Urological counseling and followup in pediatric tuberous sclerosis complex

PURPOSE: We review our experience with renal manifestations in pediatric patients with the tuberous sclerosis complex, and offer recommendations for urological counseling, followup and treatment of these patients. MATERIALS AND METHODS: We reviewed clinical notes on 41 patients with the tuberous sclerosis complex followed at our institution from childhood. Patient data were gathered in a database focusing on renal involvement. The latter was assessed by periodic clinical evaluations and ultrasound. The risk of renal involvement was evaluated in relation to patient age, genotypic pattern and number of extrarenal manifestations. RESULTS: Overall, 15 patients (36.6%) had renal involvement. The latter increased with age and was more common in cases with TSC2 genotypic pattern or multiple extrarenal manifestations. Angiomyolipomas were the most common lesions (11 patients), followed by renal cysts (2) and polycystic kidney disease (2). Cystic lesions were the most common in patients younger than 16 years. Renal failure developed in the 2 patients with polycystic kidney disease by the 2nd decade of life. Overall, treatment was required in 2 cases of symptomatic angiomyolipoma. Both patients were female, and had multiple extrarenal manifestations and bilateral renal involvement. One patient underwent open surgery at age 21.3 years and 1 underwent radiological embolization at age 23.4 years. CONCLUSIONS: Pediatric patients with the tuberous sclerosis complex should undergo urological evaluation and followup. Although most of the lesions remain silent during childhood, the incidence of renal involvement increases with age. The need for treatment is highest in females with multiple extrarenal manifestations and bilateral renal involvement.     

Renal lesions in tuberous sclerosis

The renal lesion classically associated with tuberous sclerosis is angiomyolipoma. Renal cysts are less frequent, occurring alone or in conjunction with angiomyolipomas. We reviewed the records of 274 patients with tuberous sclerosis registered at our clinic. Of 95 patients evaluated for renal lesions 51 (54 per cent) had positive findings: 45 had angiomyolipomas, 17 had renal cysts and 11 had both lesions. These lesions usually are multiple and bilateral, and are diagnosed most effectively with computerized tomography or ultrasound. Surgery (10 kidneys) was done for life-threatening hemorrhage or suspected malignant lesions.     

RENAL LESION GROWTH IN CHILDREN WITH TUBEROUS SCLEROSIS COMPLEX

Purpose

Renal lesions, including angiomyolipoma, renal cysts (simple and polycystic kidney disease) and renal cell carcinoma, develop in patients with tuberous sclerosis complex. While there is limited information that these lesions may grow in adults with tuberous sclerosis complex, the incidence, characterization and growth rate in children have not been reported. Also, the age at which these lesions first appear, thus providing insight into their natural history, is unknown. We present our data from a longitudinal renal surveillance study of children with tuberous sclerosis complex.

Materials and Methods

Since 1985 children with tuberous sclerosis complex at our hospital have undergone periodic renal imaging by ultrasonography or computerized tomography to monitor renal lesions. A total of 35 girls and 25 boys 1 to 18 years old have undergone at least 2 or more annual renal ultrasounds.

Results

On initial evaluation 33 of 60 children (55%) (mean age 6.9 years) had an identifiable renal lesion, which increased to 48 of 60 (80%) at followup (mean age 10.5 years). Angiomyolipoma was the most frequent lesion (75%) followed by simple renal cysts (17%). Angiomyolipomas increased in size and/or number in 10 of 18 boys (56%) and 18 of 27 girls (66%). The largest growth rate in 1 year was from 0 to 4 cm. and from 5 to 9 cm. in diameter. The youngest patient demonstrated lesions at age 2 years. The average age at which a normal ultrasound became abnormal was 7.2 years. While a total of 27 patients had a normal ultrasound on entering the study, lesions had developed in 15 at followup (11 with angiomyolipomas, 4 with cysts). Five patients had cysts that had disappeared at followup. A 7-year-old boy had a 9 cm. renal cell carcinoma removed. One patient has renal lesions characteristic of autosomal dominant polycystic kidney disease.

Conclusions

Renal involvement in patients with tuberous sclerosis complex begins in infancy, and angiomyolipoma is the most common lesion (75%). Angiomyolipomas are more likely to grow than remain stable, although the rate of growth varies. Simple renal cysts may appear or disappear with time but angiomyolipomas do not disappear. An initially normal renal ultrasound does not rule out future development of lesions. Periodic surveillance is indicated in children with tuberous sclerosis complex.     

Renal failure secondary to angiomyolipoma. Case of Forme-Fruste tuberous sclerosis

A fifty-four-year-old woman without the clinical features of tuberous sclerosis underwent nephrectomy at age thirty-three years for angiomyolipoma, and twenty-one years later severe renal failure developed. At necropsy the remaining kidney had extensive angiomyolipomatous involvement; not until the brain was examined was the diagnosis of tuberous sclerosis made. To date, this would appear to be the third case without clinical tuberous sclerosis in which renal involvement was the sole clinical expression of tuberous sclerosis, and the seventh reported instance of renal failure due to renal angiomyolipomatous hamartomatous transformation.     

Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors

Tuberous sclerosis complex is a genetic disorder characterized by hamartomatous lesions in multiple organs, frequently involving the kidney. We conducted a retrospective review of the clinical and radiographic records of 167 patients with tuberous sclerosis to determine the frequency of renal disease, the likelihood of significant renal morbidity, and the effects of genotype (TSC1 vs TSC2) and gender on renal phenotype. Renal lesions were seen in 57.5% of patients. Of these, angiomyolipoma (AML) occurred in 85.4%, cysts in 44.8%, and renal cell carcinoma in 4.2%. Both AML and cysts were significantly more common and more numerous in TSC2 than in TSC1. AML was significantly more common in female than in male patients, but cysts showed no correlation with gender. Eleven patients developed renal abnormalities during their care in this practice at an average age of onset of 11.3 years (range 3.8-23 years). The frequency and number of renal lesions were positively correlated with age. Interventions, including arterial embolization and nephrectomy, were performed in 11 (6.6%) patients. Among female patients with lymphangioleiomyomatosis, renal AML was universally present. Our findings confirm a high rate of renal involvement; a low rate of serious complications; significant associations between renal involvement, genotype, and gender; and a significant association between renal and pulmonary involvement in female patients.     

Renal angiomyolipoma associated with lymph node involvement and renal cell carcinoma in patients with tuberous sclerosis

Renal angiomyolipomas are found in more than half of the patients with tuberous sclerosis. We report on 3 patients with tuberous sclerosis and pathologically aggressive renal angiomyolipoma with retroperitoneal lymph node involvement and/or renal cell carcinoma. All patients have had a benign course. The literature is reviewed and supports the benign nature of this seemingly aggressive disorder. An approach to the evaluation and treatment of a child with tuberous sclerosis and renal angiomyolipoma is presented.     

Bilateral renal angiomyolipoma coexistent with pulmonary lymphangioleiomyomatosis and tuberous sclerosis

A case of bilateral renal angiomyolipoma coexistent with pulmonary lymphangioleiomyomatosis and tuberous sclerosis was described, being in shock with massive hematuria. The left giant angiomyolipoma, filling the almost entire abdomen, was complicated with two large hump and moniliform aneurysms. This life-threatening hemorrhage was successfully treated by transcatheter arterial embolization; packing mechanically detachable coils into the aneurysms and embolization of trunk of the left renal artery. Lymphangioleiomyomatosis has been suggested to be an incomplete expression of tuberous sclerosis. Although coexisting renal and pulmonary involvement in tuberous sclerosis is rare, it is important to recognize lymphangioleiomyomatosis as a pulmonary involvement of angiomyolipoma with tuberous sclerosis.     

Renal angiomyolipoma associated with tuberous sclerosis. Review of the literature

A case of bilateral renal angiomyolipoma associated with tuberous sclerosis is presented. Although in our patient right renal biopsy specimen demonstrated angiomyoma, we believe that the lipomatous element could be found in a larger specimen. Roentgenographic and therapeutic considerations are presented and the different lesions of tuberous sclerosis reviewed. Unlike most patients exhibiting stigmata of tuberous sclerosis, our patient had normal mentality and seizures preceded skin lesions. Fundoscopic examination revealed retinal arteriolitis with an occlusive phenomenon which, to our knowledge, has not been reported previously.     

Clinical evaluation of renal angiomyolipoma]

Between April 1980 and December 1999, 23 kidneys in 20 patients were diagnosed as having renal angiomyolipoma at our institution. The patients were 6 males and 14 females aged 24 to 79 years, with a mean age of 55.4 years. Two patients had associated tuberous sclerosis and 3 had bilateral disease. Of all patients the main clinical symptoms were pain (45%) and palpable mass (40%); 5 patients (25%) had asymptomatic lesions. The size of the tumor ranged from 1.3 to 24 cm (mean 7.7 cm). Treatment consisted of nephrectomy in 9 patients, partial nephrectomy in 6 and selective embolization in one. Pre-operative diagnosis was renal cell carcinoma in 5 of the 9 patients who underwent nephrectomy. Six patients with 7 diseased kidneys were followed radiologically. One patient underwent percutaneous biopsy to confirm the diagnosis. We suggest that nephron-sparing surgery for patients with renal angiomyolipoma should be the first step if tumor size is 4 cm < or = or increasing rapidly. Selective embolization is also a useful method. However, we need long-term follow-up to evaluate the effectiveness of embolization.     

Symptomatic unilateral renal angiomyolipoma in a child with tuberous sclerosis

We report a case of unilateral renal angiomyolipoma in a 10-year-old boy with tuberous sclerosis. The case is worthy of attention because the symptoms occurred at an early age and because the lesion was unilateral, the latter confirmed at 11-year follow-up. The presentation and treatment are discussed, and the pertinent literature is reviewed. The case demonstrates that it is of clinical importance to monitor renal involvement in children with tuberous sclerosis.     

Renal tumors associated with tuberous sclerosis: the case for aggressive surgical management

Tuberous sclerosis is associated commonly with renal angiomyolipoma. However, the radiographic differentiation of angiomyolipoma and renal carcinoma can be difficult, and the natural history of angiomyolipoma may be associated with serious complications. We present a case of bilateral renal cell carcinoma associated with tuberous sclerosis. Aggressive but conserving renal surgery should be considered in patients with tuberous sclerosis and enlarging renal masses.     

Spontaneous rupture of renal angiomyolipoma with tuberous sclerosis during long-term follow-up: a case report]

We present a case of spontaneous rupture of bilateral renal angiomyolipoma (AML) with tuberous sclerosis. A 46-year-old woman was admitted with sudden onset of severe left flank pain. She had been diagnosed to have bilateral AML with tuberous sclerosis 15 years earlier. Four years after the initial diagnosis, spontaneous rupture of right renal AML occurred and right renal embolization of the right renal artery was performed. The treatment for the left renal AML was not performed. Eleven years later in 2000, spontaneous rupture of contralateral renal AML occurred and left renal embolization of the left renal artery was performed. We evaluated the efficacy of selective arterial embolization in right AML and the change of the tumor size during a 10-year follow up after embolization. The right AML had decreased 86% in 11 years. Selective arterial embolization is an effective and safe treatment for AML. We evaluated the natural history of left AML and calculated the doubling time to be about 1,370 days for the first period of 4 years and about 2,075 days for the second period of 11 years. Although the growth change was very slow, we should observe the tumors carefully on computed tomography or ultrasound to prevent life-threatening hemorrhage.     

Renal angiomyolipoma: 6 case reports and literature review

We report 6 cases of renal angiomyolipomas and review the pertinent literature concerning this disease. One case involved the rare association of tuberous sclerosis and pregnancy. Another patient without tuberous sclerosis had renal cell carcinoma and later suffered a contralateral angiomyolipoma. The pathological conditions of renal angiomyolipomas with and without tuberous sclerosis are discussed. Since angiomyolipomas present with multiple clinical similarities to renal cell carcinoma, the primary task for the clinician is to differentiate this hamartoma from carcinoma. The distinguishing characteristics and the clinical management of renal angiomyolipomas are discussed.     

Transseptal crossed vasovasostomy

We examined 11 patients with acquired obstructive azoospermia resulting from irreparable obstruction of 1 vas deferens and severe damage to the contralateral testis. All of the patients underwent transseptal crossed vasovasostomy with no morbidity. Of 8 patients evaluated with postoperative semen analyses 4 (50 per cent) demonstrated total sperm counts of 29 to 205 million and 2 pregnancies (25 per cent) have been reported, with followup ranging from 5 months to 2 years. The etiologies of the vasal obstruction included previous inguinal surgery in 7 patients, vasectomy in 1, ejaculatory duct obstruction in 1, ectopic ureter in 1 and vasal agenesis in 1. Factors leading to loss of the contralateral testis were torsion in 5 patients, mumps orchitis in 2, varicocele in 1, pediatric inguinal herniorrhaphy in 1, epididymal blow out in 1 and unknown in 1. A representative case involving a unilateral ectopic ureter emptying into the seminal vesicle and subsequent contralateral testicular torsion is presented. The results indicate that a transseptal crossed vasovasostomy should be done in patients satisfying the criteria presented.     

Experience with extracorporeal surgery and autotransplantation for renal cell and transitional cell cancer of the kidney

Of 21 patients who underwent bench surgery for renal malignancies (renal cell carcinoma in 16 and transitional cell carcinoma in 5) 15 also had autotransplantation and 6 did not. In 5 patients the contralateral kidney was removed simultaneously for synchronous bilateral renal malignancy, and 16 had cancer in a solitary kidney. In the 3 patients who underwent nephrectomy for complications after autotransplantation no evidence of residual tumor was noted on histopathological examination. Of 9 patients 1 (11 per cent) had local recurrence after successful autotransplantation (renal cell carcinoma). Two patients with transitional cell carcinoma died of metastatic disease. Treatment failed in 31 per cent of the 16 patients with renal cell carcinoma (metastatic disease in 4 and metastatic disease with local recurrence in 1). Removal of solitary or synchronous bilateral renal cell cancer by bench surgery with subsequent autotransplantation is effective. For high grade transitional cell carcinoma of a solitary kidney its value is doubtful without adjuvant systemic treatment.     

Peyronie's disease: surgical experience and presentation of a proximal approach

A total of 29 patients underwent 32 operations for correction of penile curvature. Of these patients 22 underwent placement of a semirigid prosthesis and 94 per cent of those available for followup were able to resume coitus. Of the 8 patients who underwent operative correction of penile curvature and who maintained potency only 3 (38 per cent) were able to resume intercourse. Vascular compromise and/or skin slough after degloving of the penile skin was noted in 3 patients. A proximal approach to penile reconstruction is presented.     

Relationship of leukoplakia to urothelial malignancy

The records of 108 patients presenting with leukoplakia of the urinary tract during the last 35 years were reviewed to define the natural history of this disease, with emphasis upon its association with urothelial cancer. Of the 108 patients 24 had upper urinary tract, 78 bladder and 10 urethral leukoplakia (1 with renal and bladder involvement, 3 with bladder and urethral involvement, and 1 with ureteral and renal involvement). Presenting complaints were primarily irritative. To date, 41 patients (37 per cent) have had associated carcinoma of the urothelium: 23 (21 per cent) presented with a concomitant or previous carcinoma and 18 of 85 (21 per cent) presenting without a concomitant or previous neoplasm have had documented progression to cancer. These figures support the concept that leukoplakia is a premalignant disease and that patients with this diagnosis deserve careful and frequent followup.     

Hématome rétropéritonéal spontané : cause rare de choc hémorragique

A spontaneous retroperitoneal haematoma is an uncommon cause of haemorrhagic shock. We report a case of spontancous rupture of a renal angiomyolipoma resulting in haemorrhagic shock in a 52-year-old woman. The renal tumor was recognized by sonography and diagnosed by CT-scan. Renal angiography was performed, but embolization was not successful. During the surgical procedure, nephrectomy was required because of persistent bleeding, related to disseminated intravascular coagulation. Outcome was uneventful. Diagnosis and treatment of renal angiomyolipoma are discussed. The Lenk's triad, consisting of acute lumbar pain, symptoms of internal bleeding and lumbar tumefaction, is the usual clinical picture of retroperitoneal haemorrhage. The kidney is the most frequent cause and renal angiomyolipoma is the most frequent benign tumor. Renal angiomyolipoma is either isolated or associated with tuberous sclerosis in up to 20 per cent of patients. Diagnosis is suggested by sonography and confirmed by CT-scan. Renal angiography, performed in haemodynamically stable patients, shows the origin of bleeding and allows embolization. Considering the frequent bilaterality of angiomyolipoma, surgery should be as conservative as possible in order to preserve renal function.     

Angiomyolipoma: a case report and a statistical study of 147 cases in Japanese literature

A 32-year-old housewife with gross hematuria and right flank pain had excretory urography and angiography performed. A large right renal mass with neovascularity was demonstrated. Computerized tomography also revealed a large well-demarcated renal mass with low value of HU. Right nephrectomy was done and histopathological diagnosis was angiomyolipoma weighing 1100 g. A statistical study was made on 147 cases of renal angiomyolipoma in the Japanese literature including this case. The male to female ratio was 1 to 2.9, and the average age of male and female patients was 37.8 and 39.0 years, respectively. Thirty-eight per cent of the cases were associated with tuberous sclerosis. The main clinical signs were flank pain, flank mass and hematuria. In 80% of the cases, nephrectomy was done because of the difficulty of preoperative differential diagnosis from renal cell carcinoma. Recently, CT and sonography have become a great help in diagnosing angiomyolipoma, because they can demonstrate the fat in the renal mass. Conservative or surgical treatment to save the kidney can be used more often when it becomes possible to make a clear differential diagnosis between angiomyolipoma and other malignant diseases.     

Bilateral Chromophobe Cell Renal Carcinoma in Tuberous Sclerosis Comple

We report on a patient with tuberous sclerosis complex and polycystic kidney disease who developed bilateral chromophobe cell renal carcinoma. We discuss the tuberous sclerosis complex, associated bilateral renal cell carcinoma, polycystic kidney disease and chromophobe cell renal carcinoma; a recently established subtype with a rather favorable prognosis.
In a patient with tuberous sclerosis complex and multiple space-occupying lesions, a diagnosis of angiomyolipoma should be considered first but bilateral and/or multifocal renal cell carcinoma is a likely diagnosis.