Juxtaglomerular Cell Tumor Research Articles

Renal Juxtaglomerular Cell Tumors Exhibit Distinct Genomic and Epigenomic Features and Lack Recurrent Gene Fusions: Comprehensive Molecular Analysis of a Multi-institutional Series.

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6. The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.

Reninoma: Radiological Approach for a Rare Kidney Tumor (Case Report)

Reninoma (juxtaglomerular cell tumor) is a rare and benign kidney tumor responsible for renin–mediated hypertension. We report a case of severe hypertension in a female child. Contrast-mediated CT scan especially in the delayed phase was the key of diagnosis. Different elements helped with the diagnostic approach, including clinical and biological data, especially severe hypertension and elevated blood levels of renin and aldosterone. Histological examination after tumor enucleation confirmed the diagnosis.

Juxtaglomerular Cell Tumor With Cytohistological Correlation: A Case Report.

Juxtaglomerular cell tumors (JCT) are uncommon renin-secreting tumors of the kidney with cytologic findings of JCT rarely reported. We describe a case of JCT in a 37-year-old man with uncontrolled hypertension that was cured by removal of the tumor via partial nephrectomy. Cytology material was prepared by scraping of the freshly sectioned tumor mass and stained with Diff-Quik and Papanicolaou stains. Cytohistological findings and immunohistochemistry studies are discussed regarding diagnosis and differential diagnoses.

Renovascular hypertension following by juxtaglomerular cell tumor: a challenging case with 12-year history of resistant hypertension and hypokalemia

BackgroundAdolescents with secondary hyperaldosteronism often present with severe and treatment-resistant hypertension, along with hypokalemia. Renovascular hypertension is frequently caused by renal artery stenosis, primarily due to atherosclerosis and fibromuscular dysplasia (FMD). The presence of an accessory renal artery (ARA) is a common anatomical variation that can contribute to secondary renal vascular hypertension. However, FMD occurring in the ARA is a rare cause of renal vascular hypertension. Juxtaglomerular cell tumor (JGCT) represents a rare etiology of renal hypertension. The co-occurrence of the pathogenic ARA with JGCT is infrequently reported in the existing literature.Case presentationsThis case study presents a young individual with a 12-year history of resistant hypertension, initially diagnosed with pathogenic ARA but later confirmed as JGCT 4 years later. Following surgery for JGCT, the patient experienced only temporary stabilization of blood pressure without anti-hypertensive medication. Stenosis of the ARA was definitively diagnosed one and a half years post-surgery, with FMD occurring on the ARA strongly suspected. The patient underwent balloon dilatation angioplasty 3 years later, leading to sustained blood pressure stability with the use of two medications.ConclusionsThe case study discussed herein involves a patient with resistant hypertension initially diagnosed with ARA but later determined to have late-onset JGCT and renal artery stenosis. It is imperative to consider atypical JGCT in young patients exhibiting resistant hypertension, hypokalemia, and hyperreninemia. Adequate management of renal artery stenosis is crucial in the management of hyperreninemic hypertension.

A locally infiltrative juxtaglomerular cell tumor with unusual histologic features.

Juxtaglomerular cell tumor (JGCT) is an exceptionally rare renal tumor with a predominantly benign clinical course and classically bland histology. It commonly presents in young adults and manifests as hypertension related to renin secretion. We report a JGCT initially thought to be a renal cell carcinoma. It was unique because of its size, high-grade histologic features and locally infiltrative nature-extension into the renal pelvis. It is unclear whether features such as tumor necrosis, pleomorphism and increased proliferative activity are predictive of metastatic potential and/or locally aggressive behavior. Clinical follow-up may be warranted in such cases.

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.

Juxtaglomerular Cell Tumor Mimicking Renal Cell Carcinoma on 99m Tc-MIBI SPECT/CT.

Juxtaglomerular cell tumor or reninoma is an extremely rare, typically benign, renin-secreting tumor of the kidney that causes secondary hypertension. We describe 99m Tc-MIBI SPECT/CT findings in a case of juxtaglomerular cell tumor. The renal tumor showed isodensity and photopenia on 99m Tc-MIBI SPECT/CT. This case indicates that juxtaglomerular cell tumor can appear cold on 99m Tc-MIBI SPECT/CT, mimicking renal cell carcinoma.

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.

How to identify juxtaglomerular cell tumor by ultrasound: a case series and review of the literature

PurposeTo study the value of ultrasound in the diagnosis of juxtaglomerular cell tumor (JGCT).MethodsFrom January 2005 to July 2020, fifteen patients diagnosed as JGCT by surgical pathology in Peking Union Medical College Hospital were collected. All patients underwent preoperative ultrasound examination. The clinical, laboratory, ultrasound, computed tomography (CT), surgical, and pathological features of the patients were analyzed retrospectively.ResultsThe 15 patients were 5 males and 10 females with a median age of 29 years (10∼72 years). 14 of them had hypertension and one had normal blood pressure. The tumors were all solitary, with a median diameter of 1.5 cm (0.9–5.9 cm). Among the fifteen patients, eleven were correctly detected by preoperative ultrasound, and four were missed. There was a significant difference in tumor size (2.64 ± 1.48 cm vs. 1.23 ± 0.21 cm) and whether the tumor protruded outward (9/11 vs. 0/4) between the ultrasound-detected group and the ultrasound-missed group (p = 0.010, p = 0.011). Of the 11 tumors detected by ultrasound, four were extremely hypoechoic, two were hypoechoic, three were isoechoic, and two were hyperechoic. Color Doppler showed no blood flow in five tumors with the size range from 0.9 to 2.0 cm, and mild blood flow in six tumors with the size range from 2.8 to 5.9 cm.ConclusionsJGCT is rare, and has characteristic clinical manifestations. Diagnosis should be suspected in case of secondary hypertension, particularly in young women, if no renal vascular cause was found. Ultrasound, combined with clinical manifestations, was helpful for the diagnosis.

Case report: juxtaglomerular cell tumour with unusual clinical and histopathological features

Case report: juxtaglomerular cell tumour with unusual clinical and histopathological features

A case of hypertension secondary to juxtaglomerular cell tumor in a young female patient

A case of hypertension secondary to juxtaglomerular cell tumor in a young female patient

A case of pediatric secondary hypertension caused by juxtaglomerular cell tumor.

A case of pediatric secondary hypertension caused by juxtaglomerular cell tumor.

Pregnancy complicated by juxtaglomerular cell tumor of the kidney: A case report

Juxtaglomerular cell tumor (JGCT) of the kidney, also known as reninoma, is a rare renal tumor that typically clinically manifests as hypertension, hypokalemia, high renin, and high aldosterone. It is a cause of secondary hypertension. Pregnancy with JGCT is rarer and easily misdiagnosed as pregnancy-induced hypertension, thus affecting treatment. A 28-year-old woman presented in early pregnancy with hypertension (blood pressure of 229/159 mmHg), nausea, and occasional dizziness and headache. The patient was diagnosed with pregnancy-induced hypertension, and no relief was found after symptomatic treatment; hence, the pregnancy was terminated by artificial abortion. Her blood pressure remained high following termination of pregnancy. Blood tests suggested hypokalemia (2.997 mmol/L), blood aldosterone measured 613 ng/L, and computed tomography urography showed a tumor in the right kidney. Therefore, laparoscopic partial nephrectomy was performed. After surgery, the patient's blood pressure returned to normal, and blood potassium, aldosterone, and renin normalized. Postoperative pathological examination revealed JGCT. After long-term follow-up, the patient became pregnant again 6 mo after surgery. No hypertension occurred during pregnancy, and the patient delivered a healthy female neonate. Patients with pregnancy complicated by JGCT are difficult to diagnose. Herein, we advise surgeons on proper handling of such situations.

JS-NG-10: A RARE CAUSE OF TREATMENT-RESISTANT HYPERTENSION

Objective: To present an educational case report. Design and method: In a 22-year old female arterial hypertension was diagnosed and she was treated to blood pressure target values with a combination of candesartan and lercanidipine. At the age of 27 years she planned a pregnancy, therefore antihypertensive treatment was switched to alpha-methyl-dopa and metoprolol. Blood pressure control was no longer achieved, the patient was symptomatic, mostly headaches. A diagnostic work-up for secondary causes of hypertension was performed. Results: There were no signs of kidney disease, renal artery stenosis was ruled out by color-coded duplex-ultrasound, plasma metanephrines were normal, sleep apnea syndrome and hypercortisolism were clinically very unlikely and not formally ruled out. No signs of hypertensive end-organ damage (left ventricular hypertrophy, microalbuminuria, carotid artery alterations) were detected. The only pathologic finding confirmed was a marked secondary hyperaldosteronism. Plasma renin concentration was 230 pg/ml, plasma aldosterone concentration 508 pg/ml, along with low normal serum potassium (3.5 to 4 mmol/l). Addition of nifedipine and low-dose HCT did not achieve blood pressure control, daytime ABPM mean was 144/102 mmHg, nighttime ABPM mean 127/86 mmHg. Because of suspected missed renal artery stenosis (fibromuscular dysplasia) an MR-angiography of the renal arteries was performed revealing normal renal arteries and normal adrenal glands but a left kidney tumor - not observed in the previous ultrasound examination but confirmed with contrast-enhanced ultrasound. Surgical removal of the tumor was performed. The histology was suggestive for a juxtaglomerular cell tumor (reninoma). After surgery, plasma aldosterone normalized to 57 pg/ml and plasma renin concentrations were low (3.4 pg/ml). Within 3 months after surgery, all antihypertensive medication could be discontinued and home blood pressure measurements averaged 119/78 mmHg. Soon thereafter the patient became pregnant and delivered a healthy girl. There were no pregnancy related complications and the patient remained normotensive. A juxtaglomerular cell tumor represents a rare curable cause of hypertension. The first report dates for 1967, until 2019 only about 100 cases were reported in the literature. It may be suspected that the diagnosis juxtaglomerular cell tumors is missed in many cases since these tumors are not easy to detect in standard diagnostic workup of hypertension and many antihypertensive drugs interfere with plasma renin concentrations.

PS-BPR03-9: A CASE OF RENAL JUXTAGLOMERULAR CELL TUMOR THAT WAS PREOPERATIVELY DIAGNOSED BY SELECTIVE RENAL VENOUS SAMPLING

A 26-year-old woman without a family history of hypertension was referred to our hospital for a further examination of juvenile hypertension. At 25 years of age, she had headaches, and hypertension (210/120 mmHg) was first noted. A diagnostic examination to assess the hypertension was performed and she was hypokalemic with serum K 2.9 mEq/L. Moreover, the plasma renin activity (PRA) and plasma renin concentration (PRC) was markedly elevated (18.7 ng/mL/h and 196.3 pg/mL), and plasma aldosterone concentration (PAC) was also elevated (291 pg/mL). A captopril challenge test showed a mildly increased PRA response (15.5 ng/mL/h to 20.3 ng/mL/h), but MR angiography and renogram showed no findings suggestive of renal vascular hypertension. On the other hand, dynamic contrast-enhanced CT showed a small neoplastic lesion (10 mm in diameter) without enhancement in the early phase, but with slight enhancement in the late phase, on the left renal upper pole. We performed renal vein sampling, but no obvious lateralization in PRA was found at the main trunk level of the left and right renal veins (14.0 vs. 14.3 ng/mL/h). Therefore, we performed more selective sampling of the branches of the left renal vein and found that PRA in the upper pole branch of the left renal vein was approximately 3.7 times higher than in the inferior pole branch, the main trunk of the left and right renal veins, and the inferior vena cava (51.5 ng/mL/h vs. 14.0–15.1 ng/mL/h). Based on these results, we made a preoperative diagnosis that the tumor in the upper pole of the left kidney was a juxtaglomerular cell tumor producing renin excessively and decided to perform partial left nephrectomy. Juxtaglomerular cell tumors (JCT) are very rare diseases that primarily occur in adolescents and young adults. Excessive renin secretion from the tumor causes secondary hypertension, and hypokalemia. It has been reported that renal vein sampling, in addition to CT and MRI scans, is useful for preoperative localization of JCT. However, the usual method of sampling only the main trunk of the renal vein fails to detect lateralization of the PRAs in many cases. In the present case, we were able to identify the localization of the tumor by performing sampling of the branches of the renal vein. We herein report on the usefulness of selective renal vein sampling for the preoperative diagnosis of JCT.

Hypertension in Young Adults: Think Juxtaglomerular Cell Tumor!

Abstract Introduction/Objective Juxtaglomerular cell tumor is a benign, renin-secreting neoplasm. The tumor arises from the juxtaglomerular apparatus cells of the kidney. Because the tumor is hormonally active, patients usually suffer from hypokalemia, hyperaldosteronism, and hypertension. The typical patient population is adolescents and young adults with slight female predominance. Herein, we describe a case of a 19-year-old Asian female with a somewhat atypical presentation. Methods/Case Report A 19-year-old Asian female presented with upper extremity weakness, numbness, and tingling. On physical examination, the only notable finding was hypertension. Extensive work up reveled an aldosterone level of 71 nanograms per deciliter and plasma renin activity of 6.25 nanograms per milliliter per hour. A CT scan of the abdomen revealed a 2.4cm mass in the lower pole of the left kidney. The mass was resected by partial nephrectomy. Sectioning of the specimen revealed a 2.4cm well-circumscribed, encapsulated tumor. On microscopic evaluation, the tumor had glomoid appearance with sheets of uniform, round to polygonal cells with clear to eosinophilic cytoplasm. The stroma was scanty, mitoses were rare, and necrosis was not identified. Immunohistochemical stains showed the tumor cells to be positive for CD117, CD34, Cathepsin K, Synaptophysin, and CD10 and negative for ER, PR, CK7, PAX-8, pancytokeratin, EMA, S100, Melan-A, HMB45, SMA and CAIX. Diagnosis of Juxtaglomerular cell tumor was rendered. The patient was alive and well and without signs of recurrence 14 months after surgery. Results (if a Case Study enter NA) NA. Conclusion This case highlights the importance of a regular physical exam and having a high index of suspicion in patients presenting with unusual complaints.

Immunohistochemical expression of renin and GATA3 help distinguish juxtaglomerular cell tumors from renal glomus tumors

Juxtaglomerular cell tumors and glomus tumors both arise from perivascular mesenchymal cells. Juxtaglomerular cells are specialized renin-secreting myoendocrine cells in the afferent arterioles adjacent to glomeruli, and juxtaglomerular tumors derived from these cells are therefore unique to the kidney. In contrast, glomus tumors have been described at numerous anatomic sites and may show significant morphologic and immunophenotypic overlap with juxtaglomerular tumors when occurring in the kidney. Although ultrastructural studies and immunohistochemistry for renin may distinguish these entities, these diagnostic modalities are often unavailable in routine clinical practice. Herein, we studied the clinicopathologic features of a large series of juxtaglomerular tumors (n=15) and glomus tumors of the kidney (n=9) to identify features helpful in their separation, including immunohistochemistry for smooth muscle actin (SMA), CD34, collagen IV, CD117, GATA3, synaptophysin, and renin. Markers such as SMA (juxtaglomerular tumors: 12/13, 92%; glomus tumors: 9/9, 100%), CD34 (juxtaglomerular tumors: 14/14, 100%; glomus tumors: 7/9, 78%), and collagen IV (juxtaglomerular tumors: 5/6, 83%; glomus tumors: 3/3, 100%) were not helpful in separating these entities. In contrast to prior reports, all juxtaglomerular tumors were CD117 negative (0/12, 0%), as were glomus tumors (0/5, 0%). Our results show that juxtaglomerular tumors have a younger age at presentation (median age: 27 years), female predilection, and frequently exhibit diffuse positivity for renin (10/10, 100%) and GATA3 (7/9, 78%), in contrast to glomus tumors (median age: 51 years; renin: 0/6, 0%; GATA3: 0/6, 0%). These findings may be helpful in distinguishing these tumors when they exhibit significant morphologic overlap.

Renin Production by Juxtaglomerular Cell Tumors and Clear Cell Renal Cell Carcinoma and the Role of Angiotensin Signaling Inhibitors

ObjectiveTo profile juxtaglomerular cell tumors (JXG) and histologic mimics by analyzing renin expression; to identify non-JXG renin-producing tumors in The Cancer Genome Atlas (TCGA) data sets; and to define the prevalence of hypertension (HTN) and patient outcomes with angiotensin signaling inhibitor (ASI) use in tumors of interest. Patients and MethodsThirteen JXGs and 10 glomus tumors (GTs), a histologic mimic, were evaluated for clinicopathologic features; TCGA data were analyzed to identify non-JXG renin-overexpressing tumors. An institutional registry was queried to determine the incidence of HTN, the use of ASIs in hypertensive patients, and the impact of ASIs on outcomes including progression-free survival (PFS) in a tumor type with high renin expression (clear cell renal cell carcinoma [CC-RCC] diagnosed between January 1, 2005, and December 31, 2012). ResultsWe found an association between renin production and HTN in JXG compared with GT. Analysis of TCGA data found that a subset of CC-RCCs overexpress renin relative to 29 other tumor types. Furthermore, analysis of our institutional registry revealed a high prevalence (64%) of HTN among 1203 patients treated with radical or partial nephrectomy for nonmetastatic CC-RCC. On multivariable Cox regression, patients with HTN treated with ASIs (34%) had improved PFS (hazard ratio, 0.76; 95% CI, 0.57 to 1.00; P=.05) compared with patients with HTN not treated with ASIs (30%). ConclusionThe identification of renin expression in a subset of CC-RCC may provide a biologic rationale for the high prevalence of HTN and improved PFS with ASI use in hypertensive patients with nonmetastatic CC-RCC.

Juxtaglomerular cell tumour of the kidney: a rare cause of resistant hypertension.

SummaryJuxtaglomerular cell tumour (JGCT) is an unusually encountered clinical entity. A 33-year-old man with severe long-standing hypertension and hypokalaemia is described. The patient also suffered from polyuria, polydipsia, nocturia and severe headaches. On admission, laboratory investigation revealed hypokalaemia, kaliuresis, high aldosterone and renin levels, and the abdomen CT identified a mass of 4 cm at the right kidney. Kidney function was normal. Following nephrectomy, the histological investigation revealed the presence of a JGCT. Immunostaining was positive for CD34 as well as for smooth muscle actin and vimentin. Following surgery, a marked control of his hypertension with calcium channel blockers and normalization of the serum potassium, renin or aldosterone levels were reached. According to our findings, JGCT could be included in the differential diagnosis of secondary hypertension as it consists of a curable cause. The association of JGCT with hypertension and hypokalaemia focusing on the clinical presentation, diagnostic evaluation and management is herein discussed and a brief review of the existing literature is provided.Learning pointsJuxtaglomerular cell tumours (JGCT), despite their rarity, should be included in the differential diagnosis of secondary hypertension as they consist of a curable cause of hypertension.JGCT could be presented with resistant hypertension along with hypokalaemia, kaliuresis and metabolic alkalosis. Early recognition and management can help to prevent cardiovascular complications.Imaging (enhanced CT scans) may be considered as the primary diagnostic tool for the detection of renal or JGCT.For the confirmation of the diagnosis, a histopathologic examination is needed.

A Case of Asymptomatic Juxtaglomerular Cell Tumor (JGCT)

A Case of Asymptomatic Juxtaglomerular Cell Tumor (JGCT)