Burca Aydin

Pediatric and young adult nasopharyngeal carcinoma patients treated with preradiation Cisplatin and docetaxel chemotherapy.

PURPOSE To evaluate treatment results for pediatric and young adult (aged <21 years) patients with nonmetastatic nasopharyngeal carcinoma treated with neoadjuvant cisplatin + docetaxel and radiotherapy. METHODS AND MATERIALS Ten patients with nasopharyngeal carcinoma who received diagnoses between 2004 and 2007 were treated with four cycles of cisplatin 100 mg/m(2) + docetaxel 75 mg/m(2) on Day 1 with premedication every 3 weeks. All patients were treated with fractionated external beam radiotherapy after chemotherapy to a median dose of 59.4 Gy (range, 54-59.4 Gy) to the primary disease and 40 Gy to the supraclavicular field with the clavicles shielded. Five children were monitored with serum EBV DNA quantification at diagnosis, after each cycle of chemotherapy, before radiotherapy, and at follow-up. RESULTS The median age of the patients was 14 years (range, 9-20 years), with a male:female ratio of 6:4. Stage distribution was as follows: 2 patients had Stage IIb disease, 2 had Stage III, 4 had Stage IVa, and 2 had Stage IVb disease. After cisplatin+docetaxel chemotherapy 1 patient had a complete response, 5 had a partial response, 3 had stable disease, and 1 had disease progression. The 2-year overall survival rate in our series was 90% and the event-free survival rate was 70%. No major chemotherapy toxicity was observed. The EBV DNA titers were higher in 2 of the 5 monitored patients at the time of diagnosis. CONCLUSION As neoadjuvant chemotherapy before radiotherapy, the cisplatin+docetaxel combination is safe for use in the treatment of childhood nasopharyngeal carcinoma.

Renal Involvement of Non-Hodgkin’s Lymphoma and Its Prognostic Effect in Childhood

Objective: To evaluate renal involvement in childhood lymphoma and define its prognostic effects. Patients and Methods: One hundred and four patients with non-Hodgkin’s lymphoma and renal involvement on admission to a single center between 1972 and 2003 were evaluated retrospectively. Blood urea nitrogen, serum creatinine, uric acid, electrolytes, and lactate dehydrogenase levels, as well as urinalysis, were evaluated. One or more of the following imaging methods were performed: intravenous urogram, ultrasound, computed tomography, and magnetic resonance imaging. The χ2 test was used to compare the groups. The Kaplan-Meier survival method was used to calculate survival rates, and the log-rank test was used to compare groups with respect to survival. Survival rates were also compared in two different time periods (before 1991 and after 1991). Results: There were 76 boys and 28 girls with a median age of 6 (0.9–16) years. The renal infiltration pattern was nodular in 62 patients (59.6%) and diffuse in 40 patients (38.5%). Two patients had tumoral masses that originated from their kidneys (1.9%). Renal involvement was bilateral in 75 patients (72.1%); the remaining 29 patients had unilateral involvement. The overall survival rate was 42.5% with a median follow-up of 64 months. The factors that had a statistically significant impact on survival were high creatinine (p = 0.00001) and blood urea nitrogen levels (p = 0.0001), the onset of tumor lysis syndrome (p = 0.01), and the need for dialysis (p = 0.009). The survival rate was higher in the time period after 1991 (p = 0.01). Conclusion: Impaired renal function is a poor prognostic factor for non-Hodgkin’s lymphoma. Renal function should therefore be monitored closely. Renal dysfunction caused by direct tumoral involvement may complicate therapy and shorten survival.

Wilms tumor, AML and medulloblastoma in a child with cancer prone syndrome of total premature chromatid separation and Fanconi anemia

To the Editor: We are writing to address an issue in the paper by Sari et al. [1], in which they state that a child with Wilms tumor, acute myeloid leukemia (AML), and medulloblastoma had a cancer prone syndrome with the combination of total premature chromatid separation (PCS) and Fanconi anemia (FA). They question the relationship between PCS and FA, regarding whether these are ‘‘two separate but co-existing events,’’ or that ‘‘one condition predisposes to the other.’’ In our opinion, it appears that the latter is the correct answer: FA predisposes to a cytogenetic pattern consistent with what has been called ‘‘PCS.’’ It appears to us that the primary diagnosis of the patient is FA: consanguineous parents, growth retardation, café au lait spots, hypopigmented lesions, and chromosome damage in lymphocytes treated with diepoxybutane. The combination of three neoplasms (Wilms tumor [WT], AML, and medulloblastoma,) is consistent with the FANCD1/BRCA2 genotype. Sari et al. state that only one case of FA with ‘‘medulloblastoma and WT was reported,’’ and that there are no cases with triple malignancies. They also state that patients with FANCD1/BRCA2 have WT and medulloblastomas, and not leukemia, and that ‘‘excluding the D1 subtype, solid tumors are very rare in FA.’’ Their references [2,3] do not include our report which indicates that solid tumors are quite common in any type of FA [4]. In addition, AML does occur in FANCD1/BRCA2, WT and medulloblastoma were reported in two patients, and triple malignancy in one patient and quadruple in another were also noted in our review of that FA subgroup [5]. Thus the case in the article by Sari et al. [1] is consistent with FANCD1/BRCA2, although they did not describe investigating that genotype. Sari et al. suggested that the combination of malignancies in their patient could be due to PCS, citing papers describing Wilms tumor, growth retardation, mental retardation, CNS abnormalities, and mosaic variegated aneuploidy (MVA). However, PCS is considered to be a marker of genomic instability, and is commonly seen in samples from patients with FA and other genomic instability syndromes [6], as well as with exposure to industrial chemicals [7] and chemotherapies [8]. In addition, the gene responsible for the distinctive entity of autosomal dominant total PCS has been identified as BUB1B (MIM 176430); the characteristic cytogenetic abnormality is found in more than 5% of mitotic cells, and carrier individuals have no phenotypic features. Patients with biallelic mutations in BUB1B have mosaic variegated aneuploidy (MVA, MIM 257300) [9]. These patients usually have growth retardation, microcephaly, and a high risk of Wilms tumor or rhabdomyosarcoma; multiple tumors have not been reported [10]. In the absence of genotypic or protein evidence involving BUB1B to support the diagnosis of PCS or MVA, it appears to us that the case reported by Sari et al. is one of FA with WT, AML, and medulloblastoma possibly due to FANCD1/BRCA2, rather than an unusual combination of separate entities. The speculation that ‘‘uncorrected DNA damage in FA may result in total PCS by influencing adhesion proteins’’ is more appropriate, although according to OMIM the term ‘‘total PCS’’ refers to individuals with a mutation in one BUB1B allele. Thus in the context of FA and cancer, the cytogenetic observation of PCS is most likely a manifestation of the well-known genetic instability of FA, rather than a separate primary process. The most parsimonious explanation for this case is FA as the sole genetic explanation for the findings.

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‐Hodgkins 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.

Pediatric intramedullary spinal cord tumors: A single center experience

AIM To evaluate clinical and radiological findings, pathological features and treatment modalities in pediatric patients with intramedullary spinal cord tumors. PATIENTS AND METHODS The medical records of 36 patients with intramedullary spinal tumors were reviewed for clinical, radiological and histopathological data, chemotherapy, radiotherapy, surgical resection, treatment responses, events, and final outcome. Survival analyses were performed. RESULTS The median age was 7.9 years (range: 1-16 years; male/female ratio:1.4). Majority of the tumors were histopathologically diagnosed as astrocytomas (n = 16, 44.4%) and ependymomas (n = 19, 52.8%); whereas one was unclassified glioma. Overall, 94% of the astrocytomas and 84% of the ependymomas were low-grade, only three tumors were high-grade. In one patient with ependymoma, histopathological grade was undetermined. The primary tumor was commonly located in thoracic (47%) and cervical segments (28%). All patients had undergone surgery (gross-total resection, 33%; subtotal resection, 45%; biopsy, 22%). Radiotherapy was administered to 26 patients (72%) and chemotherapy to 15 patients (42%). The 3-, 5- and 10-year overall survival rates were 72%, 63% and 56%, respectively; and event-free survival rates were 43%, 40% and 40%. Survival did not significantly differ with gender, age groups, lag-time, neurologic status, histopathological tumor type, tumor location, extent of resection, treatment, or treatment responses in univariate survival analyses. Survival rates were significantly higher in patients with low-grade tumors and in ependymoma patients with resected tumors. CONCLUSIONS Patients with low-grade tumors and those who underwent gross-total tumor resection had better prognosis. Surgery remains the main treatment in intramedullary spinal tumors. The role of radiotherapy and chemotherapy is limited and even controversial in low-grade tumors.

The treatment of retinoblastoma with four-drug regimen including cisplatin, etoposide, vincristine, and cyclophosphamide.

Over an 11-year period, 59 patients (83 eyes) were treated with four-drug chemotherapy (cisplatin, etoposide, cyclophosphamide, and vincristine) at Hacettepe University, Departments of Ophthalmology and Pediatric Oncology. We evaluated the clinical features, treatment modalities, and outcome of these patients with a median follow-up of 55 months (range 9–130 months). Enucleation was performed as a first-line treatment for 30 eyes due to iris neovascularization and neovascular glaucoma, tumor in the anterior chamber regardless of the tumor stage, and for the patients with the Reese–Ellsworth (RE) group Vb. Chemotherapy was given regardless of tumor stages according to the RE groups in all 59 patients (83 eyes). Fifty-three eyes were treated with chemoreduction (CRD) and focal treatment. The rates of globe preservation were 87% for bilateral tumors and 35% for unilateral tumors in the CRD group. The 5-year overall (OS) and enucleation-free survival (EnFS) was 86.9% and 40%, respectively, for the whole group. At 3rd year, ocular survival rate for the eyes with vitreal or subretinal seeding was 58% and without seeding was 66% (P = .78). Seeding or subretinal collection may not indicate poor prognosis under intensive chemotherapy. The intensive four-drug chemotherapy protocol might have satisfactory results in the retinoblastoma (RBL) patients.

Evaluation of Patients with Intracranial Tumors and Central Diabetes Insipidus

The aim of the study is to evaluate the etiologic and clinical characteristics, treatment regimens, and outcome of the patients with intracranial tumors presenting with central diabetes insipidus (DI). Sixty-nine patients with intracranial tumors presenting with central DI between 1972 and 2012 were retrospectively evaluated. Fifty-three out of 69 patients were included in the analysis. Male/female ratio was 1.52, median age was 7.6 years. Of 53 patients, 37 patients (69.8%) were diagnosed with Langerhans cell histiocytosis, 14 patients (26.4%) with germinoma, 1 (1.9%) with astrocytoma, and 1 (1.9%) with optic glioma. 10-year overall survival (OS) rate and disease-free survival rate for all patients were 91.7% and 52%. 10-year OS rate according to diagnostic criteria was 91% for Langerhans cell histiocytosis (LCH) cases, 79% for intracranial germinoma, which was statistically significant (P = .0001). Central DI may be very important clinical presentation of serious underlying disease in children. Intracranial tumors are the most frequent cause of DI. Most frequent diagnosis were LCH and germ cell tumors in our series.

Blue rubber bleb nevus syndrome: Promising response to sirolimus

BackgroundBlue rubber bleb nevus syndrome is a rare disease involving venous malformations.Case characteristicsWe present a 6-year-old female with the syndrome, and consumptive coagulopathy.Intervention/OutcomeAfter management with sirolimus, symptoms resolved.MessageSirolimus may be a valuable option for reducing bleeding complications and cosmetic sequelae for the patients with this syndrome.

Denosumab treatment in aneurysmal bone cyst: Evaluation of nine cases

Aneurysmal bone cyst (ABC) is a benign bone tumor. Curettage and bone grafting is the common treatment. Here, we retrospectively evaluate nine patients treated with denosumab.

Lipoblastoma in children: Review of 12 cases

Lipoblastoma is a rare benign mesenchymal tumor of infancy and early childhood. Symptoms vary depending on localization, and signs of compression of adjacent organs may be seen.