Renin-producing Hepatoblastoma in an Infant: A Case Report

ABSTRACT

A rare case of renin-secreting hepatoblastoma in a 1-year-old infant is presented, marked by unexplained hypertension. Elevated renin levels and immunohistochemical confirmation established the diagnosis. Surgical removal of the tumor normalized blood pressure. The case highlights the need to consider secondary hypertension in pediatric liver tumors for timely diagnosis and treatment.

INTRODUCTION

Hepatoblastoma is the most common primary liver malignancy in children, constitutes 1% of all pediatric malignancies.[1] Patients usually present with complaints of abdominal lump and failure to thrive in advanced stages. On examination, the right abdomen slightly distended extending right hypochondrium, epigastrium, and right lumbar region. The diagnosis is made by cross-sectional imaging, serum alpha feto-protein levels, and histopathological examination. Para-neoplastic syndromes are fewer and rarely reported with hepatoblastoma.[2] Some of them are thrombocytosis, erythrocytosis, hypokalcemia, hypoglycemia, and precocious puberty.[3] We report the rare case of an infant with hepatoblastoma-associated renin-mediated hypertension.

CASE REPORT

A 1-year-old boy admitted to the pediatric surgery unit, presented with a 2-month history of abdominal distension, poor appetite, and weight loss. Examination revealed blood pressure in the borderline raised and preoperatively 2 readings were (122/58 mmHg, >99^th percentile for age) which was overlooked. Laboratory tests showed thrombocytosis and markedly elevated alpha-fetoprotein (AFP) (18,900 ng/mL). Imaging identified an operable liver tumor involving segments IVb and V-Hepatoblastoma [Figure 1a and b] and underwent a right hepatectomy uneventfully [Figure 1c].

Figure 1.

(a and b) Computed tomography imaging, (c) Intraoperative image, (d) cut surface of shows a grey white greenish tinged tumor which has a lobulated growth pattern

In the immediate postoperative period, the patient had persistent hypertension for which pediatrician’s opinion was sought and antihypertensive was started. Renal and ophthalmologic evaluations for hypertensive changes were normal. Further investigation revealed elevated plasma renin (149.4 mIU/L) with normal aldosterone (8.67 ng/dL), suggesting a possible renin-secreting hepatoblastoma. By postoperative day 4, blood pressure normalized and antihypertensive was discontinued.

Grossly, the tumor was well-circumscribed, gray-white, and lobulated surface [Figure 1d]. Microscopy revealed trabecular and nesting pattern with polygonal cells, eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli, with tumor-free margins. Mitotic activity and nuclear crowding confirmed a diagnosis of mitotically active fetal hepatoblastoma [Figure 2a]. Immunohistochemistry showed diffuse cytoplasmic renin expression (Cat. #: DF4419, Affinity Biosciences) [Figure 2b].

Figure 2.

(a) Section shows a tumor arranged in trabecular pattern. The tumor cells are polygonal having distinct moderate eosinophilic cytoplasm, round to oval nuclei with high nucleus to cytoplasmic ratio, vesicular nuclei and conspicuous to prominent nucleoli. Few mitotic figures are seen (white arrow) ×400, (b) Tumor cells are showing diffuse granular cytoplasmic immunoexpression of Renin (Cat.#: DF4419, Affinity Biosciences). The background capillaries are negative for Renin which are the internal negative control ×100

The patient received two cycles of cisplatin monotherapy. He has been under the follow-up for 1 year. His blood pressure is normal, imaging shows no tumor recurrence and serum AFP is normal (4.65 ng/mL). Plasma renin activity is also within the normal range.

DISCUSSION

Primary reninism, first described by Conn in 1955, defined it as hypertension arising from the excessive secretion of renin from the kidneys or extra-renal tissue.[4] The tumor may secrete renin, pro-renin, or immunoreactive variants, which stimulate aldosterone production and causes malignant hypertension.

Hypokalemia may be absent when prorenin predominates.[4] Neoplastic mass-associated reninism was first reported by Robertson, followed by Kinara, in juxtaglomerular cell tumors in adults. There have been the reports of renin production in lung cancers, paraovarian tumors, renal and adrenal tumors, pancreatic malignancies, and orbital hemangiopricytoma.[5]

Renin-secreting hepatoblastoma is being increasingly recognized, with limited case reports in the literature.[5] Among other reports, the patients aged between 22 months and 12 years, all presented with malignant hypertension. Encephalopathy occurred in two of three patients and all were diagnosed with renin-secreting hepatoblastoma based on elevated plasma renin activity. While in 1 case, renin-secreting cells were identified through immunohistochemistry on histopathology.[5] Histological findings varied among cases. Unfortunately, most patients had poor outcomes in inoperable tumor.

In our case, hypertension was overlooked preoperatively, as it is uncommonly associated with hepatoblastoma. This case underscores the importance of vigilant blood pressure monitoring in children with hepatoblastoma and the need to evaluate for secondary causes of hypertension. The diagnosis is confirmed by elevated plasma renin activity and evidence of renin production on histopathology and immunohistochemistry.

CONCLUSION

Renin-secreting hepatoblastoma is an uncommon phenomenon and a rare cause of malignant hypertension in children. Such atypical presentations could be easily overlooked in the preoperative period and should prompt a thorough evaluation for the secondary causes of hypertension. Overall, the prognosis depends on the treatment of hepatoblastoma.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.