Neuroblastoma diagnosis

Diagnosis
The first symptoms of neuroblastoma are often vague and may include fatigue and loss of appetite. Later symptoms depend on tumor locations. In the abdomen, a tumor may cause a swollen belly and constipation. A tumor in the chest may cause breathing problems. Tumors pressing on the spinal cord cause a feeling of weakness. A tumor in the head may cause the eyes to start to swell outwards and turn black due to the pressure from behind. Often because symptoms are so unclear, half of all neuroblastomas have already spread (metastasized) to other parts of the body by the time suspicions are raised and a diagnosis is made.

Diagnosis of neuroblastoma can be complicated. It has been called the "great masquerader" because its symptoms mimic so many other diseases. Even a pathological study (biopsy) might reveal cells that can resemble other small round blue tumor cells, likelymphomas and rhabdomyosarcomas. Only a pathologist familiar with neuroblastoma can distinguish the difference (and neuroblastoma is rare). Other characteristics of the suspected neuroblastoma cells can be studied by immunohistochemistry and electron microscopy. In about 90% of cases of neuroblastoma, elevated levels of catecholamines or its metabolites are found in the urine or blood. Catecholamines and their metabolites include dopamine, homovanillic acid (HVA), and/or vanillylmandelic acid (VMA).

Another way to detect neuroblastoma is the mIBG scan (meta-iodobenzylguanidine), but it doesn't diagnose the disease in 100% of the cases. It works like this: mIBG is taken up by sympathetic neurons, and is a functioning analog of the neurotransmitter norepinephrine. When it is radio-ionated with I-131 (a radioactive iodine), it is a very good radiopharmaceutical for diagnosis of this disease.

Identification
Other tumors also have similar origins and show a wide pattern of differentiation ranging from benign ganglioneuroma to partially differentiated ganglioneuroblastoma to highly malignant neuroblastoma.

The diagnosis is usually confirmed by a surgical pathologist, taking into account the clinical presentation, microscopic findings, and other laboratory tests. On microscopy, the tumor cells are typically described as small, round and blue, and rosette patterns (Homer-Wright pseudo-rosettes) may be seen. A variety of immunohistochemical stains are used by pathologists to distinguish neuroblastomas from histological mimics, such as rhabdomyosarcoma, Ewing's sarcoma, lymphoma and Wilms' tumor. The N-myc amplification is characteristic, and sometimes electron microscopy is also required. In February 2007, Althea Technologies announced the development of a molecular diagnostic capable of clearly differentiating various types of childhood cancers, developed in cooperation with the U.S. National Cancer Institute (NCI).

Stages
Neuroblastoma is stratified 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 ispilateral 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: 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).