VON HIPPEL-LINDAU SYNDROME WITH

UNUSUAL PRESENTATIONS IN TWO BROTHERS

RUBEN SARANGA, M.D.

HAIM MATZKIN, M.D.

JOSEPH PAPO, M.D.

ZVI BRAF. M.D.

From the Department of Urology, Tel-Aviv Medical Center, Ichilov Hospital and the Sackler Faculty of Medicine, Tel-Aviv University, Israel

ABSTRACT- Two cases arc reported of von Hippel-Lindau syndrome in two brothers. One had an asymptomatic adrenal pheochromocytoma (probably bilateral) and a synchronous metastatic hy- pernephroma which presented as a rather “innocent”rena1 colic. The second asymptomatic brother underwent urologic investigation which revealed multifocal tumors of the kidney. High clinical suspicion based on family history only is mandatory. The literature related to von Hippel-Lindau syndrome is reviewed.

The von Hippel-Lindau syndrome consists of retinal angiomatosis malformations which may lead to hemorrhage, exudation, and possibly retinal detachment of cerebellar hemangioblas- tomas.] ? Other malformations seen in this syn- drome are hemangiomas of the spinal cord, cysts of the pancreas, kidney, lungs, and epidid- ymis, and unilateral or bilateral renal cell carcinoma.3 A strong family history plus one of the aforementioned findings is also presumptive elridence for Lindau disease.4

Pheochromocytoma, also associated with Lindau syndrome, is often bilateral and tends to occur in certain families with this syndrome.”

We had the opportunity to study 2 unusual cases in which a strong family history caused initiation of a meticulous urologic investigation in an otherwise healthy sixty-three-year-old man \vho presented to the emergency room with acute renal colic and on investigation a si- lent renal tumor Lvas discovered in his brother.

Case 1

Case Reports

A sixty-two-year-old man was admitted to the department of urology because of right re- nal colic. A few days before his admission, painless macroscopic hematuria had occurred. On physical examination, the right costo\.erte- bra1 angle was tender.

His past history revealed diagnosis of von Hippel-Lindau syndrome for retinal angiomas. No urologic investigation had been done. His mother died during surgery for removal of an adrenal tumor. His son was operated during childhood for pheochromocytoma of the adrenal gland.

Intravenous pyelography (IVP) w’as not done because of suspected sensitivity to contrast agents. The plain film of the abdomen showed a small calcification in the right pelvis which caused the suspicion of a ureteral stone. The

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FIGURE 1. Renal scan shows cold area in central portion of left kidney (aTrowS).

renal scan showed a “cold area” in the middle portion of the left kidney (Fig. 1). After admis- sion to the hospital, he started to complain of left flank pain, and macroscopic hematuria oc- curred.

At cystoscopy efflux of blood from the left ureteral orifice was seen. Ultrasound of the kid- neys showed a solid mass in the left kidney and a cortical cyst in the lower pole (Fig. 2). Com- puterized tomography (CT) revealed a solid mass in the left kidney, bilateral adrenal masses, and cyst of the right kidney (Fig. 3). Because of pain in the right shoulder, a bone scan was or- dered and showed metastasis in the right clavi- cle. Bone biopsy confirmed the diagnosis of me- tastasis from renal cell carcinoma. Renal and selective adrenal angiograms showed bilateral adrenal tumor with tumoral vessels and tumor of the left kidney (Fig. 4A and B).

Preoperative embolization of the renal artery was performed. The left kidney and the adrenal tumor vvere removed en bloc (Fig. 5). Patho- logic examination confirmed the diagnosis of renal cell carcinoma and pheochromocytoma. Single bone metastasis of the clavicle was treated with radiation therapy.

FI(:UIW 2. Ultrasound showing echogenic ma.Ey in left kidney (white arroux) and cortical cyst in lower pole (black arrow).

FI(:UHE: 3. CT on lower portion o_f both kidneys rc- z;eals renal tumor in central and lateral aspect of left kidne!y (long white arrow), bilateral adrenal tremor (short arrows). cyst of right kidney (long black ar- rou>).

Case 2

The brother of the patient presented as Case 1 was sixty years of age and also had retinal an- giomas. There were no complaints. A urologic investigation including ultrasonography (US), computerized tomography, and renal angio- gram revealed a silent tumor of the right kidney, and cortical cyst of the lower pole. Radical nephrectomy. was done. On gross examination of the surgical specimen three foci of tumor

302 UHOLOGY / I\‘OVEMHEH 19X9 i VOI,L’ME XXXIV. SUMHEH 5

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were present (Fig. 6). Microscopic examination showed renal cell carcinoma in parenchyma of kidney and at the wall of the cyst. The patient is doing well three months after surger!:

Comment

Renal lesions in van Hippel-Lindau s\n- drome are either simple cysts or adenocarcino- mas4 and ha\,e been reported to 1~. present in 35-60 percent of autopsied patients w,hereas 2,5 percent ha\,e been diagnowd in li\ing pa- tients.” ti

The renal lesions are usuall!. latcs rnanifesta- tions of the disease. \vhile in most patients the Irrimary s!mptonis are either wrt4~cllar or oc’u- lar. There are onl!~ rare reports of patients \\~hosc earliest complaints \\.ere due to one of the other associated abnormalitic.~s.~

In 19.31 Kernohan, \Ihltman, and Adson” Irointed out that the renal comporwnt of this s\ndrome ma\’ be a malignant tumor and not a l&nign h\Iwr~nephroid trunor as described lo!, 1,indau in 1926.’

The tumor is multicentral. and th(l majorit!. of patients hale in\vlvement of both kidncls. ’ The renal cell carcinoma is metastatic irr bne third of the cases” and is different from sporadic occurrence 111. its rather earlier age incidence. slight male predominance. anal mlllticcmtric origin. As the appearance of bilateral kidncb!. in- \.ol\wnent nna\. be s!xwhronous 01. nletachro- IIOIIS. our finding based on an!. nlodalities (US. renal scan, CT, arteriography) ‘of a unilateral in\.ol\-clmcnt. does not ol)\riatc tlrc need for

further annual screening for contralateral in- volvement .

In 1953 Glushien, Mansny, and Littmang re- ported 2 patients suffering from pheochromo- cytoma associated with von Hippel-Lindau dis- ease, both with overt clinical symptoms of adrenal involvement. By 1971 Wise and Gib- sonlo pointed to only 8 cases mentioned in the literature with von Hippel-Lindau syndrome and pheochromocytomas. Since then a few other cases have been published,6.1’ all with severe hypertension. Although less than 10 per- cent of all individuals with the syndrome have pheochromocytoma, there is a tendency to fam- ily clustering of cases. l1 Our demonstration of a silent bilateral adrenal tumor, proved histologi- cally to be pheochromocytoma in one excised adrenal, suggests the possibility of a higher per- centage of von Hippel-Lindau syndrome with nonfunctioning adrenal pheochromocytomas. The use of computerized tomography as an im- aging modality for the adrenal silent tumors is suggested in every case of Hippel-Lindau syn- drome. A thorough urologic investigation of the relatives of patients with von Hippel-Lindau syndrome is necessary to detect asymptomatic cases.”

Ichilov Hospital 6 Weizmann Street

Tel Aviv 64239, Israel (DR. MATZKIN)

References

1. van Hippel E: Uber eine sehr seltene Erkrankung der Netzhant. Klinishe Beo Beachtungen, Arch Opth 59: 85 (1904).

2. Lindau A: Cysts in cerebelum: structure, pathogencsis and relations to angiomatosis retina, Acta Path01 Microbial Stand (Suppl) 1: 1-128 (1926).

3. Christoferson LA, Gustafson MB, and Petersen AC: van Hippel Lindau’s disease, JAMA 178: 280 (1961).

4. Fetner CD, et al: Bilateral renal cell carcinoma in van Hippel-Lindau syndrome: treatment with staged bilateral nephrectomy and hemodialysis, J Ural 117: 534 (1977).

5. Chapman RC, Kemp VE, and Taliaferro I: Phcochromocy- toma associated with multiple neuro fibromatosis and intracra- nial hemangioma, Am J Med 26: 883 (1959).

6. Horton WA, Wang V, and Eldridge R: van Hippel Lindau’s disease, Arch Intern Med 136: 769 (1976).

7. Melmon KL, and Rosen SW: Lindau‘s disease, Am J Med 36: 595 (1964).

8. Kernohan JW, Woltman HW, and Adcon AW: Intramedu- lary tumors of spinal cord: review of fifty-one cases with at- tempted histologic classification, Arch Neural Psycho1 25: 6i9 (1931).

9. Glushien AS, Mansny MM, and Littman DS: Pheochromo- cytoma, its relationship to the neurocutaneous syndrome, Am J Med 14: 318 (1953).

10. Wise KS, and Gibson JA: van Hippel Lindau‘s disease with pheochromocytoma. Br Med J 1: 441 (1971).

11. Sander S, Normann T, and Mathisen W: Pheochromocy- toma associated with van Hippel Lindau’s disease in a family, Stand J Ural Nephrol 4: 253 (1970).

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