Neuroblastoma
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-525-6884
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Overview
Neuroblastoma is the most common extracranial solid cancer in infancy and childhood. It is a neuroendocrine tumor, arising from any neural crest element of the sympathetic nervous system. Close to 50 percent of neuroblastoma cases occur in children younger than two years old.[1]
Description
Neuroblastoma is a cancer of the sympathetic nervous system -- a nerve network that carries messages from the brain throughout the body. Its solid tumors, which take the form of a lump or mass, commonly begin in one of the adrenal glands, though they can also develop in nerve tissues in the neck, chest, abdomen, or pelvis.
The cause of neuroblastoma is unknown, though most physicians believe that it is an accidental cell growth that occurs during normal development of the adrenal glands.
Neuroblastoma is one of the rare human malignancies known to demonstrate spontaneous regression from an undifferentiated state to a completely benign cellular appearance.
- VIDEO - Neuroblastoma, Jeannie Yang, MD, gives an overview at the University of Wisconsin Department of Surgery Grand Rounds (2007)
Etiology
The etiology of neuroblastoma is not well understood. Several risk factors have been proposed and are the subject of ongoing research. Due to characteristic early onset many studies have focussed on parental factors around conception and during gestation. Factors investigated have included occupation (i.e. exposure to chemicals in specific industries), smoking, alcohol consumption, use of medicinal drugs during pregnancy and birth factors, however results have been inconsistent.[1]
Other studies have examined possible links with atopy and exposure to infection early in life[1], use of hormones and fertility drugs[1] ,and maternal use of hair dye[1].
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, like lymphomas 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).[1]
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).
Screening
In a controlled study whose results were published in 2002, screening of all healthy infants' urine for markers of neuroblastoma was compared to deaths of infants whose urine was not tested. The overall death rate from the cancer was the same. Screening identified infants with harmless neuroblastomas that would have melted away without treatment; the infants were then subjected to surgery and chemotherapy.[1]
Treatment
Current
When the lesion is localized, it is generally curable. However, long-term survival for children with advanced disease is poor despite aggressive multimodality therapy.
Recent biologic and genetic characteristics have been identified, which, when added to classic clinical staging, has allowed accurate patient assignment to risk groups so that treatment strategies can be more effectively undertaken. These criteria include the age of the patient, extent of disease spread, microscopic appearance, and several other biological features, most importantly MYCN oncogene amplification, into low, intermediate, and high risk disease. The therapy for these different risk categories is very different. Low risk patients can frequently be observed without any treatment at all, while intermediate risk patients are treated with chemotherapy. High-risk neuroblastoma is treated with intensive chemotherapy, surgery, radiation therapy, bone marrow / Hematopoietic stem cell transplantation and biological-based therapy with Cys-Retinoic acid (Accutane). With current treatments, patients with low and intermediate risk disease have an excellent prognosis with cure rates above 90%. In contrast, therapy for high-risk neuroblastoma results in cures only about 30% of the time.
Clinical trials for new treatments
In November 2006, DRAXIS Health received approval from the U.S. Food and Drug Administration (FDA) to run two clinical trials using radioactive Iobenguane I-131 Injection (I-131 MIBG) to treat high-risk neuroblastoma. Both will be coordinated by a group of 11 children’s hospitals and two universities in the United States known as the New Advances in Neuroblastoma Therapy (NANT) consortium, and are continuations of earlier NANT studies. The trials were expected to start in December 2006 or early 2007. [1]
In February 2007, a study in in Sweden reported that a common painkiller, might inhibit the development of neuroblastoma and help make treatment of the disease more effective. Celecoxib, an analgesic, anti-inflammatory substance that works by inhibiting the effect of the inflammatory enzyme, Cox-2, and thus could affect neuroblastoma tumors, which depend on Cox-2 for their growth and proliferation. Clinical studies are now planned; research to date has been done only in animals and cell cultures. [1]
Post-treatment prognosis
After it is declared that the disease is gone, it often comes back. Further treatment is then required. This can be problematic because some treatments, such as chemotherapy, have cumulative effects and side-effects therefore can increase significantly if used again.
Intensive chemotherapy and radiation therapy have known long-term negative consequences. An estimated two of three survivors of childhood cancer will ultimately develop at least one chronic and sometimes life-threatening health problem within 20 to 30 years after the cancer diagnosis.[1][1]
Notes
References
- Neuroblastoma: biological insights into a clinical enigma. Brodeur GM. Nature Reviews Cancer. 2003 Mar;3(3):203-16. PMID 12612655
- Current aspects of biology, risk assessment, and treatment of neuroblastoma. Haase GM, Perez C, Atkinson JB. Semin Surg Oncol. 1999 Mar;16(2):91-104. PMID 9988866
External links
- Children's Neuroblastoma Cancer Foundation
- [3] at Neuroblastoma Warriors Gateway to sufferers and Survivers of Neuroblastoma
- Overview at National Cancer Institute
- Overview at American Cancer Society
- The Neuroblastoma Society - Fighting Childhood Cancer (UK)
- 00869 at CHORUS
- Treatment at National Cancer Institute
- Overview at Memorial Sloan-Kettering Cancer Center
- Medical Image Database at Uniformed Services University of the Health Sciences
de:Neuroblastom fr:Neuroblastome it:Neuroblastoma ja:神経芽細胞腫
Acknowledgements
The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.
List of contributors:
Suggested Reading and Key General References
Suggested Links and Web Resources
For Patients
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
