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Enlargement of Regional Lymph Nodes in Renal Cell Carcinoma is Often not Due to Metastases
oo22-5347~Yo/1442-02433S02.00/C T H E JOGRNAL O F UROLOGY Copyright % 1990by AMERICAN UROLOGICAL ASSOCIATION. INC
Vol. 114, August Prinied In C.S.A.
ENLARGEMENT OF REGIONAL LYMPH NODES IN RENAL CELL CARCINOMA IS OFTEN NOT DUE TO METASTASES U R S E. S T U D E R , S T E P H A N I E S C H E R Z , J U R G S C H E I D E G G E R , R A I N E R K R A F T , R O L A N D S O N N T A G , D A N I E L A C K E R M A N N A N D ERNST J. ZINGG From the Department of Urology and Institutes for Diagnostic Radiology, Medical Oncology and Pathology, Inselspital, University of Berne, Berne, Switzerland
ABSTRACT
Preoperative axial computerized tomography scans i n 163 patients with renal cell carcinoma were reviewed t o assess t h e predictive value for t h e diagnosis of regional lymph node metastases. Computerized tomography was falsely negative in 5 patients: 2 h a d metastatic lymph nodes in t h e renal hilus adjacent t o t h e primary tumor measuring 2 a n d 2.5 cm., a n d 3 h a d micrometastases i n nodes of less t h a n 1cm. I n 43 patients enlarged lymph nodes with a diameter of 1t o 2.2 cm. (median 1.4 cm.) were diagnosed o n t h e preoperative scan a n d this was confirmed a t nephrectomy a n d pathologically. I n 18 of these 43 patients (42%) histological study showed metastases of t h e renal cell carcinoma i n t h e enlarged lymph nodes. I n t h e other 25 patients (58%) t h e enlarged nodes showed only inflammatory changes and/or follicular hyperplasia. T h i s finding was significantly more frequent i n patients with t u m o r involvement of t h e renal vein a n d tumor necrosis (p = 0.0044). W e conclude t h a t t h e sensitivity of preoperative computerized tomography is good for t h e detection of enlarged l y m p h nodes i n patients with renal cell cancer (95%). However, significant lymph node enlargement frequently may be caused by inflammatory changes, especially in t h e presence of t u m o r necrosis. T h i s radiological finding should not be misinterpreted as metastatic disease, unless it h a s been proved cytologically by fine needle aspiration. (J.Urol., 144: 243-245, 1990) The presence of regional lymph node metastases implies a poor prognosis for patients with renal cell carcinoma. Reported 5-year survival after radical nephrectomy combined with regional lymphadenectomy in series with more than 10 patients who had positive nodes varies between 7 and 17%.1-4Moreover, most of the long-term survivors had microscopic nodal metastases found only a t histological examination. In the series by Petkovic with gross nodal involvement only 1 of 46 patients (2%) survived longer than 5 years.' Due to the prognostic importance of macroscopic regional lymph node involvement in patients with renal cell carcinoma the preoperative assessment can be important. We analyzed whether this can be done accurately by axial computerized tomography (CT). PATIENTS AND METHODS
The nodal status was analyzed retrospectively on preoperative axial CT scans in 163 consecutive patients who underwent radical nephrectomy (158) or partial nephrectomy (5) combined with regional lymph node dissection for renal cell cancer at our institution between 1980 and 1988. The 100 men and 63 women were 39 to 85 years old (mean age 61.6 years) at operation. The tumor was on the right side in 95 patients and on the left side in 68. Nephrectomy usually was performed through a subcostal, tenth or eleventh interspace extrapleural incision or a thoracoretroperitoneal approach. Basically, the regional lymph nodes were removed according to the proposal of Marshall and Powell.' On the right side the nodes were removed all around the vena cava from the gonadal vein or bifurcation to the crus of the diaphragm and along the renal artery towards the aorta. On the left side the nodes were removed along the ventral and lateral aspects of the aorta from the inferior mesenteric artery to the diaphragm. The tumors were classified according to the tumor, nodes and metastasis system of the International Union Against C a n ~ e rThe . ~ majority of the tumors invaded the renal capsule or perirenal fat (stage pT2 or pT3, table 1). Of the patients 16 Accepted for publication February 1, 1990.
had evidence of distant metastases at operation. In general, the small bowel was filled with radiopaque fluid before the preoperative CT examination. The areas of the kidneys and regional lymph nodes were analyzed twice at 8 to 10 mm. intervals, that is before and after intravenous contrast medium was given. Without knowing the postoperative pathological nodal status, 1 of us (J. R. S.) reviewed all CT scans unless the nodal status was reported to be normal on preoperative CT, intraoperatively at lymph node dissection and at histological examination. One of us (R. K.) reviewed the histological status of all lymph node specimens in these patients. RESULTS
One to 4 regional lymph nodes measuring 1 to 2.2 cm. (median 1.4 cm.) were diagnosed in 43 of the 163 preoperative CT scans analyzed in patients with renal cell carcinoma (fig. 1). The presence of these enlarged nodes was confirmed intraoperatively and at pathological examination. Histologically, the enlarged lymph nodes in these 43 patients revealed metastatic disease from renal cell carcinoma in 18 (4276, table 2). In 2 of these 18 patients the enlarged lymph nodes contained only small foci of metastatic tissue. In the remaining 25 patients (58%) the histological specimen showed no malignant tissue. Instead, chronic inflammatory changes were found (fig. 2): all enlarged lymph nodes showed dilated lymph sinuses filled with TABLE1. Pathological tumor stage and nodal status in 163patients who underwent a n operation for renal cell carcinoma Pathological Tumor Stage
PT1 P T ~ PT3 pT4 Totals
No, Pts.
15 68 74
6 163
No. (%) Combined With Nodal Metastases (ON+) O(0) 9 (13) 11 (15) - 3 (50) 23 (14)
NO. (5%) Combined With Tumor Thrombus in Vein (pV1/2)
2 (13) 19 (28) 44 (59) 70 (43)
No' With Distant Metastases (Ml - --i
0 (0) 5 (7) 1 0 (13)
1(17) 1 6 110)
244
STUDER AND ASSOCIATES
histological study of the kidney showed tumor involvement of the renal veins, usually together with extensive necrosis of the carcinoma (table 3). Among the 115 patients with nonmetastatic normal sized lymph nodes (less than 1 cm.) thrombotic occlusion of renal veins was found in only 38 specimens (33%). This difference is statistically significant (Pearson's chi-square p = 0.0044). DISCUSSION
FIG. 1. Preoperative CT scans of 2 of 43 patients with enlarged, nonmetastatic lymph nodes (arrows). Typically, large necrotic areas are found within renal tumor. numerous macrophages. The cytoplasm often was clear, containing many small vacuoles and lipid or hemosiderin material. Most of the enlarged, nonmetastatic lymph nodes also showed enlarged germinal centers (fig. 2, A ) . In 2 of 120 patients with regional lymph nodes smaller than 1 cm. on the preoperative CT scan lymph node dissection revealed metastatic nodes 2 and 2.5 cm. in diameter, respectively. In both patients with a false negative CT scan the diseased lymph nodes were in the renal hilus, adjacent to the tumor. In 3 of 118 patients with normal sized lymph nodes on CT, intraoperatively and a t gross pathological examination nodal micrometastases were found histologically. In 16 of the 25 patients (64%) with enlarged nonmetastatic lymph nodes
In urological malignancies other than renal cell cancer enlarged regional lymph nodes (1cm. or more) found on CT imply a high probability of metastatic disease. In prostate cancer, this has been reported to be between 90 and 100%,s-10and in bladder cancer between 80 and 90%.11," Enlarged regional lymph nodes in patients with renal cell carcinoma caused by nonmalignant - ~ ~retrospective changes have been reported o ~ c a s i o n a l l y . ' ~Our study shows that significant lymph node enlargement due t o inflammatory changes is a frequent finding. In more than half of the patients (25 of 43, or 58%) with regional lymph nodes measuring 1 cm. or more no metastatic tissue could be found. Instead, reactive inflammatory changes showing dilated lymph sinuses filled with macrophages containing lipid and hemosiderin material were present, often combined with follicular hyperplasia. Indeed, this finding occurred especially when the primary tumor contained larger areas of necrotic tissue caused by venous occlusions from tumor thrombi. If the 2 patients with microscopic metastasis found in enlarged inflammatory nodes would have been added to the 25 with hyperplastic nodes (because the enlargement was not caused by the micrometastasis but rather by the follicular hyperplasia), the ratio of nonmetastatic-to-metastatic, enlarged lymph nodes would be 2:l. The inability to detect microscopic metastatic deposits with CT and to differentiate between benign and malignant tissue is well known,",17 and accounts for the false negative results in 3 patients with small nodes. In the 2 patients with a 2 and 2.5 cm, nodal metastasis, respectively, not diagnosed on preoperative CT the anatomical situation was identical. In both the metastatic node was in the renal hilus directly adjacent to the tumor and kidney. The lack of fatty tissue between the nodes and kidneys made detection of the enlarged nodes impossible. In our analysis no false positive enlarged nodes were observed, which probably is partly due to enteral and intravenous administration of contrast medium. This makes it unlikely to interpret a nonopacified intestinal loop or prominent renal vessel as an enlarged lymph node. While the sensitivity of CT for the detection of enlarged regional lymph nodes in our patients with renal cell cancer is high (95%),the probability that these enlarged nodes are metastatic is relatively low (42%),especially if the diseased kidney contains extensive areas of necrotic tumor material. Whether magnetic resonance imaging (MRI) would enable better inter-
TABLE2. Findings on preoperative CT, intraoperatively and at histological examination of regional lymph nodes i n 163 patients with renal cell carcinoma Size of Regional Lymph Nodes Intraop. and Gross Pathology
Preop. C T Cm. 1-2.2 (suspicious for metastases)
tases)
No. Pts.
Cm.
No. Pts.
43
1-2.2
43
120
22 <1
2
118
Histological Findings
Metastases No metastases (follicular hyperplasia, inflammatory changes) Metastases Micrometastases No metastases
No. Pts.
18* 25 2t 3 115
Intraoperative/pathological findings confirmed the preoperative CT diagnosis of enlarged lymph nodes (1 to 2.2 cm.) in 43 of 45 patients (sensitivity 95%). However, only 18 of 43 enlarged lymph nodes (42%) contain metastatic tissue. * I n 2 patients the enlarged lymph nodes contained micrometastases only. t In both patients the enlarged metastatic lymph nodes were in the renal hilus and not discernible from the primary tumor in the CT.
ENLARGEMENT O F REGIONAL LYMPH NODES I N RENAL CELL CARCINOMA
245
renal cell carcinoma patients should not be influenced by the presence of enlarged regional lymph nodes on C T alone. Should the presence of regional lymph node metastases from renal cell cancer influence the treatment plan, C T or ultrasound guided fine needle aspiration of the enlarged nodes would be recommended. REFERENCES 1. Bassil, B., Dosoretz, D. E. and Prout, G. R., Jr.: Validation of the
2. 3.
4.
5.
6.
7. 8.
tumor, nodes and metastasis classification of renal cell carcinoma. J . Urol., 134: 450, 1985. Skinner, D. G., Vermillion, C. D. and Colvin, R. B.: The surgical management of renal cell carcinoma. J . Urol., 107: 705, 1972. Marshall, F. F.: Lymphadenectomy for renal cell carcinoma. In: Tumors of the Kidney. International Perspectives in Urology. Edited by J . B. deKernion and M. Pavone-Macaluso. Baltimore: Williams & Wilkins, vol. 13, chapt. 6, pp. 88-97, 1986. Golimbu, M., Joshi, P., Sperber, A., Tessler, A., Al-Askari, S. and Morales, P.: Renal cell carcinoma: survival and prognostic factors. Urology, 27: 291, 1986. Petkovic, S.: The value of tumor tissue penetration into the renal veins and lymph nodes as anatomical classification and kidney tumor prognostic parameters. Eur. Urol., 6: 289, 1980. Marshall, F. F. and Powell, K. C.: Lymphadenectomy for renal cell carcinoma: anatomical and therapeutic considerations. J . Urol., 128: 677, 1982. Harmer, M. H.: T N M Classification of Malignant Turnours. Geneva: International Union Against Cancer, 1978. Levine, M. S., Arger, P. H., Coleman, B. G., Mulhern, C. B., Jr., Pollack, H . M. and Wein, A. J.: Detecting lymphatic metastases from prostatic carcinoma: superiority of CT. AJR, 137: 207,
1981. 9. Mazeman, E., Lemaitre, L., Rigot, J. M. and Lambert, I.: Place of
FIG. 2. Enlarged, nonmetastatic lymph node specimens reveal follicular hyperplasia with numerous germinal centers. A, arrows show some germinal centers. H & E, reduced from X13. B, dilated lymph sinuses are usually filled with macrophages and cytoplasm often is foamy, containing lipid material or hemosiderin possibly deriving from necrotic tumor material. H & E, reduced from X175. TABLE3. Incidence of renal vein tumor thrombus ipVl and pV2, usually comb~nedwith extensive tumor necrosis) in patients with enlarged or normal sized, nonmetastatic lymph nodes
Lymph Nodes (em.)
Nonmetastatic, enlarged (1-2.2) Nonmetastatic, normal sized (
No. Pts.
25
115
Histology Showed Renal Vein Tumor Involvement No. ( Z ) 16 (64) 38 (33)
T h e incidence of renal vein tumor ~nvolvementis significantly higher in the patients with enlarged nonmetastatic lymph nodes (inflammator~.changes plus follicular hyperplasia) t h a n in those with nonmetastatic normal sized lymph nodes (Pearson's chi-square p = 0.0044).
the computed tomography in the staging of prostatic cancer. In: Prostate Cancer, Part B: Imaging Techniques, Radiotherapy, Chemotherapy and Management Issues. Editedby G. P . Murphy, S. Khoury, R. Kuss, C. Chatelain and L. Denis. New York: Alan R. Liss, Inc., vol. 243 B, pp. 55-64, 1987. 10. Platt, J . F., Bree, R. L. and Schwab, R. E.: The accuracy of C T in the staging of carcinoma of the prostate. AJR, 149: 315, 1987. 11. Koss, J . C., Arger, P. H., Coleman, B. G., Mulhern, C. B., Jr., Pollack, H. M. and Wein, A. J.: CT staging of bladder carcinoma. AJR, 137: 359, 1981. 12. Vock, P., Haertel, M., Fuchs, W. A., Karrer, P., Bishop, M. C. and Zingg, E. J.: Computed tomography in staging of carcinoma of the urinary bladder. Brit. J. Urol., 54: 158, 1982. 13. Weyman, P . J., McClennan, B. L., Stanley, R. J., Levitt, R. G. and Sagel, S. S.: Comparison of computed tomography and angiography in the elevation of renal cell carcinoma. Radiology, 137: 417, 1980. 14. Probst, P., Hoogewoud, H. M., Haertel, M., Zingg, E. and Fuchs, 15. 16.
17.
pretation of the regional lymph nodes in renal cancer than C T will need to be analyzed in the future. To date the first reports 18. on diagnostic accuracy of MRI for lymph nodes in the chest and pelvis do not show a better specificity than that of CT.18,19 We conclude that enlarged regional lymph nodes on C T in 19. patients with renal cell carcinoma do not necessarily indicate metastatic disease. Reactive inflammatory changes causing lymph node enlargement are mainly combined with the finding of tumor thrombi in renal veins and large areas of necrotic tumor tissue. Therefore, the indication for nephrectomy in
W. A,: Computerized tomography versus angiography in the staging of malignant renal neoplasm. Brit. J . Rad., 54: 744. 1981. ~ c ~ l e n i a B. n , L.: Computed tomography in the diagnosis and staging of renal cell carcinoma. Sem. Urol., 3: 111, 1985. Barrb, C., Boccon-Gibod, L.and Steg, A.: Qu'attendre de la tomodensitometrie dans le bilan d'extension loco-r6gionale des cancers du rein? Ann. Urol.. 19: 159, 1985. Lee, J . K., Stanley, R. J., Sagel, S. S. and McClennan, B. L.: Accuracy of CT in detecting intraabdominal and pelvic lymph node metastases from pelvic cancers. AJR, 131: 675, 1978. Hricak, H., Dooms, G. C., Jeffrey, R. B., Avallone, A,, Jacobs, D., Benton, W. K., Narayan, P . and Tanagho, E. A,: Prostatic carcinoma: staging by clinical assessment, CT, and MR imaging. Radiology, 162: 331, 1987. Poon, P . Y., Bronskill, M. J., Henkelman, R. M., Rideout, D. F., Shulman, H. S., Weisbrod, G. L., Steinhardt, M. I., Dunlap, H. J . , Ginsberg, R. J., Feld, R., Sutcliffe, S. B , and Williams, J. I.: Mediastinal lymph node metastases from bronchogenic carcinoma: detection with MR imaging and CT. Radiology, 162: 651, 1987.
Vol. 114, August Prinied In C.S.A.
ENLARGEMENT OF REGIONAL LYMPH NODES IN RENAL CELL CARCINOMA IS OFTEN NOT DUE TO METASTASES U R S E. S T U D E R , S T E P H A N I E S C H E R Z , J U R G S C H E I D E G G E R , R A I N E R K R A F T , R O L A N D S O N N T A G , D A N I E L A C K E R M A N N A N D ERNST J. ZINGG From the Department of Urology and Institutes for Diagnostic Radiology, Medical Oncology and Pathology, Inselspital, University of Berne, Berne, Switzerland
ABSTRACT
Preoperative axial computerized tomography scans i n 163 patients with renal cell carcinoma were reviewed t o assess t h e predictive value for t h e diagnosis of regional lymph node metastases. Computerized tomography was falsely negative in 5 patients: 2 h a d metastatic lymph nodes in t h e renal hilus adjacent t o t h e primary tumor measuring 2 a n d 2.5 cm., a n d 3 h a d micrometastases i n nodes of less t h a n 1cm. I n 43 patients enlarged lymph nodes with a diameter of 1t o 2.2 cm. (median 1.4 cm.) were diagnosed o n t h e preoperative scan a n d this was confirmed a t nephrectomy a n d pathologically. I n 18 of these 43 patients (42%) histological study showed metastases of t h e renal cell carcinoma i n t h e enlarged lymph nodes. I n t h e other 25 patients (58%) t h e enlarged nodes showed only inflammatory changes and/or follicular hyperplasia. T h i s finding was significantly more frequent i n patients with t u m o r involvement of t h e renal vein a n d tumor necrosis (p = 0.0044). W e conclude t h a t t h e sensitivity of preoperative computerized tomography is good for t h e detection of enlarged l y m p h nodes i n patients with renal cell cancer (95%). However, significant lymph node enlargement frequently may be caused by inflammatory changes, especially in t h e presence of t u m o r necrosis. T h i s radiological finding should not be misinterpreted as metastatic disease, unless it h a s been proved cytologically by fine needle aspiration. (J.Urol., 144: 243-245, 1990) The presence of regional lymph node metastases implies a poor prognosis for patients with renal cell carcinoma. Reported 5-year survival after radical nephrectomy combined with regional lymphadenectomy in series with more than 10 patients who had positive nodes varies between 7 and 17%.1-4Moreover, most of the long-term survivors had microscopic nodal metastases found only a t histological examination. In the series by Petkovic with gross nodal involvement only 1 of 46 patients (2%) survived longer than 5 years.' Due to the prognostic importance of macroscopic regional lymph node involvement in patients with renal cell carcinoma the preoperative assessment can be important. We analyzed whether this can be done accurately by axial computerized tomography (CT). PATIENTS AND METHODS
The nodal status was analyzed retrospectively on preoperative axial CT scans in 163 consecutive patients who underwent radical nephrectomy (158) or partial nephrectomy (5) combined with regional lymph node dissection for renal cell cancer at our institution between 1980 and 1988. The 100 men and 63 women were 39 to 85 years old (mean age 61.6 years) at operation. The tumor was on the right side in 95 patients and on the left side in 68. Nephrectomy usually was performed through a subcostal, tenth or eleventh interspace extrapleural incision or a thoracoretroperitoneal approach. Basically, the regional lymph nodes were removed according to the proposal of Marshall and Powell.' On the right side the nodes were removed all around the vena cava from the gonadal vein or bifurcation to the crus of the diaphragm and along the renal artery towards the aorta. On the left side the nodes were removed along the ventral and lateral aspects of the aorta from the inferior mesenteric artery to the diaphragm. The tumors were classified according to the tumor, nodes and metastasis system of the International Union Against C a n ~ e rThe . ~ majority of the tumors invaded the renal capsule or perirenal fat (stage pT2 or pT3, table 1). Of the patients 16 Accepted for publication February 1, 1990.
had evidence of distant metastases at operation. In general, the small bowel was filled with radiopaque fluid before the preoperative CT examination. The areas of the kidneys and regional lymph nodes were analyzed twice at 8 to 10 mm. intervals, that is before and after intravenous contrast medium was given. Without knowing the postoperative pathological nodal status, 1 of us (J. R. S.) reviewed all CT scans unless the nodal status was reported to be normal on preoperative CT, intraoperatively at lymph node dissection and at histological examination. One of us (R. K.) reviewed the histological status of all lymph node specimens in these patients. RESULTS
One to 4 regional lymph nodes measuring 1 to 2.2 cm. (median 1.4 cm.) were diagnosed in 43 of the 163 preoperative CT scans analyzed in patients with renal cell carcinoma (fig. 1). The presence of these enlarged nodes was confirmed intraoperatively and at pathological examination. Histologically, the enlarged lymph nodes in these 43 patients revealed metastatic disease from renal cell carcinoma in 18 (4276, table 2). In 2 of these 18 patients the enlarged lymph nodes contained only small foci of metastatic tissue. In the remaining 25 patients (58%) the histological specimen showed no malignant tissue. Instead, chronic inflammatory changes were found (fig. 2): all enlarged lymph nodes showed dilated lymph sinuses filled with TABLE1. Pathological tumor stage and nodal status in 163patients who underwent a n operation for renal cell carcinoma Pathological Tumor Stage
PT1 P T ~ PT3 pT4 Totals
No, Pts.
15 68 74
6 163
No. (%) Combined With Nodal Metastases (ON+) O(0) 9 (13) 11 (15) - 3 (50) 23 (14)
NO. (5%) Combined With Tumor Thrombus in Vein (pV1/2)
2 (13) 19 (28) 44 (59) 70 (43)
No' With Distant Metastases (Ml - --i
0 (0) 5 (7) 1 0 (13)
1(17) 1 6 110)
244
STUDER AND ASSOCIATES
histological study of the kidney showed tumor involvement of the renal veins, usually together with extensive necrosis of the carcinoma (table 3). Among the 115 patients with nonmetastatic normal sized lymph nodes (less than 1 cm.) thrombotic occlusion of renal veins was found in only 38 specimens (33%). This difference is statistically significant (Pearson's chi-square p = 0.0044). DISCUSSION
FIG. 1. Preoperative CT scans of 2 of 43 patients with enlarged, nonmetastatic lymph nodes (arrows). Typically, large necrotic areas are found within renal tumor. numerous macrophages. The cytoplasm often was clear, containing many small vacuoles and lipid or hemosiderin material. Most of the enlarged, nonmetastatic lymph nodes also showed enlarged germinal centers (fig. 2, A ) . In 2 of 120 patients with regional lymph nodes smaller than 1 cm. on the preoperative CT scan lymph node dissection revealed metastatic nodes 2 and 2.5 cm. in diameter, respectively. In both patients with a false negative CT scan the diseased lymph nodes were in the renal hilus, adjacent to the tumor. In 3 of 118 patients with normal sized lymph nodes on CT, intraoperatively and a t gross pathological examination nodal micrometastases were found histologically. In 16 of the 25 patients (64%) with enlarged nonmetastatic lymph nodes
In urological malignancies other than renal cell cancer enlarged regional lymph nodes (1cm. or more) found on CT imply a high probability of metastatic disease. In prostate cancer, this has been reported to be between 90 and 100%,s-10and in bladder cancer between 80 and 90%.11," Enlarged regional lymph nodes in patients with renal cell carcinoma caused by nonmalignant - ~ ~retrospective changes have been reported o ~ c a s i o n a l l y . ' ~Our study shows that significant lymph node enlargement due t o inflammatory changes is a frequent finding. In more than half of the patients (25 of 43, or 58%) with regional lymph nodes measuring 1 cm. or more no metastatic tissue could be found. Instead, reactive inflammatory changes showing dilated lymph sinuses filled with macrophages containing lipid and hemosiderin material were present, often combined with follicular hyperplasia. Indeed, this finding occurred especially when the primary tumor contained larger areas of necrotic tissue caused by venous occlusions from tumor thrombi. If the 2 patients with microscopic metastasis found in enlarged inflammatory nodes would have been added to the 25 with hyperplastic nodes (because the enlargement was not caused by the micrometastasis but rather by the follicular hyperplasia), the ratio of nonmetastatic-to-metastatic, enlarged lymph nodes would be 2:l. The inability to detect microscopic metastatic deposits with CT and to differentiate between benign and malignant tissue is well known,",17 and accounts for the false negative results in 3 patients with small nodes. In the 2 patients with a 2 and 2.5 cm, nodal metastasis, respectively, not diagnosed on preoperative CT the anatomical situation was identical. In both the metastatic node was in the renal hilus directly adjacent to the tumor and kidney. The lack of fatty tissue between the nodes and kidneys made detection of the enlarged nodes impossible. In our analysis no false positive enlarged nodes were observed, which probably is partly due to enteral and intravenous administration of contrast medium. This makes it unlikely to interpret a nonopacified intestinal loop or prominent renal vessel as an enlarged lymph node. While the sensitivity of CT for the detection of enlarged regional lymph nodes in our patients with renal cell cancer is high (95%),the probability that these enlarged nodes are metastatic is relatively low (42%),especially if the diseased kidney contains extensive areas of necrotic tumor material. Whether magnetic resonance imaging (MRI) would enable better inter-
TABLE2. Findings on preoperative CT, intraoperatively and at histological examination of regional lymph nodes i n 163 patients with renal cell carcinoma Size of Regional Lymph Nodes Intraop. and Gross Pathology
Preop. C T Cm. 1-2.2 (suspicious for metastases)
tases)
No. Pts.
Cm.
No. Pts.
43
1-2.2
43
120
22 <1
2
118
Histological Findings
Metastases No metastases (follicular hyperplasia, inflammatory changes) Metastases Micrometastases No metastases
No. Pts.
18* 25 2t 3 115
Intraoperative/pathological findings confirmed the preoperative CT diagnosis of enlarged lymph nodes (1 to 2.2 cm.) in 43 of 45 patients (sensitivity 95%). However, only 18 of 43 enlarged lymph nodes (42%) contain metastatic tissue. * I n 2 patients the enlarged lymph nodes contained micrometastases only. t In both patients the enlarged metastatic lymph nodes were in the renal hilus and not discernible from the primary tumor in the CT.
ENLARGEMENT O F REGIONAL LYMPH NODES I N RENAL CELL CARCINOMA
245
renal cell carcinoma patients should not be influenced by the presence of enlarged regional lymph nodes on C T alone. Should the presence of regional lymph node metastases from renal cell cancer influence the treatment plan, C T or ultrasound guided fine needle aspiration of the enlarged nodes would be recommended. REFERENCES 1. Bassil, B., Dosoretz, D. E. and Prout, G. R., Jr.: Validation of the
2. 3.
4.
5.
6.
7. 8.
tumor, nodes and metastasis classification of renal cell carcinoma. J . Urol., 134: 450, 1985. Skinner, D. G., Vermillion, C. D. and Colvin, R. B.: The surgical management of renal cell carcinoma. J . Urol., 107: 705, 1972. Marshall, F. F.: Lymphadenectomy for renal cell carcinoma. In: Tumors of the Kidney. International Perspectives in Urology. Edited by J . B. deKernion and M. Pavone-Macaluso. Baltimore: Williams & Wilkins, vol. 13, chapt. 6, pp. 88-97, 1986. Golimbu, M., Joshi, P., Sperber, A., Tessler, A., Al-Askari, S. and Morales, P.: Renal cell carcinoma: survival and prognostic factors. Urology, 27: 291, 1986. Petkovic, S.: The value of tumor tissue penetration into the renal veins and lymph nodes as anatomical classification and kidney tumor prognostic parameters. Eur. Urol., 6: 289, 1980. Marshall, F. F. and Powell, K. C.: Lymphadenectomy for renal cell carcinoma: anatomical and therapeutic considerations. J . Urol., 128: 677, 1982. Harmer, M. H.: T N M Classification of Malignant Turnours. Geneva: International Union Against Cancer, 1978. Levine, M. S., Arger, P. H., Coleman, B. G., Mulhern, C. B., Jr., Pollack, H . M. and Wein, A. J.: Detecting lymphatic metastases from prostatic carcinoma: superiority of CT. AJR, 137: 207,
1981. 9. Mazeman, E., Lemaitre, L., Rigot, J. M. and Lambert, I.: Place of
FIG. 2. Enlarged, nonmetastatic lymph node specimens reveal follicular hyperplasia with numerous germinal centers. A, arrows show some germinal centers. H & E, reduced from X13. B, dilated lymph sinuses are usually filled with macrophages and cytoplasm often is foamy, containing lipid material or hemosiderin possibly deriving from necrotic tumor material. H & E, reduced from X175. TABLE3. Incidence of renal vein tumor thrombus ipVl and pV2, usually comb~nedwith extensive tumor necrosis) in patients with enlarged or normal sized, nonmetastatic lymph nodes
Lymph Nodes (em.)
Nonmetastatic, enlarged (1-2.2) Nonmetastatic, normal sized (
No. Pts.
25
115
Histology Showed Renal Vein Tumor Involvement No. ( Z ) 16 (64) 38 (33)
T h e incidence of renal vein tumor ~nvolvementis significantly higher in the patients with enlarged nonmetastatic lymph nodes (inflammator~.changes plus follicular hyperplasia) t h a n in those with nonmetastatic normal sized lymph nodes (Pearson's chi-square p = 0.0044).
the computed tomography in the staging of prostatic cancer. In: Prostate Cancer, Part B: Imaging Techniques, Radiotherapy, Chemotherapy and Management Issues. Editedby G. P . Murphy, S. Khoury, R. Kuss, C. Chatelain and L. Denis. New York: Alan R. Liss, Inc., vol. 243 B, pp. 55-64, 1987. 10. Platt, J . F., Bree, R. L. and Schwab, R. E.: The accuracy of C T in the staging of carcinoma of the prostate. AJR, 149: 315, 1987. 11. Koss, J . C., Arger, P. H., Coleman, B. G., Mulhern, C. B., Jr., Pollack, H. M. and Wein, A. J.: CT staging of bladder carcinoma. AJR, 137: 359, 1981. 12. Vock, P., Haertel, M., Fuchs, W. A., Karrer, P., Bishop, M. C. and Zingg, E. J.: Computed tomography in staging of carcinoma of the urinary bladder. Brit. J. Urol., 54: 158, 1982. 13. Weyman, P . J., McClennan, B. L., Stanley, R. J., Levitt, R. G. and Sagel, S. S.: Comparison of computed tomography and angiography in the elevation of renal cell carcinoma. Radiology, 137: 417, 1980. 14. Probst, P., Hoogewoud, H. M., Haertel, M., Zingg, E. and Fuchs, 15. 16.
17.
pretation of the regional lymph nodes in renal cancer than C T will need to be analyzed in the future. To date the first reports 18. on diagnostic accuracy of MRI for lymph nodes in the chest and pelvis do not show a better specificity than that of CT.18,19 We conclude that enlarged regional lymph nodes on C T in 19. patients with renal cell carcinoma do not necessarily indicate metastatic disease. Reactive inflammatory changes causing lymph node enlargement are mainly combined with the finding of tumor thrombi in renal veins and large areas of necrotic tumor tissue. Therefore, the indication for nephrectomy in
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