months after the lobectomy, almost 5 years after the nephrectomy, abdominal CT showed an enhancing tumor, 4.5 cm in diameter, at the site of the cancer in the left upper pole.
Dr. Mueller: The recurrent tumor was treated with radiofrequency ablation four times during a single procedure, with needles in different positions. Two years later, there has been no recurrence of tumor within the kidney (Figure 4B).
Anatomical Diagnosis
Renal-cell carcinoma, clear-cell type, involving both kidneys, with solitary metastasis to the right lung.
No potential conflict of interest relevant to this article was reported.
Source Information
From the Departments of Urology (W.S.M.), Medicine (M.D.M.), Radiology (P.R.M.), and Pathology (K.B.) and the Division of Nephrology (N.E.T.-R.), Massachusetts General Hospital; and the Departments of Urology (W.S.M.), Medicine (N.E.T.-R., M.D.M.), Radiology (P.R.M.), and Pathology (K.B.), Harvard Medical School.
References
Stewart JR, Carey JA, McDougal WS, Merrill WH, Koch MO, Bender HW Jr. Cavoatrial tumor thrombectomy using cardiopulmonary bypass without circulatory arrest. Ann Thorac Surg 1991;51:717-722.
Ficarra V, Righetti R, Martignoni G, et al. Prognostic value of renal cell carcinoma nuclear grading: multivariate analysis of 333 cases. Urol Int 2001;67:130-134.
Farrell MA, Charboneau WJ, DiMarco DS. Image-guided radiofrequency ablation of solid renal tumors. AJR Am J Roentgenol 2003;180:1509-1513.
Gervais DA, McGovern FJ, Arellano RS, McGovern WS, Mueller PR. Radiofrequency ablation of renal cell carcinoma. I. Indications, results, and role in patient management over a 6-year period and ablation of 100 tumors. AJR Am J Roentgenol 2005;185:64-71.
Mayo-Smith WW, Dupuy DE, Parikh PM, Pezzullo JA, Cronan JJ. Imaging-guided percutaneous radiofrequency ablation of solid renal masses: techniques and outcomes of 38 treatment sessions in 32 consecutive patients. AJR Am J Roentgenol 2003;180:1503-1508.
McGovern FJ, Wood BJ, Goldberg SN, Mueller PR. Radiofrequency ablation of renal cell carcinoma via image guided needle electrodes. J Urol 1999;161:599-600.
Zagoria RJ, Hawkins AD, Clark PE, et al. Percutaneous CT-guided radiofrequency ablation of renal neoplasms: factors influencing success. AJR Am J Roentgenol 2004;183:201-207.
McDougal WS, Gervais DA, McGovern FJ, Mueller PR. Long-term follow up of patients with renal cell carcinoma treated by radiofrequency ablation with curative intent. J Urol 2005;174:61-63.
Dupuy DE, Goldberg SN. Image-guided radiofrequency tumor ablation: challenges and opportunities. J Vasc Interv Radiol 2001;12:1135-1148.
Hofmann HS, Neef H, Krohe K, Andreev P, Silber RE. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol 2005;48:77-81.(W. Scott McDougal, M.D., )