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Hematuria in Seizure Disorder Patient
0022-534 7/79/1216-0797$02. 00/0 Vol. 121, June
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1979 by The Williams & Wilkins Co.
Clinicopathologi cal Conference HEMATURIA IN SEIZURE DISORDER PATIENT DENNIS D. GARVIN,* CARL H. WEBER, JR.,t DAVID J. CONFER,+ THOMAS P. BALL, JR.§ JAMES D. MULLINSII
AND
From the Department of Urology, Division of Surgery and the Department of Anatomic Pathology, Division of Support Services, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas
PRESENTATION OF CASE,J
Dr. Dennis D. Garvin. A 32-year-old man had right flank pain and gross hematuria. He had suffered intermittent gross, painless hematuria for 4 years and several radio-contrast studies had not disclosed any evidence of upper tract abnormality. Previous cystoscopy examinations had revealed only friable vessels in the prostatic urethra as a possible etiology of the hematuria. Also of significance in the history was a congenital seizure disorder, treated with diphenylhydantoin and phenobarbital. The patient was admitted to the urology service, where physical examination revealed a young man with below normal intelligence. In addition to the positive physical finding of right costovertebral angle tenderness the patient had multiple skin lesions, including hypopigmented and hyperpigmented areas, subungual fibromas and papillary growths on the nose and in the nasolabial folds. Laboratory parameters were normal except for a hematocrit of 42. An excretory urogram (IVP) revealed a slightly enlarged right kidney with an increasingly dense nephrogram carried through delayed films. Cystoscopy disclosed no lower tract abnormalities, while gross blood was seen coming from the right orifice. Retrograde ureteropyelography revealed virtual non-filling of the renal pelvis, with the configuration of the filling defects that suggested an extensive blood clot. A computer tomography (CT) scan revealed only enlargement of the right kidney with probable clots in the pelvis. Angiography revealed a 3 cm. moderately vascular renal mass in the mid portion of the right kidney, with no definite neovascularity (fig. 1). The left kidney and the remainder of the right kidney demonstrated normal vascularity. A dermatology consultant agreed that the facial lesions were adenoma sebaceum, while an ophthalmology consultant was unable to find a retinal phakoma. A cranial CT scan did not reveal any cerebral calcification and all bone films were negative except for the skull film (fig. 2). A bone scan was negative. Throughout the evaluation the patient had difficulty with the bleeding, requiring catheterization and continuous irrigation after 2 episodes of clot retention. RADIOGRAPHIC FINDINGS
Dr. Carl H. Weber. The IVP, obtained while the right kidney apparently was obstructed by blood clots, fails to visualize the collecting system and demonstrates only a ne* Chief Resident, Department of Urology.
t Assistant Chairman, Department of Urology. :j:
Staff Urologist, Department of Urology.
§ Chairman, Department of Urology.
II Department of Anatomic Pathology.
,r Case presented at Grand Rounds on April 13, 1978. The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air Force.
phrogram of a slightly enlarged kidney of normal contour. The retrograde ureterogram is compatible with obstruction of the right upper ureter by clots. Neither of these studies identifies a mass in the kidney. Similarly, the CT scan demonstrates some filling defects in the right renal pelvis, with a relative density index suggestive of blood clot. The renal contour appears normal and no evidence of an intrarenal mass is seen, although enhancement of the renal parenchyma is unsatisfactory in this obstructed kidney. In addition no areas of fat density are identified within the kidney. However, the angiographic studies reveal a definite 3½ cm. mass in the mid portion of the right kidney, as evidenced by the splaying of the intrarenal vessels around the area of the mass that subsequently is seen as a blush, which becomes more prominent on the delayed films. There are mild vascular irregularities about and within this area of blush but no neovascularity, aneurysms or venous communications can be identified. The lower pole, supplied by a second right renal artery, appears normal, as does the left kidney. No renal veins were seen on the right side during the arterial study but 2 patent right renal veins were demonstrated by a venous study. The remainder of the radiographic studies, including full chest tomography, revealed no abnormalities except for the impressive skull films demonstrating the multiple rounded, cotton-wool densities and the marked thickening of the posterior calvarium. Collectively, the radiographic studies demonstrate a hypovascular mass in the mid portion of the poorly functioning right kidney that appears to be obstructed by blood clots, patent right renal veins, a normal appearing left kidney, a thickened calvarium and multiple densities on the skull films. The CT scan would indicate that the renal mass is of tissue density comparable to the renal parenchyma, without significant areas of fatty tissue. Careful study of several plain radiographs of the right kidney fail to demonstrate areas of lucency, a sign suggested as pathognomonic of angiomyolipoma but its absence does not exclude the diagnosis. 1 The vessels within the mass do not demonstrate the multiple arterial aneurysms and cork-screw vessels usually associated with an angiomyolipoma but, likewise, their absence does not rule out an angiomyolipoma. 1• 2 Hypovascular angiomyolipomas do occur, although they usually demonstrate more evidence oflipomatous elements. Similarly, the absence of disorganized neovascularity does not exclude adenocarcinoma of the kidney and about 5 per cent of the adenocarcinomas are avascular or hypovascular. 3 The absence of any demonstrable arteriovenous communication would make an arteriovenous malformation unlikely. A metastatic tumor to the kidney or benign primary renal tumor cannot be excluded on the basis of the radiographic studies. The thickened calvarium is explained readily in this patient as a recognized side effect of diphenylhydantoin. The multiple
797
798
CLINICOPATHOLOGICAL CONFERENCE
Fm. 1. A, arteri~ phase of selective. r~ght renal angiogram shows subtle draping of vessels around hypovascular mass. B, late nephrogram phase with lower arrows outlmmg mass as blush. Upper arrow indicates dilated upper calix behind pelvis that contained blood clot.
Fm. 2. Skull film shows the multiple rounded cotton-wool densities in skull and thickening of posterior calvarium.
densities seen on the skull films are most consistent with bony involvement of tuberous sclerosis, Paget's disease or metastatic carcinoma of the prostate, all other sources of blastic metastases being much less likely possibilities. Metastatic renal adenocarcinoma to the skull can be excluded as a cause since such metastases are always lytic lesions. In summary, the radiologic studies demonstrate a solid, hypovascular mass in the right kidney that lacks pathognomonic features to suggest its specific etiology. The skull films demonstrate multiple densities compatible with involvement by tuberous sclerosis and a thickened calvarium resulting from diphenylhydantoin usage. DISCUSSION AND DIFFERENTIAL DIAGNOSIS
Dr. David J. Confer. Obviously, this patient has tuberous sclerosis, meeting the 3 classic diagnostic criteria of mental retardation, seizure disorder beginning in early childhood and adenoma sebaceum. He also had periungual fibroma and classic skull radiographic lesions.
The somewhat vascular right renal lesion did not have the classic radiographic findings of an angiomyolipoma, yet up to 80 per cent of the patients with tuberous sclerosis have these lesions and other primary renal tumors in this disease are unusual. Often the angiomyolipomas of tuberous sclerosis are multiple, small and bilateral with these lesions first manifesting themselves in patients 25 to 30 years old. This is in contrast to the larger unilateral angiomyolipoma, which appears sporadically in the population. These angiomyolipomas usually do not present until patients are in the fifth or sixth decade of life and often present a most difficult diagnostic problem. Of the other entities in our differential diagnosis renal cell carcinoma was another primary consideration. Although rarely reported in association with tuberous sclerosis it certainly is a possibility. It is interesting that patients with documented renal cell carcinomas that have been associated with tuberous sclerosis have had an apparently improved survival rate, leading some investigators to consider these possible angiomyolipomas that appeared more neoplastic pathologically. However, similarly, on angiography we do not have the neovascularity and associated arteriovenous shunting that would be helpful in the diagnosis of renal cell carcinoma. One also could list a number of other primary and secondary neoplastic lesions to complete the differential diagnosis but these are less likely in this clinical presentation. It is important to mention that the right collecting system was not visualized on any of our studies on this admission but an IVP 1 year earlier was entirely normal in that regard. With this patient having tuberous sclerosis the overwhelming likelihood is that this is an angiomyolipoma manifesting itself for the last 4 years by intermittent hematuria. An occult renal cell carcinoma is a far less likely alternative. However, without the classic angiographic findings associated with angiomyolipoma we are not willing to consider non-surgical management, such as embolization, without the definitive diagnosis. It is equally important to stress the fact that surgical intervention in any vascular lesion of the kidney' in patients with tuberous sclerosis should be as conservative as possible in that they are apt to suffer enlargement of present lesions or have new lesions on the contralateral kidney. It is
799
HEMATURIA IN SEIZURE DISORDER PATIENT
unfortunate that this relatively small lesion in our patient does not reside in either the upper or lower pole or more near the surface of the kidney where segmental nephrectomy is more easily accomplished. PROVISIONAL DIAGNOSIS
sclerosis and typically is bilateral when associated with this process. 7 FINAL DIAGNOSIS
Small (2 cm.) well differentiated clear cell adenocarcinoma of the right kidney, pathologic stage I.
Angiomyolipoma, rule out renal cell carcinoma. COMMENTS DISCUSSION OF SURGERY
Doctor Garvin. Exploration was done transperitoneally through a right anterior subcostal incision. The kidney was palpated through Gerota's fascia. Although the kidney was lobulated it had no areas· of palpable firmness. The anterior surface had multiple punctate ecchymoses. There again was noted the lobulation of the mid body of the kidney, which was visually and palpably identical to the remainder of the kidney substance. It was possible to visualize the anterior surface of the left kidney through this incision, with no abnormalities being noted. With angiographic and surgical confirmation of a normal left kidney we decided to do a right radical nephrectomy in view of the symptoms and the inability to make an immediate surgical diagnosis. DISCUSSION OF PATHOLOGY
Dr. James D. Mullins. The gross specimen was consistent with a right radical nephrectomy, including the right kidney and adrenal gland. On external gross examination the kidney was unremarkable. Bisection revealed a solitary, pale yellow, homogeneous, subcapsular cortical mass that had a greatest diameter of 2 cm. The mass was well demarcated from the adjacent compressed renal parenchyma in most areas by a thin, incomplete fibrous capsule. Grossly, there was no evidence of invasion of the overlying renal capsule, renal veins or pelvis. Two grossly unremarkable hilar lymph nodes, the largest having a diameter of0.8 cm., were found on dissection of the hilar fat. Microscopically, the neoplasm demonstrated a uniform pattern, consisting of closely packed tubules of variable sizes. The tubules were lined by columnar cells, possessing abundant clear cytoplasm with distinct cell membranes and relatively small uniform basally located nuclei. Cellular pleomorphism was minimal and no mitotic figures or areas of necrosis were seen. The lumina of most of the neoplastic tubules appeared empty, while a few were filled with masses of intact red blood cells or acellular eosinophilic proteinaceous debris. Except for the peripheral fibrous capsule the accompanying fibrous stroma was inconspicious and contained scattered thin walled vessels with a few lymphocytes and hemosiderin laden macrophages. The peripheral fibrous capsule was focally absent and invaded in multiple areas by neoplastic tubules that even extended into the adjacent compressed normal renal parenchyma in a few areas. Microscopically, the 2 previously mentioned hilar lymph nodes were free of metastatic tumor. Despite the small size of this lesion (2 cm.) the histology was unquestionably that of well differentiated clear cell adenocarcinoma of the kidney and not a renal cell adenoma. Further histological evidence of the malignant nature of this small neoplasm was the prominence of capsular invasion. Extensive sampling of the neoplasm revealed no areas of papillary growth pattern characterized by prominent fibrovascular cores lined by neoplastic cells. 4 The papillary histological pattern, although uncommon (14 per cent of the renal cell carcinoma cases in 1 large series), 4 accounts for almost half of the renal cell carcinomas that appear hypovascular or avascular on arteriography. 3• 6 There also was no gross or microscopic evidence of any associated angiomyolipoma in the resected kidney. This peculiar hamartomatous neoplasm occurs in the kidneys of anywhere from 40 to 80 per cent of the patients with tuberous
Dr. Thomas P. Ball, Jr. This is a classic case to illustrate the trap into which one may fall if emotions, impressions and, worse yet, assumptions are permitted to govern our therapy. It was tempting to accept the statistical implications in this case and to assume that the mass from which the patient bled was an angiomyolipoma. The clinical picture was typical with the mass even presenting on the right side as the majority of unilateral angiomyolipomas do. Even the age of the patient tended to swing the pendulum away from renal cell adenocarcinoma, although malignancies of this type certainly do occur in the young. The facts were that the possibility of a carcinoma could not be eliminated and that the angiogTam and CT scan that we had hoped would show the characteristic fat density in the mass did nothing to strengthen our convictions either way. While flank exploration and biopsy had been recommended with unilateral lesions in patients with tuberous sclerosis,8' " we thought that this lesion was, in fact, indistinguishable from hypernephroma and, thus, opted to do a radical nephrectomy when the opposite kidney was palpably and radiographically normal, and the nature of the lesion could not be further determined at exploration. Had the lesion been polar in location partial nephrectomy would have been a viable alternative, 10 in view of the likelihood of developing a lesion on the other side. However, the central location and difficulty in palpation suggested radical nephrectomy as the more conservative approach. How fortunate we were that the persistence of symptoms and bleeding forced our hand toward more extensive efforts to obtain a definitive diagnosis, since previous pyelograms had revealed nothing. While this case is rare it serves to emphasize further that each case and lesion must be judged on its own merit and caution advised when specific treatment is prescribed on the basis of statistical averages. Another interesting feature of this case is the obvious discrepancy in the size of the lesion on x-ray and its actual size pathologically. In this case a 3.5 cm. lesion on x-ray proved to be only 2 cm. on cut section. When small intraparenchymal lesions that are hypovascular are evaluated size is judged by the displacement and draping of vessels around the lesion. One must be aware that the lesion will be magnified by the rim of compressed normal parenchyma that surrounds it and this was quite evident in our case. Combined with the slight magnification inherent in the x-ray itself the lesion appeared almost twice its actual size. One further point is worthy of re-emphasis, that being the choice of incision in this patient. While exploration and radical nephrectomy could have been performed from the flank approach, an anterior approach permitted palpation and visual inspection of the opposite kidney. This was of major concern in the decision to proceed with an extirpative operation. REFERENCES
l. Baron, M., Leiter, E. and Brendler, H.: Preoperative diagnosis of renal angiomyolipoma. J. Urol., 117: 701, 1977. 2. Silbiger, M. L. and Peterson, C. C., Jr.: Renal angiomyolipoma: its distinctive angiographic characteristics. J. Urol., 106: 363, 1971. 3. McAninch, J. W. and Stutzman, R. E.: Avascular renal adenocarcinoma: variations and characteristics. Urology, 9: 212, 1977.
800
CLINICOPATHOLOGICAL CONFERENCE
4. Mancilla-Jimenez, R., Stanley, R. J. and Blath, R. A.: Papillary renal cell carcinoma: a clinical, radiologic and pathologic study of34 cases. Cancer, 38: 2469, 1976. 5. Blath, R. A., Mancilla-Jimenez, R. and Stanley, R. J.: Clinical comparison between vascular and avascular renal cell carcinoma. J. Urol., 115: 514, 1976. 6. Watson, R. C., Fleming, R. J. and Evans, A. J.: Arteriography in the diagnosis of renal carcinoma. Review of 100 cases. Radiology, 91: 888, 1968. 7. Chonko, A. M., Weiss, S. M., Stein, J. H. and Ferris, T. F.:
Renal involvement in tuberous sclerosis. Amer. J. Med., 56: 124, 1974. 8. McCullough, D. L., Scott, R., Jr. and Seybold, H. M.: Renal angiomyolipoma (hamartoma): review of the literature and report of7 cases. J. Urol., 105: 32, 1971. 9. Walker, D. E., Barry, J. M. and Hodges, C. V.: Angiomyolipoma: diagnosis and treatment. J. Urol., 116: 712, 1976. 10. Novick, A. C., Stewart, B. H., Straffon, R. A. and Banowsky, L. H.: Partial nephrectomy in the treatment of renal adenocarcinoma. J. Urol., 118: 932, 1977.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1979 by The Williams & Wilkins Co.
Clinicopathologi cal Conference HEMATURIA IN SEIZURE DISORDER PATIENT DENNIS D. GARVIN,* CARL H. WEBER, JR.,t DAVID J. CONFER,+ THOMAS P. BALL, JR.§ JAMES D. MULLINSII
AND
From the Department of Urology, Division of Surgery and the Department of Anatomic Pathology, Division of Support Services, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas
PRESENTATION OF CASE,J
Dr. Dennis D. Garvin. A 32-year-old man had right flank pain and gross hematuria. He had suffered intermittent gross, painless hematuria for 4 years and several radio-contrast studies had not disclosed any evidence of upper tract abnormality. Previous cystoscopy examinations had revealed only friable vessels in the prostatic urethra as a possible etiology of the hematuria. Also of significance in the history was a congenital seizure disorder, treated with diphenylhydantoin and phenobarbital. The patient was admitted to the urology service, where physical examination revealed a young man with below normal intelligence. In addition to the positive physical finding of right costovertebral angle tenderness the patient had multiple skin lesions, including hypopigmented and hyperpigmented areas, subungual fibromas and papillary growths on the nose and in the nasolabial folds. Laboratory parameters were normal except for a hematocrit of 42. An excretory urogram (IVP) revealed a slightly enlarged right kidney with an increasingly dense nephrogram carried through delayed films. Cystoscopy disclosed no lower tract abnormalities, while gross blood was seen coming from the right orifice. Retrograde ureteropyelography revealed virtual non-filling of the renal pelvis, with the configuration of the filling defects that suggested an extensive blood clot. A computer tomography (CT) scan revealed only enlargement of the right kidney with probable clots in the pelvis. Angiography revealed a 3 cm. moderately vascular renal mass in the mid portion of the right kidney, with no definite neovascularity (fig. 1). The left kidney and the remainder of the right kidney demonstrated normal vascularity. A dermatology consultant agreed that the facial lesions were adenoma sebaceum, while an ophthalmology consultant was unable to find a retinal phakoma. A cranial CT scan did not reveal any cerebral calcification and all bone films were negative except for the skull film (fig. 2). A bone scan was negative. Throughout the evaluation the patient had difficulty with the bleeding, requiring catheterization and continuous irrigation after 2 episodes of clot retention. RADIOGRAPHIC FINDINGS
Dr. Carl H. Weber. The IVP, obtained while the right kidney apparently was obstructed by blood clots, fails to visualize the collecting system and demonstrates only a ne* Chief Resident, Department of Urology.
t Assistant Chairman, Department of Urology. :j:
Staff Urologist, Department of Urology.
§ Chairman, Department of Urology.
II Department of Anatomic Pathology.
,r Case presented at Grand Rounds on April 13, 1978. The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Air Force.
phrogram of a slightly enlarged kidney of normal contour. The retrograde ureterogram is compatible with obstruction of the right upper ureter by clots. Neither of these studies identifies a mass in the kidney. Similarly, the CT scan demonstrates some filling defects in the right renal pelvis, with a relative density index suggestive of blood clot. The renal contour appears normal and no evidence of an intrarenal mass is seen, although enhancement of the renal parenchyma is unsatisfactory in this obstructed kidney. In addition no areas of fat density are identified within the kidney. However, the angiographic studies reveal a definite 3½ cm. mass in the mid portion of the right kidney, as evidenced by the splaying of the intrarenal vessels around the area of the mass that subsequently is seen as a blush, which becomes more prominent on the delayed films. There are mild vascular irregularities about and within this area of blush but no neovascularity, aneurysms or venous communications can be identified. The lower pole, supplied by a second right renal artery, appears normal, as does the left kidney. No renal veins were seen on the right side during the arterial study but 2 patent right renal veins were demonstrated by a venous study. The remainder of the radiographic studies, including full chest tomography, revealed no abnormalities except for the impressive skull films demonstrating the multiple rounded, cotton-wool densities and the marked thickening of the posterior calvarium. Collectively, the radiographic studies demonstrate a hypovascular mass in the mid portion of the poorly functioning right kidney that appears to be obstructed by blood clots, patent right renal veins, a normal appearing left kidney, a thickened calvarium and multiple densities on the skull films. The CT scan would indicate that the renal mass is of tissue density comparable to the renal parenchyma, without significant areas of fatty tissue. Careful study of several plain radiographs of the right kidney fail to demonstrate areas of lucency, a sign suggested as pathognomonic of angiomyolipoma but its absence does not exclude the diagnosis. 1 The vessels within the mass do not demonstrate the multiple arterial aneurysms and cork-screw vessels usually associated with an angiomyolipoma but, likewise, their absence does not rule out an angiomyolipoma. 1• 2 Hypovascular angiomyolipomas do occur, although they usually demonstrate more evidence oflipomatous elements. Similarly, the absence of disorganized neovascularity does not exclude adenocarcinoma of the kidney and about 5 per cent of the adenocarcinomas are avascular or hypovascular. 3 The absence of any demonstrable arteriovenous communication would make an arteriovenous malformation unlikely. A metastatic tumor to the kidney or benign primary renal tumor cannot be excluded on the basis of the radiographic studies. The thickened calvarium is explained readily in this patient as a recognized side effect of diphenylhydantoin. The multiple
797
798
CLINICOPATHOLOGICAL CONFERENCE
Fm. 1. A, arteri~ phase of selective. r~ght renal angiogram shows subtle draping of vessels around hypovascular mass. B, late nephrogram phase with lower arrows outlmmg mass as blush. Upper arrow indicates dilated upper calix behind pelvis that contained blood clot.
Fm. 2. Skull film shows the multiple rounded cotton-wool densities in skull and thickening of posterior calvarium.
densities seen on the skull films are most consistent with bony involvement of tuberous sclerosis, Paget's disease or metastatic carcinoma of the prostate, all other sources of blastic metastases being much less likely possibilities. Metastatic renal adenocarcinoma to the skull can be excluded as a cause since such metastases are always lytic lesions. In summary, the radiologic studies demonstrate a solid, hypovascular mass in the right kidney that lacks pathognomonic features to suggest its specific etiology. The skull films demonstrate multiple densities compatible with involvement by tuberous sclerosis and a thickened calvarium resulting from diphenylhydantoin usage. DISCUSSION AND DIFFERENTIAL DIAGNOSIS
Dr. David J. Confer. Obviously, this patient has tuberous sclerosis, meeting the 3 classic diagnostic criteria of mental retardation, seizure disorder beginning in early childhood and adenoma sebaceum. He also had periungual fibroma and classic skull radiographic lesions.
The somewhat vascular right renal lesion did not have the classic radiographic findings of an angiomyolipoma, yet up to 80 per cent of the patients with tuberous sclerosis have these lesions and other primary renal tumors in this disease are unusual. Often the angiomyolipomas of tuberous sclerosis are multiple, small and bilateral with these lesions first manifesting themselves in patients 25 to 30 years old. This is in contrast to the larger unilateral angiomyolipoma, which appears sporadically in the population. These angiomyolipomas usually do not present until patients are in the fifth or sixth decade of life and often present a most difficult diagnostic problem. Of the other entities in our differential diagnosis renal cell carcinoma was another primary consideration. Although rarely reported in association with tuberous sclerosis it certainly is a possibility. It is interesting that patients with documented renal cell carcinomas that have been associated with tuberous sclerosis have had an apparently improved survival rate, leading some investigators to consider these possible angiomyolipomas that appeared more neoplastic pathologically. However, similarly, on angiography we do not have the neovascularity and associated arteriovenous shunting that would be helpful in the diagnosis of renal cell carcinoma. One also could list a number of other primary and secondary neoplastic lesions to complete the differential diagnosis but these are less likely in this clinical presentation. It is important to mention that the right collecting system was not visualized on any of our studies on this admission but an IVP 1 year earlier was entirely normal in that regard. With this patient having tuberous sclerosis the overwhelming likelihood is that this is an angiomyolipoma manifesting itself for the last 4 years by intermittent hematuria. An occult renal cell carcinoma is a far less likely alternative. However, without the classic angiographic findings associated with angiomyolipoma we are not willing to consider non-surgical management, such as embolization, without the definitive diagnosis. It is equally important to stress the fact that surgical intervention in any vascular lesion of the kidney' in patients with tuberous sclerosis should be as conservative as possible in that they are apt to suffer enlargement of present lesions or have new lesions on the contralateral kidney. It is
799
HEMATURIA IN SEIZURE DISORDER PATIENT
unfortunate that this relatively small lesion in our patient does not reside in either the upper or lower pole or more near the surface of the kidney where segmental nephrectomy is more easily accomplished. PROVISIONAL DIAGNOSIS
sclerosis and typically is bilateral when associated with this process. 7 FINAL DIAGNOSIS
Small (2 cm.) well differentiated clear cell adenocarcinoma of the right kidney, pathologic stage I.
Angiomyolipoma, rule out renal cell carcinoma. COMMENTS DISCUSSION OF SURGERY
Doctor Garvin. Exploration was done transperitoneally through a right anterior subcostal incision. The kidney was palpated through Gerota's fascia. Although the kidney was lobulated it had no areas· of palpable firmness. The anterior surface had multiple punctate ecchymoses. There again was noted the lobulation of the mid body of the kidney, which was visually and palpably identical to the remainder of the kidney substance. It was possible to visualize the anterior surface of the left kidney through this incision, with no abnormalities being noted. With angiographic and surgical confirmation of a normal left kidney we decided to do a right radical nephrectomy in view of the symptoms and the inability to make an immediate surgical diagnosis. DISCUSSION OF PATHOLOGY
Dr. James D. Mullins. The gross specimen was consistent with a right radical nephrectomy, including the right kidney and adrenal gland. On external gross examination the kidney was unremarkable. Bisection revealed a solitary, pale yellow, homogeneous, subcapsular cortical mass that had a greatest diameter of 2 cm. The mass was well demarcated from the adjacent compressed renal parenchyma in most areas by a thin, incomplete fibrous capsule. Grossly, there was no evidence of invasion of the overlying renal capsule, renal veins or pelvis. Two grossly unremarkable hilar lymph nodes, the largest having a diameter of0.8 cm., were found on dissection of the hilar fat. Microscopically, the neoplasm demonstrated a uniform pattern, consisting of closely packed tubules of variable sizes. The tubules were lined by columnar cells, possessing abundant clear cytoplasm with distinct cell membranes and relatively small uniform basally located nuclei. Cellular pleomorphism was minimal and no mitotic figures or areas of necrosis were seen. The lumina of most of the neoplastic tubules appeared empty, while a few were filled with masses of intact red blood cells or acellular eosinophilic proteinaceous debris. Except for the peripheral fibrous capsule the accompanying fibrous stroma was inconspicious and contained scattered thin walled vessels with a few lymphocytes and hemosiderin laden macrophages. The peripheral fibrous capsule was focally absent and invaded in multiple areas by neoplastic tubules that even extended into the adjacent compressed normal renal parenchyma in a few areas. Microscopically, the 2 previously mentioned hilar lymph nodes were free of metastatic tumor. Despite the small size of this lesion (2 cm.) the histology was unquestionably that of well differentiated clear cell adenocarcinoma of the kidney and not a renal cell adenoma. Further histological evidence of the malignant nature of this small neoplasm was the prominence of capsular invasion. Extensive sampling of the neoplasm revealed no areas of papillary growth pattern characterized by prominent fibrovascular cores lined by neoplastic cells. 4 The papillary histological pattern, although uncommon (14 per cent of the renal cell carcinoma cases in 1 large series), 4 accounts for almost half of the renal cell carcinomas that appear hypovascular or avascular on arteriography. 3• 6 There also was no gross or microscopic evidence of any associated angiomyolipoma in the resected kidney. This peculiar hamartomatous neoplasm occurs in the kidneys of anywhere from 40 to 80 per cent of the patients with tuberous
Dr. Thomas P. Ball, Jr. This is a classic case to illustrate the trap into which one may fall if emotions, impressions and, worse yet, assumptions are permitted to govern our therapy. It was tempting to accept the statistical implications in this case and to assume that the mass from which the patient bled was an angiomyolipoma. The clinical picture was typical with the mass even presenting on the right side as the majority of unilateral angiomyolipomas do. Even the age of the patient tended to swing the pendulum away from renal cell adenocarcinoma, although malignancies of this type certainly do occur in the young. The facts were that the possibility of a carcinoma could not be eliminated and that the angiogTam and CT scan that we had hoped would show the characteristic fat density in the mass did nothing to strengthen our convictions either way. While flank exploration and biopsy had been recommended with unilateral lesions in patients with tuberous sclerosis,8' " we thought that this lesion was, in fact, indistinguishable from hypernephroma and, thus, opted to do a radical nephrectomy when the opposite kidney was palpably and radiographically normal, and the nature of the lesion could not be further determined at exploration. Had the lesion been polar in location partial nephrectomy would have been a viable alternative, 10 in view of the likelihood of developing a lesion on the other side. However, the central location and difficulty in palpation suggested radical nephrectomy as the more conservative approach. How fortunate we were that the persistence of symptoms and bleeding forced our hand toward more extensive efforts to obtain a definitive diagnosis, since previous pyelograms had revealed nothing. While this case is rare it serves to emphasize further that each case and lesion must be judged on its own merit and caution advised when specific treatment is prescribed on the basis of statistical averages. Another interesting feature of this case is the obvious discrepancy in the size of the lesion on x-ray and its actual size pathologically. In this case a 3.5 cm. lesion on x-ray proved to be only 2 cm. on cut section. When small intraparenchymal lesions that are hypovascular are evaluated size is judged by the displacement and draping of vessels around the lesion. One must be aware that the lesion will be magnified by the rim of compressed normal parenchyma that surrounds it and this was quite evident in our case. Combined with the slight magnification inherent in the x-ray itself the lesion appeared almost twice its actual size. One further point is worthy of re-emphasis, that being the choice of incision in this patient. While exploration and radical nephrectomy could have been performed from the flank approach, an anterior approach permitted palpation and visual inspection of the opposite kidney. This was of major concern in the decision to proceed with an extirpative operation. REFERENCES
l. Baron, M., Leiter, E. and Brendler, H.: Preoperative diagnosis of renal angiomyolipoma. J. Urol., 117: 701, 1977. 2. Silbiger, M. L. and Peterson, C. C., Jr.: Renal angiomyolipoma: its distinctive angiographic characteristics. J. Urol., 106: 363, 1971. 3. McAninch, J. W. and Stutzman, R. E.: Avascular renal adenocarcinoma: variations and characteristics. Urology, 9: 212, 1977.
800
CLINICOPATHOLOGICAL CONFERENCE
4. Mancilla-Jimenez, R., Stanley, R. J. and Blath, R. A.: Papillary renal cell carcinoma: a clinical, radiologic and pathologic study of34 cases. Cancer, 38: 2469, 1976. 5. Blath, R. A., Mancilla-Jimenez, R. and Stanley, R. J.: Clinical comparison between vascular and avascular renal cell carcinoma. J. Urol., 115: 514, 1976. 6. Watson, R. C., Fleming, R. J. and Evans, A. J.: Arteriography in the diagnosis of renal carcinoma. Review of 100 cases. Radiology, 91: 888, 1968. 7. Chonko, A. M., Weiss, S. M., Stein, J. H. and Ferris, T. F.:
Renal involvement in tuberous sclerosis. Amer. J. Med., 56: 124, 1974. 8. McCullough, D. L., Scott, R., Jr. and Seybold, H. M.: Renal angiomyolipoma (hamartoma): review of the literature and report of7 cases. J. Urol., 105: 32, 1971. 9. Walker, D. E., Barry, J. M. and Hodges, C. V.: Angiomyolipoma: diagnosis and treatment. J. Urol., 116: 712, 1976. 10. Novick, A. C., Stewart, B. H., Straffon, R. A. and Banowsky, L. H.: Partial nephrectomy in the treatment of renal adenocarcinoma. J. Urol., 118: 932, 1977.