Neurofibromatosis type 1 and malignancy in childhood.

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary neurocutaneous syndrome characterized by multi-system involvement and an increased incidence of both benign and malignant tumors. In this study, we evaluated the clinical presentation and prognosis of NF1 and malignancy. Between 1975 and 2013, 26 (5%) of the 473 patients with NF1 at our center developed non-neurofibroma neoplasms. The patient files of 26 subjects with tumors, other than optic glioma, were analyzed retrospectively to evaluate clinical features and treatment results. The age at diagnosis of NF1 ranged from 3 months to 16 years (median 5.5 years). The age range at tumor diagnosis was 1.5-33 years (median 8 years) in these 26 patients. The tumor histological subtypes included the following: 12 soft-tissue tumors (6 malignant peripheral nerve sheath tumors (MPNST), 5 rhabdomyosarcomas (RMS) and 1 malignant fibrous histiocytoma), 11 brain tumors (6 low-grade gliomas, 3 high-grade gliomas, and 2 medulloblastoma), 2 neuroblastomas and 1 non-Hodgkin's lymphoma. Twelve of 26 patients were alive at the time of the study. Although benign brain tumors with NF1 are more common, high-grade brain tumors also occur. Thus, careful and regular follow-up is crucial for early detection of malignancy in NF1 patients.

Increasing performance of a hospital-based cancer registry: Hacettepe University hospitals experience.

PURPOSE: High-quality hospital-based cancer registry systems are the key elements of a healthy population-based cancer data. The purpose of this study was to present a recent history of establishing a valuable and reliable hospital- based cancer registry in a university hospital in Turkey, and the data gathered by this system in the last 9 years. METHODS: This study included the cancer registry records of Hacettepe University Hospitals between 1-Jan-2003, and 31-Dec-2011. The study cohort included data of 39351 cancer patients and the cancer registry system was based on active data acquisition method. RESULTS: Most frequent departments of reference were Medical Oncology, Radiation Oncology, General Surgery, Urology, and Pediatrics. The annual number of records gradually increased from 2675 in 2003 to 5152 in 2011. The 5 cancer types most frequency seen in adults were lung (15.5%), prostate (13.5%), stomach (6.6%), bladder (6.2%), and colon (5.8%) in men; and breast (32.7%), ovary (6.4%), uterine corpus (6.2%), uterine cervix (5.6%), and thyroid (5.0%) in women. Childhood cancers were classified according to the International Classification of Childhood Cancers, 3rd Edition (ICCC-3), and the most frequent 5 cancer types in children were tumors of the central nervous system (20.1%), lymphomas (14.6%), leukemia (14.1%), retinoblastoma (9.4%), and tumors of the sympathetic nervous system (7.7%). CONCLUSION: Active data acquisition from departments that deal with oncologic patients in a hospital is the precise method for establishing a high-quality cancer registry system that is able to resemble the general population. Hospital- based cancer registry systems also provide highly critical information for planning, monitoring, and measuring the cancer-related services, research, and education.

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.

The state of research into children with cancer across Europe: new policies for a new decade.

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.

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.

Pulmonary metastases in children: an analysis of surgical spectrum.

Pulmonary surgery is frequently used for the treatment of metastasis or nodules in children with various types of malignancies. However, the indications and effectiveness of pulmonary metastatectomy have not been evaluated recently. Therefore, a retrospective study was conducted to analyse the results of pulmonary metastatectomy in children. Children who underwent pulmonary metastatectomy at our department between 1990 and 2000 were reviewed. Eighteen children consisting of 11 boys and 7 girls (age range, 3 to 18 years) underwent thoracotomy for pulmonary metastasis excision. The primaries were osteosarcoma (n = 2), synovial sarcoma (n = 1), fibrosarcoma (n = 1), Ewing's sarcoma (n = 2), mesenchymal chondrosarcoma (n = 1), Wilms' tumour (n = 4), clear-cell sarcoma (n = 1), Hodgkin lymphoma (n = 3), hepatoblastoma (n = 1), hepatocellular carcinoma (n = 1) and haemangioendotheliosarcoma (n = 1). Pulmonary metastases were encountered either at the time of initial diagnosis (22 %) or occurred within 6 months to 5 years. They were frequently nodular (94 %), unilateral (94 %) and located in the right lung (70 %). The number of metastases were frequently one (56 %) or two (28 %). Excision was done by means of wedge resection (88 %), segmentectomy (6 %), and lobectomy + wedge resection (6 %). The nodules contained tumour cells in most cases (n = 14) (78 %), mature nephrogenic elements (6 %) and no tumour tissue (16 %) in the remaining cases. Histology was similar to that of the original tumour in 12 cases. However, synovial sarcoma was encountered in metastasis in one case with fibrosarcoma primary. Re-thoracotomy was performed in 22 % of cases for the recurrent lesion, which in only one case was a true local recurrence. Overall disease-free survival rate was 56 % during the follow-up period (mean, 36.4 +/- 31.8 months). Pulmonary metastatectomy may increase survival in carefully selected children, though it is unlikely to cure the patient. Therefore combined therapies such as chemotherapy and/or radiotherapy should be continued in the postoperative period.

Urticaria pigmentosa associated with Wilms tumor.

Urticaria pigmentosa is the most common manifestation of mastocytosis, with the majority of cases undergoing spontaneous resolution, especially in children. Several reports have documented hematologic malignancies developing in patients with urticaria pigmentosa. We present a 4.5-year-old boy with urticaria pigmentosa who developed Wilms tumor. To our knowledge, coexisting urticaria pigmentosa and Wilms tumor have not previously been described.

Monotherapy with meropenem versus combination therapy with piperacillin plus amikacin as empiric therapy for neutropenic fever in children with lymphoma and solid tumors.

The purpose of this study was to compare meropenem monotherapy with combination therapy for empirical treatment of neutropenic fever in children with lymphoma and solid tumors. Ninety episodes of neutropenic fever in children (0.7-16.0; mean age 7.7 years) with solid tumors in a single center were randomized to receive either meropenem (50 mg/kg/dose-maximum 1 g, every 8 hours) or piperacillin (200 mg/kg/dose, every 6 hours) plus amikacin (15 mg/kg daily). Failure was defined as treatment modification. Non-Hodgkin's lymphoma (NHL) accounted for 62.2 percent of all episodes, and solid tumors (37.8%) for the rest. Blood cultures were positive in 23 percent of all episodes. Sixty-seven percent of all isolated microorganisms stained Gram-positive. Overall success was 70.0 percent (63/90). The success with meropenem was comparable to that seen with piperacillin plus amikacin: 76.6 versus 64.6 percent (p = 0.25). The failure rate was 33 percent with Gram-positive culture and 78 percent with Gram-negative or mixed cultures. The solid tumor group had significantly less bacteremia (4/34 versus 17/56; p < 0.05) and treatment failure (3/34 versus 24/56; p < 0.001) than the NHL group. No serious drug-related adverse event was noticed. Meropenem monotherapy was as effective as piperacillin plus amikacin combination in the empirical treatment of neutropenic fever in children with lymphoma and solid tumors.

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.

Intraperitoneal involvement in rhabdomyosarcoma CT findings in a child.

Intraperitoneal neoplastic involvement in rhabdomyosarcoma is rare and its incidence and imaging characteristics need to be further described. We present the computerized tomography (CT) findings of a case with pelvic rhabdomyosarcoma and intraperitoneal neoplastic involvement. Enhanced peritoneal and retroperitoneal masses were seen around the liver, spleen, in the paracolic gutters, and in the lesser sac without evidence of ascites, mesenteric nodules or omental caking. Our case also showed that absence of ascites does not preclude the presence of peritoneal involvement. Progression in the peritoneal disease was also well demonstrated by CT.

Malignant ovarian tumors in children: 22 years of experience at a single institution.

PURPOSE: Malignant ovarian tumors of childhood are relatively rare and thus, management is still unclear. We reviewed our experience with these tumors to evaluate their histopathologic characteristics, treatment, and outcome. PATIENTS AND METHODS: From January 1975 to December 1997, 56 patients had their malignant ovarian tumors diagnosed, treated, and followed-up in our institution. All tumors were completely excised when possible; otherwise, biopsy was performed. Staging was made according to Federation Internationale de Gynecologie Oncologique classification. Chemotherapy was recommended for all patients. Twelve cases were treated with vincristine, actinomycin, cyclophosphamide (VAC) before 1986; 12 with cisplatin, vinblastine, and bleomycin (PVB) from 1986 to 1989; and 23 with the bleomycin, etoposide, and cisplatin (BEP) regimen from 1989 to present. The Kaplan-Meier survival method was used to calculate the survival. The log-rank test was used to compare groups with respect to survival. RESULTS: Age range was 0 to 16 years (median 11 yrs; average 9.8 yrs). Only two patients were younger than 1 year. The most common presenting symptom was abdominal pain, occurring in 27 patients (48.2%). Thirty-three patients (60%) had total one-sided salpingo-oophorectomy and three patients had bilateral salpingo-oophorectomy. Nineteen patients had stage I, 15 had stage II, 19 had stage III, and 3 had stage IV disease. Dysgerminoma was the most common type. Overall survival (OAS) and event-free survival were 68% (median follow-up time: 71 mos) and 57%, respectively, after 22 years. Histopathology was not correlated with survival. Two important predictors for survival are age (P < 0.0001) and treatment protocol (P = 0.013). The BEP protocol was superior to the other regimens. The OAS was 74.6% in BEP, 55% in PVB, and 63.6% in VAC regimens. CONCLUSION: Although age at diagnosis and treatment with BEP regimen have major roles in determining prognosis of the ovarian tumors in childhood, for patients with advanced ovarian germ cell tumors, intensification of chemotherapy or the development of new approaches is necessary.

Hypertrophic osteoarthropathy in a child with nasopharyngeal carcinoma.

We report a 13-year-old boy with nasopharyngeal carcinoma, skull metastases and hypertrophic osteoarthropathy. Although the metastases and the primary tumour responded well to chemotherapy, hypertrophic osteoarthropathy persisted during follow-up.

Benign melanocytic tumor in infancy: discussion on a rare case and review of the literature.

Meningeal melanocytoma is an infrequent neoplasm of the central nervous system (CNS), especially in childhood and infancy. It was first described as an entity different from pigmented meningiomas and schwannomas in 1972, and few cases have been published so far. In this article, a 5-month-old male patient with meningeal melanocytoma is presented. This midline lesion was localized in the posterior fossa and manifested by hydrocephalus. The entire dural origin and extradural growing pattern in addition to the destruction of the adjacent occipital bone were the unexpected presentations since these tumors usually tend to locate on leptomeninges and to extend into the adjacent neural compartment rather than the outside. On the other hand, this case is the only one which had identical lesions in both surrenal glands and the left renal capsule, the structures containing neural-crest-derived cells outside the CNS. The prognostic criteria, differential diagnosis and its embryological aspects are discussed with an extensive review of the related existing literature.

Hodgkin's disease and renal paraneoplastic syndromes in childhood.

The purpose of this study was to investigate children followed as having both Hodgkin's disease (HD) and nephropathy and discuss the factors which might play roles in the pathogenesis of this association by reviewing the pertinent literature. Our experience among 661 children with HD revealed ten cases (1.5%) with nephropathy; eight of these were biopsy proven. Tissue diagnoses were amyloidosis (AA type) in four cases, and membranoproliferative glomerulonephritis and minimal change glomerulopathy in two cases each. Sex distribution was equal. There was a predominance of the mixed cellular (MC) histologic type in our patients with HD. Nephropathy was shown to antedate the diagnosis of HD in two cases and to herald a relapse in one. In brief, the development of a nephropathy in a patient with HD can be considered as a paraneoplastic phenomenon. Renal amyloidosis may already be present at the time of diagnosis of HD and must be kept in mind as a cause of proteinuria due to preexisting nephropathy. Developing renal paraneoplastic syndrome, even in early-staged HD, in children, may be a poor prognostic factor.

Nasal-paranasal-oronasopharyngeal lymphomas in childhood: the role of staging system on prognosis.

Most of the patients with nasal-paranasal and oropharyngeal-nasopharyngeal (NPONP) lymphomas had early-stage disease according to the Murphy system. But the survival rates are not correlated with the stages. Treatment results were analyzed to see the effects of the staging in NPONP lymphomas. Fifty-five children (median age 8 years, M/F: 4.5) with NPONP lymphoma were included in this study. The Murphy staging system was used at diagnosis and all cases were restaged according to the TNM system: primary tumor, regional lymph node, and metastasis. The survival rates were analyzed by grouping the patients according to the treatment and stages. The disease was located in Waldeyer's ring, the sinonasal region, and the nasopharynx in 45.4, 27.3, and 27.3% of patients, respectively. Thirty-nine patients had stage I or II disease according to the Murphy system. When the TNM system was used, 92% of these patients were upstaged to stage III-IV. Five-year overall and event-free survival rates were 52.1 and 50.4%, respectively, for the whole group. Five-year event-free survival rates for Murphy stage I, II, and III disease were 66.7, 56.9, and 45.4%, respectively. The rates for TNM stage III and IV patients were 64.3 and 43.8%. Treatment protocols were intensified in most of the early-stage disease treated with modified LSA2-L2 regimen and better survival rates were obtained in these patients. The intensification of the treatment by using intrathecal treatment and doxorubicin in patients with early-stage disease at NPONP location seems effective. In conclusion, the Murphy staging system is not suitable for the staging of NPONP lymphomas. It should be revised to predict the prognosis and decision-making for treatment.

DNA content and proliferative activity in children with neuroblastoma.

Many studies have reported that neuroblastoma patients with aneuploid DNA content and a low cellular proliferative activity have better outcome; other studies have reported contradictory results. Formalin-fixed, paraffin-embedded archival pretreatment specimens of 56 neuroblastomas were studied. Thick sections from paraffin blocks were deparaffinized, and rehydrated. Following enzymatic digestion and filtration, cellular suspensions were analyzed by flow cytometry. Six tumors were aneuploid (13.3%) and 39 samples were diploid (86.7%). S-phase fraction (SPF) ranged from 1 to 78% with a median of 31%. DNA ploidy and proliferative activity results showed no correlation with the prognostic variables. There was no significant difference between the 5-year overall and event-free survival rates of the aneuploid and the diploid neuroblastomas or between the neuroblastomas with a high and low proliferative activity. The results revealed the prognostic significance of neither DNA ploidy nor the cellular proliferative activity in neuroblastoma in contrast to other studies.