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Primary lung adenocarcinomas are rare in pediatric patients, and even rarer in patients without precedent malignancy or congenital malformation. Here we present the first reported case of primary lung cribriform adenocarcinoma with squamoid morules in a previously healthy adolescent female. Molecular testing identified CTNNB1 mutation in the tumor and excluded other common mutations in lung adenocarcinoma. Our case suggests molecular alterations to the same signaling pathway can lead to similar histomorphology regardless of the tissue of origin.

Before the prophylactic use of anti-D antibodies in pregnancy, hemolytic anemia of the newborn was the most common cause of hyperbilirubinemia. Nowadays, given the rarity of hemolytic anemia of the newborn, hepatobiliary abnormalities, perinatal infections, and metabolic disorders have become the most common conditions in the differential diagnosis of neonatal cholestasis. Here, we report 3 instances of cholestatic giant cell hepatitis in 3 infants who had Coombs' positive hemolysis due to ABO incompatibility in 1, Rh incompatibility in another, and combined ABO and Rh incompatibility in the third. Although rare, cholestatic neonatal giant cell hepatitis associated with hemolysis still needs to be considered in patients with neonatal cholestasis. A marked elevation of aspartate aminotransferase over alanine aminotransferase can be a helpful clue to an early diagnosis.

Primary lung adenocarcinomas are rare in pediatric patients, and even rarer in patients without precedent malignancy or congenital malformation. Here we present the first reported case of primary lung cribriform adenocarcinoma with squamoid morules in a previously healthy adolescent female. Molecular testing identified

The relevancy of the urinary tract as a source of infection during febrile neutropenia is not known. The authors sought to determine the frequency of urinary tract infections (UTIs) in pediatric cancer patients with febrile neutropenia. Urine was collected from a mid-stream void before the administration of antibiotics. Demographic, clinical, and laboratory data were collected. The frequency of UTI and usefulness of urinalysis and localizing signs in predicting UTI in pediatric cancer patients with fever and neutropenia were determined. Forty-five patients had 58 febrile neutropenic episodes eligible for study participation. No patient presented with localizing signs. The urinalysis was negative in 53 episodes and positive in 5 episodes. Four patients had 5 UTIs. The frequency of UTI was 8.6% (5 of 58 febrile neutropenia episodes). Four patients had bacteremia, none of whom had a UTI. The sensitivity, specificity, and negative predictive value of urinalysis was 40%, 94%, and 94%, respectively, and for localizing signs was undefined, 100%, and 91%, respectively. UTI is as common as bacteremia in the current pediatric cancer patients with fever and neutropenia. Urinalysis and urine culture should be obtained routinely as part of the diagnostic evaluation of patients with fever and neutropenia.

Telomeres of hematopoietic cells shorten with age, possibly contributing to the aging-associated hematopoietic pathology (immunosenescence, malignant transformation). Accelerated telomere shortening is seen with replicative stress, such as during administration of serial chemotherapy cycles for the treatment of childhood cancer. To define the long-term consequences of pediatric cancer treatment on hematopoietic cell telomere length, we undertook a prospective 4-year follow-up study of a 61-patient cohort of pediatric malignancies in a community-based setting. We found that mononuclear cells (MNC) and granulocytes of children with standard-risk acute lymphoblastic leukemia (ALL) suffered minimal telomere shortening throughout therapy (less than 1 kbp; average follow-up, 20 months), while those of children with solid tumors showed greater and more heterogenous telomere attrition (0.5-2.8 kbp, average follow-up, 9 months). In addition, we evaluated the role of telomerase, the enzyme commonly up-regulated in pediatric leukemic and solid tumor cells for telomere length maintenance, as a disease marker. Serial determinations of telomerase in MNC were useful to confirm disease remission in leukemia, but play no role in the follow-up of children with solid tumors.

PCR-based detection of minimal residual disease (MRD) in children with precursor B cell acute lymphoblastic leukemia (pre-B ALL) by amplification of clone-specific antigen gene rearrangements has been labor-intensive. In this study we present a simpler, yet accurate, method to assess and quantitate MRD in pediatric pre-B ALL that utilizes these markers. From the sequence of the immunoglobulin heavy chain (IgH) and T cell receptor (TcR) gene rearrangements characterized at the time of diagnosis or relapse, primers were designed and tested in a clone-specific, single-round PCR assay, then analyzed by fluorescence staining of the PCR products. The most critical step involved an adherence to a new set of guidelines for the design of clone-specific primers. Application of this method to 54 IgH and 13 TcR (nine Vdelta2Ddelta3 and four Ddelta2-Ddelta3) gene rearrangements in 47 patients resulted in an intense band within the region of the predicted molecular weight, confirming the reproducibility of the assay. Quantitative applications of the approach were examined by performing a 10-replicate limiting dilution clone-specific PCR on six diagnostic samples and an asymptotic response model of the Von Krogh form was found to fit the data well. From this model, estimation of leukemic cells of remission bone marrow samples was achieved at a detection sensitivity of 2 x 10(-6). The method is demonstrated on 18 patients whose marrows were prospectively analyzed during therapy. We conclude this methodology is useful in the quick and accurate assessment of MRD in children with pre-B ALL, and could be applied to other DNA quantitation assays.

This prospective, double-blind, randomized study compares the antiemetic efficacy of an equivalent dose of ondansetron administered as a single high dose or as multiple standard doses in pediatric oncology patients. Thirty-one chemotherapy-naive patients were randomized at diagnosis to receive either single high-dose ondansetron (0.6 mg/kg, maximum dose 32 mg) or multiple standard-dose ondansetron (0.15 mg/kg, maximum dose 8 mg, every 4 hr for four doses). Antiemetic efficacy was assessed by an emesis scale described as follows: 1, no nausea or emesis; 2, nauseous but able to eat; 3, nauseous and unable to eat; and 4, emesis. Sixteen patients received high-dose and 15 received standard-dose ondansetron. Patients receiving moderately or severely emetogenic chemotherapy were evenly distributed between the two treatment groups. Eighty-one percent of patients receiving high-dose and 80% receiving standard-dose ondansetron rated 1 or 2 on the emesis scale (p = 0.93). No patient experienced any clinical or laboratory toxicity. Our study suggests that single high-dose ondansetron is as efficacious as the multiple standard-dose regimen and is well tolerated. Its use will facilitate the administration of ondansetron in pediatric patients receiving chemotherapy.

Diamond-Blackfan anemia (DBA) is associated with congenital anomalies especially of the midline. When present, facial anomalies are reminiscent of Treacher-Collins syndrome, and both DBA and Treacher-Collins syndrome are disorders of ribosomal biogenesis. Herein, we describe a female infant with multiple midline defects associated with DBA and reaffirm the absence of RPS-19 mutations in DBA patients with facial anomalies.

Isochromosome 7q is a nonrandom cytogenetic abnormality in Wilms tumor. Two notable cases are described: (1) a case of bilateral Wilms tumor in which only the left-sided tumor contained isochromosome 7q and (2) a case of left-sided Wilms tumor in which the tumor contained isochromosome 7q, in addition to four other chromosomal abnormalities associated with Wilms tumor.

Background Central venous lines are placed in children with acute lymphoblastic leukemia at diagnosis, despite significant cytopenias, to facilitate the administration of chemotherapy and blood sampling. The present study aimed to determine the safety of central line placement in these patients. Methods We reviewed the charts of 115 consecutive patients treated during a 10-year period. Data abstracted comprised age, gender, presenting and preoperative blood counts, type of central line, blood products transfused preoperatively, duration of neutropenia (absolute neutrophil count [ANC]

Purpose: This report describes a female infant with stage 4 multifocal ganglioneuroblastoma with gastric involvement. Patient: The patient had a right cervical tumor, a left posterior mediastinal tumor, bilateral adrenal tumors, and bony and bone marrow metastases. The tumor cells were diploid and lacked N-myc gene amplification. The gastric involvement, which did not produce clinical symptoms, was only detected by meticulous exploration during laparotomy. Results: Our patient achieved only a partial response to alternating cycles of cyclophosphamide, vincristine, and adriamycin; and etoposide and cisplatin. She currently has stable, unresectable disease with elevated catecholamines. Conclusions: Multifocal ganglioneuroblastomas may arise from either neuroblastic rests or aberrant deposits of neuroblasts. The latter mechanism may have accounted for our patient's gastric tumor. Patients with multifocal ganglioneuroblastomas warrant meticulous radiographic and surgical evaluation to completely document the full extent of disease, and to ensure appropriate staging and therapy.

This open-label pilot study was designed (1) to determine the effect of hydroxyurea on the hemoglobin level in children with sickle cell anemia, (2) to evaluate the toxicity of hydroxyurea, and (3) to assess any impact of hydroxyurea on the frequency of vaso-occlusive crises (VOCs).Ten children (group 1) with three or more VOCs of the extremities or two or more VOCs of the lungs (acute chest syndrome) in the preceding 12 months, and five children (group 2) with hemoglobin levels less than 70 gm/L were treated with hydroxyurea in doses of 20 to 35 mg/kg per day. The frequency of VOCs before hydroxyurea therapy was compared with the frequency during therapy, and the peak hemoglobin levels during hydroxyurea therapy were compared with the pretreatment values.One patient in group 1 was removed from the study within 1 month because of nausea. Seven of the remaining nine patients in group 1 had a decrease in the frequency of VOCs. The number of VOCs per patient-year for all 14 patients decreased from 2.5 before hydroxyurea therapy to 0.87 during hydroxyurea therapy, a decrease of 65% (p0.00001). Two of five patients in group 2 had an increase in hemoglobin of 27 gm/L and 34 gm/L over the baseline. The median rise in hemoglobin was 19 gm/L (range, 7 to 37) for all 14 patients. Nine patients are still receiving hydroxyurea for a median period of 23 months (range, 18 to 59).Hydroxyurea decreases the severity of anemia in some patients, and it may decrease the frequency of VOC. Its short-term hematologic toxicity is minimal.

Purpose Iron deficiency anemia (IDA) causes benign intracranial hypertension (BIH). Patients and methods A case of an 11-year-old girl with severe IDA and benign intracranial hypertension is presented. Results Treatment of iron deficiency resulted in the resolution of BIH. Recurrence of BIH is observed with the recurrence of IDA. Chronic intermittent blood loss from the intestinal polyps was the etiology of recurrent IDA. Conclusions A thorough search to determine the etiology of IDA is essential for proper treatment. Although BIH is a rare complication of IDA, its association with IDA should be recognized for prompt treatment before an extensive and costly workup for BIH is done.

Our patient first developed thrombotic thrombocytopenic purpura (TTP) at age 10 years with an initial platelet count of 10,000/microL. She achieved remission with plasmapheresis (PE), but suffered 2 relapses in the next 2 years, each approximately 1 year from PE, with ADAMTS13 levels of

A program was established in which the parents of children with cancer were trained to administer intravenous chemotherapy to the children in their homes. The main objectives of this program (Home Intravenous Chemotherapy by Parents [HICP]) were to improve the quality of life for children with cancer and their parents and to decrease the cost of medical care for these children by decreasing the number of clinic visits and hospital stays intended solely for the administration of chemotherapy. Twenty-four months of experience with this program indicates that with a close communication network and a good working relationship among a home care organization (HCO), the parents of the patient, a pediatric oncology nurse, and an attending pediatric oncologist, many chemotherapeutic agents can be safely administered to these children by their parents in their homes. The patients and their parents are enthusiastic about this program because of the valuable time saved and the increased participation in care. In addition, this program greatly decreased the cost of medical care for these children.

We describe a case of pediatric acute lymphoblastic leukemia (ALL) with trisomy 5 as a sole cytogenetic abnormality. A comparison is made with the two cases of adult acute lymphoblastic leukemia with trisomy 5 in the literature. This rare cytogenetic abnormality may portend an especially poor prognosis in patients with ALL.

Cervical lymphadenitis is a common pediatric finding prompting medical evaluation. The most common etiologies are infectious and reactive. The location of the involved lymph node group may provide clues to the origin of the underlying pathologic process. We describe a 21-month-old boy with metastatic neuroblastoma who presented with classic findings of infectious lymphadenitis. Surgical intervention and careful examination of histopathology led to this unexpected diagnosis.

Background To determine the clinical features and treatment outcomes of infants with immune thrombocytopenic purpura (ITP). Methods Retrospective analysis of 79 infant ITP patients treated from 1987 to 2002. The data abstracted comprised age, gender, clinical features, and treatment outcomes. A score test for the trend in the odds ratios was used to determine the risk of chronic ITP with advancing age. The infants were compared to a group of contemporaneous older children with regard to bleeding severity and incidence of chronic ITP. Results The 34 female and 45 male infants had a median age of 16 months. Seventy-four presented with purpura, four with viral illnesses, and one was asymptomatic. Eight percent had active mucosal bleeding. The median platelet count was 8,000/μl. Forty infants received intravenous immunoglobulin, nine intravenous anti-D immunoglobulin, six steroids, and seven were observed without treatment. Fifty-five (76%) responded to a single course of treatment. Only 9% of infants developed chronic ITP compared to 18% of children between the ages of 25 and 119 months and 47% of children 120 months or older (P

We describe a case of relapsed pediatric pre-B acute lymphoblastic leukemia (ALL) with a simultaneous presentation of an intracerebral lymphoid mass. Cytogenetic, immunophenotypic and molecular analysis (immunoglobulin heavy chain and T-cell receptor gene rearrangements) revealed that the brain neoplasm was distinct from the relapsed leukemia. We discuss the etiology of this extremely rare event, and raise issues about the clonality of lymphoid neoplasms and the behavior of hematopoietic cells within the central nervous system (CNS).

The objective of this study was to determine the clinical and laboratory features of children with severe iron deficiency anemia. The authors retrospectively reviewed the charts of 198 children with iron deficiency anemia to ascertain cases of severe iron deficiency anemia. Forty-two children with severe iron deficient anemia were evaluated. The median age was 21 months (range, 7-240 months) at diagnosis and 27 children were 13-24 months of age. For 35 children the major source of calories was derived from cow's milk. The median hemoglobin was 4.6 g/dL (range, 2.1-6 g/dL) and the median serum ferritin was 5 microg/L (range, 1-11 microg/L). Twenty-nine received oral iron and 13 required parked red blood cell transfusions because of co-morbid cardiorespiratory distress. Severe iron deficiency anemia mostly affects children during their second year of life. Oral iron therapy is sufficient for most children, but packed red blood cell transfusions may be needed.

Hyperdiploidy is useful in defining histologic variants of Wilms tumor and prognosis in other childhood cancers. We describe a case of hyperdiploid favorable histology Wilms tumor (50,XY,+6,+7,+8,+10,+12,-21[2]/51,idem,+9[6]/46,XY[12]) in a 3-year-old boy, and review the literature for other hyperdiploid childhood renal lesions.

Telomerase activity and telomere length in mononuclear cells (MNCs) and granulocytes from peripheral blood (PB) and bone marrow (BM) specimens were studied in pediatric acute leukemia (ALL, n = 15; AML, n = 11) and pediatric solid tumor (ST) patients (n = 9) at diagnosis, during and after chemotherapy. In four ST patients, tumor tissue was also available. For comparative analysis, MNCs from healthy donors (n = 53) were analyzed. Telomerase was evaluated using a modified telomeric repeat amplification protocol (TRAP) assay, and telomere length by terminal restriction fragment (TRF) analysis. At diagnosis, high telomerase activity was detected in MNCs from all leukemia patients, which was similar to the activity from ST biopsy specimens. This exceeded by 10- to 20-fold the activity in PB MNCs from ST patients and healthy donors (P < 0.05). Granulocyte fractions lacked telomerase activity in all groups. BM MNCs in leukemia patients revealed a four-fold higher telomerase activity than PB (P = 0.005). After induction chemotherapy and response to treatment, telomerase activity decreased to borderline or undetectable levels in PB MNCs in leukemia (P < 0.01). Average telomeres in PB MNCs from pediatric patients were significantly longer (n = 25; 10.9 kbp) than telomeres in PB and BM MNCs from adult healthy donors (7.45 kbp) (P < 0.0001). At diagnosis, telomeres were shorter from BM compared to PB specimens in leukemia (P < 0.05), and two peak TRFs were observed corresponding to the malignant and normal cell clones. With the attainment of remission, the lower TRF peak, reflecting the leukemic population, was lost. In leukemia patients, mean TRFs increased on average 2.2 kbp after induction chemotherapy, but decreased thereafter on consolidation and maintenance chemotherapy (1 kbp). This was comparable to an average telomere loss of 1.2 kbp in PB specimens from ST patients after chemotherapy. In all patients, telomere loss in granulocytes as compared to MNCs was more pronounced with 1.8 vs 1 kbp, respectively (P = 0.014). Our results demonstrate that at diagnosis, telomerase was consistently and highly upregulated in BM and PB specimens in leukemia, decreased after induction therapy, and correlated with remission. BM specimens in leukemia had higher telomerase activity, probably due to the greater leukemic burden than in PB. Telomeres were significantly longer in children than in adults, but shortened as a consequence of chemotherapy with repeated cycles of hematopoietic regeneration. In acute leukemia, with the loss of the leukemic burden after induction chemotherapy, longer mean TRFs were found, a reflection of the repopulation with normal cells. Our findings suggest that telomerase activity may be useful in the management of childhood malignancies. The significance of telomere length shortening in pediatric patients undergoing chemotherapy and possible telomere regeneration after myelosuppressive treatment remain to be determined.

BACKGROUND Prenatally diagnosed neuroblastomas have been reported in increasing numbers over the past several years, and there are now a few reviews based on up to 21 cases. The purpose of this article is to review the clinical and biologic features of prenatally diagnosed neuroblastoma based on a review of 55 cases. METHODS A review was conducted of 3 cases seen at the study institution and 52 other cases reported thus far in the literature. RESULTS Prenatal diagnosis was made usually after 32 weeks of gestation. Approximately 93% of the tumors were adrenal in origin, and 44% of these were cystic. Thirty-seven patients (67%) had Stage I disease, 12 (22%) had Stage IV-S disease, and only 3 (5%) had Stage IV disease. The DNA index was favorable (>1) in 14 of 16 patients studied. None of these 16 patients studied had amplification of the N-myc oncogene. Catecholamines were elevated in only 33% of the patients. The liver was the most common site of dissemination, which was observed in 25% of patients; bone involvement was not observed in any patient. Ultrasonography failed to detect existing hepatic metastasis in three patients. Primary surgical resection was performed in 47 patients (85%). Chemotherapy was given to five patients and radiotherapy to three. Of the 50 patients for whom follow-up information was available, 45 (90%) were alive at a range of 2-120 months from diagnosis. CONCLUSIONS Prenatally diagnosed neuroblastomas are predominantly adrenal in origin and frequently cystic. The liver is the most common site of dissemination and bone involvement is notably absent. The vast majority of these infants have a favorable stage of disease (I, II, and IV-S) and favorable biologic features, and consequently have an excellent prognosis. Although surgery alone is curative for most patients, a period of observation may avoid surgery in some individuals who may achieve spontaneous regression. Cancer 1997; 80:304-10. © 1997 American Cancer Society.

Abstract 4464 Background Immune thrombocytopenic purpura (ITP) occurs in children with an estimated incidence of 5/100,000; however, it is not known whether racial disparities in the incidence of pediatric ITP exist. We hypothesize that because petechiae may go unrecognized in black children the observed incidence of ITP in this race may be less. The purpose of this study was to analyze an established pediatric ITP population at New York Medical College in order to assess whether such disparities exist amongst races and to determine the presenting features of ITP in black children. Methods Retrospective chart review of 630 pediatric ITP patients diagnosed and treated at New York Medical College from 1985 to 2009 was performed to determine the incidence in various races and to study the presenting features in black children. The patients' race was determined by review of medical records, physician recollection and when necessary by contacting patients by phone. Observed rates of ITP in various races were compared to expected rates given the incidence of ITP and the area's demographic construct. Census of children younger than 19 years residing in the Hudson Valley (Westchester, Putnam, Dutchess, and Rockland counties and Danbury, Connecticut) was obtained from the United States Census Bureau. We used a χ2 “goodness-of-fit” test to determine whether the sample distribution differed from the population distribution. Results Racial demographics were available for 530 of 630 (84%) ITP patients. The estimated racial demographics of children younger than 19 years residing in the Hudson Valley are as follows: total population, 468,550; 75% Caucasian; 10% Hispanic 10% black; and 5% Asian. Of the 530 identified, 406 (76.6%) were found to be Caucasian, 55 (10%) Hispanic, 36 (7.5%) Black, and 33 (6.2%) Asian. If ITP is detected equally amongst races, one would expect to find 397.5 White patients (observed expected difference [O – E] 8.5 with a residual of 0.426), 53 Hispanic (O - E 2 with a residual of 0.275), 53 black patients (O – E -17 with a residual of -2.335), and 26 Asian (O – E 6.5 with a residual of 1.263). The distribution of our sample over race groups compared with the distribution of the population over race groups had a p-value of 0.063 with the largest contribution due to under-representation of black children in our sample. Of the 36 black children with ITP 18 (50%) were found to present with bruising/petechiae, 4 (11%) presented with a combination of wet purpura and bruising/petechiae, 3 (8%) presented with wet purpura alone, and 11 (31%) were asymptomatic. Conclusion The incidence of ITP in black children may be less than in Caucasian, Hispanic, and Asian children. Disclosures: No relevant conflicts of interest to declare.

Chyloperitoneum is an extremely rare complication of abdominal surgery in children and a combined occurrence of chylothorax and chyloperitoneum after abdominal surgery has never been reported in children. Chylous ascites usually occurs as a result of operative trauma to the thoracic duct, cisterna chyli, or its tributaries. About one third of all patients with chylous ascites after retroperitoneal lymph node dissection also develop secondary chylothorax. Diaphragmatic defects have been shown to be responsible for the occurrence of chylothorax secondary to chyloperitoneum. Congenital diaphragmatic weakness may result in evagination of the peritoneum causing diaphragmatic blebs, the rupture of which results in the movement of the peritoneal fluid into the pleural cavity. In the authors' patient, the rent in the diaphragm that occurred during surgery was probably responsible for the chylothorax. The role of chemotherapy, if any, in the pathophysiology of this complication is unknown. Total parenteral nutrition (TPN) is a simple and effective treatment for postoperative chylous effusions. Surgical treatments such as abdominal exploration for the repair of leaking lymphatics and peritoneovenous shunt should be reserved for patients who fail TPN.