Recurrent malignant juxtaglomerular cell tumor: A rare cause of malignant hypertension in a child.

A juxtaglomerular cell tumor or reninoma is a very rare renin-secreting tumor of the kidney and can be an unusual cause of secondary hypertension. We report a case of recurrence of this uncommon tumor at the hilum of left kidney in an 8-year-old male child.

INTRODUCTION

Juxtaglomerular cell tumor (JCT) (reninoma) is a very rare renin-secreting tumor of the kidney. The tumor is typically found in young adults, with a peak incidence in the second and third decades.[1-3] It is reported in children only occasionally. The patients usually present with hypertension, hyperaldosteronism, and hypokalemia, secondary to tumor renin secretion.[45] Although pathologically considered to be benign, JCT has got a definite malignant potential. We report one such case of recurrence of this type of tumor, favoring its malignant tendency. The aim of this report is to emphasize that JCT should be kept in mind as a possible differential diagnosis while evaluating secondary hypertension in a child as well as the possibility of its malignant potential.

CASE REPORT

An 8-year-old boy was referred to the emergency department with one-day history of two episodes of transient loss of consciousness. This was preceded by a sense of warmth, light headedness, and chest discomfort. There was no history of fever, vomiting, abnormal body movements, frothing from mouth, incontinence, or post-episode confusion. His pulse was 100/min, regular, good volume, synchronous with other peripheral pulses, and there was no radiofemoral delay. His blood pressure was 210/140 mmHg. Examination of the cardiovascular system revealed a heaving apex, normal first heart sound, and a widely split second heart sound. Auscultation revealed a short systolic murmur at the apex. All the baseline investigations were normal, except serum potassium of 2.8 mmol/l and ECG showing a long QT interval (0.47 seconds). Echocardiography was performed which showed concentric left ventricular hypertrophy. Renal doppler was also ordered which revealed normal renal vessels with normal flow pattern. An ultrasonography showed a left renal mass with grade two hydronephrosis. Serum cortisol and 24-hour urinary vanillylmandelic acid levels were within normal limits. At laparotomy, a mass of 8 × 8 cm was seen at hilum of left kidney which could not be resected without sacrificing the kidney [Figure 1]. One para-aortic node was also enlarged and left suprarenal gland was grossly normal. A provisional diagnosis of Wilms tumor arising from left kidney was made. Left nephrectomy was performed with excision biopsy of the enlarged para-aortic lymph node.

Figure 1

Cut section of mass located at hilum of left kidney

Intraoperatively, the patient had a drop in the blood pressure once the renal pedicle was ligated. The post-operative period was, however, uneventful and the patient was discharged on 13th postoperative day with well-controlled blood pressure, without antihypertensive medication. Histopathology of the nephrectomy specimen and the lymph node was suggestive of multicentric juxtaglomerular tumor (reninoma). Immunohistochemistry suggested tumor cells positive for synaptophysin and chromogranin and negative for cytokeratin. The patient was put on multidisciplinary follow-up. An ultrasound was advised every three monthly. At the end of one year, the patient again developed hypertension and needed antihypertensive medication. Ultrasound examination revealed a recurrent mass in the left renal fossa. Abdominal computed tomography disclosed a 5.6 × 4.3 cm lobulated, homogenously enhancing mass lesion involving left renal fossa, extending medially up to para-aortic region and superiorly up to the perigastric region. Plasma renin activity was 9.3 ng/ml/hr. The patient was again planned for surgical exploration and excision of the recurrent left renal fossa mass was done. Intraoperatively, the patient remained hemodynamically stable with minimal fluctuations in blood pressure during manipulation of the tumor. Blood pressure then decreased predictably once the feeding vessel to the tumor was being ligated. And postoperatively, the patient had no fluctuations in the blood pressure.

The patient was discharged from the hospital on 11th postoperative day. Pathologic examination revealed a lobulated, globular soft tissue structure measuring 5 × 4 × 2 cm surrounded by a fibrous capsule, on gross examination. The cut surface was yellowish brown. Histology showed a capsulated neoplasm with nests and diffuse sheets of tumor cells interrupted by abundant vascularity in the form of capillary channels and sinusoids. The tumor had high mitotic activity and pericapsular invasion was present. The overall features were suggestive of malignant form of JCT. Immunohistochemistry revealed tumor cells positive for synaptophysin and chromogranin and negative for cytokeratin.

DISCUSSION

The prevalence of hypertension in children ranges from 1 to 3%.[6] Renin-producing renal lesion causing severe hypertension was first described in 1967 by Robertson et al.[2] Kihara coined the term “juxtaglomerular cell tumor.” The incidence of JCT is very low, with only 95 cases reported in the published literature to date.[7] It has a peak incidence in the second and third decades of life, and is rarely included in the list of causes of hypertension in children.[3] JCTs are seen more frequently in women than in men and commonly present with a clinical triad of hypertension, hypokalemia, and an elevated plasma renin activity.[4]

Preoperative diagnosis of JCTs is not always easy as these tumors are usually small[58] and superficially located in the renal cortex.[29] Radiological images of JCTs can be easily confused with those of cystic and other benign kidney lesions. Reninoma must be considered in the radiological interpretation of a renal cyst and differential diagnosis of intermittent paroxysmal hypertension.[10] The diagnosis of JCT typically results from identification of plasma renin levels two- to seven-fold greater than the normal. Nearly all these tumors are visible on CT imaging and are weakly enhancing isodense or hypodense lesions when compared with renal medulla. Accelerated hypertension in a young patient should be rigorously evaluated as the potential etiologies include phaeochromocytoma, coarctation of aorta, renal artery stenosis, and aldosteronoma. Once a patient is found to have hyper-reninism, it is important to differentiate between a primary source (e.g., secretion by a renal tumor) and secondary causes (e.g., renal artery stenosis or renal parenchymal disease). Primary renal lesions such as JCT and Wilms tumor may secrete renin (100% and 60% occurrence, respectively), but there are also reports of renin-secreting extrarenal tumors such as lung carcinoma, pancreatic adenocarcinoma, and fallopian tube adenocarcinoma.[11] A JCT is usually a surgically curable cause of hypertension[212] and this tumor type has usually been considered benign. Only two case reports have suggested vascular invasion and questioned its benign nature.[1314] But in our patient, since malignancy could not be ruled out and the mass being located at hilum, kidney had to be sacrificed. It was only after histopathology that the diagnosis was made. The malignant potential of this tumor is further substantiated by the tumor recurrence and vascular invasion on histopathology. The case illustrates the importance of keeping in view this diagnosis while dealing with a renal mass associated with hypertension in an older child. Most of the time, JCTs are superficial and can easily be removed laparoscopically by nephron-sparing partial nephrectomy.[58] Radical nephrectomy should be considered for a presumed reninoma that is located deep in the renal parenchyma or one that is very large with suspicion of malignancy, as in the present case. This case has presented some unique features which make it different from the earlier reported cases in more than one way. Ours is one of the youngest cases of JCT as only three cases have been reported in the literature till date with age less than 10 years.[15] Thus, there is a need for keeping the possibility of its existence in mind in children with hypertension, particularly if it is malignant or paroxysmal.[10] The tumor mass in our patient was one of the largest sizes of JCTs reported in literature. Reninomas are usually small tumors, peripherally located, and usually have a largest diameter of 2 to 3 cm,[14] and the only tumor of comparable size (9.8 cm) has been reported by Beaudoin et al. in 2008.[14] The most important histological observation suggestive of potential malignancy is the presence of a focus of vascular invasion which should be specifically looked for as the cell morphology is otherwise typically of a benign reninoma. The first case of reninoma showing histological features of vascular invasion was reported in 2008.[14] Our patient thus becomes the second one to show features of vascular invasion on histopathology—a feature suggestive of malignant potential.

Multicentric origin of reninoma has not been reported in the literature so far. Our patient is thus distinct from the earlier reported cases as it showed a multicentric origin. During first surgery, there were two tumor masses, one at the hilum of the kidney and the other in the para-aortic region. Both were completely excised and histopathology confirmed the complete excision and separate origin of the tumors. Recurrence of a third mass in the renal fossa, one year after surgery, is a unique feature of our case, not observed before. Recurrence after complete excision has not been reported in the literature before. All these features make this case an extremely rare clinical entity.

CONCLUSION

Although JCTs are very rare, the possibility of their presence should be kept in mind when a patient presents with secondary hypertension, especially if it is malignant or paroxysmal. Possibility of malignancy, recurrence after surgery, multicentric origin, and metastasis should also be kept in all cases of JCTs, especially when they are of larger size as in our case. Surgery is the curative treatment. However, the patients should be regularly followed up post-operatively for checking blood pressure and undergoing abdominal ultrasonography every three monthly postoperatively; and plasma renin activity should be estimated if any fluctuation is noted in the blood pressure, to detect a recurrence at the earliest.