Nephrogenic Metaplasia of Urinary Tract in Children

Nephrogenic metaplasia of the urinary tract, originally thought to be a benign tumor with possible malignant potential, is commonly called nephrogenic adenoma. It predominantly affects male adults and is rarely seen in children. In this report 18 pediatric cases are reviewed and some clinical and pathologic parameters are compared with the condition in adults. Male to female ratio is reversed (3. 7:1 in adults and 1:3.5 in children). Recurrences are more common and are more frequently multiple in the pediatric age group. Although no malignant transformation has been reported, prolonged follow-up is recommended since the natural history of this lesion is still uncertain.     

Rare cause of macroscopic hematuria in a pediatric patient: Nephrogenic adenoma of the bladder

Pediatric nephrogenic adenoma (NA) is an uncommon benign metaplastic lesion occurring in the urothelium. Herein we report a case of NA of the urinary bladder in a 14‐year‐old boy. The patient presented with macroscopic hematuria and had a history of ureteral surgery and long‐term smoking. NA should be considered in the differential diagnosis of any urinary tract tumor in the pediatric population.     

Hereditary Nephrogenic Diabetes Insipidus Type-2

Nephrogenic diabetes insipidus (NDI) in a fetus in utero was suspected because of the family history, and evidence of increased amniotic fluid by echosonography. The mother's karyo-type was 46 XX/47 XXX. After birth, the patient was diagnosed as NDI type-2 which is partially resistant to antidiuretic hormone.     

Pediatric Chordoid Glioma withChondroid Metaplasia

Chordoid gliomas are uncommon primary brain tumors that arise in the region of the third ventricle. Reports of this entity to date have been limited to adults. We present a case of a chordoid glioma arising in the hypothalamic/third ventricle region of a 12-year-old male who presented with visual symptoms. The neoplasm consisted of cords and clusters of well-differentiated, spindled-to-rounded cells containing abundant eosinophilic cytoplasm within a prominent mucinous matrix. Unlike other chordoid gliomas, this lesion contained islands and sheets showing cartilaginous differentiation intermixed with the glial component. A graded transition between neoplastic glial and chondroid regions was evident, and cells in both regions were strongly immunoreactive for GFAP and S-100. Cartilaginous metaplasia is infrequent in gliomas, but occurs most often in pediatric neoplasms of the midline such as this chordoid glioma. Thus, chondroid metaplasia represents an unusual histopathologic feature of chordoid glioma—in this case, presenting in a child. Received March 30, 2001; accepted May 31, 2001.     

Nephrogenic Rest Associated with a Mesoblastic Nephroma—What does it Tell Us?

A 3-year-old girl presented with a tumor in the right kidney that was found to be a mesoblastic nephroma on histological examination. In addition, between the tumor and renal parenchyma there was a large perilobar sclerosing nephrogenic rest—a finding that has rarely been reported previously in non-Wilms renal tumors of childhood. We believe this supports the theory that both mesoblastic nephroma and Wilms tumor arise from the developing kidney but the key difference is the time point at which induction of neoplasm occurs.     

Growth Failure in an Infant with Congenital Nephrogenic Diabetes Insipidus During Sodium Restriction

Congenital nephrogenic diabetes insipidus (CNDI) is an inherited disorder characterized by renal tubular insensitivity to antidiuretic hormone, resulting in an inability to concentrate urine. We report on an infant boy with CNDI who showed growth failure during treatment with sodium restriction. At the age of 4 mo, he was diagnosed as having CNDI, judging from fever with hypernatremia (serum Na 153 mEq/L), diluted urine (urine osmolarity 193 mOsm/kg), high antidiuretic hormone (plasma antidiuretic hormone 53 pg/mL), and normal renal function (serum creatinine 0.3 mg/dL). His length and weight were mean +0.4 and –1.1 SD, respectively, at that time. He was treated with sodium restriction (sodium intake; 0.53 mEq/kg/day) using low sodium formula in addition to trichlormethiazide, spironolactone, and mefenamic acid. Growth failure developed: his length and weight were mean –2.4 and –3.3 SD, respectively, at the age of 10 mo. After withdrawal of sodium restriction to 1.5 mEq/kg/day of sodium intake without any change of caloric intake and medication, catch-up growth was observed. At the age of 39 mo, the patient’s height and weight were mean –0.8 and –0.6 SD, respectively. We conclude that excessive sodium restriction can cause growth failure in infants with CNDI.     

A Novel Mutation of the Arginine Vasopressin Receptor 2 Gene in a Patient with Congenital Nephrogenic Diabetes Insipidus

We have identified a novel mutation of the arginine vasopressin receptor 2 (AVPR2) gene in a case of congenital X-linked nephrogenic diabetes insipidus (NDI). The patient was a 2-mo-old Japanese boy with persistent fever and failure to thrive. He was diagnosed as having congenital NDI by clinical and laboratory findings. Molecular analysis demonstrated that he was hemizygous for a G to C transversion in exon 2 of the AVPR2 gene which resulted in a glycine to arginine substitution (G107R) at the 107th codon of the first extracellular loop. His mother was heterozygous for the same mutation. We speculated that the G107R mutation would interfere with the binding capacity of the AVPR2, since G107R is located near F105 and R106, both of which are crucial for ligand binding. In cases of X-linked NDI, mutations in the AVPR2 gene are distributed widely. Thus, DNA analysis throughout the gene is of clinical value for the identification of female carriers, and it also gives precise information for genetic counseling.     

Nephrogenic metaplasia of the ureter

A case of nephrogenic metaplasia of the left ureter occurring in a 7-year-old male child, associated with recurrent urinary infection and previous surgical intervention, is described. This is to our knowledge the third reported case of this entity. Nephrogenic metaplasia involves the transitional epithelium of the urinary tract and results in the formation of structures histologically similar to renal tubules.     

The varied spectrum of nephroblastomatosis,nephrogenic rests,and Wilms tumors: Review of current definitions and challenges of the field

The diagnosis of multiple or diffuse renal lesions in a child is challenging by imaging and/or pathology. Optimal management requires distinguishing benign lesions such as nephrogenic rests from cancerous lesions such as Wilms tumor, but this is often difficult or impossible. This difficulty is compounded by the overlapping nature of our current radiologic and pathologic definitions of lesions along the spectrum of nephrogenic rests/nephroblastomatosis. We provide a review of these issues, as a collaborative effort between the Children's Oncology Group Renal Tumor Committee and International Society of Pediatric Oncology Renal Tumor Study Group. Our aim is to discuss current challenges in diagnosis and management of these renal lesions, encouraging future work toward consensus definitions for research and patient care.     

Expression of Glial Cell Line-Derived Neurotrophic Factor and Neurturin in Mature Kidney,Nephrogenic Rests,and Nephroblastoma: Possible Role as Differentiating Factors

Kidney development involves a series of complex interactions between the ureteric bud and undifferentiated mesenchyme, resulting in the production of the nephron unit. Among locally derived soluble factors, a particular relevance has been recognized to glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) for the mesenchyme-to-epithelial conversion of a metanephron. Nephroblastoma is a developmental tumor of the kidney deriving from metanephric blastema that mimics renal development and may offer an adequate model of human nephrogenesis. We investigated the immunohistochemical expression of GDNF, NTN, and their receptors (GFR1, 2, and 3, and Ret) in normal human kidney and in 42 nephroblastomas, 20 of which were associated with nephrogenic rests (group A) and 22 were not (group B). We compared the immunostaining pattern in group A vs. group B and correlated clinical course with stage, grade, presence of nephrogenic rests, and immunohistochemical findings. GDNF, NTN, and their receptors were expressed in mature kidney and in 67% (GDNF) and 33% (NTN) of tumors, particularly in the epithelial component; precursor lesions were negative. No significant differences of expression were observed between groups A and B tumors. Low stage (P = 0.012), absence of nephrogenic rests (P = 0.016), intense expression of GDNF (P = 0.034), and NTN (P = 0.05) were associated with a more favorable outcome. Besides inductive activity in nephrogenesis, GDNF and NTN may play a role in maintaining differentiation and survival functions in mature kidney and may contribute to induce differentiation of nephroblastoma cells toward the less aggressive epithelial component. The pathway of activation seems to follow an autocrine/paracrine mechanism, as neurotrophic factors, GFR1-2-3 receptors and Ret are coexpressed.     

Retrocaval ureter in children: a report of two cases

Retrocaval ureter is a relatively rare anomaly that usually manifests in the third or fourth decades. Symptoms are due to ureteric obstruction, either extrinsic by the abnormal inferior vena cava (IVC), or intrinsic ureteric hypoplasia. Surgery is needed for symptomatic cases and involves transection and relocation of the ureter anterior to the IVC. We report our experience with two such children who needed surgery because of increasing hydronephrosis and who have done well since.     

兄弟同患遗传性肾性尿崩症 2 例报告并文献复习

目的加强对遗传性肾性尿崩症(CNDI)的认识。方法回顾性分析2例同患CNDI的同胞兄弟的临床资料,并复习相关文献。结果 2例同胞男性患儿,分别为6岁、3岁,均有多饮多尿,持续低比重尿。一代基因测序发现AQP2基因第254位精氨酸突变成组氨酸,为未报道的新型移码突变,导致AQP2蛋白延长。确诊后给予阿米洛利治疗,短期随访尿量减少,无电解质紊乱。结论基因检查可以帮助确诊CNDI,复方阿米洛利治疗有效。     

Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms' tumor

A new classification and terminology is proposed for precursor lesions of Wilms' tumor (WT), based upon morphology and natural history. The generic term nephrogenic rest (NR) is used for all WT precursors. Two major categories of NR are recognized: perilobar (PLNR) and intralobar (ILNR). Nephroblastomatosis signifies the presence of multiple or diffuse NRs. Nephroblastomatosis can be classified into four categories: (a) perilobar (PLNR only); (b) intralobar (ILNR only; (c) combined (PLNR and ILNR); and (d) universal. The individual rests can be subdivided into (a) nascent or dormant NRs; (b) maturing or sclerosing NRs; (c) hyperplastic NRs; and (d) neoplastic NRs. Of 282 evaluable unilateral WT specimens, 28.4% were definitely rest-positive, and an additional 12.4% were probably positive, with equal prevalence of PLNRs and ILNRs. Median age at diagnosis of WT was 36 months with PLNRs, 16 months with ILNRs, and 12 months if both types were present. PLNRs were strongly associated with synchronous bilateral WTs, and ILNRs with metachronous contralateral WTs. ILNRs were associated with aniridia and Drash syndrome, whereas PLNRs were more commonly found with hemihypertrophy and/or Beckwith-Wiedemann syndrome. The delineation of two distinct categories of WT precursors suggests pathogenetic heterogeneity for WTs. The biological and clinical implications of NRs are considered in the context of this classification.     

Hyperplastic perilobar nephroblastomatosis: long-term survival of 52 patients

BACKGROUND: This study provides insight into the clinical behavior, diagnostic complexities, and long-term management of patients with hyperplastic perilobar nephroblastomatosis (HPLN). PROCEDURE: Fifty-two patients with HPLN with available long-term follow-up were retrospectively analyzed for pathologic, radiologic, and clinical features. RESULTS: The mean age at diagnosis was 16 months; the lesions were bilateral in 49 patients. Of 33 patients who initially underwent diagnostic biopsy and adjuvant chemotherapy, 18 (55%) developed Wilms tumor (WT) at a mean of 35 months from diagnosis. Of 16 patients whose initial therapy included nephrectomy and adjuvant therapy, three (19%) developed WT at a mean of 36 months from diagnosis. All three patients who underwent initial diagnostic biopsy and received no adjuvant therapy during their initial course developed WT 4, 4, and 10 months following diagnosis. 24/52 patients developed either a single (13 patients) or multiple (11 patients) WT throughout their course; 8/24 (33%) of WT were anaplastic. The time from initial diagnosis to the development of the last WT ranged from 13 to 116 months (mean 42 months). Three children with HPLN died of WT at 3, 5, and 6 years of age; 2/3 were anaplastic. CONCLUSIONS: HPLN is a self-limited, pre-neoplastic proliferative process associated with a high risk of developing WT. The accurate diagnosis and the choices of therapy during the often-complex course of HPLN depend on the availability and accurate interpretation of a combination of pathologic, radiologic, and clinical information. When such information is appropriately obtained, the long-term survival of patients with HPLN is excellent.     

Ossifying Renal Tumor of Infancy: A Clinicopathologic Study of Nine Cases

We studied nine ossifying renal tumors of infancy (ORTI), including all five previously reported cases. There were eight boys and one girl ranging in age from 6 days to 14 months. Cross hematuria was the presenting sign in all nine patients. Eight tumors arose in the left kidney and six in the upper pole. All seven patients with follow-up information were free of recurrence. All lesions were attached to a renal papilla and presented mainly within the calyceal lumen. Two resembled staghorn calculiclinically. All tumors contained varying proportions of osteoid, osteoblastic cells, and spindle cells. The spindle cell component had features strongly suggesting that they represented hyperplastic intralobar nephrogenic rests (ILNR). The proportion of osteoid and degree of osseous maturation increased with increasing age of the patient. ORTI is a distinctive clinicopathologic entity, possibly representing a distinctive interaction between ILNR in the renal papilla with distal collecting duct or urothelial cells in the developing kidney.     

Nephrogenic adenoma of the bladder: ultrasound demonstration. A case report

A 4-year-old girl developed a space-occupying lesion in the bladder. This was demonstrated by US after resection of a huge ureterocoele and bilateral re-implantation of ureters at 3 months of age and after three episodes of urinary tract infection. The mass developed outside the field of surgery and was removed endoscopically. Histology revealed a nephrogenic adenoma. US findings have not been emphasised previously. US should be useful in the detection of such lesions and for surveillance of recurrence. Received: 21 December 1997 Accepted: 24 September 1998