Molecular Characterization of Juxtaglomerular Cell Tumors: Evidence of Alterations in MAPK-RAS Pathway.

Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.

Clinical features, laboratory findings and treatment of juxtaglomerular cell tumors: a systemic review.

Juxtaglomerular cell tumors (JGCTs) or reninoma are rare kidney tumors leading to secondary hypertension, and the non-specific clinical manifestations bring about challenges to the diagnosis. This study is to summarize the clinical features, laboratory findings, and treatment of JGCTs. The PubMed, EMBASE database, and manual search were utilized to find all cases, and 158 reports containing 261 patients were identified. Data on patients' demographics, clinical features, diagnostic methods, and treatment options were collected and analyzed. JGCTs occurred predominantly in female patients (female to male ratio, 2.1:1). The median age of patients was 25 years (IQR:18-34 years). Hypertension (97.24%) was the cardinal manifestation. Hypokalemia was reported in 78.71% (159/202) of subjects, and normal serum potassium accounted for 20.79% (42/202). In cases with assessed plasma renin activity (PRA) levels, the median PRA was 7.89 times the upper limit of normal (IQR:3.58-14.41), and 3.82% (5/131) of cases in the normal range. Tumors were detected in 97.8% (175/179) computed tomography (CT), 94.7% (72/76) magnetic resonance imaging (MRI), and 81.5% (110/135) ultrasound, respectively. For 250/261 patients undergoing surgical procedures, 89.14% (197/221), 94.94% (150/158), and 100% (131/131) of patients were restored to normal blood pressure, PRA, and serum potassium, respectively. JGCTs are commonly associated with hypertension, hypokalemia, and hyperreninemia, whereas patients with normotension, normokalemia, and PRA should be systematically pursued after drug-elution lasting for 2 weeks. CT and MRI are more sensitive imaging diagnostic methods. The blood pressure and biochemical parameters of most patients returned to normal after surgery.

Tumor de células yuxtaglomerulares (reninoma) como causa de hipertensión arterial en la adolescencia. A propósito de un caso / Juxtaglomerular cell tumor (reninoma) as a cause of arterial hypertension in adolescents. A case report

La hipertensión arterial (HTA) grave en pediatría responde fundamentalmente a causas secundarias. Presentamos una paciente adolescente de 14 años con HTA grave, alcalosis metabólica e hipopotasemia, secundaria a un tumor de células yuxtaglomerulares productor de renina, diagnosticado luego de dos años de evolución de HTA.

Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN, metabolic alkalosis, and hypokalemia, secondary to a renin-secreting juxtaglomerular cell tumor diagnosed after 2 years of HTN progression.

Nephron-sparing surgery for treatment of reninoma: a rare renin secreting tumor causing secondary hypertension

Main findings A 25-year-old hypertensive female patient was referred to our institution. Initial workup exams demonstrated a 2.8 cm cortical lower pole tumor in the right kidney. She underwent laparoscopic partial nephrectomy without complications. Histopathologic examination revealed a rare juxtaglomerular cell tumor known as reninoma. After surgery, she recovered uneventfully and all medications were withdrawn. Case hypothesis Secondary arterial hypertension is a matter of great interest to urologists and nephrologists. Renovascular hypertension, primary hyperadosteronism and pheocromocytoma are potential diagnosis that must not be forgotten and should be excluded. Although rare, chronic pyelonephritis and renal tumors as rennin-producing tumors, nephroblastoma, hypernephroma, and renal cell carcinoma might also induce hypertension and should be in the diagnostic list of clinicians. Promising future implications Approximately 5% of patients with high blood pressure have specific causes and medical investigation may usually identify such patients. Furthermore, these patients can be successfully treated and cured, most times by minimally invasive techniques. This interesting case might expand knowledge of physicians and aid better diagnostic care in future medical practice. .

Juxtaglomerular cell tumor as a rare cause of hypertension in adults

The juxtaglomerular cell tumor is a cause of secondary hypertension in adults. A 35-year-old female patient suffering from hypertension and low serum potassium had a 3 x 3 cm solid mass at the lower pole of left kidney diagnosed by abdominal sonography. Partial nephrectomy was performed and the postoperatory was uneventful. Normalization of blood pressure was observed within the first month.