Primitive neuroectodermal tumors of the central nervous system associated with genetic and metabolic defects.

AIM: To evaluate the genetic, congenital and metabolic disorders which were detected concurrently with primitive neuroectodermal tumors (PNET) of the central nervous system in children. METHODS: Medical records of 1030 children who were admitted to our department with diagnosis of brain tumor between 1975 and 2005 were reviewed retrospectively. Medulloblastoma and supratentorial PNETs were detected in 289 patients. They were reviewed for associated metabolic conditions, genetic and congenital defects. RESULTS: One of the following conditions were detected in 10 patients with medulloblastoma and supratentorial PNETs: Neurofibromatosis type 1, Gorlin syndrome, juvenile polyposis coli, cancer prone syndrome of total premature chromatid separation and Fanconi anemia, bilateral retinoblastoma, L-2-hydroxyglutaric aciduria, Gilbert syndrome, gray platelet syndrome, cleft lip-palate and left renal agenesis. In the patients with multiple malignant diseases, cancer prone syndrome of total premature chromatid separation and Fanconi anemia, Gorlin syndrome and juvenile polyposis coli were diagnosed after diagnosis of the malignant tumors. Medulloblastoma was the first manifestation in the case with Gorlin syndrome. In case with retinoblastoma, pineal PNET was detected 2 months after diagnosis of retinoblastoma. Cleft lip-palate and L-2-Hydroxyglutaric aciduria were detected previously in the patients before their brain tumors whereas Gray platelet, Gilbert syndrome and left renal agenesis were diagnosed during treatment of medulloblastoma. CONCLUSION: Associated genetic, metabolic and congenital conditions were detected in 3.5% of the cases. Thus the patients with PNET should be followed for these defects.

Maxillofacial osteosarcoma successfully treated with surgery and adjuvant chemotherapy in a child.

Maxillofacial osteosarcoma constitutes a minor percentage of all the head and neck tumors. We describe a 10 year-old girl presenting with swelling and pain in left maxillary region and diagnosed as low grade osteosarcoma. The patient was operated and given a chemotherapy protocol consisted of Cisplatin and Doxorubicin. After six courses of chemotherapy the patient was in complete remission and she is well with no evidence of disease for five years. Since high local recurrence rates have been reported in craniofacial osteoarcoma and we know the deleterious side effects of radiation therapy in children, we believe that best management strategy for osteosarcomas in maxillofacial region in children is radical surgical excision and postoperative chemotherapy (Fig. 3, Ref. 11).

Clinical value of cystatin c determination in children with lymphoma.

Cystatin, a proteinase inhibitor, is involved in the intracellular catabolism of proteins. We investigated the change in concentration of serum Cystatin C (CysC) in children with lymphomas and its diagnostic utility. Twenty-eight newly diagnosed patients with lymphoma were included in this study. The male/female ratio was 20/8, with a median age of 8.5 years (range 3-17 years). Thirteen patients had Hodgkin's lymphoma (HL) and 15 had non-Hodgkin's lymphoma (NHL). Cystatin C concentration was determined at the time of diagnosis and during remission. In the entire group, CysC concentrations at diagnosis and during remission were 0.87+/-0.29 mg/L and 0.86+/-0.21 mg/L, respectively (p=0.93). In the NHL group, CysC concentrations at diagnosis and remission were 0.89+/-0.32 mg/L and 0.85+/-0.23 mg/L, respectively (p=0.73). The CysC concentrations in the HL group at diagnosis and remission were 0.88+/-0.36 mg/L and 0.88+/-0.18 mg/L, respectively (p=0.73). No significant difference was observed between CysC concentrations in the HL (0.88+/-0.36 mg/L) and NHL (0.89+/-0.32 mg/L) groups. Cystatin C concentrations in all the patients with localized versus those with advanced disease were 0.91+/-0.41 mg/L and 0.88+/-0.3 mg/L, respectively (p=0.83). Cystatin C concentrations of the patients with localized and advanced HL were 0.95+/-0.45 mg/L and 0.77+/-0.14 mg/L, respectively, (p=0.41). Cystatin C level was higher in patients with localized disease, in those without B symptoms, and, at diagnosis, in those with an unfavorable response (Tab. 2, Ref. 20). Full Text in free PDF www.bmj.sk.

Pineal region tumors in children: a single center experience.

Pineal region tumors are a relatively uncommon, deep-seated heterogeneous group of mass lesions of the brain. Their management is much more complicated in children with cancer, both in terms of survival and sequelae, due to primary location of the tumor and treatment modality. The goal of this retrospective study was to report the presentation, treatment, and outcome of tumors that arose from this region in 24 children treated at our institution between March 1975 and May 2006. In all, 15 (62.5%) of the 24 children were initially treated with partial or complete resection, adjuvant radiotherapy was given to 18 (75%) patients, and chemotherapy was given to 15 (62.5%) of the patients. Overall survival was 44.5%. Although statistically insignificant, the most favorable outcome were obtained in patients with grossly resected tumors (66%) and in children >10 years of age (80%). Long-term sequelae occurred at a high rate in this study due to the primary location of the tumors and treatment modalities, which warrants further investigation.

Varicella vaccination in children with lymphoma and solid tumours.

BACKGROUND: Varicella infection can be a severe disease, especially in immunosuppressed patients. Here, experience with live varicella vaccine to prevent varicella infection is reported in children who were undergoing treatment for lymphoma and solid tumours. METHODS: 40 children, aged between 12 months and 15 years with no clinical history of varicella, were vaccinated with live varicella vaccine. All received two doses of the vaccine subcutaneously 4 weeks apart. Serum samples were taken before the first dose and 6 weeks after the second dose of vaccine. RESULTS: Before vaccination, 32 patients were seronegative for varicella and eight were seropositive. Seroconversion was observed 6 weeks after the second dose in 24 of the 32 (75%) seronegative children. In 4 of 8 previously seropositive patients, antibody titres increased after immunisation. Zoster infection occurred 5 weeks after the second dose of vaccine in only one previously seronegative child. 7 children, who had responded to the vaccine, have been exposed to varicella in their families or in school without contracting clinical disease. CONCLUSION: Although the small number of patients in our group prevents us from drawing definitive conclusions, the varicella vaccine seems to be well tolerated and can be administered to children with lymphoma and solid tumours undergoing treatment.

Primary lacrimal sac non-Hodgkin's lymphoma in a child.

Primary lacrimal sac lymphoma is extremely rare in children. To our knowledge, only two previous cases have been reported in the literature. Here, we report the case of a 9-year-old girl with primary lacrimal sac lymphoma who has recurrent mass.

Urinary neutrophil gelatinase associated lipocalin as a biomarker in ifosfamide induced chronic renal failure.

OBJECTIVE: Neutrophil gelatinase associated lipocalin (NGAL) have been used with great success in acute renal failure and in some cases in chronic nephrotoxicity. In this work, we aimed to investigate urinary NGAL as an early marker of chronic renal failure (CRF). PATIENTS AND METHODS: We investigated urinary NGAL of 29 children treated with ifosfamide chemotherapy and compared them with those of 12 healthy children. Urinary ß2 microglobulin, serum cystatin C, and creatinine clearance analyses were also studied. RESULTS: The median age was 11 years (4-21) and median remission time was 4.3 years (1.8-14.4). The cumulative dose of ifosfamide was 36 g. Glomerular filtration rate was decreased in 41.4% and urine ß2 microglobulin levels and serum cystatin C levels were elevated in 31% of the patients. As the remission time increased, serum creatinine and cystatin C levels were also increased. The sensitivity for ß2 microglobulin and cystatin C in demonstrating CRF was 35.2% and 23% and specificity was 33.2% and 50% respectively. The 24-hour urine NGAL cut-off level for demonstrating CRF was found to be 1.065 ng/mL/24 hours. The sensitivity and specificity for this cut-off value were 83% and 77%, respectively. CONCLUSIONS: NGAL levels were significantly higher in the study group as compared with the control group. Although ifosfamide treatment was suggested to be safe with no complication of renal failure under a dose of 80 g/m2, chronic renal failure and deficits in glomerular and tubular function could be seen when the remission time increased. Elevated NGAL levels may be a good option in determining CRF.

Management of bilateral Wilms tumor over three decades: The perspective of a single center.

INTRODUCTION: Outcomes of Wilms tumor improved in last 50 years and excellent survival rates can be achieved especially in case of non-metastatic disease and favorable histology. Nevertheless, bilateral cases still stand as a therapeutic challenge. Prognosis of bilateral Wilms tumor (BWT) is not as good as the unilateral tumors of similar stage and histology in terms of survival and renal function. OBJECTIVE: Management of BWT is constantly evolving and still stands as a therapeutic challenge. This study is designed to review and share our experiences on this topic from a surgical standpoint. STUDY DESIGN: The records of patients treated in our clinic between 1980 and 2013 according to Turkish Pediatric Group of Oncology protocol were analyzed retrospectively and clinical data, surgical details, pathology results, long term outcomes were analyzed. RESULTS: Thirteen girls and 7 boys with a mean age of 2,5 years were treated. There were 2 patients with Wilms tumor-Aniridia-Growth Retardation complex and one with isolated hemihypertrophy. Metastasis were detected in lungs of 4 patients; liver of 2 and in the cranium of one. All patients except one with the presumptive diagnosis of unilateral Wilms tumor were given preoperative chemotherapy. To sum up; 19 nephroureterectomies, 8 partial nephrectomies and 13 enucleations were performed to 36 kidneys without any major early or late postoperative complications. Pathologic results revealed positive surgical margins in 2 lesions with enucleation and in 2 with partial nephrectomies and anaplasia in 4 patients. Two patients were not operated due to parental disapproval. Two patients had the need of dialysis; one was anephric and the others' renal functions recovered over a year. Seven patients received radiotherapy for pulmonary metastasis, positive surgical margins or local recurrences. Overall, 13 patients survived and 7 died due to metastasis, recurrences, and complication of dialysis and refusal of surgical treatment. Survival among all patients was 65% and 72.2% among operated ones. Of the 7 patients with the partial nephrectomy, 2 died and 5 survived. Among enucleation group, 8 out of 10 survived and 2 died. Survival was slightly higher among enucleation group (80% vs 71.4%). Median time of follow-up for survivors of disease is 5.8 years (min: 6 months and max: 14 years). DISCUSSION: Outcomes of BWT management have changed dramatically during the last few decades from only survival, to a long life expectancy without the need of renal replacement therapy owing to improvements in treatment options. We argue that positive surgical margins do not necessarily lead to local recurrence. For this reason it may be wiser to favor on more nephron sparing surgery than to achieve negative surgical margins. Adjuvant chemotherapy and radiotherapy may be adequate to prevent local recurrence. Also, survival did not differ significantly between different ways of nephron sparing surgeries, so it may be wiser to choose enucleation over partial nephrectomy which preserves more nephrons. Nephron-sparing surgery should have utmost importance despite the risk of positive margins. On the other hand, there is not enough data to interpret if positive surgical margins have role on distant metastases or not. Presence of metastasis and recurrence seems to be an important determinant of prognosis given the fact that none of the survivors had any metastasis or recurrence. CONCLUSION: Nephron preservation should be the aim while taking positive surgical margin risk on nephron sparing surgery side relying on postoperative chemotherapy and carefully planned radiotherapy to avoid recurrence. However, there is significant diversity on the management BWT in different centers and a certain validated guideline or protocol to provide the optimal treatment is still lacking.

Evaluation of therapy response in children with untreated malignant lymphomas using technetium-99m-sestamibi.

UNLABELLED: The aim of this study was to investigate the relationship between 99mTc-sestamibi accumulation in tumors and response to chemotherapy in children with untreated malignant lymphomas. METHODS: Twenty-four children with malignant lymphoma (16 with Hodgkin's disease and 8 with non-Hodgkin's lymphoma) were studied with 201Tl and then with 99mTc-sestamibi scintigraphy before any therapeutic intervention. Visual and quantitative interpretation of 201Tl and 99mTc-sestamibi scans were performed. Visual uptake scores > or = 2+ were considered positive studies for 201Tl and 99mTc-sestamibi scintigraphy. Remission rates were evaluated at the end of induction therapy; patients were then followed clinically for 1-2 yr. RESULTS: All 17 patients who had positive 99mTc-sestamibi scans subsequently had a complete response to chemotherapy; all seven patients who had negative 99mTc-sestamibi scans subsequently had partial or no response to chemotherapy, irrespective of the lymphoma type. The mean tumor-to-background ratios of patients with complete response and with partial or no response were 1.395 +/- 0.2 and 1.031 +/- 0.05 (p = 0.0002), respectively. Thallium-201 scintigraphy results were not related to the response to chemotherapy. CONCLUSION: Technetium-99m-sestamibi scintigraphy can provide information predicting the response to chemotherapy in patients with malignant lymphoma.

Scleroderma in a child after chemotherapy for cancer.

The association of malignancy with scleroderma is very rare in childhood. A 13-year-old girl was diagnosed as having thymic carcinoma and received systemic chemotherapy. She presented with symptoms of Raynaud's phenomenon 9 months after the cessation of chemotherapy. She also had difficulty in swallowing. Based on the presence of Raynaud's phenomenon, characteristic skin changes over the face and hands, oesophageal involvement and pulmonary restrictive defect demonstrated by pulmonary function tests, the diagnosis of generalised scleroderma was established. There was no evidence of tumor recurrence. Although she was treated with penicillamine and prednisolone, no significant improvement was achieved in her condition during the 14-month follow up.

Serum carnitine levels during the doxorubicin therapy. Its role in cardiotoxicity.

Doxorubicin is an anthracycline antibiotic with a broad spectrum of antineoplastic activity. Cardiotoxicity is a serious long-term complication of the drug. Simultaneous administration of carnitine has been proposed to prevent cardiotoxicity. We aimed to monitor the serum carnitine levels during the treatment of doxorubicin and to determine a relationship between serum carnitine levels and cardiac dysfunction. Fifteen patients were evaluated prospectively. Measurement of carnitine levels and evaluation of cardiac function were performed prior to treatment, and after cumulative doses of 180 and 300 mg/m2 of doxorubicin. A group of 20 healthy children served as control group to obtain reference values. We found subclinical abnormalities in cardiac function, while the cumulative doses of the doxorubicin was increasing. The mean end diastolic and end systolic left ventricular dimensions of the patient group after completion of the treatment were significantly increased compared with initial values. The ejection and shortening fraction of the patient group after cumulative doses of 300 mg/m2 of doxorubicin were significantly lower than those of the control group. A statistically significant augmentation was observed in mitral A, with a decrease in mitral E/A ratio. There was a trend towards lower serum carnitine levels with higher cumulative doses of doxorubicin, although it was not statistically significant. Our results invite new detailed investigations depending on the measurement of serum and urinary free and acyl carnitine and myocardial carnitine levels to evaluate possible roles of carnitine in the prevention of doxorubicin-induced cardiotoxicity.

Congenital neuroblastoma, neuroblastoma in situ, and the normal fetal development of the adrenal.

In normal fetal development nodular collections of neuroblast cells were found in the adrenal glands from 7 wk gestation; there nodules increased in size and number, and in all specimens from fetuses of 14-18 wk gestation, aggregates of nodules closely resembling neuroblastoma in situ could be found. From about 12 wk gestation the large neuroblast nodules appear to split into smaller nodules and differentiation into chromaffin cells takes place. The mean nuclear size of neuroblasts at all stages of development studied was 4.25 +/- 0.84 mu, statistically significantly less than the mean nuclear size of the cells measured in 7 neonatal neuroblastomas. Measurement of nuclear size may be a way of distinguishing a true potentially malignant neuroblastoma in situ from a normal benign residual neuroblast nodule.

A rare presentation of trilateral retinoblastoma.

Retinoblastoma and intracranial tumors are rarely found together. Here we report on a case with unilateral retinoblastoma and pineal tumor without symptoms of an intracranial mass at the time of diagnosis. The patient was found to have a retinoblastoma of the other eye at the 10th month of follow-up.

Pleuropulmonary blastoma in a child presenting with pneumothorax.

Pleuropulmonary blastoma is an uncommon primary malignant tumor of the lung. Surgery is the most important part of the treatment. Despite the use of chemotherapy with or without radiotherapy, the prognosis is poor. Here we report on the case of a 2.5 year-old boy presenting with pneumothorax who turned out to have a right hemithoracic mass. The patient underwent surgical resection of the mass. Pathologic diagnosis was type II pleuropulmonary blastoma. Postoperative thoracic CT showed nodular residual densities so the patient was given adjuvant combination chemotherapy with cisplatin and etoposide. He has been disease free for 12 months.

Neuroblastoma presenting as protein-losing enteropathy.

Protein-losing enteropathy is often reported to be associated with malignancies such as Hodgkin's disease, non-Hodgkin's lymphoma, and mesenteric mesenchymoma, but it seldom complicates neuroblastoma. In this report, we describe a case of neuroblastoma presenting as protein-losing enteropathy in which neurohumoral mechanisms were involved.

Primary osteosarcoma presenting in axial bones in childhood.

Six cases of osteosarcoma occurring between 1971 and 1992 and involving the axial bones were reviewed. They constituted 4% of 129 osteosarcomas occurring in the skeleton in childhood during the same period at our center. The patients' ages ranged from eight to seventeen years. Four of the six patients were female. The distribution of axial bones of osteosarcoma was as follows: one case was in the vertebrae, two cases in the craniofacial bones (maxilla and mandible), two cases in the pelvis and one case in the ribs. The prognosis was very poor, with only one case of mandible osteosarcoma still alive. The other five patients died three to sixteen months after diagnosis. A combination of wide surgical resection and aggressive chemotherapy may offer the best chance for longterm survival.

A case of hemophilia A associated with Hodgkin's disease.

Lymphoreticular malignancies are more common in patients with hemophilia, but it is usually attributed to human immunodeficiency virus (HIV) infection associated with repeated use of blood products. However, there are a couple of hemophiliac patients with malignancies but without HIV infection in the literature. We report a case of a hemophiliac patients who had Hodgkin's disease at 2.3 years old without any congenital or acquired immunodeficiency and without use of any blood products. This patient showed that malignancy can develop in hemophiliacs without HIV infection, but further studies are needed to clarify whether hemophiliacs are more susceptible to malignancies.

Immune thrombocytopenic purpura in a child with Hodgkin's disease.

The occurrence of immune thrombocytopenic purpura (ITP) in Hodgkin's disease is uncommon. This report describes a patient who developed ITP twice before splenectomy, and for the third time several years later, preceding an abdominal relapse of the disease. We suggest that patients with a history of Hodgkin's disease undergo diligent searches for active disease when ITP is diagnosed. ITP may be the only manifestation of active disease and may precede histologic documentation of Hodgkin's disease by months or years.

Benign vascular tumors and vascular malformations in childhood: a retrospective analysis of 1127 cases.

Vascular lesions in childhood are classified as vascular malformations and hemangiomas. Vascular malformations are congenital abnormalities thought to arise from defects during embryological development of vascular tissue. Hemangiomas are benign tumors of vascular endothelium and can spontaneously become involuted in almost all cases. One thousand one hundred and twenty-seven patients with vascular lesions were followed by the Department of Pediatric Oncology, Hacettepe University, for 19 years. Diagnosis was based mainly on history, clinical condition and follow-up data in 98.2 percent of cases. The distribution of the vascular lesions was as follows: 969 patients had hemangiomas, 120 had lymphatic malformations, 18 had combined vascular malformations, 11 had venous malformations, six had port-wine stain, and three had angiokeratoma. Except for ten cases with Klippel-Trenaunay Weber syndrome, vascular malformations were not accompanied by any syndrome.

Fatal agranulocytosis developed in the course of carbamazepine therapy. A case report and review of the literature.

A case of fatal agranulocytosis in an adolescent who was on carbamazepine therapy is presented. The clinical and laboratory findings suggest that the primary cause of the disorder was neutropenia rather than infection, and the preceding factor for neutropenia was carbamazepine. The timing of occurrence of the hematologic picture, its dependency on dose increments, and the lack of symptoms until infection supervened are consistent with an idiosyncratic-toxic drug reaction (type 2 drug reaction). This is the first reported agranulocytosis case due to crabamazepine in adolescence.