- Email: [email protected]
Diagnosis and management of renal angiomyolipoma
SCIENTIFIC
ARTICLES
DIAGNOSIS AND MANAGEMENT OF RENAL ANGIOMYOLIPOMA DOV PODE,
M.D.
SHIMON MERETIK, AMOS SHAPIRO, MARCO CAINE,
M.D.
M.D. M.S., F.R.C.S.
From the Department of Urology, Hadassah University Hospital, Jerusalem, Israel
ABSTRACT-Renal angiomyolipoma (hamartoma) is an uncommon benign tumor of the kidney. Although about 400 cases of renal angiomyolipoma have been reported, it still causes difficulties in diagnosis and treatment. Until a few years ago it was almost impossible to arrive at a correct diagnosis preoperatively, and most of the cases underwent nephrectomy with the wrong diagnosis of renal carcinoma. More recently, abdominal computerized tomography and renal sonography have made it possible to reach the correct preoperative diagnosis in many cases, and thus to avoid unnecessary nephrectomies. We report on our experience with 13 cases of renal angiomyolipoma, and our conservative approach in a number of cases, which has enabled us to preserve renal tissue and function.
Renal angiomyolipoma (hamartoma) is an uncommon benign tumor with a broad spectrum of symptomatology. The tumor is composed of tissues normally present in the kidney, but these are abnormal in quantity, arrangement, or degree of maturation. It is composed mainly of fat, vascular tissue, and smooth muscle. Hajdu and Foote’ in a histopathologic study of 8,501 renal tumors found only 27 (0.3%) cases of angiomyolipoma, 50 per cent of which were associated with tuberous sclerosis. In this condition the renal lesions are usually bilateral, small, multifocal and have an equal sex distribution.2+3 In cases without tuberous sclerosis the disease occurs mainly in females, and the renal lesion is unilateral, unifocal, and frequently large in size. 4s Some patients are asymptomatic, and the tumor is discovered during a routine plain abdominal film or intravenous pyelogram. In others an abdominal mass may be palpated on physical examination or during an exploratory laparotomy performed for some
UROLOGY
/ MAY 1985
/ VOLUME
XXV, NUMBER 5
other cause. The presenting symptoms are most commonly flank or abdominal pains, hematuria, or spontaneous retroperitoneal hemorrhage. The latter may result in hemorrhagic shock, necessitating urgent surgical intervention. Although more than 400 cases of renal angiomyolipomas have been described since 1880, frequently there are difficulties in arriving at the correct preoperative diagnosis in those patients not suffering from tuberous sclerosis, and until recent years this had been achieved rarely. As a result, most patients have undergone unnecessary nephrectomies for this benign tumor. The routine use of renal angiography in the investigation of renal tumors has not proved to be reliable in differentiating angiomyolipoma from renal adenocarcinoma. However, more recently, the growing experience with renal sonography and abdominal computerized tomography has enabled a preoperative presumptive diagnosis to be made in a number of cases of renal angiomyolipoma. Such a preoperative
461
FKXJFlE 1. Case 2. (A) Angiography shows large hypervascular tumor arising from lower pole of right kidney and smaller tumor in left kidney. (B) Histology shows typical features of smooth muscle, primitive blood vessels, and adipose tissue (original magnification x 400). (C) Postoperative IVP shows distorted but well-functioning right kidney.
diagnosis, or the awareness of the possibility of this diagnosis at the time of operation, may enable a conservative approach to be used. We summarize our experience with 13 cases of renal angiomyolipoma, and illustrate our management in various cases, with the aim of maximal conservation of renal tissue and function whenever possible. Material and Methods Since 1958, 13 patients with renal angiomyolipoma have been hospitalized on our urologic service. In all cases except 1 the diagnosis has been confirmed by pathologic examination of excised tissue. The remaining patient had tuberous sclerosis, and multiple bilateral renal tu-
462
mors were demonstrated on IVP and renal angiography: The appearance on abdominal ultrasound supported the diagnosis of angiomyolipoma, and in this case the clinical diagnosis of multiple renal angiomyolipomas was made, with a resultant decision against operation. Patients
with tuberous
sclerosis
Three patients had tuberous sclerosis, all of whom suffered from epilepsy or mental retardation, intracerebral calcifications, retinal phakomata, adenoma sebaceum, and shagreen patches, which are typical dermal lesions over the lumbosacral region. Case 1. An eighteen-year-old female patient suffered from intermittent pain in the right
UROLOGY
/ MAY 1985
I
VOLUME
XXV, NUMBER 5
flank and abdomen. Physical examination revealed typical signs of tuberous sclerosis, and a large mass was palpable in the right lower quadrant of the abdomen. IVP and renal angiogram showed a large vascular mass virtually replacing the entire right kidney Exploratory laparotomy confirmed the presence of a right renal tumor, and intraoperative histologic examination of the tumor confirmed the suspected diagnosis of angiomyolipoma. Insufficient normal renal tissue remained to allow a conservative operation in this case, and therefore a right nephrectomy was performed. Case 2. A twelve-year-old male patient who had been known to have tuberous sclerosis since the age of seven months was admitted because of right lower quadrant abdominal pains and massive hematuria following mild blunt trauma to the right flank. On physical examination a large mass in the right side of the abdomen was revealed. Excretory urography showed multiple masses in both kidneys, and a very- large space-occupying lesion in the right kidney, Renal arteriography demonstrated a large hypervascular tumor emerging from the lower pole (Fig. 1A). A preoperative diagnosis of multiple angiomyolipomata was made, but in view of the large size, the hypervascularity, and the massive bleeding from the large tumor in the right kidney, it was decided that operation was necessary, and this was performed with the aim of removing the tumor and leaving the rest of the kidney intact. At operation the tumor, which was 15 x 20 cm in size, was removed from the lower and anterior part of the kidney, and pathologic examination confirmed it to be an angiomyolipoma (Fig. 1B). A postoperative IVP showed good function of the remaining part of the right kidney (Fig. 1C). Case 3. A twenty-eight-year-old male patient had suffered several times from left renal colic and macroscopic hematuria. Physical examination showed signs of tuberous sclerosis. He had a palpable mass in the left hypochondrium; an IVP showed several space-occupying lesions in both kidneys, and calyceal stones in the left kidney. A clinical diagnosis of renal angiomyolipomas associated with tuberous sclerosis was made. This diagnosis was supported by the findings on abdominal ultrasound examination, and since there were no complications which justified surgical intervention the patient was sent home without an histologic confirmation of the diagnosis. Follow-up examination of the patient two years later, which included both
UROLOGY
i
MAY 1985
i
VOLUME
XXV, NUMBER 5
Case 3. (A) Abdominal CT shows fatty tissue in tumor of right kidney (arrows l-5), calculus in left kidney (arrow 6), and contrast material in duodenum (arrow 7).
FIGURE2.
abdominal CT (Fig. 2) and ultrasound, did not show any progression of the disease. Patients
without
tuberous
sclerosis
There were 10 patients with no evidence of tuberous sclerosis accompanying the kidney tumors, of whom 2 were males and 8 were females. Their ages ranged from thirty-four to seventy-four (average 50 years old). Four patients suffered from flank pains, 5 patients had abdominal pains, and 5 patients had hematuria. Four patients presented with massive retroperitoneal hemorrhage which necessitated urgent surgical intervention. Seven patients had a palpable abdominal mass. One patient was asymptomatic, and the tumor was discovered on a routine IVP performed prior to colon surgery In all our patients the preoperative IVP showed the renal tumor, but renal angiography, when performed, did not help in making the correct preoperative diagnosis. Seven patients underwent radical nephrectomy without intraoperative histologic examination. Three patients who were operated on during the last few years were correctly diagnosed, and were treated conservatively, as described, Case 4. A forty-five-year-old male patient was admitted for a left hemicolectomy because of carcinoma of the colon. Routine preoperative IVP showed a space-occupying lesion, 3 cm in diameter, in the lower pole of the right kidney. Exploration of the kidney during laparotomy
463
FIGURE 3. Case 6. (A) Right renal angiogram, late phase, shows tumor at lower pole. (B) Longitudinal renal sonography shows varying. density of echogenic mass in lower pole tumor. (C) Follow-up IVP after excision of tumor from lower pole of right kidney.
for resection of the colon tumor revealed a fatty mass of the lower pole of the right kidney, and open biopsy confirmed the diagnosis of angiomyolipoma. The tumor was not excised because it was small and nonsymptomatic. Case 5. A fifty-year-old woman was admitted to the emergency ward because of right lower quadrant pain, vomiting, and fever. She had signs of peritoneal irritation in the right lower abdomen. Acute appendicitis was suspected, and on exploration the appendix was found to be normal, but a large retroperitoneal hematoma was found extending from a mass in the right kidney. Intraoperative excretory urography demonstrated a right renal tumor, and because of the spontaneous extrarenal hemorrhage there was the possibility of an angiomyolipoma. This diagnosis was confirmed by frozen section of an open biopsy specimen, and the tumor was removed by lower partial nephrec-
464
tomy. A new IVP three months later showed good function of the remaining part of the right kidney. Case 6. A fifty-year-old woman was admitted to the emergency ward because of syncope. A few hours later her blood pressure dropped to 80160, she complained of right abdominal pains, and macroscopic hematuria appeared. On physical examination there were signs of peritoneal irritation over the right side of the abdomen. Abdominal puncture revealed free blood in the peritoneal cavity. A plain abdominal film showed a large soft tissue mass in the right abdomen, and an IVP demonstrated a large space-occupying lesion displacing the right ureter medially and distorting the right kidney. With the suspicion of spontaneous hemorrhage from a large renal angiomyolipoma, renal angiography was performed, which showed
UROLOGY
I MAY1985 / VOLUMEXXV,NUMBER5
a tumor in the lower pole of the right kidney, with a large hematoma (Fig. 3A). Renal sonography supported our clinical diagnosis of angiomyolipoma (Fig. 3B). The patient immediately underwent a right lower partial nephrectomy. Her postoperative recovery was uneventful. A follow-up IVP seven months later showed good architecture and function of this kidney (Fig. 3C). Comment In the past the preoperative diagnosis of renal angiomyolipoma was difficult, and rarely made. Most cases were diagnosed and treated as renal adenocarcinoma, and only on the subsequent pathologic examination was the true nature of the lesion revealed. Macroscopically it is a soft yellow or gray tumor without a capsule, containing hemorrhagic and necrotic areas. Microscopic examination reveals fatty tissue consisting of mature cells, rich vascular tissue with many tortuous vessels, and smooth muscle sometimes with pleomorphic cells and hyperchromatic nuclei. Renal angiomyolipoma is probably always a benign tumor. Until 1960 some cases had been diagnosed as angiomyoliposarcoma according to histologic criteria, but their subsequent clinical course over many years showed that they had a markedly better prognosis than patients with renal sarcoma, and revision of their histologic examinations suggested that they were truly benign angiomyolipomas.6 Approximately 50 per cent of the cases seen clinically are associated with tuberous sclerosis. Bourneville’ was the first to describe tuberous sclerosis in 1880. It is a congenital disorder transferred by a rare autosomal dominant gene, and consists of tumor-like malformations of ectodermal origin occurring in the brain, skin, and retina, as well as multiple hamartomas in mesenchymal tissues such as the kidneys, heart, and lungs.s Many patients have epilepsy or mental retardation. The clinical diagnosis is usually based on the finding of the characteristic cutaneous lesions such as adenoma sebaceum, subungual fibromas, or shagreen patches. There may be cystic lesions in the lungs and bones, and retinal phakomata. Multiple renal hamartomas are common in these patients, and on postmortem examination can be found in up to 80 per cent of the cases.2 The natural course of the disease does not normally lead to terminal renal failure, although a decrease in renal function
UROLOGY
/ MAY 1985 i
VOLUME XXV, NUMBER 5
Presenting symptoms and signs in 13 patients with renal angiomyolipoma _
TABLE I.
Symptom/Sign Flank pain Abdominal pain Fever Microscopic hematuria Massive hematuria Retroperitoneal hemorrhage Peritonitis Palpable abdominal mass Hemorrhagic shock Recurrent UT1 Nephrolithiasis
With TS* (3 Cases)
Without TS (10 Cases)
1 2 1 1 2
4 5 2 5
. . *. 3
. . . . 1
. . 4 2 4 1 1 1
‘TS = Tuberoussclerosis.
may sometimes be encountered.!j Although the vast majority of renal tumors in patients with tuberous sclerosis are angiomyolipomata, there is still the possibility that a renal adenocarcinema could develop, as in any other patient.‘OJ’ For that reason it has been suggested that an open biopsy be performed on every solitary tumor in these patients. Ten of our cases occurred in patients without any evidence of tuberous sclerosis. They were 4 times more common in females, and the average age at diagnosis was fifty years. Although some cases of bilateral renal angiomyolipoma have been reported in patients without tuberous sclerosis, EW all our patients had a unilateral solitary tumor. Mouded et aL5 reviewed the symptomatology in 97 cases of angiomyolipoma and found a wide variety of symptoms: flank or abdominal pains in 95 per cent, microscopic or massive hematuria in 30 per cent, and spontaneous retroperitoneal hemorrhage in 15 per cent. Physical examination disclosed a palpable abdominal mass in 40 per cent of the patients, and sometimes there was abdominal tenderness and signs of peritonitis. The symptoms and signs in our patients were similar to those in this collected series (Table I). The reported complications of renal angiomyolipoma include partial obstruction of the collecting system, sometimes with urinary tract infection or nephrolithiasis, and spontaneous hemorrhage with hematuria or retroperitoneal hemorrhage, which can lead to hemorrhagic shock in 20 per cent of the cases.g The latter complication is uncommon in renal adenocarcinema, and its occurrence should always alert one to the possibility of the diagnosis of hamartoma, as it was in our Cases 5 and 6. In the event of massive hemorrhage, an emergency operation may be essential, but the
465
aim should be to resect the bleeding tumor with maximal conservation of functional renal tissue (Case 6). It must always be remembered that bilateral lesions may be present, and further trouble may occur from the second kidney. Jardin et dQ reviewed 18 cases of bilateral angiomyolipoma which had been treated by unilateral nephrectomy. Five patients eventually had spontaneous contralateral hemorrhage: 1 died because of uncontrollable bleeding, and 4 underwent excision of the remaining kidney. In 2 other patients, chronic renal failure developed after unilateral nephrectomy. Until the last decade the pathognomonic features which could aid in reaching a preoperative diagnosis were very limited. The plain abdominal films were reported to show a soft tissue mass with radiolucent areas in 9 per cent of the cases, sometimes associated with calcifications.4 These nonspecific features could be demonstrated better by tomography. The excretory urogram demonstrates solitary or multiple space-occupying lesions, sometimes distorting the collecting system, but these radiologic features do not differentiate between cystic kidneys, renal adenocarcinoma, and angiomyolipoma. Renal angiography shows a hypervascular renal tumor with pathologic tortuous vessels, anteriovenous fistulas, and microaneurysms, which cause retention of the contrast material in the tumor. However, such findings are similar in adenocarcinoma and angiomyolipoma,i4 and it may still prove impossible to differentiate between them. During the last decade renal sonography has been shown to demonstrate many echogenic areas in these solid renal tumors, due to the intratumoral fatty tissue, although this examination cannot entirely exclude a hematoma, or necrotic tissue in a renal adenocarcinoma. Probably abdominal computerized tomography (CT) is the best diagnostic aid available at present. It can demonstrate clearly the radiolucent fatty tissue inside the tumors, and thus increase the chances of a preoperative radiologic diagnosis.15@ These tumors are rare, and the help of an experienced radiologist is a crucial factor in the correct interpretation of the CT scan. Management
of angiomyolipoma
Although as long ago as 1964 Dahlen, and Gebhart” suggested partial nephrectomy in suitable giomyolipoma, until a few years
466
McQueeney, conservative cases of anago most pa-
tients underwent radical nephrectomy because of a diagnosis of adenocarcinoma, as was the case in 7 of our patients. Only the postoperative pathologic examination showed that sometimes an unnecessary nephrectomy had been done.14,18 In patients with tuberous sclerosis and multiple renal tumors, there is the highest degree of likelihood as to the diagnosis, and surgical intervention should probably be reserved for those in whom complications exist or are threatened (Cases l-3). In cases of tuberous sclerosis associated with a solitary renal tumor, the real possibility of this tumor being a carcinoma exists, and unless this can be ruled out by ancillary studies, such cases should be explored, the diagnosis established intraoperatively, and the appropriate surgery performed. Renal tumors associated with spontaneous retroperitoneal hemorrhage are likely to be angiomyolipomas. It is widely accepted that in most such cases immediate surgical intervention is indicated, although these days not all agree with this. Lingeman et uZ.,‘~ for example, have suggested that surgery should now play a minor role and that embolization of the bleeding artery should be the treatment of choice. In practice, however, there is little doubt that operations will continue to be done in many cases, but in most of these it should be possible to do some preliminary diagnostic studies to obtain some information as to the nature of the lesion and, at the very least, to obtain information on the state of the contralateral kidney. Then, at operation, examination by frozen-section of biopsy specimens will verify the diagnosis, and wherever possible removal of the tumor alone by partial nephrectomy, with preservation of the remaining kidney tissue, should be performed (Cases 5 and 6). The biggest problem remains in those cases of a solitary tumor not associated with stigmata of tuberous sclerosis, in whom the presumptive diagnosis will be carcinoma, and the chance of it being an angiomyolipoma will be small. Here, it is to be hoped that with the increasing use of ultrasonography and of CT scans in the diagnostic work-up of these cases, and with increasing recognition of the characteristics of angiomyolipoma on these examinations, more cases will be picked up. These cases still will need to be explored, but awareness of the possibility that a given lesion might be an angiomyolipoma rather than the usual malignant tumor will enable an intraoperative frozen-section of
UROLOGY
/ MAY 1985
/ VOLUME
XXV, NUMBER 5
biopsy specimen to be made, and appropriate surgery can then be performed in accordance with the findings. I?O.B. 12000 Jerusalem 91-120, Israel (DR. PODE)
References 1. Hajdu SI, and Foote FW: Angiomyolipoma of the kidney report of 27 cases and review of the literature, J Urol 102: 396 (1969). 2. Critchley M, and Earl CJC: Tuberous sclerosis and allied conditions, Brain 55: 311 (1932). 3. Crosett AD Jr: Roentgenographic findings in the renal lesion of tuberous sclerosis, AJR 98: 739 (1966). 4. Deeths TM, and Melson CL: Calcifications in an angiomyolipoma: a case report, J Urol 114: 613 (1975). 5. Mouded IM. Tolia BM. Bernie IE. and Newman HR: Svmn, _ tomatic renal angiomyolipoma: report of 8 cases, 2 with spontaneous rupture, ibid 119: 684 (1978). 6. Keshin JG: Three cases of renal hamartoma: two cases presenting with spontanous rupture and massive retroperitoneal hemorrhage, ibid 94: 336 (1965). 7. Bourneville DM: Contributions a l’etude d l’idiotie sclerose tubereuse des circonvolutions cerebrales. Arch Nemo1 1: 81 (1880). I
UROLOGY
!
MAY 1985
1
,
VOLUME
XXV, NUMBER
5
8. Moolten SE: Hamartial nature of the tuberous sclerosis complex and its bearing on the tumor problem, Arch Intern Med 69: 589 (1942). 9. Jardin A, et al: Diagnosis and treatment of renal angiomyoliooma (based on 15 cases). Eur Urol6: 69 (1980). i0. Honey RJ, and Honey RM: Tuberous sclerosis and bilateral renal carcinoma, Br J Urol 49: 441 (1977). 11. Lynne CM, et al: Renal angiomyolipoma, polycystic kidney and renal cell carcinoma in patient with tuberous sclerosis, Urology 14: 174 (1979). _ 12. Whitemore DM. and Wendel RG: Bilateral involvement of renal hamartoma in’2 cases without tuberous sclerosis, J Urol 125: 99 (1981). 13. Shah PJR, and Gashes CGC: Bilateral renal angiomyolipoma, a case report, Eur Urol 6: 361 (1980). 14. McCullough DL, Scott R Jr, and Seybold HM: Renal angiomyolipoma (hamartoma), review of the literature and report of 7 cases, J Urol 105: 32 (1971). 15. Shawker TH, Horvath KL, Dunnick NR, and Javadapour N: Renal angiomyolipoma, diagnosis by combined ultrasound and comnuterized tomoa’raohv. ibid 121: 675 (1979). 16. B&h WH Jr, Freeny PC, and Orme ‘BM:‘Angiomyolipoma: characteristic images by ultrasound and computed tomography, Urology 14: 531 (1979). 17. McQueeney AJ, Dahlen GA, and Gebhart WF: Cystic hamartoma, angiomyolipoma of the kidney simulating renal carcinoma, J Urol 92: 98 (1964). 18. McCullough DL: Renal hamartoma: current concepts of diagnosis and surgical management, Urology 4: 235 (1974). 19. Lingeman JE, Donohue JP Madura JA, and Selke F: Anibid 20: 566 giomyolipoma: emerging concepts in management, (1982).
467
ARTICLES
DIAGNOSIS AND MANAGEMENT OF RENAL ANGIOMYOLIPOMA DOV PODE,
M.D.
SHIMON MERETIK, AMOS SHAPIRO, MARCO CAINE,
M.D.
M.D. M.S., F.R.C.S.
From the Department of Urology, Hadassah University Hospital, Jerusalem, Israel
ABSTRACT-Renal angiomyolipoma (hamartoma) is an uncommon benign tumor of the kidney. Although about 400 cases of renal angiomyolipoma have been reported, it still causes difficulties in diagnosis and treatment. Until a few years ago it was almost impossible to arrive at a correct diagnosis preoperatively, and most of the cases underwent nephrectomy with the wrong diagnosis of renal carcinoma. More recently, abdominal computerized tomography and renal sonography have made it possible to reach the correct preoperative diagnosis in many cases, and thus to avoid unnecessary nephrectomies. We report on our experience with 13 cases of renal angiomyolipoma, and our conservative approach in a number of cases, which has enabled us to preserve renal tissue and function.
Renal angiomyolipoma (hamartoma) is an uncommon benign tumor with a broad spectrum of symptomatology. The tumor is composed of tissues normally present in the kidney, but these are abnormal in quantity, arrangement, or degree of maturation. It is composed mainly of fat, vascular tissue, and smooth muscle. Hajdu and Foote’ in a histopathologic study of 8,501 renal tumors found only 27 (0.3%) cases of angiomyolipoma, 50 per cent of which were associated with tuberous sclerosis. In this condition the renal lesions are usually bilateral, small, multifocal and have an equal sex distribution.2+3 In cases without tuberous sclerosis the disease occurs mainly in females, and the renal lesion is unilateral, unifocal, and frequently large in size. 4s Some patients are asymptomatic, and the tumor is discovered during a routine plain abdominal film or intravenous pyelogram. In others an abdominal mass may be palpated on physical examination or during an exploratory laparotomy performed for some
UROLOGY
/ MAY 1985
/ VOLUME
XXV, NUMBER 5
other cause. The presenting symptoms are most commonly flank or abdominal pains, hematuria, or spontaneous retroperitoneal hemorrhage. The latter may result in hemorrhagic shock, necessitating urgent surgical intervention. Although more than 400 cases of renal angiomyolipomas have been described since 1880, frequently there are difficulties in arriving at the correct preoperative diagnosis in those patients not suffering from tuberous sclerosis, and until recent years this had been achieved rarely. As a result, most patients have undergone unnecessary nephrectomies for this benign tumor. The routine use of renal angiography in the investigation of renal tumors has not proved to be reliable in differentiating angiomyolipoma from renal adenocarcinoma. However, more recently, the growing experience with renal sonography and abdominal computerized tomography has enabled a preoperative presumptive diagnosis to be made in a number of cases of renal angiomyolipoma. Such a preoperative
461
FKXJFlE 1. Case 2. (A) Angiography shows large hypervascular tumor arising from lower pole of right kidney and smaller tumor in left kidney. (B) Histology shows typical features of smooth muscle, primitive blood vessels, and adipose tissue (original magnification x 400). (C) Postoperative IVP shows distorted but well-functioning right kidney.
diagnosis, or the awareness of the possibility of this diagnosis at the time of operation, may enable a conservative approach to be used. We summarize our experience with 13 cases of renal angiomyolipoma, and illustrate our management in various cases, with the aim of maximal conservation of renal tissue and function whenever possible. Material and Methods Since 1958, 13 patients with renal angiomyolipoma have been hospitalized on our urologic service. In all cases except 1 the diagnosis has been confirmed by pathologic examination of excised tissue. The remaining patient had tuberous sclerosis, and multiple bilateral renal tu-
462
mors were demonstrated on IVP and renal angiography: The appearance on abdominal ultrasound supported the diagnosis of angiomyolipoma, and in this case the clinical diagnosis of multiple renal angiomyolipomas was made, with a resultant decision against operation. Patients
with tuberous
sclerosis
Three patients had tuberous sclerosis, all of whom suffered from epilepsy or mental retardation, intracerebral calcifications, retinal phakomata, adenoma sebaceum, and shagreen patches, which are typical dermal lesions over the lumbosacral region. Case 1. An eighteen-year-old female patient suffered from intermittent pain in the right
UROLOGY
/ MAY 1985
I
VOLUME
XXV, NUMBER 5
flank and abdomen. Physical examination revealed typical signs of tuberous sclerosis, and a large mass was palpable in the right lower quadrant of the abdomen. IVP and renal angiogram showed a large vascular mass virtually replacing the entire right kidney Exploratory laparotomy confirmed the presence of a right renal tumor, and intraoperative histologic examination of the tumor confirmed the suspected diagnosis of angiomyolipoma. Insufficient normal renal tissue remained to allow a conservative operation in this case, and therefore a right nephrectomy was performed. Case 2. A twelve-year-old male patient who had been known to have tuberous sclerosis since the age of seven months was admitted because of right lower quadrant abdominal pains and massive hematuria following mild blunt trauma to the right flank. On physical examination a large mass in the right side of the abdomen was revealed. Excretory urography showed multiple masses in both kidneys, and a very- large space-occupying lesion in the right kidney, Renal arteriography demonstrated a large hypervascular tumor emerging from the lower pole (Fig. 1A). A preoperative diagnosis of multiple angiomyolipomata was made, but in view of the large size, the hypervascularity, and the massive bleeding from the large tumor in the right kidney, it was decided that operation was necessary, and this was performed with the aim of removing the tumor and leaving the rest of the kidney intact. At operation the tumor, which was 15 x 20 cm in size, was removed from the lower and anterior part of the kidney, and pathologic examination confirmed it to be an angiomyolipoma (Fig. 1B). A postoperative IVP showed good function of the remaining part of the right kidney (Fig. 1C). Case 3. A twenty-eight-year-old male patient had suffered several times from left renal colic and macroscopic hematuria. Physical examination showed signs of tuberous sclerosis. He had a palpable mass in the left hypochondrium; an IVP showed several space-occupying lesions in both kidneys, and calyceal stones in the left kidney. A clinical diagnosis of renal angiomyolipomas associated with tuberous sclerosis was made. This diagnosis was supported by the findings on abdominal ultrasound examination, and since there were no complications which justified surgical intervention the patient was sent home without an histologic confirmation of the diagnosis. Follow-up examination of the patient two years later, which included both
UROLOGY
i
MAY 1985
i
VOLUME
XXV, NUMBER 5
Case 3. (A) Abdominal CT shows fatty tissue in tumor of right kidney (arrows l-5), calculus in left kidney (arrow 6), and contrast material in duodenum (arrow 7).
FIGURE2.
abdominal CT (Fig. 2) and ultrasound, did not show any progression of the disease. Patients
without
tuberous
sclerosis
There were 10 patients with no evidence of tuberous sclerosis accompanying the kidney tumors, of whom 2 were males and 8 were females. Their ages ranged from thirty-four to seventy-four (average 50 years old). Four patients suffered from flank pains, 5 patients had abdominal pains, and 5 patients had hematuria. Four patients presented with massive retroperitoneal hemorrhage which necessitated urgent surgical intervention. Seven patients had a palpable abdominal mass. One patient was asymptomatic, and the tumor was discovered on a routine IVP performed prior to colon surgery In all our patients the preoperative IVP showed the renal tumor, but renal angiography, when performed, did not help in making the correct preoperative diagnosis. Seven patients underwent radical nephrectomy without intraoperative histologic examination. Three patients who were operated on during the last few years were correctly diagnosed, and were treated conservatively, as described, Case 4. A forty-five-year-old male patient was admitted for a left hemicolectomy because of carcinoma of the colon. Routine preoperative IVP showed a space-occupying lesion, 3 cm in diameter, in the lower pole of the right kidney. Exploration of the kidney during laparotomy
463
FIGURE 3. Case 6. (A) Right renal angiogram, late phase, shows tumor at lower pole. (B) Longitudinal renal sonography shows varying. density of echogenic mass in lower pole tumor. (C) Follow-up IVP after excision of tumor from lower pole of right kidney.
for resection of the colon tumor revealed a fatty mass of the lower pole of the right kidney, and open biopsy confirmed the diagnosis of angiomyolipoma. The tumor was not excised because it was small and nonsymptomatic. Case 5. A fifty-year-old woman was admitted to the emergency ward because of right lower quadrant pain, vomiting, and fever. She had signs of peritoneal irritation in the right lower abdomen. Acute appendicitis was suspected, and on exploration the appendix was found to be normal, but a large retroperitoneal hematoma was found extending from a mass in the right kidney. Intraoperative excretory urography demonstrated a right renal tumor, and because of the spontaneous extrarenal hemorrhage there was the possibility of an angiomyolipoma. This diagnosis was confirmed by frozen section of an open biopsy specimen, and the tumor was removed by lower partial nephrec-
464
tomy. A new IVP three months later showed good function of the remaining part of the right kidney. Case 6. A fifty-year-old woman was admitted to the emergency ward because of syncope. A few hours later her blood pressure dropped to 80160, she complained of right abdominal pains, and macroscopic hematuria appeared. On physical examination there were signs of peritoneal irritation over the right side of the abdomen. Abdominal puncture revealed free blood in the peritoneal cavity. A plain abdominal film showed a large soft tissue mass in the right abdomen, and an IVP demonstrated a large space-occupying lesion displacing the right ureter medially and distorting the right kidney. With the suspicion of spontaneous hemorrhage from a large renal angiomyolipoma, renal angiography was performed, which showed
UROLOGY
I MAY1985 / VOLUMEXXV,NUMBER5
a tumor in the lower pole of the right kidney, with a large hematoma (Fig. 3A). Renal sonography supported our clinical diagnosis of angiomyolipoma (Fig. 3B). The patient immediately underwent a right lower partial nephrectomy. Her postoperative recovery was uneventful. A follow-up IVP seven months later showed good architecture and function of this kidney (Fig. 3C). Comment In the past the preoperative diagnosis of renal angiomyolipoma was difficult, and rarely made. Most cases were diagnosed and treated as renal adenocarcinoma, and only on the subsequent pathologic examination was the true nature of the lesion revealed. Macroscopically it is a soft yellow or gray tumor without a capsule, containing hemorrhagic and necrotic areas. Microscopic examination reveals fatty tissue consisting of mature cells, rich vascular tissue with many tortuous vessels, and smooth muscle sometimes with pleomorphic cells and hyperchromatic nuclei. Renal angiomyolipoma is probably always a benign tumor. Until 1960 some cases had been diagnosed as angiomyoliposarcoma according to histologic criteria, but their subsequent clinical course over many years showed that they had a markedly better prognosis than patients with renal sarcoma, and revision of their histologic examinations suggested that they were truly benign angiomyolipomas.6 Approximately 50 per cent of the cases seen clinically are associated with tuberous sclerosis. Bourneville’ was the first to describe tuberous sclerosis in 1880. It is a congenital disorder transferred by a rare autosomal dominant gene, and consists of tumor-like malformations of ectodermal origin occurring in the brain, skin, and retina, as well as multiple hamartomas in mesenchymal tissues such as the kidneys, heart, and lungs.s Many patients have epilepsy or mental retardation. The clinical diagnosis is usually based on the finding of the characteristic cutaneous lesions such as adenoma sebaceum, subungual fibromas, or shagreen patches. There may be cystic lesions in the lungs and bones, and retinal phakomata. Multiple renal hamartomas are common in these patients, and on postmortem examination can be found in up to 80 per cent of the cases.2 The natural course of the disease does not normally lead to terminal renal failure, although a decrease in renal function
UROLOGY
/ MAY 1985 i
VOLUME XXV, NUMBER 5
Presenting symptoms and signs in 13 patients with renal angiomyolipoma _
TABLE I.
Symptom/Sign Flank pain Abdominal pain Fever Microscopic hematuria Massive hematuria Retroperitoneal hemorrhage Peritonitis Palpable abdominal mass Hemorrhagic shock Recurrent UT1 Nephrolithiasis
With TS* (3 Cases)
Without TS (10 Cases)
1 2 1 1 2
4 5 2 5
. . *. 3
. . . . 1
. . 4 2 4 1 1 1
‘TS = Tuberoussclerosis.
may sometimes be encountered.!j Although the vast majority of renal tumors in patients with tuberous sclerosis are angiomyolipomata, there is still the possibility that a renal adenocarcinema could develop, as in any other patient.‘OJ’ For that reason it has been suggested that an open biopsy be performed on every solitary tumor in these patients. Ten of our cases occurred in patients without any evidence of tuberous sclerosis. They were 4 times more common in females, and the average age at diagnosis was fifty years. Although some cases of bilateral renal angiomyolipoma have been reported in patients without tuberous sclerosis, EW all our patients had a unilateral solitary tumor. Mouded et aL5 reviewed the symptomatology in 97 cases of angiomyolipoma and found a wide variety of symptoms: flank or abdominal pains in 95 per cent, microscopic or massive hematuria in 30 per cent, and spontaneous retroperitoneal hemorrhage in 15 per cent. Physical examination disclosed a palpable abdominal mass in 40 per cent of the patients, and sometimes there was abdominal tenderness and signs of peritonitis. The symptoms and signs in our patients were similar to those in this collected series (Table I). The reported complications of renal angiomyolipoma include partial obstruction of the collecting system, sometimes with urinary tract infection or nephrolithiasis, and spontaneous hemorrhage with hematuria or retroperitoneal hemorrhage, which can lead to hemorrhagic shock in 20 per cent of the cases.g The latter complication is uncommon in renal adenocarcinema, and its occurrence should always alert one to the possibility of the diagnosis of hamartoma, as it was in our Cases 5 and 6. In the event of massive hemorrhage, an emergency operation may be essential, but the
465
aim should be to resect the bleeding tumor with maximal conservation of functional renal tissue (Case 6). It must always be remembered that bilateral lesions may be present, and further trouble may occur from the second kidney. Jardin et dQ reviewed 18 cases of bilateral angiomyolipoma which had been treated by unilateral nephrectomy. Five patients eventually had spontaneous contralateral hemorrhage: 1 died because of uncontrollable bleeding, and 4 underwent excision of the remaining kidney. In 2 other patients, chronic renal failure developed after unilateral nephrectomy. Until the last decade the pathognomonic features which could aid in reaching a preoperative diagnosis were very limited. The plain abdominal films were reported to show a soft tissue mass with radiolucent areas in 9 per cent of the cases, sometimes associated with calcifications.4 These nonspecific features could be demonstrated better by tomography. The excretory urogram demonstrates solitary or multiple space-occupying lesions, sometimes distorting the collecting system, but these radiologic features do not differentiate between cystic kidneys, renal adenocarcinoma, and angiomyolipoma. Renal angiography shows a hypervascular renal tumor with pathologic tortuous vessels, anteriovenous fistulas, and microaneurysms, which cause retention of the contrast material in the tumor. However, such findings are similar in adenocarcinoma and angiomyolipoma,i4 and it may still prove impossible to differentiate between them. During the last decade renal sonography has been shown to demonstrate many echogenic areas in these solid renal tumors, due to the intratumoral fatty tissue, although this examination cannot entirely exclude a hematoma, or necrotic tissue in a renal adenocarcinoma. Probably abdominal computerized tomography (CT) is the best diagnostic aid available at present. It can demonstrate clearly the radiolucent fatty tissue inside the tumors, and thus increase the chances of a preoperative radiologic diagnosis.15@ These tumors are rare, and the help of an experienced radiologist is a crucial factor in the correct interpretation of the CT scan. Management
of angiomyolipoma
Although as long ago as 1964 Dahlen, and Gebhart” suggested partial nephrectomy in suitable giomyolipoma, until a few years
466
McQueeney, conservative cases of anago most pa-
tients underwent radical nephrectomy because of a diagnosis of adenocarcinoma, as was the case in 7 of our patients. Only the postoperative pathologic examination showed that sometimes an unnecessary nephrectomy had been done.14,18 In patients with tuberous sclerosis and multiple renal tumors, there is the highest degree of likelihood as to the diagnosis, and surgical intervention should probably be reserved for those in whom complications exist or are threatened (Cases l-3). In cases of tuberous sclerosis associated with a solitary renal tumor, the real possibility of this tumor being a carcinoma exists, and unless this can be ruled out by ancillary studies, such cases should be explored, the diagnosis established intraoperatively, and the appropriate surgery performed. Renal tumors associated with spontaneous retroperitoneal hemorrhage are likely to be angiomyolipomas. It is widely accepted that in most such cases immediate surgical intervention is indicated, although these days not all agree with this. Lingeman et uZ.,‘~ for example, have suggested that surgery should now play a minor role and that embolization of the bleeding artery should be the treatment of choice. In practice, however, there is little doubt that operations will continue to be done in many cases, but in most of these it should be possible to do some preliminary diagnostic studies to obtain some information as to the nature of the lesion and, at the very least, to obtain information on the state of the contralateral kidney. Then, at operation, examination by frozen-section of biopsy specimens will verify the diagnosis, and wherever possible removal of the tumor alone by partial nephrectomy, with preservation of the remaining kidney tissue, should be performed (Cases 5 and 6). The biggest problem remains in those cases of a solitary tumor not associated with stigmata of tuberous sclerosis, in whom the presumptive diagnosis will be carcinoma, and the chance of it being an angiomyolipoma will be small. Here, it is to be hoped that with the increasing use of ultrasonography and of CT scans in the diagnostic work-up of these cases, and with increasing recognition of the characteristics of angiomyolipoma on these examinations, more cases will be picked up. These cases still will need to be explored, but awareness of the possibility that a given lesion might be an angiomyolipoma rather than the usual malignant tumor will enable an intraoperative frozen-section of
UROLOGY
/ MAY 1985
/ VOLUME
XXV, NUMBER 5
biopsy specimen to be made, and appropriate surgery can then be performed in accordance with the findings. I?O.B. 12000 Jerusalem 91-120, Israel (DR. PODE)
References 1. Hajdu SI, and Foote FW: Angiomyolipoma of the kidney report of 27 cases and review of the literature, J Urol 102: 396 (1969). 2. Critchley M, and Earl CJC: Tuberous sclerosis and allied conditions, Brain 55: 311 (1932). 3. Crosett AD Jr: Roentgenographic findings in the renal lesion of tuberous sclerosis, AJR 98: 739 (1966). 4. Deeths TM, and Melson CL: Calcifications in an angiomyolipoma: a case report, J Urol 114: 613 (1975). 5. Mouded IM. Tolia BM. Bernie IE. and Newman HR: Svmn, _ tomatic renal angiomyolipoma: report of 8 cases, 2 with spontaneous rupture, ibid 119: 684 (1978). 6. Keshin JG: Three cases of renal hamartoma: two cases presenting with spontanous rupture and massive retroperitoneal hemorrhage, ibid 94: 336 (1965). 7. Bourneville DM: Contributions a l’etude d l’idiotie sclerose tubereuse des circonvolutions cerebrales. Arch Nemo1 1: 81 (1880). I
UROLOGY
!
MAY 1985
1
,
VOLUME
XXV, NUMBER
5
8. Moolten SE: Hamartial nature of the tuberous sclerosis complex and its bearing on the tumor problem, Arch Intern Med 69: 589 (1942). 9. Jardin A, et al: Diagnosis and treatment of renal angiomyoliooma (based on 15 cases). Eur Urol6: 69 (1980). i0. Honey RJ, and Honey RM: Tuberous sclerosis and bilateral renal carcinoma, Br J Urol 49: 441 (1977). 11. Lynne CM, et al: Renal angiomyolipoma, polycystic kidney and renal cell carcinoma in patient with tuberous sclerosis, Urology 14: 174 (1979). _ 12. Whitemore DM. and Wendel RG: Bilateral involvement of renal hamartoma in’2 cases without tuberous sclerosis, J Urol 125: 99 (1981). 13. Shah PJR, and Gashes CGC: Bilateral renal angiomyolipoma, a case report, Eur Urol 6: 361 (1980). 14. McCullough DL, Scott R Jr, and Seybold HM: Renal angiomyolipoma (hamartoma), review of the literature and report of 7 cases, J Urol 105: 32 (1971). 15. Shawker TH, Horvath KL, Dunnick NR, and Javadapour N: Renal angiomyolipoma, diagnosis by combined ultrasound and comnuterized tomoa’raohv. ibid 121: 675 (1979). 16. B&h WH Jr, Freeny PC, and Orme ‘BM:‘Angiomyolipoma: characteristic images by ultrasound and computed tomography, Urology 14: 531 (1979). 17. McQueeney AJ, Dahlen GA, and Gebhart WF: Cystic hamartoma, angiomyolipoma of the kidney simulating renal carcinoma, J Urol 92: 98 (1964). 18. McCullough DL: Renal hamartoma: current concepts of diagnosis and surgical management, Urology 4: 235 (1974). 19. Lingeman JE, Donohue JP Madura JA, and Selke F: Anibid 20: 566 giomyolipoma: emerging concepts in management, (1982).
467