Neriman Sari

Infantile hepatic hemangioendothelioma with elevated serum alpha-fetoprotein.

Infantile hemangioendothelioma is the most common hepatic vascular tumor in infants less than 6 months of age, with a prevalence of 1%. Serum α-fetoprotein levels have been used as an important tumor marker for hepatoblastoma, hepatocellular carcinoma, and germ cell tumors. It is rarely elevated in hepatic hemangioendothelioma. The authors report an infant with a hepatic hemangioendothelioma associated with elevation of serum α-fetoprotein who was treated with corticosteroids. In young infants, a solitary hepatic mass and elevated serum AFP level may not always be associated with hepatoblastoma. Infantile hemangioendothelioma must be differentiated by MRI or other radiological techniques before performing invasive procedures.

Comparison of accelerated and rapid schedules for monovalent hepatitis B and combined hepatitis A/B vaccines in children with cancer.

The aim of this study was to determine the efficacy of immunization against hepatitis A and B infections with “rapid” or “accelerated” schedules in children with cancer receiving chemotherapy. Fifty-one children were recruited to receive either vaccination schedule, in the “rapid vaccination schedule”; hepatitis B (group I) or combined hepatitis A/B vaccines (group III) were administered at months 0, 1, 2, and 12; in the “accelerated vaccination schedule,” hepatitis B (group II) or combined hepatitis A/B (group IV) vaccines were administered on days 0, 7, 21, and 365 intramuscularly. The seroconversion rates at months 1 and 3 were 35.7 and 57.1% in group I and 25 and 18.8% in group II, respectively. Group I developed higher seroconversion rates at month 3. In group III the seroconversion rates for hepatitis B at months 1 and 3 were 54.5 and 60% and in group IV 50 and 70%, respectively. For hepatitis A, the seroconversion rates at months 1 and 3 were 81.8 and 90% in group III and 80 and 88.9% in group IV, respectively. The accelerated vaccination schedule seems to have no advantage in children receiving cancer chemotherapy except for high antibody levels at month 1. In conclusion, the accelerated vaccination schedules are not good choices for cancer patients. The combined hepatitis A/B vaccine is more effective than monovalent vaccine in cancer patients, which probably can be explained by an adjuvant effect of the antigens. The seroconversion of hepatitis A by the combined hepatitis A/B vaccination is very good in cancer patients.

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.

An unusual cause of acute renal failure: renal lymphoma

Renal involvement is a common finding in non-Hodgkin’s lymphoma (NHL). Acute renal failure at initial presentation due to lymphomatous infiltration of the kidneys has been described infrequently. We report a 17-year-old male who presented with acute renal failure due to massive lymphomatous infiltration of the kidneys, which necessitated hemodialysis. The diagnosis of B-cell NHL was established by tru-cut biopsy of the kidneys and the patient had an excellent response to high-dose chemotherapy with no major complication. The presence of extrarenal involvement in the testes and the retroperitoneal lymph nodes made the diagnosis of primary renal lymphoma debatable. However, considering the delay in diagnosis and the high proliferative rate of B-cell NHL, we might postulate that the disease had originated primarily in the kidneys. We recommend that in NHL cases with severe renal involvement, full-dose chemotherapy should be instituted with meticulous clinical and laboratory follow-up in order to improve clinical and renal failure status rapidly and to avoid further dissemination of NHL.

Renal Cell Carcinoma in Children: Experience of a Single Center

Objective: To evaluate the clinical features and outcome of children withrenal cell carcinoma (RCC). Patients and Methods: Eleven patients with RCC who were diagnosed between 1972 and 2004 were retrospectively analyzed. Clinical features, histopathology, treatment regimens and outcomes of the patients were evaluated. Results: The male/female ratio was 3:8, with a median age of 10 years. The stage distribution was as follows: 3 patients in stage I, 1 patient in stage II, 3 patients in stage IIIb, and 4 patients in stage IV. Five of 7 patients with stage II-IV received an actinomycin D-based regimen, one received a cisplatin-based regimen, and the other was given 5-fluorouracil (5-FU). In the last patient, interferon-α was given in combination with 5-FU; 1 of the patients on the actinomycin D regimen received interferon-α as well. All of the stage I patients are alive without disease. Three patients with stage IIIb, stage IV and stage II disease are alive without disease 8, 14 and 26 years after their diagnosis, respectively. The other stage IV and stage IIIb patients died of the disease. Conclusion: Nephroureterectomy is the main treatment modality, and it is sufficient for stage I patients. For patients with stage II-IV RCC, interferon-α and/or actinomycin D-based chemotherapy is the treatment of choice.

Irinotecan and Temozolamide Treatment for Relapsed Ewing Sarcoma: A Single-Center Experience and Review of the Literature

Long-term survival in relapsed Ewing sarcoma (ES) is less than 20%. Encouraging results have been reported with irinotecan and temozolomide combinations (IRN/TMZ). We aimed to share our experience and compare it with previously published studies using this combination to treat relapsed ES. We retrospectively evaluated 20 patients treated with a combination of IRN (20 mg/m2/d × 5 for 2 weeks) and temozolomide (100 mg/m2/d × 5). Patients received a total of 97 courses. An objective response was achieved in 11 patients (55%) and maintained for a median of 12 months. Five patients were alive for a median of 12 months. Median time to progression was 5.5 (2–57) months. After the IRN/TMZ treatment, 1-year overall and event-free survival rates were 54.2% and 44.4%, respectively. Grade 3–4 toxicities included diarrhea (9.2%), neutropenia (11.3%), and thrombocytopenia (6.2%). Three retrospective trials were found in our literature review, which used an IRN/TMZ combination to treat ES. There was one other study which retrospectively evaluated the efficacy of vincristine, IRN, and TMZ combination in relapsed ES. A total of 81 patients were treated with IRN/TMZ in four studies including ours. The objective response rate was 55.1%, and median time to progression ranged from 5.5 to 8.3 months. Twenty-six (7.5%) of a total of 346 courses were associated with grade 3–4 diarrhea. Grade 3–4 neutropenia and thrombocytopenia were reported in 9.2% and 7.2% of the courses, respectively. Results showed that an IRN/TMZ combination is effective and tolerable in patients with relapsed ES.

Treatment results of the Ewing sarcoma of bone and prognostic factors

The purpose of this study is to assess the clinical outcome of patients with ESFT of the bone treated with the European Intergroup Cooperative Ewings Sarcoma Study (EICESS)‐92 treatment protocol at a single center, and to identify prognostic factors.

IMMUNOGENICITY OF HEPATITIS A VACCINE IN CHILDREN WITH CANCER

This study evaluated the immuned response of the hepatitis A vaccine in children with cancer who were receiving chemotherapy. Twenty-eight patients with lymphomas or solid tumors and who had negative serology for hepatitis A were enrolled. The median age was 4.7 years (range 2–16). The patients received 1440 IU hepatitis A vaccine at 0 and 6 months. Seroconversion rates at the first and seventh months were 60% (n = 17/28 patients) and 89% (n = 24/27 patients). No adverse effects were observed. The hepatitis A vaccine was found to be effective and safe in children with cancer.

EXTRANODAL TYPE T/NK-CELL LYMPHOMA WITH AN ATYPICAL CLINICAL PRESENTATION

Peripheral-type natural killer (NK)-or T-cell lymphomas are rare disorders characterized with clonal proliferation of mature lymphocytes. They have been linked to chronic and active Epstein-Barr virus infection (CAEBV), which itself is not defined as a malignant hematological disorder. The authors present a patient with T/NK-cell lymphoma involving skin, kidneys, spleen, pancreas, and meninges. She was remarkable for having the mosaic feature of more than one type of extranodal T/NK-cell lymphoma. She also had mixed findings of CAEBV that might have been attributed both to hypersensitivity to mosquito bites and to hemophagocytic lymphohistiocytosis.

Long-Term Survival Results of Pediatric Rhabdomyosarcoma Patients: A Single-Center Experience From Turkey

The characteristics and clinical outcomes of 409 children with rhabdomyosarcoma, treated in a single center between 1972 and 2003, were evaluated to identify those characteristics that may have improved the outcome. Retrospective analysis was performed on 409 children for variables such as age, sex, primary tumor site, TNM (Tumor, Node, Metastasis) stage, Intergroup Rhabdomyosarcoma Studies (IRS) clinical group, histological subtypes, treatment. The mean age was 5.4 years and the male/female ratio was 1.6/1.0. Most of the patients were at stage III and the most common site of metastases was the lung. The median time of follow-up was 114 months. The 10-year event-free survival and overall survival rates were 27% and 33%, respectively. All parameters apart from sex and histological subtypes were found to be correlated with clinical outcome. Orbital and genitourinary system tumors (bladder-prostat tumors excluded), patients >1 year of age, TNM stage I and II tumors, IRS clinical group I and II tumors, grossly resectable tumors, and treatment with chemotherapy protocols containing anthracyclines correlated with better prognoses. In multivariate analyses, tumor invasion to surrounding tissue, regional lymph node involvement, and debulking surgery were found to be negatively correlated with prognosis. In children with rhabdomyosarcoma, survival rates can be improved owing to factors such as advancement in diagnostic and therapeutic techniques, improved supportive care, and a multidisciplinary approach.