Juxtaglomerular Apparatus Tumor: A Rare, Surgically Correctable Cause of Hypertension

CASE REVIEW Juxtaglomerular Apparatus Tumor: A Rare, Surgically Correctable Cause of Hypertension Jonathan N. Rubenstein, MD,* Scott E. Eggener, MD,* Michael R. Pins, MD,† Karol Rosner, MD,‡ Sumant Chugh, MD,‡ Steven C. Campbell, MD§ Departments of *Urology, †Pathology, and ‡Division of Nephrology, Department of Medicine, Northwestern University Medical School, Chicago, IL; §Department of Urology and Bernadin Cancer Center, Loyola University Medical School, Maywood, IL Although uncommon, presentation of juxtaglomerular cell tumor is distinct and should allow a correct preoperative diagnosis in most patients. Typical clinical presentations include headaches, polyuria, or isolated, asymptomatic, severe hypertension. The diagnosis of a juxtaglomerular apparatus (JGA) tumor typically results from identification of plasma renin levels two- to sevenfold greater than the normal value. Although JGA tumors are considered benign, with no reports of metastases or recurrence, they are potentially lethal if left untreated. Surgical excision is curative. [Rev Urol. 2002;4(4):192–195] © 2002 MedReviews, LLC Key words: Accelerated hypertension • Juxtaglomerular apparatus tumor • Hyperreninism 25-year-old woman presented with 18 months of intermittent headaches and was found to have a blood pressure of 210/158. She denied a history of seizures, visual changes, palpitations, urinary tract infections, childhood urologic disorders, or recent change in weight. Her mother had adult-onset essential hypertension. Physical examination revealed symmetrical pulses in all extremities and no abdominal masses or bruits. Laboratory values suggested hyperreninemic hyperaldosteronism (see Table 1). A renal angiogram revealed a 4-cm hypovascular lesion in the upper pole of the left kidney (Figure 1). The renal vasculature was normal bilaterally. Computed tomography demonstrated a heterogeneous enhancing 4.3  4.9  4.0 cm left upper pole mass with no fat density (Figure 2). The patient’s blood pressure normalized after being placed on an angiotensin-converting enzyme (ACE) inhibitor, and she was then referred for nephrology consultation at our institution. Her laboratory values are detailed in Table 1. An MRI revealed the mass to have a central scar and small punctate areas of increased signal intensity on T1-weighted sequences, suggestive of hemorrhage. The adrenal glands were radiographically normal. A 192 VOL. 4 NO. 4 2002 REVIEWS IN UROLOGY Juxtaglomerular Apparatus Tumor Table 1 Clinical and Laboratory Parameters at Presentation and During Postoperative Evaluation Blood pressure Creatinine Potassium Serum aldosterone (recumbent) Serum renin (recumbent) 24-hour urine vanillylmandelic acid 24-hour urine metanephrines 24-hour urine normetanephrines Initial Presentation On ACE Inhibitor 2 Months Postoperative 210/158 mm/hg 0.6 mg/dL 2.8 mmol/L 25 ng/dL 28.8 ng/mL/hr 4.2 mg 117 g 205 g 140/108 mm/hg 0.6 mg/dL 4.5 mmol/L 13.6 ng/dL 18.3 ng/mL/hr 110/70 mm/hg 0.8 mg/dL 4.2 mmol/L 8.2 ng/dL 1.87 ng/mL/hr Normal Reference Range (age- and gender-specific)* < 1.6 mg/dL 3.5–5.0 mmol/L 1–16 ng/dL 0.15–2.33 ng/mL/hr < 6 mg per 24 hr 19–140 g per 24 hr 52–310 g per 24 hr * Normal reference range for laboratory at Northwest Memorial Hospital. After evaluation by the urology service, the patient underwent left renal exploration, and a hemi-nephrectomy was performed with the aid of low-up her blood pressure was 110/70 on no medications; serum renin and aldosterone levels had normalized. On gross inspection, the excised mass hyde-fixed tumor tissue showed electron-dense, intracytoplasmic rhomboid crystals characteristic of renin. Discussion On gross inspection, the excised mass was purple-pink with a glistening capsule. intraoperative ultrasound. The tumor was excised with negative margins, preserving the lower 35%–40% of the kidney. She was normotensive postoperatively, and at 2 months fol- was purple-pink with a glistening capsule. Histology showed a juxtaglomerular apparatus tumor (JGA) with focal cystification (Figure 3). Electron microscopy of glutaralde- Figure 1. Left renal angiogram showing a hypovascular left upper pole renal mass. Since the late 1960s, when Robertson first described a renin-producing renal lesion causing severe hypertension and Kihara coined the term “juxtaglomerular cell tumor," there have been less than 50 cases reported.1,2 Although uncommon, presentation is distinct and should allow a correct preoperative diagnosis in Figure 2. CT scan demonstrating a heterogeneous, enhancing left renal mass. VOL. 4 NO. 4 2002 REVIEWS IN UROLOGY 193 Juxtaglomerular Apparatus Tumor continued Figure 3. Histologic section of JGA tumor with characteristic findings. most patients. Accelerated hypertension in a young patient should be rigorously evaluated, as potential etiologies include pheochromocytoma, coarctation of the aorta, renal artery stenosis, and aldosteronoma. Once a patient is found to have hyperreninism, it is important to differentiate between a primary source (eg, secretion by a renal tumor) and secondary causes (eg, renal artery stenosis or renal parenchymal disease). Primary renal lesions such as JGA and Wilms’ tumors may secrete renin (100% and 60% occurrence, respectively), but there are also reports of renin-secreting extrarenal tumors, such as lung carcinoma, Typical clinical presentations included headaches, polyuria, or isolated, asymptomatic, severe hypertension (average 207/134); average age at diagnosis was 22 years (range: 7 to 58 years).4 The mean tumor size was 2.4 cm (range: 1.0 to 5.0 cm).4 The diagnosis of a JGA tumor typically results from identification of plasma renin levels two- to sevenfold greater than the normal value.8 When pursuing an etiology for hyperreninism, the initial test of choice should be a renal angiogram to exclude renal artery stenosis; in some cases, such as this one, a hypovascular lesion can be identified.9-11 Selective renal vein sampling can be considered but is often equivocal. This may be due to the cortical nature of most JGA lesions and their pericapsular venous drainage. Nearly all JGA tumors are visible on CT imaging and are weakly enhancing isodense or hypodense lesions when compared to renal medulla. However, JGA Although JGA tumors are considered benign, with no reports of metastases or recurrence, they are potentially lethal if left untreated. pancreatic adenocarcinoma, and fallopian tube adenocarcinoma.3 Haab and colleagues described eight JGA tumors among 30,000 patients at a hypertension clinic, the largest series in the literature.4 tumors as small as 5 mm can cause severe hypertension and can be difficult to localize using standard imaging techniques.7 Juxtaglomerular tumors are typically well circumscribed, cortical, Main Points • Accelerated hypertension in a young patient should be rigorously evaluated; potential etiologies include pheochromocytoma, coarctation of the aorta, renal artery stenosis, and aldosteronoma. • If a patient is found to have hyperreninism, it is important to differentiate between a primary source (eg, secretion by a renal tumor) and secondary causes (eg, renal artery stenosis or renal parenchymal disease). • There are reports of renin-secreting extrarenal tumors, such as lung carcinoma, pancreatic adenocarcinoma, and fallopian tube adenocarcinoma. • When pursuing an etiology for hyperreninism, the initial test of choice should be a renal angiogram to exclude renal artery stenosis. • Nearly all juxtaglomerular apparatus tumors are visible on CT imaging and are weakly enhancing isodense or hypodense lesions when compared to renal medulla. 194 VOL. 4 NO. 4 2002 REVIEWS IN UROLOGY Juxtaglomerular Apparatus Tumor and encapsulated.8 Ultrastructural demonstration of rhomboid crystals with a crystalline matrix within the cytoplasm are characteristic of JGA’s “prerenin."8 Intracytoplasmic renin can also be demonstrated by immunofluorescence. There is often an unexplained infiltration of mast cells in JGA tumors that may comprise up to 25% of the total cellular content.11,12 Although JGA tumors are considered benign, with no reports of metastases or recurrence, they are potentially lethal if left untreated, as evidenced by a report of hypertension-induced intracranial hemorrhage.13 Pharmacologic treatment is feasible, and ACE inhibitors are a rational choice to control the blood pressure preoperatively; surgical excision is curative. Postoperatively, 12%–27% of patients have persistent “benign" hypertension, thought to be due to hypertension-induced vascular damage.4,8 6. 7. 8. 9. References 1. 2. 3. 4. 5. Kihara I, Kitamura S, Hoshino T, et al. A hitherto unreported vascular tumor of the kidney: a proposal of “juxtaglomerular cell tumor." Acta Pathol Jpn. 1968;18:197–206. Robertson P, Klidjian A, Harding LK, et al. Hypertension due to a renin-secreting renal tumor. Am J Med. 1967;43:963–976. Corvol P, Pinet F, Galen FX, et al. Seven lessons from seven renin secreting tumors. Kidney Int. 1988;34(25):S38–S44. Haab F, Dulcos JM, Guyenne, et al. Renin secreting tumors: diagnosis, conservative surgical approach and long-term results. J Urol. 1995;153:1781–1784. Brown JJ, Fraser R, Lever AF, et al. Hypertension and secondary hyperaldosteronism associated with a renin-secreting renal juxtaglomerular-cell tumour. Lancet. 1973;2:1228. 10. 11. 12. 13. Dennis R, McDougal WS, Glick AD, et al. Juxtaglomerular cell tumors of the kidney. J Urol. 1985;134:334–338. Robitaille P, Mongeau JG, Garel L, et al. A tiny renal renin-secreting tumor. Scand J Urol Nephrol. 1994;28:297–299. Squires JP, Ulbright TJ, Klemm SA, et al. Juxtaglomerular cell tumor of the kidney. Cancer. 1984;53:516–523. Gordon RD, Tunny TJ, Klemm SA, et al. A reninsecreting tumor sensitive to changes in central blood volume (presumably via sympathetics) but not to circulating angiotensin II. Clin Exp Pharmacol Physiol. 1990;17:185–189. Handa N, Fukunaga R, Yoneda S, et al. State of systemic hemodynamics in a case of juxtaglomerular cell tumor. Clin Exp Hypertens. 1986;A8:1–19. Baruch D, Corvol P, Alhenc-Gelas F, et al. Diagnosis and treatment of renin-secreting tumors. Report of three cases. Hypertension. 1984;6:760–766. Mimran A, Leckie BJ, Fourcade JC, et al. Blood pressure, renin-angiotensin system and urinary kallikrein in a case of juxtaglomerular cell tumour. Am J Med. 1978;65:527–536. Gherardi G, Arya S, Hickler R. A rare occult but curable cause of lethal hypertension. Hum Pathol. 1974;5:236–240. VOL. 4 NO. 4 2002 REVIEWS IN UROLOGY 195