Neuroblastoma: Difference between revisions

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== Definition/Description  ==
== Introduction ==
[[Image:Neuroblastomacells.jpg|thumb|right]]Neuroblastoma is a form of cancer that originates in the nerve cells, specifically within the [[Sympathetic Nervous System|sympathetic nervous system]]. <ref name="Mayo">Mayo Clinic: neuroblastoma. http://www.mayoclinic.com/health/neuroblastoma/DS00780 (accessed 9 March 2011).</ref>The cancer is found in the primitive cells of a fetus or an embryo, and then the cancer cells proliferate in the young child.<ref name="American Cancer Society">American Cancer Society: neuroblastoma.  http://www./Cancer/Neuroblastoma/DetailedGuide/neuroblastoma-what-is-cancer (accessed 2 March 2011).</ref> The cancer typically arises from the following areas of the body: retroperitoneal area, posterior mediastinum, [[Pelvic Floor Anatomy|pelvis]], and neck.<ref name="Patho Book">Goodman CC, Fuller KS. Pathology: Implications for the Physical Therapist. 3rd edition. St. Louis, Missouri: Saunders Elsevier, 2009.</ref>
[[File:Neuroblastoma.jpeg|right|frameless]]
Neuroblastoma is the most common solid tumour of childhood.  


== Prevalence  ==
'''Image 1: Giant neuroblastoma in an Ethiopian shepherd child'''


Neuroblastoma is most commonly diagnosed in children under the age of 5 years old, but can be diagnosed in older children as well.<ref name="Patho Book" /> Neuroblastoma is the most common form of cancer in infants under the age of one year old and accounts for approximately 28% of all infant cancers. Neuroblastoma is the most common form of cancer death in this population at an incidence of 65 per million infants under the age of one year.<ref name="National Cancer Institute">National Cancer Institute: neuroblastoma.  http://www.cancer.gov/cancertopics/types/neuroblastoma (accessed 9 March 2011).</ref> This form of childhood cancer is the most commonly diagnosed extracranial solid tumor. Currently in the United States, new neuroblastoma cases are being diagnosed at a rate of over 500 children a year. The prevalence is slightly higher among Caucasians compared to non-white children.<ref name="American Cancer Society" /> In comparison to all other childhood cancers, neuroblastoma accounts for 7.8% of cases out of all childhood cancers worldwide.<ref name="National Cancer Institute" /> About 1/100,000 children are diagnosed each year.<ref name="St. Jude's">St. Jude’s Children Research Hospital: neuroblastoma.  http://www.stjude.org/Medical/neuroblast.htm (accessed 10 March 2011)</ref>
It is almost exclusively a childhood [[Oncology|cancer]] occurring most commonly between the ages of 0-5 years. Neuroblastomas are cancers that start in early [[Neurone|nerve cells]] (called neuroblasts) of the [[Sympathetic Nervous System|sympathetic nervous system]]. This means that tumours can be found anywhere along this system; most commonly (about 50%) start in the [[Adrenal Glands|adrenal glands]] (above the [[kidney]]), or near the spine, chest, neck or [[pelvis]].


== Etiology/Causes  ==
Rarely, a neuroblastoma has spread so widely by the time it is found, doctors can’t tell exactly where it started.<ref name=":1">Neuroblastoma Australia [https://www.neuroblastoma.org.au/pages/faqs/category/what-is-neuroblastoma What is neuroblastoma?] Available:https://www.neuroblastoma.org.au/pages/faqs/category/what-is-neuroblastoma (accessed 14.10.2021)</ref>


The cause of neuroblastoma is unknown, and it is noninfectious. Neuroblastoma can sometimes be connected to a genetic link from a parent or family member. It is rare that a genetic link between a parent and a child can be connected.<ref name="Mayo" />  
Due to the high variability in its presentation, clinical signs and symptoms at presentation can range from benign palpable mass with distension to major illness from substantial tumor spread.<ref name=":2">Mahapatra S, Challagundla KB. [https://www.ncbi.nlm.nih.gov/books/NBK448111/ Cancer, neuroblastoma]. Cancer. 1918 Apr 13;10:49. 2021 Available: https://www.ncbi.nlm.nih.gov/books/NBK448111/ (accessed 14.10.2021)</ref>


== Characteristics/Clinical Presentation  ==
This video (3 minutes) is of the common symptoms of neuroblastoma
[[Image:Neuroblastoma chart.jpg|thumb|right]]
''<nowiki/>''{{#ev:youtube|L9r_y4BnIzw|300}}<ref name=":4" />
== Epidemiolgy ==
[[File:Neuroblastoma infant.jpeg|right|frameless|295x295px]]
The tumours typically occur in infants and very young children (mean age of presentation being ~22 months) with 95% of cases diagnosed before the age of 10 years. Occasionally, they may be identified antenatally or immediately at birth.<ref name=":3">Radiopedia [https://radiopaedia.org/articles/neuroblastoma Neuroblastoma] Available:https://radiopaedia.org/articles/neuroblastoma (accessed 14.10.2021)</ref>


Neuroblastoma presents in a variety of forms based upon the location of its&nbsp;manifestation and the size of the tumor. The neuroblastoma presentation changes if the cancer has spread (metastasis), and if the tumor secretes hormones. At the time of the patient's diagnosis, neuroblastoma cells have already spread to other parts of the body 73% of the time.&nbsp;The common signs and symptoms of the patient include the following descriptions.<ref name="Ped-Onc">Ped-Onc Reference Center: neuroblastoma. http://www.ped-onc.org/diseases/neuro.html (accessed on 4 March 2011).</ref>
'''Image 2''': STAGE IV-S NEUROBLASTOMA This infant has massive hepatomegaly due to metastatic neuroblastoma. Intra-abdominal pressure is partially relieved by a silastic pouch.
'''''Main Tumor Signs and Symptoms:'''''  
[[File:Neuroblastoma mets.jpg|thumb|Orbital and skull vault neuroplastoma]]
''Palpable Mass'': A lump can be found in a variety of locations in a child with neuroblastoma. The [[Abdominal Muscles|abdomen]] is the most&nbsp;common location to find a mass. The child may present with swelling around the location of the mass, have complaints&nbsp;of discomfort or pain, and may refuse to eat. The lump maybe&nbsp;palpable, but is often not painful or tender to the touch.<ref name="American Cancer Society" /> &nbsp;The child may also have [[Blood Pressure|high blood pressure]] from the tumor pressing on the [[Abdominal Aortic Aneurysm|abdominal aorta]] or other large blood vessels in the abdomen.<ref name="MacMillan">MacMillan Cancer Support: neuroblastoma. http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Childrenscancers/Typesofchildrenscancers/Neuroblastoma.aspx (accessed on 4 March 2011).</ref>
*''Edema'': If the lymph and blood vessels are blocked due to pressure from a tumor, edema will accumulate. Accumulation of swelling is common in the legs, and it is common to have swelling in the male scrotum. The clogging of the blood vessels will prevent the fluid from circulating properly through the body and back to the heart.<ref name="American Cancer Society" />
*''Bowel/Bladder Changes'': A tumor located near the bladder or colon can affect urination and bowel movements. The patient may either have an increase or decrease in bowel and bladder dysfunction, and/or discomfort in the lower abdominal region.<ref name="American Cancer Society" />
*''Facial Edema'': Tumors located in the neck near the superior vena cava can cause swelling in the neck or head region. The child may complain of or demonstrate a difficulty with swallowing and breathing.<ref name="American Cancer Society" />
*''Weakness/Movement Dysfunction'': The patient may present with a decrease in strength, decreased sensation, and decreased motion due to a tumor located near the [[Spinal cord anatomy|spine]] that is applying pressure to a nerve root. If the patient is walking, an antalgic gait maybe noted. The patient who is not walking yet will demonstrate with decreased extremity motions. Proximity of the tumor to the nerve root or spinal cord can cause compression on the cord leading to radiculopathy. Signs of [[radiculopathy]] include weakness, numbness, tingling, etc. primarily in a dermatome distribution.<ref name="American Cancer Society" />
*''Visual Changes'': The patient may present with drooping eyelids (ptosis) and decreased pupil size (miosis) due to pressure on Cranial Nerve III, [[Oculomotor Nerve|occulomotor nerve]].<ref name="American Cancer Society" />
*''[[Dyspnoea/Dyspnea|Dyspnea]]:'' A patient with a tumor located in the chest cavity may present with shortness of air and experience difficulty swallowing.<ref name="American Cancer Society" />


'''''Metastatic Tumors Signs and Symptoms:'''''[[Image:Neuroblastomaskin.jpg|thumb|alt=]]''Limping/Pain During Ambulation'': Neuroblastoma commonly metastasize to the bone and cause pain during ambulation or generalized pain in the bones. A child with neuroblastoma metastasized to the bone may present with an antalgic [[Gait Cycle|gait]], increased pain with movement, and decreased strength. If the cancer spreads to the vertebral column, the patient may have weakness, decreased sensation, and possibly even paralysis in the extremities due to pressure on the [[Spinal cord anatomy|spinal cord]] from the tumor.<ref name="American Cancer Society" /> Larger bones are common metastasis sites for infants. The proportionally larger bones include the [[femur]], [[humerus]], and [[skull]].<ref name="JAAPA">Stebbins, M. Neuroblastoma: Management of a common childhood malignancy. JAAPA 2010; November Issue.  http://www.jaapa.com/neuroblastoma-management-of-a-common-childhood-malignancy/article/189770/ (accessed 4 March 2011)</ref><ref name="Differential Diagnosis" />
== Etiology ==
There are no known reasons as to why this cancer occurs and there are no clear environmental links. Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline<ref name=":2" />.


* ''Integumentary Changes'': Skin changes such as bluish purple lesions that resemble blueberries may appear on the skin if neuroblastoma has spread to the integumentary system.<ref name="American Cancer Society" />[[File:Raccooneyes.jpg|thumb|Raccoon eyes]]''Personality Changes: ''The child may have personality changes including fatigue, irritability, and generalized weakness. These changes could indicate that the neuroblastoma has metastasized to the bone marrow causing a decrease in the white blood cell, red blood cell, and/or platelet counts. The changes could also be associated with an increase in bleeding from small cuts or scrapes and an increase in infections.''<ref name="American Cancer Society" />'<nowiki/>''
There are rare cases where neuroblastoma runs in families due to a [[Genetic Disorders|genetic mutation]], but in most cases there is no known genetic cause.<ref name=":1" />
 
== Characteristics/Clinical Presentation  ==
''<nowiki/>''
[[File:Raccooneyes.jpg|thumb|Raccoon eyes]]Neuroblastoma presents in a variety of forms based upon the location of its&nbsp; manifestation and the size of the tumor.<ref name="Ped-Onc">Thiele CJ. [https://www.nature.com/articles/nrdp201678#Sec20 Neuroblastoma]. InHuman cell culture 2002 (pp. 21-53). Springer, Dordrecht.</ref>. Presentation is typically with [[Pain Behaviours|pain]] or a palpable mass and abdominal distension. The neuroblastoma presentation changes if cancer has spread (metastasis), and if the tumor secretes [[hormones]]. At the time of the patient's diagnosis, neuroblastoma cells have already spread to other parts of the body 73% of the time due to local mass effect.[[File:Neuroblastoma mets.jpg|thumb|Orbital and skull vault neuroplastoma]]Other accompanying syndromes include:
 
*''Visual Changes'': Bruising surrounding the eyes may indicate the tumor has spread to the ocular region. The patient&nbsp;may also present with a protruding eye or eyes.<ref name="American Cancer Society" /> Ecchymosis or swelling of the eye gives the appearance of raccoon eyes. This presentation is common in children with tumors in the orbital region. It is hypothesized that the metastasis of tumors to the orbital region is due to the proportion differences in an infant regarding their larger skulls in comparison to their skeleton.<ref name="Differential Diagnosis">Goodman, Snyder. Differential Diagnosis for Physical Therapists: Screening for Referral. St. Louis Missouri. 2007.</ref>''<br>''
 
'''''Hormonal Signs and Symptoms:'''''
 
Neuroblastomas differ from many other cancer forms because although it is rare, they can release hormones. The hormones can create a variety of changes that are defined as [https://physio-pedia.com/Paraneoplastic_Syndrome paraneoplastic syndrome].<ref name="Differential Diagnosis" /> The hypothesized cause of paraneoplastic syndrome is due to the hormonal changes from the white blood cells attacking the healthy body. The immune system produces B cell producing antibodies and T lymphocytes that are directed at the tumor. The immune system wrongly attacks the body and brain, which have similar characteristics to the tumor.<ref name="Omsusa">Opsoclonus-Myoclonus USA and International: what is the opsoclonus-myoclonus syndrome? http://www.omsusa.org/ (accessed 9 March 2011)</ref> Tumors are capable of producing hormones, precursors to hormones, enzymes, and cytokines. The production of these proteins can present in utero in both embryonic and fetal cells. However, the cells might not present in normal adult cells. These substances serve as tumor markers. The symptoms can include the following: fever, diarrhea, increased blood pressure, increased heart rate, rubor (reddening/flushing) of the skin, clubbing of the fingers or toes, weight loss, and diaphoresis (sweating).<ref name="Differential Diagnosis" /> <ref name="Medscape">Medscape Reference:  neuroblastoma. http://emedicine.medscape.com/article/988284-clinical (accessed 9 March 2011).</ref>
 
A rare presentation of neuroblastoma in the paraneoplastic syndrome category is a patient with dancing eyes/dancing feet syndrome, also known as [http://www.omsusa.org/pranzatelli-Brochure1.htm opsoclonus-myoclonus-ataxia syndrom]e. This syndrome includes muscle spasms, uncoordinated movement, rapid eye motions, and difficulty speaking.<ref name="Mayo" />&nbsp;The hypothesized cause of opsoclonus-myoclonus-ataxia syndrome is the immune cells in the body attempt to fight off the cancer and confuse healthy cells, such as brain cells, for tumor cells. In other words, the brain gets caught in the crossfire of the immune systems fight and the effects are opsoclonus-myoclonus-ataxia syndrome.<ref name="Omsusa" />
 
{{#ev:youtube|UCiAz8YA0iY|400}}<ref>Wowduran. Jonah aged 5 Neuroblastoma with opsoclonus myoclonus. Available from: http://www.youtube.com/watch?v=UCiAz8YA0iY [last accessed on 3 April 2011]</ref>
 
'''''Stages of Neuroblastoma:'''''
 
<u>Stage 1:</u> The percentage of children diagnosed at this stage is 21%.  
 
The primary tumor is located and isolated to one area of the body. The lymph nodes bilaterally are negative for cancer. The neuroblastoma cancer in this stage can be removed by surgery. Microscopic residual cancerous tissue may remain after removal of the tumor.<ref name="cncf staging">Children's Neuroblastoma Cancer Foundation: neuroblastoma staging. http://www.cncfhope.org/Staging_Neuroblastoma (accessed on 7 March 2011).</ref>
 
<u>Stage 2:</u> The percentage of children diagnosed at this stage is 15%
 
*2A: The primary tumor at this stage is confined to one area. However, it cannot be completely removed through surgery because of its larger size, proximity to other organs, or general location. The lymph nodes are negative bilaterally on both sides of the body for metastases.<ref name="cncf staging" />
*2B: The primary tumor at this stage is confined to one area of the body. The tumor may or may not be completely surgically removed. The lymph nodes on the side of the body where the tumor is located are positive for metastasis of neuroblastoma. The lymph nodes on the opposite side of the body are negative for metastasis.<ref name="cncf staging" />
 
<u>Stage 3:</u> The percentage of children diagnosed at this stage is 17%.
 
The following descriptions of presentations are Stage 3. The first presentation of stage 3 occurs when the primary tumor crosses the spinal cord region/midline of the body. The lymph nodes may or may not present with metastasis. The second presentation of stage 3 could be the primary tumor is located on one side of the body, while metastasis is found in the lymph nodes on the opposite side of the body. The third presentation of stage 3 could be the primary tumor is located on one side of the body while metastasis is found bilaterally in the lymph nodes.<ref name="cncf staging" />
 
<u>Stage 4:</u> The percentage of children diagnosed at this stage is 41%.  
 
This stage presentation occurs when neuroblastoma cells are found in the distal lymph nodes, liver, bone marrow, or additional organs.<ref name="cncf staging" />
 
<u>Stage 4S:</u> The percentage of children diagnosed at this stage is 6%.


The presentation at this stage is typically found within infants. The primary tumor is isolated to one area of the body, but the tumor has metastasized to other regions of the body such as bone marrow, liver, or skin. Bone metastasis is rare in this category, with less than 10%.<ref name="cncf staging" />  
* Hutchinson syndrome: skeletal metastases may present with skeletal pain or limping and irritability or proptosis with periorbital and cranial bumps.
* Pepper syndrome: hepatomegaly due to extensive liver metastasis
* Blueberry muffin syndrome: multiple cutaneous lesions
* Opsomyoclonus: rapid, involuntary conjugate fast eye movements
* Proptosis and periorbital ecchymoses ("raccoon eyes"): orbital metastases<ref name=":3" />
This video (3 minutes) is of the common symptoms of neuroblastoma
''<nowiki/>''{{#ev:youtube|L9r_y4BnIzw|300}}<ref name=":4">
Health Apta. SYMPTOMS OF NEUROBLASTOMA. Available from: http://www.youtube.com/watch?v=L9r_y4BnIzw[last accessed on 29/ 6/2021]</ref>
== Location ==
Neuroblastomas arise from the sympathetic nervous system. Intra-abdominal disease (two-thirds of cases) is more prevalent than intrathoracic disease. Specific sites include:


* Adrenal glands: most common site of origin, 35%
* Retroperitoneum: 30-35%
* Coeliac axis
* Paravertebral sympathetic chain
* Posterior mediastinum: 20%
* Neck: 1-5%
* Pelvis: 2-3%


== Associated Co-morbidities  ==
== Treatment and Prognosis ==
Treatment depends on the patient's stage. Localised tumours considered to be 'low-risk' are surgically excised, and patients tend to do very well (see below). In 'high-risk' tumours, a combination of [[Surgery and General Anaesthetic|surgery]], [[Chemotherapy Side Effects and Syndromes|chemotherapy]] +/- [[Bone Marrow|bone marrow]] transplantation is employed, unfortunately with poor overall results. In some cases, where tumours are very large, pre-surgical chemotherapy to attempt to downstage the tumour may be administered.


Associated co-morbidities of neuroblastoma include; Down syndrome, genetic abnormalities, AIDS, radiation exposure, chemo and radiation therapy.<ref name="American Cancer Society" /> Research has found that focal nodular hyperplasia of the liver is demonstrated approximately ten years after diagnosis.<ref name="FNP">Benz-Bohm G, Hero B, Gossmann A, Simon T, Körber T, Berthold F. Focal nodular hyperplasia of the liver in longterm survivors of neuroblastoma: How much diagnostic imaging is necessary? European Journal of Radiology 2010;74 (3): pgs 1-5. http://www.ncbi.nlm.nih.gov/pubmed/19369017 (accessed 10 March 2011).</ref> Organ failure is common after treatment for neuroblastoma including, Liver failure, Kidney failure, decreased immunological resistance, loss of blood cells produced by bone marrow.<ref name="PubMed">PubMed Health: neuroblastoma. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002381/ (accessed on 3 March 2011).</ref> A presentation of a genetic link has not been confirmed. Neuroblastoma can occasionally associated with children with neurofibromatosis, Beckwith-Wiedemann syndrome, and nesidioblastosis, a pancreatic condition.<ref name="St. Jude's" />
Patients with stage 1, 2, or 4S have a better prognosis. Unfortunately 40-60% of patients present with stage 3 or 4 diseases 4. For advanced disease, the age of the child is most important.<ref name=":3" />
== Stages of Neuroblastoma ==
The International Neuroblastoma Staging System (INSS) based on surgical resection is used to stage neuroblastomas in the United States.


== Differential Diagnosis  ==
<u>'''Stage 1:'''</u> The percentage of children diagnosed at this stage is 21%.


Rhabdomyosarcoma and Wilms Tumor.<ref name="Medscape" /><br>
<u>'''Stage 2:'''</u> The percentage of children diagnosed at this stage is 15%
== Diagnostic Tests/Lab Tests/Lab Values  ==


If a child presents with signs and symptoms listed above, a scheduled physical exam should be scheduled for further testing. The doctor will need to take a thorough history including medical, surgical, medicinal, etc. The following diagnostic and lab tests might be administered to diagnose a neuroblastoma.  
<u>'''Stage 3:'''</u> The percentage of children diagnosed at this stage is 17%.  


*[http://www.nlm.nih.gov/medlineplus/ency/article/003613.htm Blood and urine tests] can detect neuroblastoma from the catecholamines present. A patient will present 9/10 times with catecholamines or its metabolites present in the urine if they are positive for a neuroblastoma.<ref name="MacMillan" /> Catecholamines are hormones released by the sympathetic nervous system, and the presence of a neuroblastoma can increase the amount of catecholamines in the urine or blood. The common catecholamines that are measured during these tests are HVA (Homovanillic acid) and VMA (Vanillylmandelic acid).<ref name="American Cancer Society" /> Blood tests will reveal a high level of norepinephrine or dopamine which is common sign in patients with neuroblastoma.<ref name="PubMed urine">PubMed Health: catecholamines-urine. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004080/ (accessed 9 March 2011.)</ref>  
<u>'''Stage 4:'''</u> The percentage of children diagnosed at this stage is 41%.  
*[http://www.nlm.nih.gov/medlineplus/ency/article/003830.htm MIBG Scan] is a radioactive scan involving an injection of metaiodobenzylguanidine into the vein of a patient who has a suspected neuroblastoma. The tumor takes up the compound and a scan of the body is preformed, sometimes multiple scans are taken up to 1-3 days. The scan locates and determines the extent of the neuroblastoma.<ref name="National Cancer Institute" />
*[http://www.cancer.org/Cancer/Neuroblastoma/DetailedGuide/neuroblastoma-diagnosis Imaging] is a variety of scans utilized to determine the diagnosis of neuroblastoma. Since neuroblastoma is diagnosed often after it has metastasized to other areas, multiple imaging could be utilized to determine the extent of metastasis.<ref name="National Cancer Institute" />
*[http://www.cancer.org/Cancer/Neuroblastoma/DetailedGuide/neuroblastoma-diagnosis Biopsy] of a neuroblastoma tumor includes dissecting the tumor and then the cells will be analyzed by a pathologist for signs of cancer. The biopsy can be of a tumor or of the bone marrow. If the bone marrow is analyzed a long hollow needle is inserted into the sternum or illium. The cells are then analyzed by a pathologist for cancer.<ref name="PubMed" />


== Systemic Involvement  ==
<u>'''Stage 4S:'''</u> The percentage of children diagnosed at this stage is 6%.<ref name="cncf staging">Children's Neuroblastoma Cancer Foundation: neuroblastoma staging. http://www.cncfhope.org/Staging_Neuroblastoma (accessed on 7 March 2011).</ref>


Neuroblastoma left untreated can metastasize to other systems in the body mentioned above in the Characteristics/Clinical Presentation. The multiple systems can be affected by a primary or a metastasized tumor. Treatments for neuroblastoma such as chemotherapy and radiation can affect multiple systems. The following systems can be affected including; Nervous System, Musculoskeletal System, Gastrointestinal System, Urogenital, and Cardiopulmonary, Reproductive, and Integumentary System.<ref name="Patho Book" /><br>
'''Poor prognostic factors:''' later age of onset: >18 months; higher stage: particularly in the presence of metastasis; N-Myc mutation; chromosome 1p deletion; unfavourable Shimada histology index


== Medical Management ==
'''Better prognostic factors:''' TRK-A expression<ref name=":3" />
''Chemotherapy'' is a non-selective drug that destroys fast growing reproducing cells at particular stages in the growth cycle.<ref name="CSM">Miale, S presenter.  Improving the Quality of Life of Children with Cancer: The Role of Rehabilitation. Presented at Combined Sections Meeting of the American Physical Therapy Association; 2011 February 9-12; New Orleans, Louisiana.</ref> The most common chemotherapy drugs used to combat neuroblastoma are: epotoside, daunorubicin, carboplatin, and cyclophosphamide.<ref name="Ped-Onc" /> Chemotherapy is most commonly administered by IV. The drug is utilized for neuroblastoma tumors that are located in the liver, lungs, lymph nodes, bone marrow, and variety of other organs. Chemotherapy is most commonly used in tandem with surgery as a neoadjunctive or adjunctive therapy.<ref name="cncf">Children's Neuroblastoma Cancer Foundation: neuroblastoma chemotherapy. http://www.cncfhope.org/Neuroblastoma_Chemotherapy (accessed 8 March 2011).</ref>
== Diagnosis ==
Neuroblastoma may be difficult to diagnose as symptoms often do not become apparent until the tumour has reached a certain size. Even then symptoms may be subtle and similar to other more common non-serious childhood diseases. As a result it often takes some time before the final diagnosis of neuroblastoma is made<ref name=":1" />.


''Radiation Therapy'' has a variety of purposes including the following; destruction of [[Image:Trilogy(1).jpg|thumb|right|http://www.google.com/imgres?imgurl=http://www.qualityoflife.org/tasks/sites/memorialcms/assets/Image/Trilogy(1).jpg&imgrefurl=http://www.qualityoflife.org/cancer/ourcancercenter/technology-services/radiation-oncology/&usg=__ZdDUVvQLH2DEkn9h2kMSy0Kc6Qk=&h=475&w=356&sz=56&hl=en&start=0&zoom=1&tbnid=4SdWkFoX1zE7kM:&tbnh=167&tbnw=121&ei=kSqbTbC7NY24sAPF4cWNBA&prev=/images%3Fq%3Dradiation%2Bpediatric%2Btherapy%26um%3D1%26hl%3Den%26rlz%3D1G1TSND_ENUS415%26biw%3D1366%26bih%3D667%26tbm%3Disch&um=1&itbs=1&iact=rc&dur=278&oei=kSqbTbC7NY24sAPF4cWNBA&page=1&ndsp=19&ved=1t:429,r:8,s:0&tx=53&ty=32]]lingering tumor cells following surgery of a tumor, reduction of tumor size prior to the surgery, treatment of large tumors that may not be affected by chemotherapy, in tandem with chemotherapy as part of high dose therapy including stem cell transplant (high risk neuroblastoma patients), and finally for pain relief.<ref name="cncf" /> Radiation destroys cancer cells by sending energy forming ions into the cancer cells which dislodges the electrons from the atoms. The result is radiation can destroy the cancer cells or change the genes. Similar to chemo, radiation cells destroy cells that are dividing.<ref name="CSM" />
The clinical presentation along with initial [[Laboratory Tests|laboratory testing]], such as complete [[Blood Physiology|blood]] count, serum [[electrolytes]], [[Liver Function Tests|liver function tests]], [[Chest X-Rays|chest radiograph]], [[urine]] or serum catecholamines may show abnormalities. Imaging such as [[CT Scans|CT]] scan (neck, chest, abdomen), [[Ultrasound Scans|ultrasound]], [[MRI Scans|MRI]], iodine-metaiodobenzylguanidine (MIBG) scan, and fluorodeoxyglucose positive emission tomography (FDG-PET) can be utilized for the detection of primary or secondary tumors. The confirmation of neuroblastoma can only be done by biopsy from a specimen obtained from a tumor or bone marrow.<ref name=":0">Pain assist Best Exercises/Activities For Neuroblastoma Patients Available:https://www.epainassist.com/fitness-and-exercise/best-exercises-activities-for-neuroblastoma-patients (accessed 14.10.2021)</ref>
 
''Surgery'' can be performed in order to remove the entire tumor or portions of the tumor, followed by radiation or chemotherapy. Tumors that have metastasized or grown into areas of high risk may not be completely removed through resection. High risk areas of tumor removal would include major blood vessels, organ involvement, and nerves.<ref name="cncf" />
 
''Stem Cell Transplant Therapy'' is used for patients who are diagnosed with high risk neuroblastoma. These patients are unlikely to improve with other treatments. Stem cell transplant involves collecting the child’s own blood to form new stem cells. The process is called apheresis, in which the blood that is collected is ran through a machine that partitions the stem cells from the blood, and then returns the blood back to the child’s body. The stem cells are then stored for future usage. The patient is then treated with high dose radiation and chemotherapy. Following the treatment the patient’s stem cells are returned to the patient’s body similar to the process of a blood transfusion. Over the course of 3 to 4 weeks the stem cells begin to form healthy blood cells in the bone marrow. There is a high risk of infection and bleeding during this treatment due to a decreased platelet count.<ref name="cncf" />
 
''Immunotherapy'' includes therapy that is both passive and active. Active therapy utilizes the current immune system to fight against the pre-existing cancer cells. Cancer vaccines are also available to only destroy cancer cells. Passive immunotherapy uses man-made immune proteins such as monoclonal antibodies.<ref name="CSM" />  


== Summary ==
Neuroblastoma is a rare abdominal tumor in young children. However, if the diagnosis is missed, the tumor is fatal. Hence, the diagnosis and treatment of neuroblastoma are best managed by an interprofessional team that includes a pediatrician, a pediatric surgeon, oncologist, radiation therapist, social workers, pharmacist, dietitian, and specialty care nurses. A team dedicated to childhood cancers is vital as these patients have special needs. All cancer treatments can stunt growth, and hence, a dietitian should be involved early in the care.<ref name=":2" />


== Physical Therapy Management  ==
== Physical Therapy Management  ==
[[Image:Wiihab.jpg|alt=|right|frameless]]Advances in treatment have led to an increase in the number of cancer survivors. However, childhood cancers are associated with a lot of late effects, such as impaired growth and development, cognition, neurological function, musculoskeletal, cardiopulmonary function, and secondary tumors. Children also experience impaired physical fitness owing to [[Chemotherapy Side Effects and Syndromes|chemotherapy]], [[Radiation Side Effects and Syndromes|radiation therapy]], and surgical intervention. It includes decreased muscle strength and cardiopulmonary function, fatigue, and altered physical function. Incorporating exercises soon after treatment can improve cardiopulmonary and musculoskeletal function and increase the opportunities for participating in recreational activities<ref name=":0" />.


Quality of life is an important theme when it comes to treating children with neuroblastoma and any form of childhood cancer. Side effects of the cancer treatment/medication (chemotherapy, radiation, etc.) and symptoms of the cancer itself can lead to a risk of the following musculoskeletal and neurological issues.<ref name="CSM" />
'''Image 5''': Wiihab
 
*Neurological changes including (peripheral neuropathy and radiculopathy)
*Musculoskeletal changes (disuse atrophy and joint contractures due to radiation fibrosis)
*Developmental Delay
*A generalized effect of decrease in endurance, increase fatigue, and decreased strength
 
The effects are not isolated to physical losses, but also include psychosocial changes as well. The following are included in psychosocial considerations when treating a child with neuroblastoma and cancer.<ref name="CSM" />
 
*Depression and anxiety
*Poor self-esteem
*Loss of purpose (due to the fact that most have changes in school life, social&nbsp;[[Image:Wiihab.jpg|thumb|right|http://www.google.com/imgres?imgurl=http://www.iuhealthlaporte.org/pics/patients/services/rehab_wii.jpg&imgrefurl=http://www.iuhealthlaporte.org/patients/services/rehabilitation/playtime.cfm&usg=__Xq2tRKtHiqP-vpkPt_KYkXoBvXA=&h=322&w=214&sz=16&hl=en&start=18&zoom=1&tbnid=5jXMHzAcTrFVhM:&tbnh=161&tbnw=114&ei=EyubTaGlDMTVgQes8PyaBw&prev=/search%3Fq%3Dwii%2Brehab%26um%3D1%26hl%3Den%26sa%3DN%26rlz%3D1G1TSND_ENUS415%26biw%3D1366%26bih%3D667%26tbm%3Disch0%2C521&um=1&itbs=1&iact=rc&dur=323&oei=DiubTbv8IoyosAOQ5Mn6Aw&page=2&ndsp=18&ved=1t:429,r:7,s:18&tx=26&ty=105&biw=1366&bih=667]]changes, and family life)
*Social Isolation
*Behavioral Issues
 
Research has also found late effects of childhood cancers including the following presentations.<ref name="CSM" />
 
*Sensory changes (eyesight changes and hearing loss)
*Developmental Changes (learning disabilities and functional deficits)
*System Changes (reproductive issues, cardiopulmonary disease, osteoporosis, uneven growth of limbs, and decreased overall growth)
*Increased risk of secondary cancer
 
The above presentations are important in screening and for determining the physical therapy&nbsp;treatment of a child who presents with cancer or neuroblastoma. Physical therapy treatment should include a variety of considerations to address the limitations or deficits of the individual patient. When it is possible therapists can utilize group therapy to decrease social isolation and to develop psychosocial benefits. Wii rehabilitation treatment can address many deficits in the child with cancer such as balance, strength, and endurance.<ref name="CSM" /><br>
 
It is recommended by the ACSM (American College of Sports and Medicine) for cancer patients to perform 30-45 minutes of cardiovascular exercise, 3-5 days a week. &nbsp;The patient can walk, bike ride, etc. to develop cardiovascular benefits, strength, and maintain functional activities. &nbsp;Research has found that patients who exercise at this recommended level have increased endurance, decreased nausea, decreased overall fatigue, and an increase in their overall quality of life.<ref name="CSCP">Cancer Supportive Care Programs: exercises for cancer supportive care. http://www.cancersupportivecare.com/exercise.html(accessed on 2 April 2011).</ref>
 
Contraindications for Aerobic Exercise Laboratory Values:<ref name="Differential Diagnosis" /><br>
 
{| width="400" align="center" border="1" cellspacing="1" cellpadding="1"
|-
| Platelet Count
| &lt;50,000/mm3<sup></sup><sup></sup><sup></sup>
|-
| Hemoglobin
| &lt;10 g/dl
|-
| White Blood Cell Count
| &lt;3000/mm3<sup></sup><sub></sub>
|-
| Absolute Granulocytes
| &lt;2500/mm3<sup></sup>
|}
 
Overall, PT treatment has been proven through research to benefit the quality of life in a cancer patient of either a terminal or treatable diagnosis.<ref name="CSM" />
 
 


[[Quality of Life|Quality of life]] is an important theme when it comes to treating children with neuroblastoma and any form of childhood cancer. Side effects of the cancer treatment/medication (chemotherapy, radiation, etc.) and symptoms of cancer itself can lead to a risk of musculoskeletal and neurological issues and psychosocial changes  <ref name="CSM">Miale, S presenter.  Improving the Quality of Life of Children with Cancer: The Role of Rehabilitation.  Presented at Combined Sections Meeting of the American Physical Therapy Association; 2011 February 9-12; New Orleans, Louisiana.</ref> eg Neurological changes including (peripheral neuropathy and radiculopathy); Musculoskeletal changes (disuse atrophy and joint contractures due to radiation fibrosis); Psychosocial (developmental delay, depression and anxiety, social Isolation, behavioral Issues)<ref name="CSM" />
== Case Reports/ Case Studies  ==
== Case Reports/ Case Studies  ==


*Retroperitoneal Mass with Intradural Extension: Value of Magnetic Resonance Imaging in Neuroblastoma: diagnositic oncology case study: https://www.ajronline.org/doi/pdf/10.2214/ajr.146.2.251
*[https://pubmed.ncbi.nlm.nih.gov/8776703/ Case-control study of neuroblastoma in West-Germany after the Chernobyl accident: case-control study.]
*Case control study of neuroblastoma in west-Germany after the Chernobyl accident: case control study: http://www.ncbi.nlm.nih.gov/pubmed/8776703
*[https://pubmed.ncbi.nlm.nih.gov/7429428/ Placental infiltration in congenital neuroblastoma: a case study with ultrastructure.]
*Placental infiltration in congenital neuroblastoma: a case study with ultrastructure: http://www.ncbi.nlm.nih.gov/pubmed/7429428
*[https://www.nature.com/articles/6605504 Paternal occupation and neuroblastoma]: a case-control study based on cancer registry data for Great Britain 1962–1999.<br>
*Paternal occupation and neuroblastoma: a case–control study based on cancer registry data for Great Britain 1962–1999: https://www.nature.com/articles/6605504<br>
 
== Resources    ==


*http://www.mayoclinic.com/health/neuroblastoma/DS00780
== References ==
*http://www.curesearch.org/
*http://www.cancer.org/Cancer/Neuroblastoma/DetailedGuide/index
*http://www.cancercare.org/get_help/help_by_diagnosis/diagnosis.php?diagnosis=pediatric
*http://www.merckmanuals.com/home/sec23/ch283/ch283c.html
*https://emedicine.medscape.com/article/439263-overview
== References ==


<references />  
<references />  

Latest revision as of 04:41, 14 October 2021

Original Editors - Colleen Mathews from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Colleen Mathews, Lucinda hampton, Khloud Shreif, Elaine Lonnemann, Admin, Fasuba Ayobami, Kim Jackson, Tony Lowe, Evan Thomas, WikiSysop and Wendy Walker

Introduction[edit | edit source]

Neuroblastoma.jpeg

Neuroblastoma is the most common solid tumour of childhood.

Image 1: Giant neuroblastoma in an Ethiopian shepherd child

It is almost exclusively a childhood cancer occurring most commonly between the ages of 0-5 years. Neuroblastomas are cancers that start in early nerve cells (called neuroblasts) of the sympathetic nervous system. This means that tumours can be found anywhere along this system; most commonly (about 50%) start in the adrenal glands (above the kidney), or near the spine, chest, neck or pelvis.

Rarely, a neuroblastoma has spread so widely by the time it is found, doctors can’t tell exactly where it started.[1]

Due to the high variability in its presentation, clinical signs and symptoms at presentation can range from benign palpable mass with distension to major illness from substantial tumor spread.[2]

This video (3 minutes) is of the common symptoms of neuroblastoma

[3]

Epidemiolgy[edit | edit source]

Neuroblastoma infant.jpeg

The tumours typically occur in infants and very young children (mean age of presentation being ~22 months) with 95% of cases diagnosed before the age of 10 years. Occasionally, they may be identified antenatally or immediately at birth.[4]

Image 2: STAGE IV-S NEUROBLASTOMA This infant has massive hepatomegaly due to metastatic neuroblastoma. Intra-abdominal pressure is partially relieved by a silastic pouch.

Etiology[edit | edit source]

There are no known reasons as to why this cancer occurs and there are no clear environmental links. Risk factors for the acquisition of mutations in key genes leading to neuroblastoma have yet to be identified, although exposures during conception and pregnancy are a topic of investigation. Neuroblastoma can develop either sporadically or be transmitted in the germline[2].

There are rare cases where neuroblastoma runs in families due to a genetic mutation, but in most cases there is no known genetic cause.[1]

Characteristics/Clinical Presentation[edit | edit source]

Raccoon eyes

Neuroblastoma presents in a variety of forms based upon the location of its  manifestation and the size of the tumor.[5]. Presentation is typically with pain or a palpable mass and abdominal distension. The neuroblastoma presentation changes if cancer has spread (metastasis), and if the tumor secretes hormones. At the time of the patient's diagnosis, neuroblastoma cells have already spread to other parts of the body 73% of the time due to local mass effect.

Orbital and skull vault neuroplastoma

Other accompanying syndromes include:

  • Hutchinson syndrome: skeletal metastases may present with skeletal pain or limping and irritability or proptosis with periorbital and cranial bumps.
  • Pepper syndrome: hepatomegaly due to extensive liver metastasis
  • Blueberry muffin syndrome: multiple cutaneous lesions
  • Opsomyoclonus: rapid, involuntary conjugate fast eye movements
  • Proptosis and periorbital ecchymoses ("raccoon eyes"): orbital metastases[4]

This video (3 minutes) is of the common symptoms of neuroblastoma

[3]

Location[edit | edit source]

Neuroblastomas arise from the sympathetic nervous system. Intra-abdominal disease (two-thirds of cases) is more prevalent than intrathoracic disease. Specific sites include:

  • Adrenal glands: most common site of origin, 35%
  • Retroperitoneum: 30-35%
  • Coeliac axis
  • Paravertebral sympathetic chain
  • Posterior mediastinum: 20%
  • Neck: 1-5%
  • Pelvis: 2-3%

Treatment and Prognosis[edit | edit source]

Treatment depends on the patient's stage. Localised tumours considered to be 'low-risk' are surgically excised, and patients tend to do very well (see below). In 'high-risk' tumours, a combination of surgery, chemotherapy +/- bone marrow transplantation is employed, unfortunately with poor overall results. In some cases, where tumours are very large, pre-surgical chemotherapy to attempt to downstage the tumour may be administered.

Patients with stage 1, 2, or 4S have a better prognosis. Unfortunately 40-60% of patients present with stage 3 or 4 diseases 4. For advanced disease, the age of the child is most important.[4]

Stages of Neuroblastoma[edit | edit source]

The International Neuroblastoma Staging System (INSS) based on surgical resection is used to stage neuroblastomas in the United States.

Stage 1: The percentage of children diagnosed at this stage is 21%.

Stage 2: The percentage of children diagnosed at this stage is 15%

Stage 3: The percentage of children diagnosed at this stage is 17%.

Stage 4: The percentage of children diagnosed at this stage is 41%.

Stage 4S: The percentage of children diagnosed at this stage is 6%.[6]

Poor prognostic factors: later age of onset: >18 months; higher stage: particularly in the presence of metastasis; N-Myc mutation; chromosome 1p deletion; unfavourable Shimada histology index

Better prognostic factors: TRK-A expression[4]

Diagnosis[edit | edit source]

Neuroblastoma may be difficult to diagnose as symptoms often do not become apparent until the tumour has reached a certain size. Even then symptoms may be subtle and similar to other more common non-serious childhood diseases. As a result it often takes some time before the final diagnosis of neuroblastoma is made[1].

The clinical presentation along with initial laboratory testing, such as complete blood count, serum electrolytes, liver function tests, chest radiograph, urine or serum catecholamines may show abnormalities. Imaging such as CT scan (neck, chest, abdomen), ultrasound, MRI, iodine-metaiodobenzylguanidine (MIBG) scan, and fluorodeoxyglucose positive emission tomography (FDG-PET) can be utilized for the detection of primary or secondary tumors. The confirmation of neuroblastoma can only be done by biopsy from a specimen obtained from a tumor or bone marrow.[7]

Summary[edit | edit source]

Neuroblastoma is a rare abdominal tumor in young children. However, if the diagnosis is missed, the tumor is fatal. Hence, the diagnosis and treatment of neuroblastoma are best managed by an interprofessional team that includes a pediatrician, a pediatric surgeon, oncologist, radiation therapist, social workers, pharmacist, dietitian, and specialty care nurses. A team dedicated to childhood cancers is vital as these patients have special needs. All cancer treatments can stunt growth, and hence, a dietitian should be involved early in the care.[2]

Physical Therapy Management[edit | edit source]

Advances in treatment have led to an increase in the number of cancer survivors. However, childhood cancers are associated with a lot of late effects, such as impaired growth and development, cognition, neurological function, musculoskeletal, cardiopulmonary function, and secondary tumors. Children also experience impaired physical fitness owing to chemotherapy, radiation therapy, and surgical intervention. It includes decreased muscle strength and cardiopulmonary function, fatigue, and altered physical function. Incorporating exercises soon after treatment can improve cardiopulmonary and musculoskeletal function and increase the opportunities for participating in recreational activities[7].

Image 5: Wiihab

Quality of life is an important theme when it comes to treating children with neuroblastoma and any form of childhood cancer. Side effects of the cancer treatment/medication (chemotherapy, radiation, etc.) and symptoms of cancer itself can lead to a risk of musculoskeletal and neurological issues and psychosocial changes [8] eg Neurological changes including (peripheral neuropathy and radiculopathy); Musculoskeletal changes (disuse atrophy and joint contractures due to radiation fibrosis); Psychosocial (developmental delay, depression and anxiety, social Isolation, behavioral Issues)[8]

Case Reports/ Case Studies[edit | edit source]

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 Neuroblastoma Australia What is neuroblastoma? Available:https://www.neuroblastoma.org.au/pages/faqs/category/what-is-neuroblastoma (accessed 14.10.2021)
  2. ↑ 2.0 2.1 2.2 Mahapatra S, Challagundla KB. Cancer, neuroblastoma. Cancer. 1918 Apr 13;10:49. 2021 Available: https://www.ncbi.nlm.nih.gov/books/NBK448111/ (accessed 14.10.2021)
  3. ↑ 3.0 3.1 Health Apta. SYMPTOMS OF NEUROBLASTOMA. Available from: http://www.youtube.com/watch?v=L9r_y4BnIzw[last accessed on 29/ 6/2021]
  4. ↑ 4.0 4.1 4.2 4.3 Radiopedia Neuroblastoma Available:https://radiopaedia.org/articles/neuroblastoma (accessed 14.10.2021)
  5. ↑ Thiele CJ. Neuroblastoma. InHuman cell culture 2002 (pp. 21-53). Springer, Dordrecht.
  6. ↑ Children's Neuroblastoma Cancer Foundation: neuroblastoma staging. http://www.cncfhope.org/Staging_Neuroblastoma (accessed on 7 March 2011).
  7. ↑ 7.0 7.1 Pain assist Best Exercises/Activities For Neuroblastoma Patients Available:https://www.epainassist.com/fitness-and-exercise/best-exercises-activities-for-neuroblastoma-patients (accessed 14.10.2021)
  8. ↑ 8.0 8.1 Miale, S presenter. Improving the Quality of Life of Children with Cancer: The Role of Rehabilitation. Presented at Combined Sections Meeting of the American Physical Therapy Association; 2011 February 9-12; New Orleans, Louisiana.
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