Neuroblastoma overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
Neuroblastoma is a malignant tumor that arises from neural crest cells, which are normally involved in the development of the sympathetic nervous system and adrenal glands.[1][2][3][4] In 1910, the term neuroblastoma was first used to describe the tumor by Dr. James Homer Wright, an American patholgist at Massachusetts General Hospital. Based on the degree of the cellular maturity and composition, neuroblastoma may be further classified into three subtypes according to the International Neuroblastoma Pathology Classification which include undifferentiated neruoblastoma, poorly differentiated neuroblastoma, and differentiating neuroblastoma.[5][6] Genes involved in the pathogenesis of neuroblastoma include NBPF10 gene, KIF1B gene, and ALK gene. Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy. The staging of neuroblastoma is based on the International Neuroblastoma Staging System (INSS).[7][8] Symptoms of neuroblastoma include fever, abdominal distension, constipation, cough, and weakness. A positive finding of a palpable abdominal mass, fever, and purple skin patches is suggestive of neuroblastoma. On labrotary studies an elevated levels of blood and urinary catecholamines, vanillylmandelic acid (VMA), and homovanillic acid (HVA) are suggestive of neuroblastoma. CT scan is the investigation of choice for the diagnosis of neuroblastoma.[8] On CT scan, neuroblastoma is characterized by a heterogeneous, calcified, and necrotic mass, that may encase surrounding vessels or invade surrounding tissues. The definitive diagnosis of nueroblastoma is confirmed by a biopsy. Children Oncology Group (COG) risk stratification system determines the protocol of management used for neuroblastoma patients. Low risk neuroblastoma patients are usually managed with either observation or surgical resection of the tumor. Intermidiate risk neuroblastoma patients are usually managed with neoadjuvant chemotherapy in advance of a definitive surgical resection. Whereas high risk neuroblastoma patients are usually managed with a combination of surgery, chemotherapy, radiation therapy, hematopoietic stem cell transplantation, differentiation therapy, and immunotherapy. Surgical intervention alone may be curative as a single therapeutic modality for the management of low risk neuroblastoma patients.[1][2][3][4]
Historical Perspective
Neuroblastoma was first described by Rudolf Virchow in 1864 as an abdominal tumor in a child as "glioma". Felix Marchand described characteristics of tumors from adrenal medulla and sympathetic nervous system in 1891. James Homer wright in 1910, described circular clumps of bone marrow ( now named "Homer-Wright pseudorosettes) and advanced the understanding that tumor originated from primitive neural cells and could metastasize to bone.
Classification
International neuroblastoma pathology classification system is used for the classification of neuroblastic tumors. It is subdivided in 02 main categories based on the morphologic features of neuroblastic tumors into; schwannian stroma-poor and schwannian stroma-rich/dominant.
Pathophysiology
Neuroblastoma arises from the neural crest cells, which are normally involved in development of sympathetic nervous system and adrenal glands. It is frequently located along the sympathetic nervous system structures including; adrenal glands, retroperitoneal organs, organ of zuckerkandl, paravertebral sympathetic chain and posterior mediastinum among others. Neuroblastoma tumor cells secrete catecholamine by products including vanillylmandelic acid (VMA) and homovanillic acid (HVA) and vasoactive intestinal polypeptide (VIP) hormone as well. It can metastasize to bone, liver, lungs and brain. The various genes involved in pathogenesis of neuroblastoma include; NBPF10, KIF1B, ALK, LMO1 and PHOX2A genes. The most common genetic mutation is gain of chromosome 17q and MYCN oncogene amplification predicts more aggressive neuroblastoma. Neuroblastoma can also be associated with a number of syndromes including; neurofibromatosis type 1, beckwith-weidman syndrome and hirschsprung disease. On gross pathology, the characteristic finding of neuroblastoma is a well defined, bulky and tan colored mass, that can be associated with fibrous pseudocapsule, necrosis or hemorrhage. On microscopic picture, the presence of round blue cells separated by thin fibrous septa are a characteristic finding.
Causes
There are no known established causes for neuroblastoma.
Differentiating Multiple Myeloma from other Diseases
Intra-abdominal neuroblastoma must be differentiated from other diseases that cause abdominal distension and constipation such as Wilms tumor and ganglioneuroma. Intra-thoracic neuroblastoma must be differentiated from other diseases that cause shortness of breath and chronic cough such as intrathoracic lymphoma and extra lobar pulmonary sequestration.
Epidemiology and Demographics
Neuroblastoma is the most common solid extracranial cancer in childhood and is the most common cancer in infancy. The overall incidence is 4.9 per 1,000,000 individuals in united states. Males are slightly more affected than females with 1.2:1 ratio. Neuroblastoma usually affects individuals of the caucasian race.
Risk Factors
There are no established risk factors for neuroblastoma.[1]
Screening
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for neuroblastoma.[9]
Natural History, Complications and Prognosis
If left untreated, patients with neuroblastoma may progress to develop fatigue, loss of appetite, joint pain, and fever. Complications of neuroblastoma may include treatment-resistant diarrhea, Horner's syndrome, and transverse myelopathy. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis of neuroblastoma is generally regarded as poor.[3][1][4][2]
Diagnosis
Staging
According to the conventional International Neuroblastoma Staging System (INSS), there are 6 stages of neuroblastoma based on the tumor size, lymph node involvement, and presence of metastesis. However, according to a newly proposed International Neuroblastoma Risk Group Staging System (INRGSS), there are four stages of neuroblastoma based on the extent of dissemination and image findings. Neuroblastoma patients are risk stratified according to the Children Oncology Group (COG) risk stratification system into a low risk group, an intermediate risk group, and a high risk group based on the tumor INSS stage, the patient's age, tumor grade, and the amplification of MYCN gene.[1][7][8][4]
History and Symptoms
Symptoms of neuroblastoma include fever, abdominal distension, constipation, cough, and weakness.[1][10][8]
Physical Examination
A positive finding of a palpable abdominal mass, fever, and purple skin patches is suggestive of neuroblastoma.[1][10][4][8]
Laboratory Findings
An elevated levels of blood and urinary catecholamines, vanillylmandelic acid (VMA), and homovanillic acid (HVA) are suggestive of neuroblastoma.[4][1][8]
X Ray
On plain radiography neuroblastoma is characterized by an intraabdominal or intrathoracic soft tissue mass. Other findings of neuroblastoma on plain radiography include calcification and remodelling of surrounding bony structures.[3]
CT
CT scan is the investigation of choice for the diagnosis of neuroblastoma.[8] On CT scan, neuroblastoma is characterized by a heterogeneous, calcified, and necrotic mass, that may encase surrounding vessels or invade the surrounding tissues.[3]
MRI
On a T1 weighted brain MRI image, neurblastoma is characterized by a hyperintense, heterogeneous, and necrotic mass.[3]
Echocardiography or Ultrasound
On ultrasound, neuroblastoma is characterized by a heterogeneous echogenicity due to the vascular, necrotic, and calcified content of the mass.[3]
Other Imaging Findings
Other imaging studies for neuroblastoma include nuclear medicine studies such as fludeoxyglucose-18F positron emission tomography scan (18F-FDG PET) and metaiodobenzylguanidine (123I-MIBG) scintigraphy.[11]
Other Diagnostic Studies
The definitive diagnosis of nueroblastoma is confirmed by a biopsy. Charecterstic findings for neuroblastoma on microscopic histopathological analysis can be found here.[2]
Treatment
Medical Therapy
Children Oncology Group (COG) risk stratification system determines the protocol of management used for neuroblastoma patients. Low risk neuroblastoma patients are usually managed with either observation or surgical resection of the tumor. Intermidiate risk neuroblastoma patients are usually managed by 4-8 cycles of chemotherapy following surgical resection. Whereas high risk neuroblastoma patients are usually managed with a combination of surgery, chemotherapy, radiation therapy, hematopoietic stem cell transplantation, differentiation therapy, and immunotherapy.[4]
Surgery
Surgical intervention alone may be curative as a single therapeutic modality for the management of low risk neuroblastoma patients.[4]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Neuroblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Neuroblastoma Accessed on October, 4 2015
- ↑ 2.0 2.1 2.2 2.3 Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Neuroblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 5 2015
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Neuroblastoma Treatment for health professionals. National Cancer Institute (2015) http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#link/_534_toc Accessed on October, 7 2015
- ↑ Neuroblastoma, Ganglioneuroblastoma and Ganglioneuroma. Stanford Medicine Surgical Pathology Criteria(2015) http://surgpathcriteria.stanford.edu/srbc/neuroblastoma-ganglioneuroblastoma-ganglioneuroma/ Accessed on October, 5 2015
- ↑ Shimada H, Umehara S, Monobe Y, Hachitanda Y, Nakagawa A, Goto S; et al. (2001). "International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group". Cancer. 92 (9): 2451–61. PMID 11745303.
- ↑ 7.0 7.1 Davidoff AM (2012). "Neuroblastoma". Semin Pediatr Surg. 21 (1): 2–14. doi:10.1053/j.sempedsurg.2011.10.009. PMC 3261589. PMID 22248965.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Colon NC, Chung DH (2011). "Neuroblastoma". Adv Pediatr. 58 (1): 297–311. doi:10.1016/j.yapd.2011.03.011. PMC 3668791. PMID 21736987.
- ↑ Recommendations. US Preventive Services Task Force(2015) http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=neuroblastoma Accessed on October, 5 2015
- ↑ 10.0 10.1 Neuroblastoma Childhood: Symptoms and Signs. Cancer.net http://www.cancer.net/cancer-types/neuroblastoma-childhood/symptoms-and-signs Accessed on October, 7 2015
- ↑ Sharp SE, Shulkin BL, Gelfand MJ, Salisbury S, Furman WL (2009). "123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma". J Nucl Med. 50 (8): 1237–43. doi:10.2967/jnumed.108.060467. PMID 19617326.