MRI showing orbital and skull vault metastatic<unk>  in 2-year-old The diagnosis is usually confirmed by a surgical pathologist, taking into account the clinical presentation, microscopic findings, and other laboratory tests. It may arise from any neural crest element of the sympathetic nervous system (SNS). Esthesioneuroblastoma, also known as olfactory<unk> , is believed to arise from the olfactory epithelium and its classification remains controversial. However, since it is not a sympathetic nervous system malignancy, esthesioneuroblastoma is a distinct clinical entity and is not to be confused with<unk> . Biochemistry In about 90% of cases of<unk> , elevated levels of catecholamines or their metabolites are found in the urine or blood. Catecholamines and their metabolites include dopamine, homovanillic acid (HVA), and/or vanillylmandelic acid (VMA). Imaging Another way to detect<unk>  is the meta-iodobenzylguanidine scan, which is taken up by 90 to 95% of all<unk> s, often termed "mIBG-avid". The mechanism is that mIBG is taken up by sympathetic neurons, and is a functioning analog of the neurotransmitter norepinephrine. When it is radio-iodinated with I-131 or I-123 (radioactive iodine isotopes), it is a very good radiopharmaceutical for diagnosis and monitoring of response to treatment for this disease. With a half-life of 13 hours, I-123 is the preferred isotope for imaging sensitivity and quality. I-131 has a half-life of 8 days and at higher doses is an effective therapy as targeted radiation against relapsed and refractory<unk> . As mIBG is not always taken up by<unk> s, researchers have explored in children with<unk>  whether another type of nuclear imaging, fluoro-deoxy-glucose – positron emission tomography, often termed "F-FDG-PET", might be useful. Evidence suggests that this might be advisable to use in children with<unk>  for which mIBG does not work, but more research is needed in this area. Histology Microscopic view of stroma-rich ganglioneuroblastoma On microscopy, the tumor cells are typically described as small, round and blue, and rosette patterns (Homer Wright pseudorosettes) may be seen. Homer Wright pseudorosettes are tumor cells around the neuropil, not to be confused with a true rosettes, which are tumor cells around an empty lumen. They are also distinct from the pseudorosettes of an ependymoma which consist of tumor cells with glial fibrillary acidic protein (GFAP)–positive processes tapering off toward a blood vessel (thus a combination of the two). A variety of immunohistochemical stains are used by pathologists to distinguish<unk> s from histological mimics, such as rhabdomyosarcoma, Ewing's sarcoma, lymphoma and Wilms' tumor.<unk>  is one of the peripheral neuroblastic tumors (pNTs) that have similar origins and show a wide pattern of differentiation ranging from benign ganglioneuroma to stroma-rich ganglioneuroblastoma with neuroblastic cells intermixed or in nodules, to highly malignant<unk> . This distinction in the pre-treatment tumor pathology is an important prognostic factor, along with age and mitosis-karyorrhexis index (MKI). This pathology classification system (the Shimada system) describes "favorable" and "unfavorable" tumors by the International<unk>  Pathology Committee (INPC) which was established in 1999 and revised in 2003. Staging The "International<unk>  Staging System" (INSS) established in 1986 and revised in 1988 stratifies<unk>  according to its anatomical presence at diagnosis: *Stage 1: Localized tumor confined to the area of origin. *Stage 2A: Unilateral tumor with incomplete gross resection; identifiable ipsilateral and contralateral lymph node negative for tumor. *Stage 2B: Unilateral tumor with complete or incomplete gross resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor. *Stage 3: Tumor infiltrating across midline with or without regional lymph node involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement. *Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S. *Stage 4S: Age <1 year old with localized primary tumor as defined in Stage 1 or 2, with dissemination limited to liver, skin, or bone marrow (less than 10 percent of nucleated bone marrow cells are tumors). Although international agreement on staging (INSS) has been used, the need for an international consensus on risk assignment has also been recognized in order to compare similar cohorts in results of studies. Beginning in 2005, representatives of the major pediatric oncology cooperative groups have met to review data for 8,800 people with<unk>  treated in Europe, Japan, USA, Canada, and Australia between 1990 and 2002. This task force has proposed the International<unk>  Risk Group (INRG) classification system. Retrospective studies revealed the high survival rate of 12–18 month-old age group, previously categorized as high-risk, and prompted the decision to reclassify 12–18 month-old children without N-myc (also commonly referred to as MYCN) amplification to intermediate risk category. The new INRG risk assignment will classify<unk>  at diagnosis based on a new International<unk>  Risk Group Staging System (INRGSS): *Stage L1: Localized disease without image-defined risk factors. *Stage L2: Localized disease with image-defined risk factors. *Stage M: Metastatic disease. *Stage MS: Metastatic disease "special" where MS is equivalent to stage 4S. The new risk stratification will be based on the new INRGSS staging system, age (dichotomized at 18 months), tumor grade, N-myc amplification, unbalanced 11q aberration, and ploidy into four pre-treatment risk groups: very low, low, intermediate, and high risk.
Neuroblastoma
Ewing's sarcoma
Central neurocytoma
Astroblastoma
Neurothekeoma
Germinoma
Sialoblastoma
Neuroma