Soft tissue sarcomas and central nervous system tumors in children with neurofibromatosis type 1.

OBJECTS: We aim to evaluate the characteristics of pediatric patients with neurofibromatosis type 1 (NF1) who developed soft tissue sarcomas (STSs) and central nervous system (CNS) tumors that have been followed up in our center. MATERIALS AND METHODS: Medical records of children with NF1 were retrospectively analyzed. RESULTS: There were 78 patients who met at least two diagnostic criteria for NF1. The median age of patients was 10 years (0.5-18), and M/F ratio was 1.3. The prevalance of the optic glioma was 11.5% (n = 9), and one patient with optic glioma also had cystic astrocytoma, one patient had brain stem tumor, and one patient had a CNS tumor (without histopathologic diagnosis). Seven of nine children were ≥ 7 years old at the time of the diagnosis of optic glioma. Visual impairment developed in four patients, and two of them were treated with radiotherapy solely on the basis of evidence of clinical and radiological progression of the tumors. Four patients developed STSs. Two of them had malignant peripheral nerve sheath tumors (MPNST), and the remaining two had bladder rhabdomyosarcoma. Three of the four patients with STSs died with progressive disease. CONCLUSION: The clinical course of malignancy in NF1 is often different from that of similar tumor types in the general population. Careful follow-up in patients with NF1 is required to enable the early diagnosis of malignancies, and the developments of new targeted therapies are needed for improvement of the outcome for patients of this group, especially with MPNST.

Atypical teratoid/rhabdoid tumor in an infant conceived by in vitro fertilization.

BACKGROUND: Atypical teratoid/rhabdoid tumor (ATsRT) is a rare tumor and extremely aggressive embryonal neoplasm of the central nervous system. Brain tumors in infant are suggestive of some oncogenic prenatal factors. CASE PRESENTATION: We report on a case of ATRT in a 4-month-old infant conceived by in vitro fertilization (IVF). Some previous reports have raised a question about the possible relation between IVF and childhood cancer, particularly embryonal tumors. CONCLUSION: Report of such cases may provide some evidence to identify if there is a real association between congenital tumors and IVF.

Aneurysmal bone cyst of rib presenting as a huge chest wall mass.

Aneurysmal bone cyst is a rare benign tumor of the bone that can be difficult to distinguish from malignant tumors, especially when it presents in an unusual location. Herein, we report a six-year-old girl with a primary aneurysmal bone cyst in an uncommon location. It originated from the 4th rib and she presented with a huge chest wall mass. Despite the large size of the cyst, the only symptom was persistent cough. She was successfully treated with total excision of tumor without any complication. The patient has been followed up for 56 months without any recurrence.

Delayed renal excretion of methotrexate after a severe anaphylactic reaction to methotrexate in a child with osteosarcoma.

Although methotrexate is an agent widely used in the practice of pediatric oncology, allergic reactions to methotrexate are most unusual. Most of these reactions typically occur after repeated administration. Here, we report a severe anaphylactoid reaction to the first dose of high-dose methotrexate infusion in a child with osteosarcoma who has also experienced a delayed excretion of methotrexate. Clinicians must be aware of the possibility of a systemic, near-fatal anaphylactic reactions with methotrexate and patients who experience severe anaphylactic reactions should be followed carefully because of the possibility of delayed methotrexate excretion.

The incidence of congenital malformations in children with cancer.

We evaluated the incidence of congenital malformations in 566 children (median age: 8, M:F 1.3) with lymphomas and solid tumors using patient records. In this study, 12.7% of children either had a congenital malformation (7.8%) or a birthmark (4.9%). The incidence of patients with a childhood cancer syndrome was 3% and these cases developed typical tumors. The rate of consanguineous marriages was 12.6%, and family history of cancer was positive in 31.2%. Median age at cancer diagnosis, gender, maternal age, history of stillbirth and missed abortion, consanguinity of parents, and family history of cancer were not significantly different in cases with and without a congenital malformation. The most frequent cancers were central nervous system tumors and lymphomas. No remarkable association between a particular anomaly and a specific cancer type could be shown. The high incidence of congenital anomalies in this study may stimulate future large cohort studies in our country.

Paravertebral malignant tumors of childhood: analysis of 28 pediatric patients.

PURPOSE: To evaluate the clinical features and treatment results of the primary paravertebral malignant tumors (PMTs) in our department. METHODS: Medical records of 28 children with primary PMTs treated between 1988-2007 were analyzed retrospectively. RESULTS: Primary PMTs constituted 4.8% of the cancer cases in our department. Tumor diagnoses were mostly neuroblastoma (46.4%) and soft tissue sarcomas (35.7%). These cases presented with pain (64.3%), motor dysfunction (42.8%), sphincter dysfunction (35.7%), palpable mass (32.1%), and sensory deficits (7.1%). All tumors were extradural. Physical examination revealed motor deficits (53.6%), deep tendon reflex alterations (53.6%), sphincter dysfunction (35.7%), pathologic reflexes (25%), abnormal cutaneous reflexes (25%), and sensory deficits (17.8%). Sixteen had cord compression (CC; 13 clinical, three radiological CC). Eleven of them presented with advanced disease. Seven were managed by surgical departments by primary surgery (three unresponsive). Others were managed by pediatric oncology: five with corticosteroids+/-chemotherapy (one unresponsive), one with radiotherapy (RT), and two with surgery for the clinical CC. Surgery was tumor excision in nine, laminectomy in nine, laminotomy in one, and delayed surgery after chemotherapy in two cases. In chemotherapy and surgery groups, there were neurologic sequela associated with the advanced disease at diagnosis in 38% and 37%, respectively. At 3-year median follow-up, nine patients died, 17 are alive (four with neurologic sequela), and two are lost of follow-up. CONCLUSION: Majority of cases presented with advanced disease. Late referral is the major cause of morbidity and mortality. The CC caused by PMTs should be initially managed with corticosteroids +/- chemotherapy to avoid the adverse late effects of RT and surgery.

Stromal-predominant mesenchymal hamartoma of the liver with elevated serum alpha-fetoprotein level.

Mesenchymal hamartoma of the liver (MHL) is an uncommon, benign, tumor-like lesion and is usually diagnosed in the first 2 years of life. Its pathogenesis remains unclear. Treatment of choice is radical excision. The authors report a case of solid stromal predominant MHL in a 12-month-old male infant who also had an elevated serum alpha-fetoprotein level. He also had hypospadias, which might represent a spectrum of developmental anomalies. It usually presents as an asymptomatic mass, however, as in the reported case, it may cause several complications due to the compression of surrounding structures. He was successfully treated with total excision of the pedunculated large tumor without any complication.

Unilateral juvenile (virginal) hypertrophy of the breast.

Juvenile hypertrophy of the breast (JHB) is an uncommon, benign disorder and typically occurs in peri-pubertal females. The etiology ofJHB is uncertain. It may represent an end-organ hypersensitivity of the breast to normal levels of sex steroids. Clinically, it is characterized by rapid enlargement of breasts, either unilateral or bilateral. The definitive diagnosis is made by histopathologic examination. Treatment recommendations include surgery and hormonal therapy, although hormonal manipulation is still controversial in pediatric patients. Here we report a 13-year-old girl with unilateral JHB who did not require surgery or medical treatment.

Pilomatricoma in children: a frequently misdiagnosed superficial tumor.

Pilomatricomas are the most common superficial tumors in children, but they are frequently misdiagnosed preoperatively. There are some characteristic features of pilomatricomas that can help clinicians differentiate it from other tumors. The authors report 3 children with head and neck pilomatricomas, one with multiple tumors. They emphasize some clinical features that may help in differential diagnosis to avoid unnecessary investigations before surgical removal.

Phyllodes tumor of the breast in an adolescent girl.

Phyllodes tumor (PT) is an uncommon tumor in adolescent girls and young women. A case of PT in a 14-year-old girl is reported. The clinical examination showed a painless tumor that had grown during 10 months. Total excision of the mass with wide margin was performed. The diagnosis, behavior, and treatment of this rare tumor are discussed.

Veno-occlusive disease in a child with rhabdomyosarcoma after conventional chemotherapy: report of a case and review of the literature.

Although veno-occlusive disease of the liver is a well-known complication of high-dose chemotherapy and bone marrow transplantation, it has rarely been observed in children who receive conventional chemotherapy. Most cases in the literature consists of children with Wilms tumor. It has been very uncommon in rhabdomyosarcoma patients until recently, although they commonly receive similar anticancer agents. Here the authors report a 2-year-old boy with rhabdomyosarcoma who developed veno-occlusive disease while receiving VAC (vincristine, actinomycin D, cyclophosphamide) chemotherapy regimen according to the IRS-IV protocol. The patient gradually recovered during 2 weeks with supportive treatment only.

Catheter-associated recurrent intracardiac thrombosis and factor V Leiden mutation in a child with non-Hodgkin's lymphoma.

Patients with cancer have an increased risk for thromboembolism, which might be related to several factors including central venous catheters and chemotherapeutics. Congenital prothrombotic risk factors might also contribute to thrombotic events. In this report, we present a catheter-related recurrent intracardiac thrombosis in a boy with non-Hodgkin's lymphoma and factor V Leiden mutation. Screening for factor V Leiden mutation in children with cancer and recurrent thrombotic events is recommended. Periodic echocardiography may be considered for a group of patients if the catheter tip is in the right atrium and therapy includes L-asparaginase and corticosteroids.

Analysis of 136 febrile neutropenic episodes in children with cancer: evaluation of treatment effectiveness and cost.

In this study, 136 febrile neutropenic episodes were overviewed retrospectively. Factors affecting treatment success and cost were analyzed. Twenty percent of the episodes were microbiologically documented and 51 % of the bacterial isolates were gram negatives. The most commonly used empirical therapies in febrile episodes were the combination of two drugs (58.0%), monotherapy (14.8%), and antibiotics plus fluconazole (20.6 %). In lymphoproliferative tumors duration of fever and discharge from the hospital were longer Administration of the hematopoietic growth factors shortened neither the duration of neutropenia nor fever and hospitalization. Treatment costs were higher in lymphoproliferative tumors, in bacteremia, and in episodes where glycopeptides, antifungal drugs, and hematopoietic growth factors were used. In conclusion, duration of neutropenia was a significant independent predictive factor for duration of fever In the lymphoproliferative tumors, duration of fever was longer and cost of treatment was more than in the solid tumors.

Prognostic significance of anaplasia and angiogenesis in childhood medulloblastoma: a pediatric oncology group study.

The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.

MLL-AF4 gene rearrangement in a child with Epstein-Barr virus-related posttransplant B-cell lymphoma.

Recipients of solid organ allografts are known to be at increased risk of developing Epstein-Barr virus-related posttransplant lymphoproliferative diseases. A 28-month-old boy who had received a heterotopic liver transplant presented with lymphadenopathy in the abdomen, multiple nodules in the liver, and bilateral renal infiltration 19 months after transplantation. He was diagnosed with a Burkitt-like lymphoma based on bone marrow examination and the finding that the blastic cells in bone marrow were EBER-1 positive. Cytogenetic analysis of the bone marrow cells showed an MLL-AF4 rearrangement. He was treated with a combined chemotherapy regimen. He has been in continuous complete remission for 15 months now.

Surveillance imaging and cost effectivity in pediatric brain tumors.

OBJECTIVE: The purpose of this study was to determine the role and cost effectiveness of surveillance imaging at the management of pediatric brain tumors. MATERIALS AND METHODS: In this study, the imaging and clinical finding of 59 patients who had been diagnosed and followed by the Dokuz Eylul University Pediatric Oncology Group as primary central nervous system tumors between 1988 and 2000 were retrospectively evaluated. RESULTS: We found that the 87.5% of tumor recurrence occurs within 21 months and 93.8% occur within 29 months. About 25% of these recurrences were asymptomatic and these (n=16) could be detected by surveillance imaging with a frequency rate of 1.59%. The cost of imaging for our patients was calculated to be 788 US$ (mean) for a follow-up period of 24 months which would have been 739 US$ if a standard surveillance protocol would have been followed. CONCLUSION: Surveillance imaging is an effective follow-up in detecting symptomatic recurrence in pediatric brain tumors.

Experience of the Izmir Pediatric Oncology Group on Neuroblastoma: IPOG-NBL-92 Protocol.

This multicentric study aimed to bring neuroblastoma patients together under IPOG-NBL-92 protocol and evaluate the results within the period between 1992 and 2001 in Izmir. Sixty-seven neuroblastoma patients from 4 pediatric oncology centers in Izmir were included in the study. IPOG-NBL-92 protocol modified from German Pediatric Oncology (GPO)-NB-90 protocol was applied: Patients in stage 1 received only surgery, while surgery plus 4 chemotherapy courses (cisplatin, vincristine, ifosfamide) were given in stage 2 and surgery plus 6 chemotherapy courses (cisplatin, vincristine, ifosfamide, epirubicin, cyclophosphamide) were given in stages 3 and 4 patients. In patients who were kept in complete remission (CR), a maintenance therapy of one year was applied. Radiotherapy was given to the primary site following induction chemotherapy plus surgery in stages 3 and 4 patients with partial remission (PR). The stages of the patients were as follows: 5% in stage 1, 39% in stage 3, 49% in stage 4, and 7% in stage 4S. Primary tumor site was abdomen in 88% of cases. CR rates were as 100% in stage 1, 76% in stage 3, 35% in stage 4, and 75% in stage 4S. Relapse was observed in 32% of patients in a median of 19 months. The median follow-up time for survivors was 33 (17-102) months. Five-year OS rate was 31% and the EFS rate was 30% in all patients. Five-year overall and event-free survival rates were 63 and 30% in stage 3, but 6 and 5%, respectively, in stage 4 patients. Univariate analysis established that the age, stage, primary tumor site, and high LDH and NSE levels conferred a significant difference. The IPOG-NBL-92 protocol has proved to be satisfactory with tolerable toxicity and reasonable CR and survival rates. However, more effective treatments suitable to Turkey's social and economic conditions are urgently needed for children over 1 year of age with advanced neuroblastoma.

Malignant pleural mesothelioma in a child: long-term survival with ICE-WAC chemotherapy regimen.

Malignant mesothelioma is a very rare tumor in childhood. Presently, treatment of this disease continues to be frustrating and prognosis remains poor. We here report a pediatric case of malignant pleural mesothelioma who gave a complete response to ICE-VAC chemotherapy regimen and achieved a long-term survival. An eight-year-old girl underwent exploratory thoracotomy and decortication because of a unilateral loculated and multicystic pleural effusion. Histopathological diagnosis was sarcomatoid pleural malignant mesothelioma. After decortication, chemotherapy with ICE (ifosfamide, carboplatin, etoposide) - VAC (vincristine, adriamycin, cyclophosphamide) combination was started. Six courses of chemotherapy resulted in complete clinical and radiological tumor response. She did not receive any further therapy and remains disease-free three years after the first remission. ICE-VAC chemotherapy combination resulted in a complete tumor response and a long-term disease-free survival for the presented case. The efficacy of this chemotherapy regimen in malignant mesothelioma needs to be documented in future trials.

Assessment of peripheral lymphadenopathies: experience at a pediatric hematology-oncology department in Turkey.

Since a large variety of disorders may lead to lymph node enlargement determining the cause of peripheral lymphadenopathy (LAP) in children can be difficult. This retrospective study evaluated 200 children who were admitted to an Oncology-Hematology department because of lymphadenopathy and aimed to determine the clinical and laboratory findings that were valuable for differential diagnosis. A specific cause for lymphadenopathy was documented in 93 (46.5%) cases. One hundred forty (70%) children were classified as having a benign cause for lymph node enlargements. Fourteen (10%) of these cases underwent an excisional lymph node biopsy, and histopathological examination showed a reactive hyperplasia. Sixty (30%) cases were classified as having a malignant disease-causing lymphadenopathy. In terms of differential diagnosis, some associated systemic symptoms, physical findings, and laboratory investigations showed significant difference between benign and malignant lymphadenopathy groups. The following findings were determined as being important to alert the physician about the probability of a malignant disorder: location of the lymphadenapathy (supraclavicular and posterior auricular), duration of the lymph node enlargement (>4 weeks), size of the lymph node (>3 cm), abnormal complete blood cell findings, abnormalities in chest X-ray, and abdominal ultrasonography.