Angiomyolipoma: clinical metamorphosis and concepts for management

In 10 years the diagnosis of renal angiomyolipoma was made in 44 patients (female-to-male ratio 8:1) at our institution; 4 cases were associated with tuberous sclerosis. Of these patients 29 underwent surgical exploration because of a renal mass; 11 patients with renal masses that were consistent with angiomyolipoma radiologically have not undergone exploration. Of the 4 patients with and the 29 patients without tuberous sclerosis 1 (25 per cent) and 2 (7 per cent), respectively, had renal cell cancer in association with angiomyolipoma. Metachronous involvement of the contralateral kidney has not been noted in any of our patients who underwent nephrectomy for unilateral involvement, nor has there been progression of the contralateral lesion in 3 patients with bilateral disease without tuberous sclerosis during a followup of about 6 years. Furthermore, we have not noted progression of lesions in the 11 patients under observation for a mean followup of almost 3 years. We recommend elective exploration and a renal preserving operation when possible, not only for patients with pain and hemorrhage but also for the complex multiple lesions occasionally seen in patients who do not have tuberous sclerosis. Lesions associated with tuberous sclerosis require surgical intervention only when they become symptomatic or enlarge silently.     

Bilateral angiomyolipomas and renal cell carcinoma in polycystic kidney

A case is presented of a twenty-eight-year-old man in whom renal failure developed at age twenty four from polycystic kidney disease known to be present since childhood. He also had cutaneous manifestations of the tuberous sclerosis complex. Intrarenal hemorrhage led to bilateral nephrectomy. Microscopic examination disclosed typical polycystic disease and multiple angiomyolipomas in each kidney. In addition several renal cell carcinomas of oncocytic, papillary, and clear cell type were found. Review of the literature disclosed the uncommon coexistence of any two of these lesions and did not uncover any reported case of the simultaneous existence of all three.     

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.     

The tuberous sclerosis complex and its highly variable manifestations

PURPOSE: Tuberous sclerosis is an autosomal dominant neurocutaneous syndrome affecting multiple organ systems and demonstrating highly variable clinical manifestations. Mutations in 2 tumor suppressor genes, TSC1 and TSC2, are linked to the evolution of the hamartomatous lesions. We describe the incidence and epidemiology, variable clinical manifestations and their relationships to renal pathology, and the management of morbid sequelae. MATERIALS AND METHODS: Using the search term tuberous sclerosis, we performed a MEDLINE search of the literature identifying 3,196 articles and selected those from urological, surgical, oncological, genetic and pediatric journals. Special focus was placed on the incidence and management of renal lesions and on different clinical manifestations and how they relate to renal tumors. RESULTS: Due to improved identification of the variable phenotypic expression, the reported incidence has increased. TSC1 and TSC2 mutations are related to various phenotypic manifestations and risks of malignancy, such as an increased incidence of the TSC2 mutation in patients with renal cell carcinoma. Renal sparing surgery and selective embolization techniques have mitigated the morbidity of the lesions. CONCLUSIONS: We now have a better understanding of the variability at the genotypic and phenotypic levels of the disease. We recommend that patients with tuberous sclerosis complex be evaluated by a multidisciplinary group of clinicians, including urologists, dermatologists, neurologists, pediatricians and geneticists. Close attention to these manifestations is necessary to ensure appropriate treatment of the sequelae of the tuberous sclerosis complex.     

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.     

Bilateral nephron sparing surgeries for multiple renal angiomyolipomas in Bourneville’s disease

Introduction Angiomyolipomas are the most common renal lesions in tuberous sclerosis complex. When symptomatic, the treatment includes nephron sparing surgery. This is especially challenging when the lesions are bilateral, large and multiple. Case-History A 22-year-old lady with bilateral multiple large symptomatic renal angiomyolipomas associated with other manifestations of tuberous sclerosis was managed with partial nephrectomies on either side. At 30 months of follow-up, the patient has normal renal functions and no evidence of recurrence. Discussion Intervention for renal angiomyolipomas is indicated in symptomatic tumors larger than four centimetres. Selective arterial embolisation is the therapeutic modality of choice in such cases. However, in bilateral cases when angioembolisation may not always be feasible, nephron sparing surgery maybe considered. Nephron sparing surgery of both kidneys for angiomyolipomas in association with tuberous sclerosis has only been sparingly reported in literature.     

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.     

伴结节性硬化症的双肾多发性血管平滑肌脂肪瘤(附四例报告)

目的 探讨伴结节性硬化症的肾血管平滑肌脂肪瘤(AML)的临床诊治特点。方法 报告4例结节性硬化症伴多发性双肾AML的临床诊治资料。男女各2例。年龄17～44岁。l例表现为典型“三联征”，3例有典型面部皮疹，2例有癫痫发作史，3例伴肝、脾、骨等多发肾外病灶，3例颅脑CT检查均发现典型的大脑钙化结节灶。结果 3例患者经CT检查确诊，l例CT检查未发现肿瘤内特异性脂肪密度组织，B超引导下穿刺活检确诊，因右肾肿瘤巨大行肾切除术。l例患者因肿瘤小且症状轻微行保守治疗，另2例肿瘤伴出血者经保守治疗症状好转，随访6～36个月，肿瘤大小无变化，无症状复发。结论 伴结节性硬化症的双肾占位即使CT检查未发现特异性脂肪密度也不能排除AML的可能，细针穿刺活检能够确诊并排除肾癌。治疗方案应根据双侧肾肿瘤大小、分布、发展情况及症状决定。     

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.     

Tuberous sclerosis complex: Recent advances in manifestations and therapy

Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin–Tuberin complex is involved in the phosphoinositide 3‐kinase–protein kinase B–mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, “a cross‐sectional medical examination system,” a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex‐associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex.     

Renal lesions in tuberous sclerosis

Renal tumours, in tuberous sclerosis, are mainly benign and correspond to angiomyolipomas, multiple and bilateral, sometimes enormous with an hemorrhagic risk, frequently associated with cysts of variable size and number and seldom with high metastatic carcinomas. Chronic renal failure is rare and related to focal glomerulosclerosis secondary to hyperfiltration due to nephronic reduction owing to surgery or to tumour invasion, in particular cysts. Data about 65 patients with tuberous sclerosis and chronic renal failure were collected thanks to a national survey. They were females in 63.1% of cases, with a mean age of 29, 2 years at the time of the diagnosis of tuberous sclerosis, revealed in near half of cases by renal involvement. There were angiomyolipomas in 23.1% of cases, cysts in 18.5%, both in 53.8% and malignancies in 12.3%. All but one of the 48 patients with end stage renal failure were treated by dialysis; 20 were transplanted, with good results.     

The spectrum of systemic involvement in adults presenting with renal lesion and mitochondrial tRNA(Leu) gene mutation

The A3243G mutation of the mitochondrial tRNA(Leu) gene has been recently reported in rare patients with focal and segmental glomerulosclerosis (FSGS). However, the full spectrum of systemic and kidney manifestations in adults presenting with this mutation remains poorly defined. Assessment of renal and nonrenal manifestations was performed in nine patients with A3243G mutation and prominent kidney disease diagnosed in adulthood. At first renal evaluation, median age was 35 years. Renal lesions consisted of FSGS (n = 2), tubulointerstitial nephropathy (n = 3), or bilateral enlarged cystic kidneys (n = 1). All but one patient exhibited extrarenal manifestations: deafness (8 of 9) requiring hearing aid in half the cases, diabetes mellitus (3 of 9), neuromuscular involvement (2 of 9), hypertrophic cardiomyopathy (1 of 9), and macular dystrophy (1 of 9). After a median follow-up of 5 yr, five patients progressed to end-stage renal disease between the ages of 15 and 51 years, four being successfully transplanted. Similarly, extrarenal manifestations progressed since all patients had deafness and diabetes (including three posttransplants), while half had neuromuscular, cardiac, or retinal involvement. In the adult patients with A3243G mutation and renal involvement, preexisting deafness is almost consistently found. While FSGS remains the most typical lesion, tubulointerstitial nephropathy or bilateral, enlarged cystic kidneys may also be encountered. In most cases, diabetes mellitus, macular dystrophy, hypertrophic cardiomyopathy, or neuromuscular features occur later in the course of the disease. The severity of the clinical course is heterogeneous, with end-stage renal failure being reached between the second and sixth decades. Renal transplantation may be offered to these patients, despite a high incidence of steroid-induced diabetes mellitus.     

双肾血管平滑肌脂肪瘤伴结节性硬化症的诊断治疗

目的总结双肾血管平滑肌脂肪瘤(RAML)伴结节性硬化症(TSC)的发病特点,以提高该病的诊治水平。方法回顾性分析4例双RAML伴TSC患者的临床资料。结果4例患者经B超、CT检查诊断。1例因左肾肿瘤出血行肾切除,1例因右肾肿瘤巨大行肾切除。另2例患者因肿瘤小且症状轻微行保守治疗,随访12~48个月,肿瘤大小无变化,无症状复发。结论B超、CT检查结合临床表现是诊断RAML伴TSC的重要手段。治疗方案应根据双肾肿瘤的大小、分布、发展情况及症状决定。手术时应注意保留正常肾组织,保护肾功能。     

Renal angiomyolipoma; polycystic kidney, and renal cell carcinoma in patient with tuberous sclerosis.

A patient with tuberous sclerosis presented with renal failure secondary to bilateral angiomyolipoma. The angiomyolipoma was associated with polycystic disease and a foci of renal cell carcinoma. This unusual combination has not been reported previously, although each entity has been described separately in tuberous sclerosis.     

Renal cysts in pediatric patients

Renal cysts are relatively common. They may be single, multiple, or innumerable, cortical or medullary. Most renal cysts are spherical, thin-walled, epithelial-lined structures that contain fluid with features of a plasma ultrafiltrate. A clinically useful classification must include characteristics such as age of onset, family history and association with extrarenal lesions, as well as morphologic parameters. Renal dysplasia is disturbed renal histogenesis, either syndromic or non-syndromic, which usually gives rise to morphologically characteristic renal cysts. Two important and distinctive familial forms of renal polycystic disease occur. Autosomal dominant polycystic disease characteristically becomes manifest in adulthood but is becoming increasingly diagnosed in young individuals. Autosomal recessive infantile polycystic disease has complex relationships with congenital hepatic fibrosis. Other cystic renal lesions are less common in young patients, but their occurrence in association with other abnormalities provokes speculation regarding pathogenesis.     

Management of renal angiomyolipomas associated with tuberous sclerosis complex

PURPOSE: Intensive management is generally recommended for angiomyolipomas associated with tuberous sclerosis complex (TSC), which are known to have a more aggressive nature than sporadic tumors. In this study we evaluated the management of these tumors. MATERIALS AND METHODS: The records of 6 men and 6 women with TSC and a mean age of 28.8 years) with angiomyolipomas treated from 1984 to 2000 were retrospectively analyzed. All patients had bilateral multiple tumors (mean size 6.6 cm). There were 10 lesions classified as small (less than 4 cm), 6 medium (4 to 10 cm) and 8 large lesions (10 cm or greater). Computerized tomography was repeated annually for followup observation and semiannually after embolization. RESULTS: Excluding from study 3 tumors treated prophylactically intervention was required in 20%, 50% and 100% of small, medium and large tumors, respectively. Among 14 tumors followed by observation, 8 grew and 4 required intervention. Uncontrollable hemorrhage did not develop in any patient. While some tumors showed remarkable growth in decade 3, growth did not exceed 1.5 cm per year. Embolization was performed in 11 tumors and tumors shrank in 10. Although 1 patient experienced renal atrophy, all patients but 1 are alive without renal failure with a mean followup of 60 months. CONCLUSIONS: Although asymptomatic angiomyolipomas associated with TSC grow gradually, severe hemorrhage is rare and most tumors can be managed conservatively with annual computerized tomography. Embolization is the first choice of intervention but should be reserved until symptoms develop.     

Huge renal angiomyolipomas in tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominance disorder with variable penetrance. Renal angiomyolipoma (AML) is one of the commonest urological manifestations. These lesions may cause significant morbidity and mortality. We report two patients with multiple and huge renal angiomyolipomas presenting with gross haematuria. They subsequently underwent unilateral nephrectomy. The difficulty in diagnosis and controversies in management will be briefly discussed.     

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.     

结节性硬化症多器官病变的临床特点及影像学诊断价(附3例报告)

目的：探讨结节性硬化症累及多器官病变的临床特点及影像学诊断价值。方法：回顾性分析3例结节性硬化症伴大脑、肾脏、皮肤、肝脏，脾脏、骨骼等多部位病灶的症状，体征及其影像学表现。结果：1例有典型的结节性硬化“三联征”表现，3例均有典型的面部皮疹，1例有癫痫发作史。3例颅脑CT均发现典型的大脑钙化结节灶，3例均伴双肾多发性错构瘤，2例CT及B超检查发现肝脏多发错构瘤，1例有脾脏占位性病变，2例行X线平片，CT及同位素骨扫描显示腰骶椎，髂骨及颅骨存在骨密度增高灶，肝、脾及骨骼病变均无明显症状，结论：结节性硬化症是一种可累及大脑，肾脏，皮肤，肝、脾，骨骼等多系统器官的综合征，颅脑CT显示脑室管膜下钙化灶，对诊断具有特异性，影像学检查可以发现多发性无症状病灶。