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Tuberous Sclerosis with Bilateral Angiomyolipomas of the Kidney: Case Report with 8-Year Followup
Vol. 106, August Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1971 by The Williams & Wilkins Co.
TUBEROUS SCLEROSIS WITH BILATERAL ANGIOMYOLIPOMAS OF THE KIDNEY: CASE REPORT WITH 8-YEAR FOLLOWUP ROBERTS. WALDBAUM, VICTOR F. MARSHALL, EDWARD C. MUECKE AND ROBIN WATSON From the Department of Surgery (Urology) and the James Buchanan Brady Foundation, The New York Hospital and Departments of Radiology and Surgery (Urology), Cornell Medical College, New York, New York
The term tuberous sclerosis refers particularly to the development of glial nodules in the brain but more generally to a complex of lesions in which adenoma sebaceum, renal tumors and phakoma of the retina are particularly frequent.1-3 Thus, mental retardation, epilepsy, adenoma sebaceum, renal masses and calcifications within the brain are encountered clinically. Many patients have only a few of the several manifestations of tuberous sclerosis and as such may represent a forme fruste of this disorder. Renal tumors are usually angiomyolipomas and may occur without evidence of the other members of the complex. 4 CASE REPORT
A. P., NYH 1098268, unfortunately had had a nephrectomy prior to being referred to us. Despite typical distribution of cutaneous adenoma sebaceum (fig. 1) and tlie complete kidney for histological examination, the complex was not recognized and the patient was given 1,500 rads to the renal area on the supposition that this was a highly malignant, albeit unusual, neoplasm. The woman remained asymptomatic for 6 years but excretory urography (IVP) revealed that the left kidney had enlarged (fig. 2). No member of her family has had epilepsy, mental retardation, renal disease or facial lesions of this type. Physical examination revealed no abnormality except the facial lesions and a readily palpable left kidney at least twice normal size. The usual laboratory tests were within normal limits. HowAccepted for publication November 1970. 1 Ross, A. T. and Dickerson, W.W.: Tuberous sclerosis. Arch. Neurol. Psychiat., 60: 233, 1943. 2 Bourneville, D. M.: Contribution a l 'etude de l 'idiotie. Sclerose tubereuse des circonvolutions cerebrales; idiotie et epilepsie hemiplegique. Arch. de neurol., 1: 81, 1880. 3 Critchley, M. and Earl, C. J. C. : Tuberose sclerosis and allied conditions. Brain, 66: 311, 1932. 4 Hajdu, S. I. and Foote, F. W., Jr.: Angiomyolipoma of the kidney: report of 27 cases and review of the literature. J. Urol., 102: 396, 1969.
ever, the urea clearance was only 29 per cent of normal. Papanicolaou smears of the urinary sediment were negative. Roentgenograms of the skull disclosed several small intracranial calcifications and studies of the spine disclosed islands of increased density (fig. 3, A). A retrograde pyelogram disclosed no major changes from the one which had been obtained 6 years earlier. Percutaneous transfemoral renal arteriography indicated an almost total replacement of abnormal vessels within the kidney and even extensions beyond the confines of the kidney (fig. 3, B). Multiple small aneurysms were noted. Specimens, obtained from the kidney removed 6 years earlier, showed proliferation of fat cells, many large hyperchromatic and some multinucleated cells. Fusiform cells with elongated nuclei also were noted. In some areas these fusiform cells were attached to the walls of numerous small blood vessels. Diagnosis was angiomyolipoma of the kidney (fig. 4). During the 2 years of followup there has been no gross change, the patient's condition remains good and without evidence of deterioration either regarding renal function or mental status (the latter being apparently normal at all times). DISCUSSION
Golgi 5 reported on 47 cases of proved tuberous sclerosis, and renal neoplasm was demonstrated in 8 of 9 autopsies (the neoplasms were bilateral and multiple in 7 cases). Particularly important was his observation that 89 per cent of the 47 patients were asymptomatic, none died as a result of the renal involvement and none had evidence of metastases. Hajdu and Foote 4 found typical angiomyolipomas of the kidney in 27 cases in the course of 8,501 postmortem examinations at the Memorial Center in New York City. Again, none of these 27 patients died of causes related to the renal tumors. In fact 26 of their 27 patients were 5 Golgi, H.: Tuberous sclerosis and renal neoplasms. J. Urol., 86: 919, 1961.
180
TUBEROUS SCLEROSIS WITH BILATERAL RENAL ANGIOMYOLIPOMA
181
Fw. 1. Patient's face, 1967. Numerous small adenomas of skin are seen located over bridge of nose and extending onto face in butterfly fashion.
Frn. 2. A, IVP (1961) reveals mass lesion in kidney, distorting its collecting system. R, retrograde pyelogram (1967) reveals mass lesion in left kidney, distorting its collecting system. No change is seen on left side since 1961 except for compensatory hypertrophy.
asymptomatic in regard to their kidneys. Of particular importance was the fact that none of these 27 patients had other manifestations of the tuberous sclerosis complex, aside from the renal masses (which were all unilateral). Most other reported cases have been of the symptomatic variety. The clinical histories were all strikingly similar~acute onset of severe flank pain with a palpable mass, tachycardia, fever and anemia, usually due to spontaneous bleeding or bleeding after minimal trauma into the tumor. Many patients were treated with neplirectomy and did well; many had tuberous sclerosis with
either its florid manifestations or minimal but definite evidence. 6• 9 Others with identical history, 6 Moolten, S. E.: Hamartial nature of the tuberous sclerosis complex and its bearing 011 the tumor problem; report of a case with tumor anomaly of the kidney and adenoma sebaceum. Arch. Intern. Med., 69: 589, 1942. 7 Inglis, K.: The nature and origin of smooth muscle-like neoplastic tissue in renal tumors of the tuberous sclerosis complex. Cancer, 13: 602, 1960. 8 Taylor, J. N. and Genters, K.: Renal angiomyolipoma and tuberous sclerosis. J. Urol., 79: 685, 1958. 9 Beck, R. E. and Hammond, R. C.: Renal and osseous manifestation of tuberous sclerosis: case report. J. Urol., 77: 578, 1957.
182
WALDBAUM AND ASSOCIATES
FIG. 3. A, lateral view of lumbar spine (1967) reveals islands of increased density within vertebral column. B, percutaneous transfemoral aortogram (1967) shows intrarenal vasculature is almost totally replaced by abnormal vessels, with gross tumor staining. Multiple arteriovenous fistulas are seen. Tumor appears to extend beyond confines of kidney.
FIG. 4. Microscopic section of right kidney removed in 1961 shows proliferation of fat cells, many with large hyperchromatic and multinucleated nuclei. Fusiform cells with elongated nuclei are seen as well as increased vascularity.
TUBEJWl~S SCLEROSIS WITH BILA"rERAL RENAL ANGIOMYOLIPOMA
lrnd no evidence of treatment and tuberous sclerosis. 7 , 10 - 11 metastase:, to local infiltration of tissue and eYen mvasion of the renal vein have been ha. Ie been u11able to find an of the with dist:111t metastases whether or not the tuberous ~clerosis 1_~,n1s rn·rsent. rrhe
the 1nmber of cases 1s small and to be short. 1s-2o CO!':CLUSION
be-
1
appearance ha~; not been borne out but 10
Itusche, C.: H.cnal
report of three cn,;es. J. C. lt. and
E. E. · H,enal b.an1ar-
66: ,50G, 12 HAYbertson, T. l) and T-land ir1trarc11al of Rtngj_ca1 to1.T1a.
1
sclerosis
dence of this In contrast Lo the and bilateral nature of the tumors in tients with tuberous lesions rn ,vithoat tubernus sclerosis tend to be .sillg;k.
with C' H V. and Hall, u.J . J. Urol., 65: K J.: Angiomyoliporrrn of ihe 1951. Berg, J. W. · Angiolipomyosarcoma of kidney ha1nn,rton12,tous in a
a bro11choge11ic lM1d
I{enal n,ngiornyo -
S4: '.203, Pontasse, E. F and Ha?iard, angiomyo!ipomas. Arch. Path .. ·i
lf
,J.
K. · Syrnpto-
Cancer)
THE JOURNAL OF UROLOGY
Copyright© 1971 by The Williams & Wilkins Co.
TUBEROUS SCLEROSIS WITH BILATERAL ANGIOMYOLIPOMAS OF THE KIDNEY: CASE REPORT WITH 8-YEAR FOLLOWUP ROBERTS. WALDBAUM, VICTOR F. MARSHALL, EDWARD C. MUECKE AND ROBIN WATSON From the Department of Surgery (Urology) and the James Buchanan Brady Foundation, The New York Hospital and Departments of Radiology and Surgery (Urology), Cornell Medical College, New York, New York
The term tuberous sclerosis refers particularly to the development of glial nodules in the brain but more generally to a complex of lesions in which adenoma sebaceum, renal tumors and phakoma of the retina are particularly frequent.1-3 Thus, mental retardation, epilepsy, adenoma sebaceum, renal masses and calcifications within the brain are encountered clinically. Many patients have only a few of the several manifestations of tuberous sclerosis and as such may represent a forme fruste of this disorder. Renal tumors are usually angiomyolipomas and may occur without evidence of the other members of the complex. 4 CASE REPORT
A. P., NYH 1098268, unfortunately had had a nephrectomy prior to being referred to us. Despite typical distribution of cutaneous adenoma sebaceum (fig. 1) and tlie complete kidney for histological examination, the complex was not recognized and the patient was given 1,500 rads to the renal area on the supposition that this was a highly malignant, albeit unusual, neoplasm. The woman remained asymptomatic for 6 years but excretory urography (IVP) revealed that the left kidney had enlarged (fig. 2). No member of her family has had epilepsy, mental retardation, renal disease or facial lesions of this type. Physical examination revealed no abnormality except the facial lesions and a readily palpable left kidney at least twice normal size. The usual laboratory tests were within normal limits. HowAccepted for publication November 1970. 1 Ross, A. T. and Dickerson, W.W.: Tuberous sclerosis. Arch. Neurol. Psychiat., 60: 233, 1943. 2 Bourneville, D. M.: Contribution a l 'etude de l 'idiotie. Sclerose tubereuse des circonvolutions cerebrales; idiotie et epilepsie hemiplegique. Arch. de neurol., 1: 81, 1880. 3 Critchley, M. and Earl, C. J. C. : Tuberose sclerosis and allied conditions. Brain, 66: 311, 1932. 4 Hajdu, S. I. and Foote, F. W., Jr.: Angiomyolipoma of the kidney: report of 27 cases and review of the literature. J. Urol., 102: 396, 1969.
ever, the urea clearance was only 29 per cent of normal. Papanicolaou smears of the urinary sediment were negative. Roentgenograms of the skull disclosed several small intracranial calcifications and studies of the spine disclosed islands of increased density (fig. 3, A). A retrograde pyelogram disclosed no major changes from the one which had been obtained 6 years earlier. Percutaneous transfemoral renal arteriography indicated an almost total replacement of abnormal vessels within the kidney and even extensions beyond the confines of the kidney (fig. 3, B). Multiple small aneurysms were noted. Specimens, obtained from the kidney removed 6 years earlier, showed proliferation of fat cells, many large hyperchromatic and some multinucleated cells. Fusiform cells with elongated nuclei also were noted. In some areas these fusiform cells were attached to the walls of numerous small blood vessels. Diagnosis was angiomyolipoma of the kidney (fig. 4). During the 2 years of followup there has been no gross change, the patient's condition remains good and without evidence of deterioration either regarding renal function or mental status (the latter being apparently normal at all times). DISCUSSION
Golgi 5 reported on 47 cases of proved tuberous sclerosis, and renal neoplasm was demonstrated in 8 of 9 autopsies (the neoplasms were bilateral and multiple in 7 cases). Particularly important was his observation that 89 per cent of the 47 patients were asymptomatic, none died as a result of the renal involvement and none had evidence of metastases. Hajdu and Foote 4 found typical angiomyolipomas of the kidney in 27 cases in the course of 8,501 postmortem examinations at the Memorial Center in New York City. Again, none of these 27 patients died of causes related to the renal tumors. In fact 26 of their 27 patients were 5 Golgi, H.: Tuberous sclerosis and renal neoplasms. J. Urol., 86: 919, 1961.
180
TUBEROUS SCLEROSIS WITH BILATERAL RENAL ANGIOMYOLIPOMA
181
Fw. 1. Patient's face, 1967. Numerous small adenomas of skin are seen located over bridge of nose and extending onto face in butterfly fashion.
Frn. 2. A, IVP (1961) reveals mass lesion in kidney, distorting its collecting system. R, retrograde pyelogram (1967) reveals mass lesion in left kidney, distorting its collecting system. No change is seen on left side since 1961 except for compensatory hypertrophy.
asymptomatic in regard to their kidneys. Of particular importance was the fact that none of these 27 patients had other manifestations of the tuberous sclerosis complex, aside from the renal masses (which were all unilateral). Most other reported cases have been of the symptomatic variety. The clinical histories were all strikingly similar~acute onset of severe flank pain with a palpable mass, tachycardia, fever and anemia, usually due to spontaneous bleeding or bleeding after minimal trauma into the tumor. Many patients were treated with neplirectomy and did well; many had tuberous sclerosis with
either its florid manifestations or minimal but definite evidence. 6• 9 Others with identical history, 6 Moolten, S. E.: Hamartial nature of the tuberous sclerosis complex and its bearing 011 the tumor problem; report of a case with tumor anomaly of the kidney and adenoma sebaceum. Arch. Intern. Med., 69: 589, 1942. 7 Inglis, K.: The nature and origin of smooth muscle-like neoplastic tissue in renal tumors of the tuberous sclerosis complex. Cancer, 13: 602, 1960. 8 Taylor, J. N. and Genters, K.: Renal angiomyolipoma and tuberous sclerosis. J. Urol., 79: 685, 1958. 9 Beck, R. E. and Hammond, R. C.: Renal and osseous manifestation of tuberous sclerosis: case report. J. Urol., 77: 578, 1957.
182
WALDBAUM AND ASSOCIATES
FIG. 3. A, lateral view of lumbar spine (1967) reveals islands of increased density within vertebral column. B, percutaneous transfemoral aortogram (1967) shows intrarenal vasculature is almost totally replaced by abnormal vessels, with gross tumor staining. Multiple arteriovenous fistulas are seen. Tumor appears to extend beyond confines of kidney.
FIG. 4. Microscopic section of right kidney removed in 1961 shows proliferation of fat cells, many with large hyperchromatic and multinucleated nuclei. Fusiform cells with elongated nuclei are seen as well as increased vascularity.
TUBEJWl~S SCLEROSIS WITH BILA"rERAL RENAL ANGIOMYOLIPOMA
lrnd no evidence of treatment and tuberous sclerosis. 7 , 10 - 11 metastase:, to local infiltration of tissue and eYen mvasion of the renal vein have been ha. Ie been u11able to find an of the with dist:111t metastases whether or not the tuberous ~clerosis 1_~,n1s rn·rsent. rrhe
the 1nmber of cases 1s small and to be short. 1s-2o CO!':CLUSION
be-
1
appearance ha~; not been borne out but 10
Itusche, C.: H.cnal
report of three cn,;es. J. C. lt. and
E. E. · H,enal b.an1ar-
66: ,50G, 12 HAYbertson, T. l) and T-land ir1trarc11al of Rtngj_ca1 to1.T1a.
1
sclerosis
dence of this In contrast Lo the and bilateral nature of the tumors in tients with tuberous lesions rn ,vithoat tubernus sclerosis tend to be .sillg;k.
with C' H V. and Hall, u.J . J. Urol., 65: K J.: Angiomyoliporrrn of ihe 1951. Berg, J. W. · Angiolipomyosarcoma of kidney ha1nn,rton12,tous in a
a bro11choge11ic lM1d
I{enal n,ngiornyo -
S4: '.203, Pontasse, E. F and Ha?iard, angiomyo!ipomas. Arch. Path .. ·i
lf
,J.
K. · Syrnpto-
Cancer)