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Renal Cell Carcinoma Presenting with Metastases to Pulmonary Hilar Nodes
Vol. ll8, October
THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
Printed in U .SA.
RENAL CELL CARCINOMA PRESENTING WITH METASTASES TO PULMONARY HILAR NODES ERICH K. LANG From the Department of Radiology, Louisiana State University School of Medicine, Shreveport and the Louisiana State University Medical Center, New Orleans, Louisiana
ABSTRACT
Mediastinal and hilar renal cell carcinoma metastases are reported in 9 patients, representing an incidence rate of 8 per cent in the series. This observation indicated an ominous prognosis since the mean survival of these patients was only 1.4 months after the discovery of the neoplasm. It is postulated that this poor prognosis is attributable to the size of the primary lesion, with direct extension into retroperitoneal structures and perhaps to an associated exhaustion of immunologic defense mechanisms of the patients. Dissemination from the involved retroperitoneal lymphatics to the thoracic duct and then in retrograde fashion via the bronchomediastinal and paratracheal trunks is advocated as the pathway for this tumor dissemination. At initial diagnosis more than a third of the patients with renal cell carcinoma have demonstrable metastases. 1• 2 The most common sites of metastases are the lungs, lymph nodes, liver and bone. 2 Invasion of small and large renal veins by the neoplasm sets the stage for hematogenous tumor embolization of the lung. 2 The cannonball lung metastasis is the hallmark of metastatic renal cell carcinoma. This type of metastasis is encountered in about half of all patients with manifest metastatic renal cell carcinoma. However, meticulous examination of the lungs by routine tomography increases recognition of metastatic renal cell carcinoma to the lung by identifying small nodular metastatic implants. 3 Despite reports emphasizing the not infrequent occurrence of mediastinal lymph node metastases this important feature has not received wide publicity nor has there been an attempt to explain properly its pathogenesis, mode of dissemination and inference on the natural course of disease. 4 , 5 Like Arkless, who reported an incidence of mediastinal adenopathy of 7 per cent (11 of 152 patients with renal cell carcinoma),4 we identified metastatic hilar adenopathy in 8 or 9 per cent of our 112 patients.
lished in 2 patients by a mediastinoscopy and lymph node biopsy, in 2 patients by autopsy and in 4 patients by transbronchial biopsy. The presence of mediastinal or hilar metastatic adenopathy infers an ominous prognosis. All 9 of our patients with this manifestation died within 6 months of the diagnosis regardless of treatment. Eight of these patients were treated with radical nephrectomy and node dissection for the primary lesion. In addition, 5 received chemotherapy and 3 external or implant radiation therapy. One patient was treated with external radiation therapy only. The diagnostic investigation for metastatic renal cell carci-
DIAGNOSIS OF METASTATIC RENAL CELL CARCINOMA TO HILAR, CARINAL AND PARATRACHEAL NODES
The roentgenographic demonstration of hilar lymphadenopathy in patients with renal cell carcinoma must be considered highly suspicious of metastatic disease to these nodes. Lateral displacement or a particularly progressive lateral shift of granulomatous calcifications on sequential radiographs suggests possible metastatic involvement of more medial nodes. High quality tomography may identify a mass in a portion of a node, causing displacement of granulomatous calcifications of different regions of the same node (fig. 1). Since renal arteriography is performed in most patients to stage renal cell carcinoma this procedure can be expanded to include bronchial arteriography, which can document the presence of renal cell carcinoma in hilar, carinal or paratracheal nodes (fig. 2). 6' 7 Of our 9 patients with hilar lymphadenopathy 7 were examined by selective bronchial arteriography and demonstrated the telltale neovascularity of renal cell carcinoma in the hilar, paratracheal and carinal nodes (figs. 3 to 5). Mediastinoscopy and appropriate biopsy or transbronchial biopsy also can be used to establish such metastatic involvement. In our series a positive histologic diagnosis was estabAccepted for publication December 17, 1976. 543
FIG. 1. Tomographic cut centered through carina and hila documents massive lymphadenopathy. Note displacement of ancient granulomatous calcifications (arrows) to periphery by metastatic neoplasm.
544
LANG
Fm. 2. Selective bronchial arteriogram demonstrates extensive neovascularity in right hilar nodes. Type ofneovascularity is identical to that seen in primary lesion-renal cell carcinoma.
Fm. 4. Autopsy specimen documents huge hypernephroma metastases to carinal nodes and to nodes in right and left hila.
Fm. 3. A, selective right bronchial arteriogram demonstrates classical neovascularity of renal cell carcinoma in enlarged azygous node, as well as in right hilar nodes (arrows). B, late phase arteriogram documents neoplastic replacement of lower half of 1 right hilar node but paucity of tumor neovascularity in upper half of this node, which may explain displacement of granulomatous calcification to periphery of node by selective tumor growth in its central portion.
RENAL CELL CARCINOMA WITH METASTASES TO PULMONARY HILAR NODES
545
Dissemination of neoplastic cells via Batson's paravertebral venous plexus offers another possibility for spread of the neoplasm into the paravertebral area and then contiguously lymphatics into the mid mediastinum. 2 However, hilar metastases of renal cell carcinoma most likely are attributable to retrograde tumor embolization from the thoracic duct via bronchomediastinal and paratracheal lymphatic trunks with incompetent lymphatic valves. The observation of isolated neoplastic involvement of hilar, carinal and paratracheai nodes without histologically demonstrable disease in the parenchyrna in 1 of our patients supports this ncithoo·pn,c.h
NATURAL HISTORY OF RENAL CELL CARCINOIV1A PRESENTING WITH METASTASES TO MEDIASTINAL NODES
5. Selective bronchial arteriogram demonstrates tumor neoin hilar nodes (solid arrow), as well as in Neovascularity again characteristic identical to pattern seen in primary tumor.
CH\JW'e"a! conditions. As discussed under modes of tumor dissemination the coexistence of mediastinal node metastases and metastases to the space of the dorsal canal is not uncommon. Because of propensity for sudden after the of contrast UL•CU.tU,U therefore, cause the cu.111~HH:,nwn LU,LLO,HW
PATHOGENESIS AND MODES OF SPREAD
Unlike the characteristic seeding to the -,--,~---M.,, dissern.ination a exµ11111,ctuuuforoc,=u,u~
;.,~uHvrncu
A severely reduced survival time distinguishes with metastatic renal cell carcinoma to mediastinal hiiar nodes from all patients with other distant metastases. Our 9 patients died of disease within 3 weeks to 6 months of the nosis, with a mean survival of 1.4 months. Conversely, mean survival of our patients with lung parenchymal or end.obronchial metastatic renal cell carcinoma was 11 months. The disparity in survival indicates that lymphatic dissemination is either a more aggTessive form or an advanced stage of renai cell carcinoma. There is reason to support the latter concept. The hematogenous spread of renal cell carcinoma may occur at any time if the tumor has permeated small renal veins and tumor emboli are then transported to sites via vascular channels. Renal vein invasion occurred in our series in several 2 cm. tumors. However, these tumors generally exhibited poorly defined margins and cytologic evidence of a more aggressive neoplasm showing many mitotic figures and a cellular pleomorphism. Spread to and via the retroperitoneal lymphatics presupposes penetration not only of a pseudocapsule, if such is present, but also of the renal capsule and extension into the perinephric fat. In general, this occurs in larger tumors. All 9 of our patients had a primary neoplasm with a diameter of more than 6 cm. and arteriograms demonstrated pern1eation of the renal capsule, extension into the perinephric fat and cannibalization of the vascular system of structures. 0 - 7 It is reasonable to assume that a sizable primary tumor with direct extension into the retroperitoneal lymphatics releasing massive amounts of tumor cells into the lymphatic circulation is more likely to overcome the immunologic resistance of the host, which otherwise may curtail the implantation and growth of only a few neoplastic cells released sporadically into the lymphatic system. This concept is supported by our ence. Direct extension of renal cell carcinoma into ~~"~'"~""' retroperitoneal structures was present in all 9 patients and other distal metastases were observed in 8 patients. Four of the 9 had metastatic disease to the dorsal spine and/or implants into the epidural space, implicating tumor dissemination via Batson's plexus. 2 The advanced stage of the disease also was reflected the lack of a favorable response or even appreciable retardation of progression of metastatic disease after removal of the ~~ .,,.. ,,~ , lesion. 2, 6 Perhaps this can be attributed to an exhaustion the immunolog{c defense mechanism of the host because of overwhelming neoplastic disease. REFERENCES
1. Holland, J.M.: Cancer of the kidney-natural history and stag-
veins. The µu,,:,,:,m1.11 embolization via observation of reflux tinal trunks and
ing. Cancer, 32: 1030, 1973. 2. Mostofi, F. K.: Pathology and Spread of Renal Cell Carcinoma, An International Symposium. Boston: Little, Brown & Co., pp. 41-86, 1967. 3. Robson, C. J., Churchill, B. M. and Anderson, W.: The results of radical nephrectomy for renal cell carcinoma. J. U rol., 101: 297, 1969.
546
LANG
4. Arkless, R.: Renal carcinoma: how it metastasizes. Radiology, 84: 496, 1965. 5. Khan, A. and Khan, F. A.: Hypernephroma: a rare cause of bilateral adenopathy and an example of the importance of tissue diagnosis in suspected cases of sarcoidosis. Chest, 66: 722, 1974. 6. Lang, E. K.: Arteriography in the diagnosis and staging of hypernephromas. Cancer, 32: 1043, 1973. 7. Khan, P. C., Wise, H. M., Jr. and Robbins, A. H.: Complete angiographic evaluation of renal cancer. J.A.M.A., 204: 753, 1968.
8. Weidner, W. A. and Steiner, R. M.: Roentgenographic demonstration of intrapulmonary and pleural lymphatics during lymphangiography. Radiology, 100: 533, 1971. COMMENT This study beautifully demonstrates the diagnostic state of the art for pulmonary hilar lymph node metastases. The variable spectrum of renal cell carcinoma metastases undoubtedly reflects differences in individual tumor reactivity (virulence) at specific organ sites, coupled with variations in the host's defense responses at these sites. W.B.G.
THE JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
Printed in U .SA.
RENAL CELL CARCINOMA PRESENTING WITH METASTASES TO PULMONARY HILAR NODES ERICH K. LANG From the Department of Radiology, Louisiana State University School of Medicine, Shreveport and the Louisiana State University Medical Center, New Orleans, Louisiana
ABSTRACT
Mediastinal and hilar renal cell carcinoma metastases are reported in 9 patients, representing an incidence rate of 8 per cent in the series. This observation indicated an ominous prognosis since the mean survival of these patients was only 1.4 months after the discovery of the neoplasm. It is postulated that this poor prognosis is attributable to the size of the primary lesion, with direct extension into retroperitoneal structures and perhaps to an associated exhaustion of immunologic defense mechanisms of the patients. Dissemination from the involved retroperitoneal lymphatics to the thoracic duct and then in retrograde fashion via the bronchomediastinal and paratracheal trunks is advocated as the pathway for this tumor dissemination. At initial diagnosis more than a third of the patients with renal cell carcinoma have demonstrable metastases. 1• 2 The most common sites of metastases are the lungs, lymph nodes, liver and bone. 2 Invasion of small and large renal veins by the neoplasm sets the stage for hematogenous tumor embolization of the lung. 2 The cannonball lung metastasis is the hallmark of metastatic renal cell carcinoma. This type of metastasis is encountered in about half of all patients with manifest metastatic renal cell carcinoma. However, meticulous examination of the lungs by routine tomography increases recognition of metastatic renal cell carcinoma to the lung by identifying small nodular metastatic implants. 3 Despite reports emphasizing the not infrequent occurrence of mediastinal lymph node metastases this important feature has not received wide publicity nor has there been an attempt to explain properly its pathogenesis, mode of dissemination and inference on the natural course of disease. 4 , 5 Like Arkless, who reported an incidence of mediastinal adenopathy of 7 per cent (11 of 152 patients with renal cell carcinoma),4 we identified metastatic hilar adenopathy in 8 or 9 per cent of our 112 patients.
lished in 2 patients by a mediastinoscopy and lymph node biopsy, in 2 patients by autopsy and in 4 patients by transbronchial biopsy. The presence of mediastinal or hilar metastatic adenopathy infers an ominous prognosis. All 9 of our patients with this manifestation died within 6 months of the diagnosis regardless of treatment. Eight of these patients were treated with radical nephrectomy and node dissection for the primary lesion. In addition, 5 received chemotherapy and 3 external or implant radiation therapy. One patient was treated with external radiation therapy only. The diagnostic investigation for metastatic renal cell carci-
DIAGNOSIS OF METASTATIC RENAL CELL CARCINOMA TO HILAR, CARINAL AND PARATRACHEAL NODES
The roentgenographic demonstration of hilar lymphadenopathy in patients with renal cell carcinoma must be considered highly suspicious of metastatic disease to these nodes. Lateral displacement or a particularly progressive lateral shift of granulomatous calcifications on sequential radiographs suggests possible metastatic involvement of more medial nodes. High quality tomography may identify a mass in a portion of a node, causing displacement of granulomatous calcifications of different regions of the same node (fig. 1). Since renal arteriography is performed in most patients to stage renal cell carcinoma this procedure can be expanded to include bronchial arteriography, which can document the presence of renal cell carcinoma in hilar, carinal or paratracheal nodes (fig. 2). 6' 7 Of our 9 patients with hilar lymphadenopathy 7 were examined by selective bronchial arteriography and demonstrated the telltale neovascularity of renal cell carcinoma in the hilar, paratracheal and carinal nodes (figs. 3 to 5). Mediastinoscopy and appropriate biopsy or transbronchial biopsy also can be used to establish such metastatic involvement. In our series a positive histologic diagnosis was estabAccepted for publication December 17, 1976. 543
FIG. 1. Tomographic cut centered through carina and hila documents massive lymphadenopathy. Note displacement of ancient granulomatous calcifications (arrows) to periphery by metastatic neoplasm.
544
LANG
Fm. 2. Selective bronchial arteriogram demonstrates extensive neovascularity in right hilar nodes. Type ofneovascularity is identical to that seen in primary lesion-renal cell carcinoma.
Fm. 4. Autopsy specimen documents huge hypernephroma metastases to carinal nodes and to nodes in right and left hila.
Fm. 3. A, selective right bronchial arteriogram demonstrates classical neovascularity of renal cell carcinoma in enlarged azygous node, as well as in right hilar nodes (arrows). B, late phase arteriogram documents neoplastic replacement of lower half of 1 right hilar node but paucity of tumor neovascularity in upper half of this node, which may explain displacement of granulomatous calcification to periphery of node by selective tumor growth in its central portion.
RENAL CELL CARCINOMA WITH METASTASES TO PULMONARY HILAR NODES
545
Dissemination of neoplastic cells via Batson's paravertebral venous plexus offers another possibility for spread of the neoplasm into the paravertebral area and then contiguously lymphatics into the mid mediastinum. 2 However, hilar metastases of renal cell carcinoma most likely are attributable to retrograde tumor embolization from the thoracic duct via bronchomediastinal and paratracheal lymphatic trunks with incompetent lymphatic valves. The observation of isolated neoplastic involvement of hilar, carinal and paratracheai nodes without histologically demonstrable disease in the parenchyrna in 1 of our patients supports this ncithoo·pn,c.h
NATURAL HISTORY OF RENAL CELL CARCINOIV1A PRESENTING WITH METASTASES TO MEDIASTINAL NODES
5. Selective bronchial arteriogram demonstrates tumor neoin hilar nodes (solid arrow), as well as in Neovascularity again characteristic identical to pattern seen in primary tumor.
CH\JW'
PATHOGENESIS AND MODES OF SPREAD
Unlike the characteristic seeding to the -,--,~---M.,, dissern.ination a exµ11111,ctuuuforoc,=u,u~
;.,~uHvrncu
A severely reduced survival time distinguishes with metastatic renal cell carcinoma to mediastinal hiiar nodes from all patients with other distant metastases. Our 9 patients died of disease within 3 weeks to 6 months of the nosis, with a mean survival of 1.4 months. Conversely, mean survival of our patients with lung parenchymal or end.obronchial metastatic renal cell carcinoma was 11 months. The disparity in survival indicates that lymphatic dissemination is either a more aggTessive form or an advanced stage of renai cell carcinoma. There is reason to support the latter concept. The hematogenous spread of renal cell carcinoma may occur at any time if the tumor has permeated small renal veins and tumor emboli are then transported to sites via vascular channels. Renal vein invasion occurred in our series in several 2 cm. tumors. However, these tumors generally exhibited poorly defined margins and cytologic evidence of a more aggressive neoplasm showing many mitotic figures and a cellular pleomorphism. Spread to and via the retroperitoneal lymphatics presupposes penetration not only of a pseudocapsule, if such is present, but also of the renal capsule and extension into the perinephric fat. In general, this occurs in larger tumors. All 9 of our patients had a primary neoplasm with a diameter of more than 6 cm. and arteriograms demonstrated pern1eation of the renal capsule, extension into the perinephric fat and cannibalization of the vascular system of structures. 0 - 7 It is reasonable to assume that a sizable primary tumor with direct extension into the retroperitoneal lymphatics releasing massive amounts of tumor cells into the lymphatic circulation is more likely to overcome the immunologic resistance of the host, which otherwise may curtail the implantation and growth of only a few neoplastic cells released sporadically into the lymphatic system. This concept is supported by our ence. Direct extension of renal cell carcinoma into ~~"~'"~""' retroperitoneal structures was present in all 9 patients and other distal metastases were observed in 8 patients. Four of the 9 had metastatic disease to the dorsal spine and/or implants into the epidural space, implicating tumor dissemination via Batson's plexus. 2 The advanced stage of the disease also was reflected the lack of a favorable response or even appreciable retardation of progression of metastatic disease after removal of the ~~ .,,.. ,,~ , lesion. 2, 6 Perhaps this can be attributed to an exhaustion the immunolog{c defense mechanism of the host because of overwhelming neoplastic disease. REFERENCES
1. Holland, J.M.: Cancer of the kidney-natural history and stag-
veins. The µu,,:,,:,m1.11 embolization via observation of reflux tinal trunks and
ing. Cancer, 32: 1030, 1973. 2. Mostofi, F. K.: Pathology and Spread of Renal Cell Carcinoma, An International Symposium. Boston: Little, Brown & Co., pp. 41-86, 1967. 3. Robson, C. J., Churchill, B. M. and Anderson, W.: The results of radical nephrectomy for renal cell carcinoma. J. U rol., 101: 297, 1969.
546
LANG
4. Arkless, R.: Renal carcinoma: how it metastasizes. Radiology, 84: 496, 1965. 5. Khan, A. and Khan, F. A.: Hypernephroma: a rare cause of bilateral adenopathy and an example of the importance of tissue diagnosis in suspected cases of sarcoidosis. Chest, 66: 722, 1974. 6. Lang, E. K.: Arteriography in the diagnosis and staging of hypernephromas. Cancer, 32: 1043, 1973. 7. Khan, P. C., Wise, H. M., Jr. and Robbins, A. H.: Complete angiographic evaluation of renal cancer. J.A.M.A., 204: 753, 1968.
8. Weidner, W. A. and Steiner, R. M.: Roentgenographic demonstration of intrapulmonary and pleural lymphatics during lymphangiography. Radiology, 100: 533, 1971. COMMENT This study beautifully demonstrates the diagnostic state of the art for pulmonary hilar lymph node metastases. The variable spectrum of renal cell carcinoma metastases undoubtedly reflects differences in individual tumor reactivity (virulence) at specific organ sites, coupled with variations in the host's defense responses at these sites. W.B.G.