Renal cell carcinoma in association with tuberous sclerosis in children

Renal cell carcinoma in association with tuberous sclerosis in children

Renal Cell Carcinoma in Association With Tuberous Sclerosis in Children By Frank M. Robertson, Marc Cendron, George T. Klauber, Boston, Massachusetts...

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Renal Cell Carcinoma in Association With Tuberous Sclerosis in Children By Frank M. Robertson,

Marc Cendron, George T. Klauber, Boston, Massachusetts

l Tuberous sclerosis, a genetically transmitted multisystern neurocutaneous disorder, is associated with renal lesions in 50% of cases. The expected lesions are angiomyolipomas or renal cysts; renal cell carcinoma has been encountered in adults who have tuberous sclerosis, but is very rare in children. The authors report the case of a B-year-old girl with tuberous sclerosis for whom atypical computed tomography findings led to the diagnosis of renal carcinoma at an early age. This experience suggests that children with tuberous sclerosis may need earlier screening.

Copyright INDEX

o 7996 by W.B. kwnders

WORDS:

Tuberous

sclerosis,

Company renal

cell carcinoma.

T

UBEROUS SCLEROSIS (TS) was first described in 1908, when Fisher reported the clinical triad of epilepsy, mental retardation, and adenoma sebaceum.l~2 More than half the patients with TS have some form of renal lesion, usually an angiomyolipoma or renal cyst.3 We recently treated a child with TS in whom renal cell carcinoma developed at a very early age. CASE REPORT A 5-year-old black girl with TS and associated seizures and developmental delay had mild renal insufficiency (blood urea nitrogen, 10; creatinine, 0.5 mg/dL), for which renal ultrasonography was performed. She was found to have multiple renal cysts scattered throughout both kidneys, with distortion of the corticomedullary junction. In addition, a solid mass (2 x 2 x 2 cm) was seen in the upper pole of the left kidney. This finding was confirmed by a computed tomographic (CT) scan, which also showed a small hypolucent area within the mass, suggestive of an angiomyolipoma (Fig 1) The mass enhanced after administration of intravenous contrast. Because of the atypical appearance, another CT scan was obtained 3 months later, which showed that the mass was 50% larger. Excision was undertaken through a retroperitoneal approach, preserving the transperitoneal route for subsequent transplantation, if necessary. A 3- x 4-cm mass was found arising from the upper pole of the kidney (Fig 2). Upper pole nephrectomy was performed using the argon-beam coagulator. Frozen sections of the tumor showed renal cell carcinoma. The resection was considered complete when multiple resection margin biopsy specimens were negative for tumor. The patient’s recovery was uneventful, and histopathology and electron microscopy confirmed the frozen section report of a stage I renal cell carcinoma. Neither radiation nor chemotherapy was considered necessary, and the child is free of disease 15 months after the operation. DISCUSSION

TS is an autosomal-dominant disorder with incomplete penetrance and variable phenotype. It belongs to a group of hereditary diseases known as the Journal

of Pecfa+tr/c

Surgery,

Vol31,

No 5 (May),

1996: pp 729-730

and Burton

H. Harris

phakomatoses, which may involve the central nervous system (cortical tubers in the brain), retina (phakomas), skin (angiofibromas), heart (rhabdomyomas), bone (sclerotic lesions), lung (lymphangiomas), and kidney (angiomyolipomas and renal cysts).4 It is relatively rare (incidence, 1 in 10,000 children). The overall prognosis of TS is poor, and 75% of the patients die by age 20 of complications of renal failure.lJ Angiomyolipomas are tumors that contain adipose, vascular, and smooth muscle elements. These lesions are commonly bilateral and multiple, and usually are seen after puberty.6 In general they are asymptomatic; however, occasionally they cause flank pain, hematuria, or hypertension. Rupture of the mass has resulted in retroperitoneal hemorrhage and shock in 10% to 20% of patients, and renal complications have occurred in 6% of cases.1’7 Renal cysts associated with TS are usually small and multiple, and occur less frequently than angiomyolipomas.8,9 The ultrasound appearance of renal cysts resembles that of lesions in polycystic kidney disease. The histopathology of these cysts shows a lining of hyperplastic eosinophilic cells that may aggregate to form intracystic masses or tumorlets.1° Cystic renal disease associated with TS may lead to hypertension and renal failure. Angiomyolipomas are considered benign but have occurred in adults with renal cell carcinoma.11J2 Radiologically, it can be difficult to distinguish angiomyolipoma and renal cell carcinoma, and CT scan is the best modality for the diagnosis of angiomyolipoma because it can detect small amounts of fat.13 As demonstrated by the present case, fat density on a CT scan does not always exclude carcinoma. Renal cell carcinoma associated with TS has been reported with increasing frequency among young patients, including young TS patients.6J0 The tumors may be single, multiple, or bilateral. In renal cell carcinoma associated with TS, the cells lining the From the Division of Pediatric Surgery and the Section of Pediatric Urology, Tufts Universzty School of Medicine and the Boston Floating Hospital, Boston, Mk Address reprint requests to Burton H. Hark, MD, Division of Pediatric Surgery, Georgetown University Medical Center, 3800 Reservoir Rd, NW Washington, DC 2000% Copyright o I996 by W B. Saunders Company 0022-3468/9613105-0031$03.00!0 729

730

Fig 1. (A) CT scan shows multiple (arrow) with fat density and contrast

ROBERTSON

renal cysts enhancement.

(arrows).

The patient

renal cysts adjacent to tumors have karyotypes similar to those of carcinoma cells and may have malignant potential. l4 Distant metastasis has been rare.9 The impact of renal cell carcinoma on mortality for patients with TS is uncertain, but aggressive management of renal cell carcinoma has been advocated for patients with TS.8 To our knowledge, our patient is the youngest to have renal cell carcinoma in association with TS. Conservative renal surgery was chosen to spare as many nephrons as possible, and partial nephrectomy is recommended. We conclude that serial screening examinations may be of value for the early detection of renal cell carcinoma in children who have TS.

had mild

renal

insufficiency.

Fig 2. Operative shows the exophytic

(B) CT scan shows

view of the left-upper-pole lesion. Partial nephrectomy

a solid

upper-pole

ET AL

mass

renal cell carcinoma was performed.

REFERENCES 1. Gomez MR: Tuberous Sclerosis. New York, NY, Raven, 1979 2. Hanno R, Beck R: Tuberous sclerosis. Neurol Clin 5:351-359, 1987 3. Stillwell TJ, Gomez MR, Kelalis PP: Renal lesions in tuberous sclerosis. J Urol138:477-481, 1987 4. Connor JM, Pirrit LA, Yates JR, et al: Linkage of the tuberous sclerosis locus to DNA polymorphism detected byv. abl. J Med Genet 24:544-546,1987 5. Wiederhold WC, Gomez MR, Kurland LT: Incidence and prevalence of tuberous sclerosis in Rochester, Minnesota, 1950 through 1982. Neurology 35:600-605,1985 6. Bernstein J, Robbins TO, Kissane JM: The renal lesions of tuberous sclerosis. Semin Diagn Path01 3:97-101, 1986 7. Shapiro RA, Skinner DG, Stanley P, et al: Renal tumors associated with tuberous sclerosis: The case for aggressive surgical management. J Urol132:1170-1174,1984 8. Stapleton FB, Johnson D, Kaplan GW, et al: The cystic renal lesion in tuberous sclerosis. J Pediatr 97:574-576,198O

9. Mitnick JS, Bosniak MA, Hilton S, et al: Cystic renal disease in tuberous sclerosis. Radiology 147:85-92,1983 10. Bernstein J, Gardner KD: Cystic disease and dysplasia of the kidney, in Murphy WM (ed): Urological Pathology. Philadelphia, PA, Saunders, 1989, pp 483-501 11. Taylor RS, Joseph DB, Kohant EC, et al: Renal angiomyolipoma associated with lymph node involvement and renal cell carcinoma in patients with tuberous sclerosis. J Urol 141:930-932, 1989 12. Webb DW, Kabala J, Osborne JP: A population study of renal disease in patients with tuberous sclerosis. Br J Urol 74:151-154, 1994 13. Bosniak MA, Megibow AJ, Hulnick DH, et al: CT diagnosis of renal angiomyolipoma: The importance of diagnosing small amounts of fat. AJR 151:497-500,1988 14. Ibrahim RE, Weinberg DS, Weidner N: Atypical cysts and carcinomas of the kidneys in the phacomatoses: A quantitative DNA study using static and flow cytometry. Cancer 63:148,1989