Leukemia kidney infiltration can cause secondary polycythemia by activating hypoxia-inducible factor (HIF) pathway

Secondary polycythemia with increased production of erythropoietin (EPO) is known to occur in kidney diseases such as hydronephrosis and cystic disease, but the mechanism remains unclear. We report an 18-year-old female with isolated renal relapse of acute lymphoblastic leukemia accompanied by polycythemia. At the relapse, she presented with bilateral nephromegaly, mild renal dysfunction, and erythrocytosis with increased serum EPO levels up to 52.1 mIU/mL (9.1–32.8). Renal biopsy demonstrated diffuse lymphoblastic infiltration. The expression of hypoxia-inducible factor (HIF)-1α, which is undetectable in normal kidney, was observed in the renal tubule epithelium compressed by lymphoblastic cells. These findings suggest that erythrocytosis was caused by renal ischemia due to leukemic infiltration. Polycythemia probably became apparent because of the lack of leukemic involvement of the bone marrow. With chemotherapy, the serum EPO level rapidly decreased to normal range accompanied by the normalization of kidney size and function. Renal leukemic infiltration may enhance EPO production, although not recognized in the majority of cases because of bone marrow involvement. C onclusion: Our case has clarified the mechanism of previously reported polycythemia associated with renal diseases as renal ischemia. Furthermore, we have added renal ischemia resulting from tumor infiltration to the list of causes of secondary polycythemia.     

Hyperuricemia in an infant with Taussig-Bing anomaly and interruption of the aortic arch

Summary Hyperuricemia is commonly recognized in adolescents and adults with cyanotic congenital heart disease. We report a case of a male infant with hyperuricemia, Taussig-Bing anomaly, and interruption of the aortic arch. The patient underwent correction of interrupted aortic arch and pulmonary arterial banding at the age of 7 days. Hyperuricemia appeared when he was 2 months old (max 17.7 mg/dl) and persisted until he underwent a Jatene operation at the age of 10 months. The hyperuricemia improved gradually after the disappearance of hypoxia and polycythemia. The laboratory findings suggest that hyperuricemia can result from uric acid overproduction due to secondary polycythemia, impairment of uric acid excretion by the kidney, or the acceleration of anaerobic metabolism. Allopurinol and benzbromarone together were partially effective treatments for hyperuricemia in this patient with cyanotic congenital heart disease.     

Metanephric adenoma: a rare differential diagnosis of renal tumor in children

Metanephric adenoma is an extremely rare tumor of the kidney. The clinical and anatomic characteristics are not yet well defined, but it is currently considered to be a benign tumor with a good prognosis, although recently two metastatic cases have been reported. Around 50% of cases are incidental findings, and symptoms include polycythemia, abdominal pain, hematuria and palpable mass. The morphological characteristics are similar to those of Wilms' tumor, suggesting a common embryological precursor. We present here the youngest girl yet to be reported with a diagnosis of metanephric adenoma.     

Polycythemia and adrenal cortex tumor in children: a case report and literature review

Brazil has the world's highest incidence of adrenal cortex tumor in childhood, mainly in Parana and Sao Paulo states. The diagnosis in children is done by the signs and symptoms secondary to the production of adrenal cortex hormones. The occurrence of polycythemia in patients with adrenal cancer is very rare, especially in children. The authors describe a case of adrenal cortex tumor in a child diagnosed during investigation of polycythemia. In the case described, the polycythemia was justified by increased production of erythropoietin.     

Metanephric adenoma of the kidney: a case report

Metanephric adenoma (MA) of the kidney is an uncommon benign epithelial tumor of the kidney that presents at any age. The histology of the lesion is well established, but the imaging findings have been described in only a few cases. We report the sonographic and computed tomographic appearance of MA in a 9-year-old girl to increase awareness among radiologists of this entity. Its recognition may facilitate nephron-sparing surgery. Received: 1 April 1998 Accepted: 14 July 1998     

Mevalonic aciduria: Does stem cell transplant fully cure disease?

MA is a rare, autosomal recessive disorder characterized by episodes of inflammation and periodic fevers. In its most severe form, it can result in facial dysmorphism, growth inhibition, ataxia, liver dysfunction, intellectual disability, and at times can be fatal. A number of case reports exist stating that SCT is curative in these patients. We present the case of a patient diagnosed with MA at birth, who underwent SCT at the age of 14 months with intent to cure. She achieved complete engraftment and urine mevalonate became undetectable. However, 18 months following transplant, she developed frequent episodes of fevers, rashes, arthritis, and a rising urinary mevalonate. She was subsequently diagnosed with relapse. She now requires treatment with steroids and canakinumab to manage her disease. This case is the first report of disease relapse following transplant for MA. It runs contrary to prior reports that SCT is fully curative of MA and suggests that transplant may instead provide a means of decreasing disease severity without entirely eradicating the condition.     

Imaging and spectroscopic findings in meningioangiomatosis

Meningioangiomatosis (MA) is an uncommon brain tumor. The role of imaging techniques is underscored in cases where the tumor location makes resection (or even biopsy) dangerous. We report the case of a child with an MA tumor located deep in the right sylvian fissure. A computed tomography (CT) scan showed calcifications in a highly vascular lesion with surrounding edema. Magnetic resonance spectroscopy (MRS) showed a distinct choline (Cho) peak, which usually suggests a proliferating tumor. Fluorodeoxyglucose positron emission tomography (FDG‐PET) showed the lesion lacked hypermetabolic features. These radiological features should put MA in the differential diagnosis. Pediatr Blood Cancer 2009;53:672–674. © 2009 Wiley‐Liss, Inc.     

Neonatal polycythemia in appropriately grown infants of hypertensive mothers

Neonatal polycythemia is a frequent finding after pregnancies complicated by diabetes and by maternal hypertension with intrauterine growth retardation (IUGR). It is still unclear if the association of polycythemia with hypertension is the result of IUGR or of hypertension per se. To establish the incidence of neonatal polycythemia in populations at risk, we analyzed the results of hematocrit values obtained from 1592 neonates born consecutively at the Hospital de Clinicas, Buenos Aires. Capillary hematocrit values were obtained by heel stick before 6 h of age. When the values were 65% or greater, new samples were obtained from an antecubital vein. The risk of polycythemia in appropriately grown infants of hypertensive mothers was 12.6-fold greater than the risk in the general population. These data show that maternal hypertension poses a significant risk for polycythemia, regardless of fetal growth. We suggest that, to prevent possible sequela, hematocrit is measured routinely in all infants of hypertensive mothers for prompt diagnosis and treatment.     

Polycythemia: A Review Article and Case Report of Erythrocytosis Secondary to Wilms' Tumor

We describe a child with Wilms' tumor whose only finding at presentation was polycythemia. A review of the mechanism of erythropoiesis regulation as well as the differential diagnosis, work-up, and management of polycythemia in children is presented. Our report emphasizes the need for a thorough evaluation of children who present with polycythemia.     

Congestive heart failure as an initial manifestation of reninoma

Reninoma or juxtaglomerular cell tumor (JCT) of the kidney is a rare but curable cause of severe hypertension. We report a case of reninoma in an 18-year-old woman. Interestingly, she initially presented with dilated cardiomyopathy, without any relevant history or signs of hypertension. Malignant hypertension, one of the cardinal signs of JCT, did not become apparent in the patient until several months later. Following a thorough evaluation, we detected a small mass in the left renal cortex as well as elevated plasma renin activity, which suggested the presence of a renin-producing tumor in the kidney. The patient's blood pressure and plasma renin activity rapidly declined after a successful laparoscopic partial nephrectomy. We postulate that hyperreninemic-hyperaldosteronism followed by fluid retention caused a sudden severe increase in ventricular afterload and subsequent congestive heart failure in this patient.     

Papillary renal cell carcinoma in a child.

AIM: To report a case of papillary renal cell carcinoma in a pediatric patient. METHOD: A seven-year-old boy complained of hematuria for one year. CT scan showed a mass in the middle zone of the right kidney. Radical nephrectomy was performed without incident. RESULT: Histology of the specimen showed papillary renal cell carcinoma. As the tumor was stage one, no chemotherapy was offered. At follow-up after 6 months the child was without recurrence or metastases. CONCLUSIONS: Papillary renal cell carcinoma is an uncommon kidney tumor in children and in its early stages it can be cured by nephrectomy alone.     

Billateral Polycystic Kidneys in a Girl with WAGR Syndrome

The WAGR contiguous gene deletion syndrome is a combination of Wilms tumor, aniridia, genito-urinary abnormalities, and mental retardation. An 8.5-year-old girl was initially investigated at the age of 18 months for congenital bilateral aniridia, cataracts, glaucoma and epicantus. The ultrasound (US) scan showed polycystic kidney disease. FISH study revealed deletion of the WT1 and PAX6 gene in the 11p13 WAGR region. Forty days after the first kidney US, the second US revealed a 3 cm tumor in the right kidney: a Wilms tumour, treated successfully with the Wilm’s tumor protocol. The authors conclude that the identification of the deletions in the WAGR region in patients with aniridia should definitely be done. In addition, Wilms tumor can have a very rapid growth, which, per se requires frequent and careful ultrasound kidney controls. Polycystic kidneys can be part of the WAGR presentation.     

Rare localization of extrarenal nephroblastoma in 1-month-old female infant

Extrarenal occurrence of Wilms' tumor is exceptional and the diagnosis is almost always made after surgery. The exact mechanism whereby a Wilms' tumor occurs in extrarenal tissue is unknown. The tumor is most commonly located in the retroperitoneum or inguinal region. Localization in subcutaneous tissue is extremely rare. In this paper, the case of a 1-month-old female infant with an extrarenal Wilms' tumor located in the lumbosacral region is presented. Surgical excision is the treatment of choice, and the same general therapeutic rules should be followed as when the kidney is affected.     

Risk markers of future microalbuminuria and hypertension based on clinical and morphological parameters in young type 1 diabetes patients

Perrin NESS, Torbjörnsdotter T, Jaremko GA, Berg UB. Risk markers of future microalbuminuria and hypertension based on clinical and morphological parameters in young type 1 diabetes patients. Background: Nephropathy is a severe complication of type 1 diabetes and develops in 30% of patients. Currently, it is not possible to identify young patients at risk prior to the development of microalbuminuria (MA) and/or hypertension (HT). Objective: To study predictors of MA and/or HT in young normoalbuminuric (NA) patients with type 1 diabetes. Subjects and methods: Forty‐six NA and normotensive (NT) type 1 diabetes patients, regularly followed since onset with checks on metabolic control, kidney function, and MA, were investigated with kidney biopsies and 24‐h ambulatory blood pressure measurements (ABPMs) after 10.6 yr of diabetes. The patients were followed another six and a half years with regard to the development of MA and HT. Results: Fifteen patients developed MA and/or HT during follow‐up. The strongest risk markers were poor metabolic control after puberty, high day‐time systolic blood pressure (BP), and increased BMT at 10 yr, which explained 62% of the outcome for MA and/or HT at 17 yr duration with 77% sensitivity and 65% specificity. The threshold values were long‐term postpubertal HbA_1c > 8.2%, day‐time systolic BP > 130 mmHg, and BMT > 490 nm/1.73 m². Conclusions: Normoalbuminuric and NT patients at risk of developing MA and HT could be identified and might benefit from an early start of antihypertensive therapy and improvement of metabolic control.     

Rhabdoid Tumor of the Kidney Is a Component of the Rhabdoid Predisposition Syndrome

The rhabdoid predisposition syndrome (RPS) is characterized by pedigrees in which two or more individuals carry germline mutations of the hSNF5/INI1 tumor suppressor gene. The tumors associated with the syndrome include atypical teratoid/rhabdoid tumor (AT/RT), choroid plexus carcinoma, medulloblastoma, and extrarenal rhabdoid tumor. Rhabdoid tumor of the kidney (RTK) has not been described as part of the RPS. We report a case of a 7-month-old boy with RTK whose sister had a malignant cerebellar tumor followed by a malignant lung and pleural tumor of childhood with typical rhabdoid histology. Molecular genetic analysis of the RTK and tissue from the pleural tumor revealed in both cases identical nonsense mutations of the hSNF5/INI1 gene on chromosome 22q11.2, where thymidine was substituted for cytosine in base 472. The proband had an identical germline mutation. This is the fifth genetically analyzed RPS pedigree and the first to include an RTK.     

Metachronous bilateral Wilms' tumor

Wilms' tumor occurs in 5-10 % of all cases of nephroblastoma. The metachronous form represents 2-3 % of cases. Most (96.2 %) metachronous tumors appear within the first 5 years of the primary tumor. Associated malformations are more common in bilateral cases. Metachronous tumors are a therapeutic challenge. We describe the case of an 11-year-old girl with left hemihypertrophy. The diagnosis was metachronous relapse of Wilms' tumor 7 years after the first diagnosis. The patient received five courses of preoperative chemotherapy and tumorectomy was performed. Because of post-surgical complications, nephrectomy was performed on her only kidney. Since she is anephric, the patient is in chronic renal failure and is dependent on dialysis. Treatment with carboplatin and etoposide was continued after surgery and the patient is currently in complete remission. The appearance of a metachronous Wilms' tumor 5 years after that of the primary tumor is rare. When a contralateral tumour develops, chemotherapy must be given until the size of the tumor is reduced in order to preserve renal function and avoid dialysis. In patients with chronic renal failure caused by bilateral nephrectomy, ongoing treatment with dialysis support can be achieved through the choice of effective drugs and knowledge of their pharmacokinetics and pharmacodynamics.     

NONFUNCTIONING ADRENOCORTICAL CARCINOMA IN A CHILD

Pediatric nonfunctioning adrenocortical carcinoma is a very rare tumor. A 4-year-old girl was admitted complaining of abdominal pain. Physical examination revealed an abdominal mass. There were no clinical or laboratory signs of hormonal abnormality. Abdominal ultrasonography revealed a polylobular mass. Intravenous pyelography showed marked compression of the kidney by a tumor. The tumor was excised together with the right kidney. The histopathological diagnosis was adrenocortical carcinoma. Although there is a greater incidence of germ line p53 mutations with adrenocortical carcinoma, the tumor suppressor gene p53 was not mutated in our case. The girl died 2 months after surgery from complications of chemotherapy.     

Partial nephrectomy in a cystic partially differentiated nephroblastoma

Cystic partially differentiated nephroblastoma (CPDN) is a rare neoplastic disorder consisting of a well-demarcated cystic lesion of the kidney where blasternal or other embryonic cells are present in the septa of the cysts. Magnetic resonance imaging can detect the cystic character of the lesion and will produce imaging features that are highly suggestive of either CPDN or cystic nephroma (CN) (synonym: multilocular cyst of the kidney), a benign entity. Although malignant potential exists in CPDN, all cases reported to date have had a favorable prognosis after surgery alone. Partial nephrectomy is considered safe, and the treatment of choice in the newborn period. We report a case of CPDN in a newborn that was successfully treated with partial nephrectomy. More than five years after nephron sparing surgery, the involved kidney shows normal anatomical structure except for a diminished upper pole, no evidence of tumor recurrence and good renal function. Med. Pediatr. Oncol. 28:416–419, 1997. © 1997 Wiley-Liss, Inc.     

Congenital pancreatoblastoma in Beckwith-Wiedemann syndrome: an emerging association

We present a male newborn (weight 4000 g) who died at age 12 days with a clinical history of persistent hypoglycemia and polycythemia. Clinical examination disclosed somatic hemihypertrophy (left side), a large umbilical hernia, macroglossia, and an intraabdominal tumor, consistent with the diagnosis of Beckwith-Wiedemann syndrome (EMG syndrome) and hemihypertrophy. Necropsy findings included visceromegaly (left kidney and adrenal), cytomegaly of the fetal cortex and nodular arrangement of both adrenals, diffuse nesidioblastosis and islet cell hyperplasia of the pancreas, and persistent glomerulogenesis. The tumor was a cystic pancreatoblastoma attached to the anterior surface of the pancreas. Three other examples of this association, congenital pancreatoblastoma and Beckwith-Wiedemann syndrome, all in males, are on record in the literature, indicating a strong relationship between both conditions.     

Congenital Pancreatoblastoma in Beckwith Wiedemann Syndrome

We present a male newborn (weight 4000 g) who died at age 12 days with a clinical history of persistent hypoglycemia and polycythemia. Clinical examination disclosed somatic hemihypertrophy (left side), a large unbilical hernia, macroglossia, and an intraabdominal tumor, consistent with the diagnosis of Beckwith-Wiedemann syndrome (EMG syndrome) and hemihypertrophy. Necropsy findings included visceromegaly (left kidney and adrenal), cytomegaly of the fetal cortex and nodular arrangement of both adrenals, diffuse nesidioblastosis and islet cell hyperplasia of the pancreas, and persistent glomerulogenesis. The tumor was a cystic pancreatoblastoma attached to the anterior surface of the pancreas. Three other examples of this association, congenital pancreatoblastoma and Beckwith-Wiedemann syndrome, all in males, are on record in the literature, indicating a strong relationship between both conditions.