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BACKGROUND The International Neuroblastoma Pathology Classification (International Classification), which was established in 1999, is significant prognostically and is relevant biologically for the evaluation and analysis of patients with neuroblastic tumors (NTs). MYCN amplification is a known molecular marker for aggressive progression of NTs. These have been used together as important prognostic factors to define risk groups for patient stratification and protocol assignment. METHODS A total of 628 NTs (535 neuroblastomas [NBs]); 21 ganglioneuroblastoma, intermixed [GNBi]; 9 ganglioneuromas [GN]; and 63 ganglioneuroblastoma, nodular [GNBn]) from the Children's Cancer Group studies were evaluated histologically (favorable histology [FH] tumors vs. unfavorable histology [UH] tumors) according to the International Classification and were tested molecularly for MYCN status (amplified vs. nonamplified). Four tumor subsets (FH‐nonamplified, FH‐amplified, UH‐nonamplified, and UH‐amplified) were defined by histopathology and MYCN status, and their prognostic effects were analyzed. Detailed analysis between morphologic indicators (grade of neuroblastic differentiation and mitosis‐karyorrhexis index [MKI]) and MYCN status was done by using tumors in the NB category. RESULTS There were 339 FH‐nonamplified tumors (5‐year event free survival [EFS], 92.1%); 8 FH‐amplified tumors (EFS, 37.5%); 172 UH‐nonamplified tumors (EFS, 40.9%); and 109 UH‐amplified tumors (EFS, 15.0%). The prognostic effects on patients with tumors in the four subsets were independent from the factors of patient age and disease stage (P < 0.0001). MYCN amplification was seen almost exclusively in tumors of the NB category, and no patients with tumors in either the GNBi category or in the GN category and only two patients with tumors in the GNBn category had amplified MYCN. Among the patients with tumors in the NB category, patients with FH‐nonamplified tumors (309 patients) had an excellent prognosis, and patients with UH‐amplified tumors (107 patients) had the poorest clinical outcome in any age group. The prognosis for children with UH‐nonamplified tumors (111 patients) was poor when they were diagnosed at age > 1.5 years. It was also noted that patients with UH‐amplified tumors (median age, 2.14 years) were diagnosed at a significantly younger age compared with the patients with UH‐nonamplified tumors (median age, 3.55 years). Histologically, MYCN‐amplified tumors lacked neuroblastic differentiation regardless of the age of patients. MYCN amplification also was linked generally to increased mitotic and karyorrhectic activities. However, MKI classes in patients with MYCN‐amplified tumors varied significantly, depending on the age at diagnosis, and younger patients had higher MKI classes. CONCLUSIONS The combination of histopathologic evaluation and MYCN status distinguishes four clinical and biologic tumor subsets in patients with NTs. MYCN amplification seems to be the powerful driving force for preventing cellular differentiation regardles...

Rituximab, a chimeric murine/human monoclonal anti-CD20 antibody, was licensed for the treatment of B-cell lymphoma and has also shown efficacy against autoimmune diseases such as immune thrombocytopenic purpura (ITP). It is relatively safe; however, about 1-20% of patients were reported to have developed rituximab-induced serum sickness, which is more common among patients with autoimmune conditions than among those with hematologic malignancies. Here we describe a pediatric patient with steroid-dependent chronic ITP who presented with arthralgia and fever ten days after the second infusion of rituximab (on day 10), and presented with malaise and maculopapular rash on day 21. Oral prednisolone was started and his symptoms resolved. He had an elevated level of human anti-chimeric antibody (HACA) on day 27; thereafter, the HACA level slowly decreased. To our knowledge, among pediatric patients who received rituximab for chronic ITP, this is the sixth documented case of serum sickness and the only one who manifested an elevated level of HACA. Rituximab is a beneficial treatment option against chronic ITP; however, the risk of serum sickness should be considered. Steroid, usually used for the treatment of serum sickness, may prevent the development of severe serum sickness when administered during and after rituximab treatment.