Question

    Neuroblastoma (Neuroblastic Tumor)

    Neuroblastoma rosettes[1]

    Neuroblastoma is a type of cancer that originates from the immature nerve cells. It can affect any part of the body that contains such type of nerve cells [1].

    Neuroblastoma develops due to the following process: neoplastic.

    Presentation

    Fever and feeling of malaise are the primary signs of neuroblastoma. Children also complain of poor appetite and eventually undergo weight loss. In addition to these, there are several other symptoms of neuroblastoma that vary with the site of the cancer.

    When the cancer has developed in the sympathetic nerves of abdomen, individuals experience abdominal pain, swelling in legs, diarrhea and presence of a mass which is not tender when touched. Individuals in whom the cancer has affected the chest suffer from wheezing, pain in the chest, drooping eye lids and difference in the pupil size.

    Liver, Gall & Pancreas
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  • Entire body system
    Anemia
    • Bone marrow metastases may cause anemia and/or thrombocytopenia.[merckmanuals.com]
    • Depending on the findings, other exams may be conducted including: Blood and urine tests Catecholamines - urine Catecholamines - blood Hormone tests (levels of hormones such as epinephrine) CBC showing anemia or other abnormality Imaging exams CT scan[uwhealthkids.org]
    • Symptoms may include: Protruding eyes and dark circles around the eyes caused by cancer that has spread to the area behind the eye Paralaysis from neuroblastoma that compresses the spinal cord Fever, anemia and high blood pressure are occasionally experienced[ucsfbenioffchildrens.org]
    • The disease can also be associated with arterial hypertension, fever, and an altered general state (weight loss, pain, irritability, and anemia).[orpha.net]
    Fever
    • Fever and feeling of malaise are the primary signs of neuroblastoma.[symptoma.com]
    • Symptoms of Neuroblastoma A person with neuroblastoma may experience one or more of the following symptoms: aches and pains fevers weight loss or poor appetite swelling of the abdomen (referred to as a distended abdomen) limping or difficulty walking[mskcc.org]
    • The initial symptoms of Neuroblastoma may include fatigue, loss of appetite, fever, or persistent diarrhea and many other very vague symptoms that mimic common childhood illnesses and viruses.[mysticforcefoundation.com]
    • […] the abdomen A lump or bump in the neck that can sometimes be accompanied by drooping of the eyelid, a small pupil, and lack of sweating on the same side of the face Bone pain Fatigue, if the disease has spread to the bone marrow Bleeding and bruising Fever[curesearch.org]
    • The first symptoms are often vague and may include irritability, being very tired, loss of appetite, and fever.[kidshealth.org]
    Leg Swelling
    • Symptoms of a tumor in the belly (abdomen) can include: A lump in the abdomen Swelling in the abdomen Loss of appetite Weight loss Swelling of the legs Swelling of the scrotum Feeling full Pain Symptoms of a tumor in the chest can include: A lump in the[phoenixchildrens.org]
    Malaise
    • Fever and feeling of malaise are the primary signs of neuroblastoma.[symptoma.com]
    • The first symptoms are usually fever, a general sick feeling ( malaise ), and pain.[nlm.nih.gov]
    • Back to Top Symptoms The first symptoms are usually fever, a general sick feeling ( malaise ), and pain.[nytimes.com]
    • Children with localized disease in the abdomen may have symptoms such as belly pain , constipation , or diarrhea , whereas patients with metastatic disease may have fever , malaise , weight loss, leg and arm pain, or difficulty walking.[britannica.com]
    Weight Loss
    • Children also complain of poor appetite and eventually undergo weight loss.[symptoma.com]
    • Symptoms of Neuroblastoma A person with neuroblastoma may experience one or more of the following symptoms: aches and pains fevers weight loss or poor appetite swelling of the abdomen (referred to as a distended abdomen) limping or difficulty walking[mskcc.org]
    • The disease can also be associated with arterial hypertension, fever, and an altered general state (weight loss, pain, irritability, and anemia).[orpha.net]
    • There may also be loss of appetite, weight loss, and diarrhea.[nlm.nih.gov]
    • loss bone pain, a limp and general irritability rarely, jerky eye and muscle movements See your GP or contact NHS 111 if you're worried your child might be seriously ill.[nhs.uk]
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  • Immune System
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  • Skin
    Flushing
    • […] symptoms depend on the site of the tumor, and may include: Bone pain or tenderness (if the cancer has spread to the bones) Difficulty breathing or a chronic cough (if the cancer has spread to the chest) Enlarged abdomen (from a large tumor or excess fluid) Flushed[nlm.nih.gov]
    • […] symptoms depend on the site of the tumor, and may include: Bone pain or tenderness (if the cancer spreads to the bones) Difficulty breathing or a chronic cough (if the cancer spreads to the chest) Enlarged abdomen (from a large tumor or excess fluid) Flushed[nytimes.com]
    • It can cause symptoms such as: Constant diarrhea Fever High blood pressure Fast heart rate Flushing or redness of skin Sweating A neuroblastoma can also cause opsoclonus-myoclonus-ataxia syndrome.[phoenixchildrens.org]
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  • gastrointestinal
    Abdominal Mass
    • Neuroblastoma Symptoms The most common symptom of neuroblastoma is a painless abdominal mass, usually found by a parent while changing the baby’s clothes or during a bath.[mottchildren.org]
    • Abdominal swelling An abdominal mass A neck mass Horner’s syndrome (unequal pupils, a drooping eyelid, and decreased sweating on one side of the face) associated with a chest mass.[hopkinsmedicine.org]
    • Symptoms may include: Abdominal mass either felt during an examination or seen as swollen abdomen Painless, bluish lumps may be seen under the skin in infants Trouble breathing due to tumors in the chest or abdomen Tumors in the face or head can cause[stanfordchildrens.org]
    • Symptoms may include: Abdominal mass, either felt during an examination or seen as a swollen abdomen Tumors in the face or head can cause swelling and bruising of the area around the eyes, uncontrolled eye movement, unsteadiness Compression of kidney[luriechildrens.org]
    Abdominal Pain
    • If the tumor is located lower in the abdomen, it may cause abdominal pain and bloating .[en.wikipedia.org]
    • When the cancer has developed in the sympathetic nerves of abdomen, individuals experience abdominal pain, swelling in legs, diarrhea and presence of a mass which is not tender when touched. [symptoma.com]
    • For example, a child may have: a swollen stomach, abdominal pain, and decreased appetite (if the tumor is in the abdomen) bone pain or soreness, black eyes, bruises, and pale skin (if the cancer has spread to the bones or bone marrow) weakness, numbness[kidshealth.org]
    • Abdominal pain or distention may occur from abdominal tumor and difficulty breathing may occur from respiratory tumor spread.[eyewiki.aao.org]
    Diarrhea
    • Some of the symptoms associated with neuroblastoma — such as high blood pressure, rapid heartbeat or diarrhea — are caused by increased catecholamines.[ucsfbenioffchildrens.org]
    • When the cancer has developed in the sympathetic nerves of abdomen, individuals experience abdominal pain, swelling in legs, diarrhea and presence of a mass which is not tender when touched. [symptoma.com]
    • The initial symptoms of Neuroblastoma may include fatigue, loss of appetite, fever, or persistent diarrhea and many other very vague symptoms that mimic common childhood illnesses and viruses.[mysticforcefoundation.com]
    • Difficulty breathing if the tumor is present in the chest Weakness or paralysis if the tumor is near the spinal cord Less frequent symptoms caused by hormones released by the neuroblastoma cells include: High blood pressure Rapid heartbeat Persistent diarrhea[curesearch.org]
    • […] may be present; diarrhea is caused by a substance produced by the tumor (vasoactive intestinal peptide or VIP) Fever High blood pressure and increased heart rate may occur depending on location of tumor and the organs the tumor compresses The symptoms[stanfordchildrens.org]
    Loss of Appetite
    • “As with Hope, a lot of children just feel a little off colour to begin with, including loss of appetite and tiredness.[lifestyle.one]
    • The initial symptoms of Neuroblastoma may include fatigue, loss of appetite, fever, or persistent diarrhea and many other very vague symptoms that mimic common childhood illnesses and viruses.[mysticforcefoundation.com]
    • There may also be loss of appetite, weight loss, and diarrhea.[nlm.nih.gov]
    • […] of appetite and weight loss bone pain, a limp and general irritability rarely, jerky eye and muscle movements See your GP or contact NHS 111 if you're worried your child might be seriously ill.[nhs.uk]
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  • musculoskeletal
    Bone Pain
    • Bone pain and limp can be interpreted as synovitis of the hip.[orpha.net]
    • The most common symptoms are A lump in the abdomen, neck or chest Bulging eyes Dark circles around the eyes Bone pain Swollen stomach and trouble breathing in babies Painless, bluish lumps under the skin in babies Inability to move a body part Treatments[nlm.nih.gov]
    • pain, walks with a limp, or refuses to walk, at which point the disease has already metastasized.[mysticforcefoundation.com]
    • pain Fatigue, if the disease has spread to the bone marrow Bleeding and bruising Fever Difficulty breathing if the tumor is present in the chest Weakness or paralysis if the tumor is near the spinal cord Less frequent symptoms caused by hormones released[curesearch.org]
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  • cardiovascular
    Chest Pain
    • For example, a tumor in the chest area may cause breathing difficulty , chest pain , and trachea compression .[en.wikipedia.org]
    • Symptoms Symptoms of neuroblastoma consist of fever, malaise, wheezing, development of non–tender mass beneath the skin, diarrhea, chest pain, swelling in legs, bone pain, unexplained weight loss, changes in appetite and development of protopsis.[symptoma.com]
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  • Eyes
    Heterochromia Iridis
    • iridis: cervical, mediastinal neuroblastoma (prenatal / postnatal interruption of sympathetic tracts that mediate pigmentation of iris) Horner's syndrome (damage to sympathetic trunk resulting in miosis, ptosis, enophthalmos, anhidrosis): head, neck,[pathologyoutlines.com]
    Miosis
    • […] movements, ataxia, irregular muscle movements Heterochromia iridis: cervical, mediastinal neuroblastoma (prenatal / postnatal interruption of sympathetic tracts that mediate pigmentation of iris) Horner's syndrome (damage to sympathetic trunk resulting in miosis[pathologyoutlines.com]
    Ptosis
    • […] ataxia, irregular muscle movements Heterochromia iridis: cervical, mediastinal neuroblastoma (prenatal / postnatal interruption of sympathetic tracts that mediate pigmentation of iris) Horner's syndrome (damage to sympathetic trunk resulting in miosis, ptosis[pathologyoutlines.com]
    • Any ptosis should be measured and anisocoria documented.[eyewiki.aao.org]
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  • Workup

    Neuroblastoma is diagnosed by the following methods:

    • Physical examination: A preliminary thorough physical examination is carried out for studying the signs and symptoms of the disease.
    • Blood and urine tests: Complete blood count is performed which would reveal presence of anemia. In addition, urine analysis would show elevated levels of chemicals that are released by the cancer cells. Blood test to detect the levels of catecholamine hormone is also done.
    • Imaging studies: Several imaging studies are employed to locate the primary site of the tumor and also to analyze the extent of spread of tumor. Various imaging tests that are performed include bone scan, X-rays of the bone, CT and MRI scan of the chest and abdomen and X-ray of the chest. 
    • Biopsy: Biopsy helps in designing an individualized treatment plan [7]. Bone marrow biopsy is conducted to see whether the cancer has spread to the bone marrow.

    Laboratory

    Serum
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  • Imaging

    X-ray
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  • Treatment

    Treatment of neuroblastoma majorly depends on the location of the tumor and stage of the disease. In many cases, surgery is the treatment of choice and is often successful. This may be combined with chemotherapy and radiation therapy to arrest the growth of the cancer cells [8] [9].

    Immunotherapy is also given to children with high risk tumors. In this method, the children are given drugs to stimulate their immune system. The efficacy of stem cell transplantation is still being studied, for children with high risk tumors [10].

    Prognosis

    The prognosis of neuroblastomas varies with the nature of tumor cells. In some cases, the tumor disappears without any treatment; whereas in some, the tumor is benign in nature known as ganglioneuroma. Such type of tumors can be surgically removed. However, in cases, when the tumor is malignant in nature, the cancer quickly spreads which makes the treatment process more difficult [6].

    Complications

    Cerebellar Ataxia
    • […] exception is that bone marrow involvement occurs less frequently in adolescents, and there is a greater frequency of metastases in unusual sites such as lung or brain.[ 32 ] Opsoclonus/myoclonus syndrome Paraneoplastic neurologic findings, including cerebellar[dana-farber.org]
    Edema
    • Neurosurgical interventions serve to decrease edema, control hemorrhage, and remove bulky tumor before starting therapy.[dana-farber.org]
    Horner's Syndrome
    • Abdominal swelling An abdominal mass A neck mass Horner’s syndrome (unequal pupils, a drooping eyelid, and decreased sweating on one side of the face) associated with a chest mass.[hopkinsmedicine.org]
    • Horner’s Syndrome in Children.[eyewiki.aao.org]
    • […] the bones or bone marrow) weakness, numbness, inability to move a body part, or difficulty walking (if the cancer presses on the spinal cord) drooping eyelid, unequal pupils, sweating, and red skin, which are signs of nerve damage in the neck known as Horner's[kidshealth.org]
    • (6%) Opsoclonus-myoclonus-ataxia syndrome: rapid eye movements, ataxia, irregular muscle movements Heterochromia iridis: cervical, mediastinal neuroblastoma (prenatal / postnatal interruption of sympathetic tracts that mediate pigmentation of iris) Horner's[pathologyoutlines.com]
    • Rare but characteristic presentations include transverse myelopathy (tumor spinal cord compression, 5% of cases), treatment-resistant diarrhea (tumor vasoactive intestinal peptide secretion, 4% of cases), Horner's syndrome (cervical tumor, 2.4% of cases[en.wikipedia.org]
    Hypertension
    • Neuroblastomas do not typically cause severe hypertension because these tumors do not usually secrete epinephrine .[merckmanuals.com]
    • The disease can also be associated with arterial hypertension, fever, and an altered general state (weight loss, pain, irritability, and anemia).[orpha.net]
    • 5% of cases), treatment-resistant diarrhea (tumor vasoactive intestinal peptide secretion, 4% of cases), Horner's syndrome (cervical tumor, 2.4% of cases), opsoclonus myoclonus syndrome and ataxia (suspected paraneoplastic cause, 1.3% of cases), and hypertension[en.wikipedia.org]
    • The patient is a woman, 73 years old, hypertensive, with hypothyroidism, associated for 15 years with hypercholesterolemia and hypertriglyceridemia, which had frequent complaints of low back pain.[cancerindex.org]
    • Fever, hypertension, and anemia : Occasionally found in patients without metastasis.[dana-farber.org]
    Nephroblastoma
    • Examples are nephroblastoma , medulloblastoma and retinoblastoma .[en.wikipedia.org]
    • Differential diagnosis Differential diagnoses include nephroblastoma, which makes it necessary to systematically check urinary catecholamines in case of an abdominal tumor.[orpha.net]
    Opsoclonus-Myoclonus Syndrome
    • […] tachycardia ) Brain and nervous system problems may include: Inability to empty the bladder Loss of movement ( paralysis ) of the hips, legs, or feet (lower extremities) Problems with balance Uncontrolled eye movements or leg and feet movements (called opsoclonus-myoclonus[nlm.nih.gov]
    • Hero, High dose pulsatile dexamethasone therapy in children with opsoclonus-myoclonus syndrome.[kinderklinik.uk-koeln.de]
    • Although rare, some kids with neuroblastoma develop opsoclonus-myoclonus syndrome, a condition where the immune system attacks normal nerve tissue.[kidshealth.org]
    • Pranzatelli MR: The neurobiology of the opsoclonus-myoclonus syndrome.[dana-farber.org]
    • myoclonus syndrome and ataxia (suspected paraneoplastic cause, 1.3% of cases), and hypertension (catecholamine secretion or renal artery compression, 1.3% of cases).[en.wikipedia.org]
    Paraplegia
    • […] deformity requiring fusion but there is no evidence that functional deficit is improved with laminoplasty.[ 23 ] In a series of 34 infants with symptomatic epidural spinal cord compression, both surgery and chemotherapy provided unsatisfactory results once paraplegia[dana-farber.org]
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  • Etiology

    The exact factors that trigger the development of these malignant tumor cells in the nerve cells of children are not clear. Heredity or environmental factors do not seem to have any role in the development of neuroblastoma [3].

    Typically, the cancer begins with a genetic mutation that signals the cells to grow in an uncontrollable fashion. The resultant reaction of cell overgrowth is a malignant tumor. Neuroblastoma begins in the neuroblasts which are essentially immature nerve cells that are naturally made during the fetal growth. In many instances, these neuroblasts mature at birth, some which fail to mature either disappear or mature eventually as the child grows. In some cases, however, tumor develops in the neuroblasts causing neuroblastoma.

    Epidemiology

    Neuroblastoma affects majorly the pediatric population, exclusively those aged 10 years and below. Boys are slightly at an increased risk of contracting this disease condition than girls. It has been estimated that each year about 600 cases of neuroblastoma are diagnosed in the US. Such a type of cancer is more common in whites [4].

    Statistics have also shown that about 36% cases of neuroblastoma are diagnosed in infants, 79% cases are diagnosed in children less than 4 years and 97% cases are diagnosed in children aged 10 years.

    Sex distribution
    Age distribution

    Pathophysiology

    Neuroblastoma is a type of cancer that affects the immature cells of the sympathetic nervous system. This type of nervous system is a vital part of autonomic nervous system which essentially governs the functioning of majority of the body organs. In majority of the cases, neuroblastomas begin in the adrenal glands, others in the sympathetic nerves present in the abdomen.

    Several type of karyotopic abnormalities occur in neuroblastoma, but deletion of short arm of chromosome 1 is a major characteristic finding in the majority (70–80%) of cases. The sequence of events that cause such a type of phenomenon to occur is poorly understood [5].

    Prevention

    So far there are no established guidelines for preventing development of neuroblastoma. However, there are small pieces of evidence suggesting that intake of vitamins and folic acid supplements during pregnancy can prevent the onset of such type of cancer.

    Summary

    Neuroblastoma mostly strikes infants and children younger than 10 years. Older children are rarely affected by this disease. Neuroblastoma is characterized by development of small, round, blue colored tumor cells in the nerve tissues. It is the 4th most common type of cancer affecting children. It commonly originates in areas such as adrenal glands. However, in many instances it is also found in abdomen, neck, and chest and in the neighboring areas of the spine [2].

    Patient Information

    Definition

    Neuroblastoma is a type of cancer that originates in the immature nerve cells. A cancer of this type mostly strikes the infant and children population. It is considered to be the 4th most common type of cancer after lymphoma, leukemia and tumors of central nervous system.

    Cause

    The exact cause behind development of malignant tumors in the nerve cells is yet not known. Genetic mutations in the immature nerve cells cause uncontrolled growth of cells that finally develop into malignant tumor cells.

    Symptoms

    Symptoms of neuroblastoma consist of fever, malaise, wheezing, development of non–tender mass beneath the skin, diarrhea, chest pain, swelling in legs, bone pain, unexplained weight loss, changes in appetite and development of protopsis.

    Diagnosis

    Diagnosis of neuroblastoma begins with a preliminary physical examination followed by blood and urine tests to detect levels of chemicals and hormones. In addition, imaging studies are also carried out to locate the site of the tumor cells. Biopsy of the tumor cells are also done to analyze its nature.

    Treatment

    In many cases, surgery is often successful in removing the malignant cells. However, other treatment methods such as chemotherapy, radiation therapy and immunotherapy are also employed.

    Self-assessment

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    References

    1. Brodeur GM, Hogarty MD, Mosse YP, Maris JM. Neuroblastoma. In: Principles and Practice of Pediatric Oncology, Pizzo PA, Poplack DG (Eds), Lippincott Williams & Wilkins, Philadelphia 2011. p.886
    2. Golden CB, Feusner JH. Malignant abdominal masses in children: quick guide to evaluation and diagnosis. Pediatr Clin North Am 2002; 49:1369.
    3. Bunin GR, Ward E, Kramer S, et al. Neuroblastoma and parental occupation. Am J Epidemiol 1990; 131:776.
    4. Goodman MT, Gurney JG, Smith MA, Olshan AF. Sympathetic nervous system tumors. In: Cancer Incidence and Survival among Children and Adolescents: United States SEER Program, 1975-1995, Ries, LA, Smith, MA, Gurney, JG, et al (Eds), National Cancer Institute, Bethesda, MD 1999. p.35.
    5. Brodeur GM, Green AA, Hayes FA. Cytogenetic studies of primary human neuroblastomas. Prog Cancer Res Ther. 1980;12:73.
    6. D'Angio GJ, Evans AE, Koop CE. Special pattern of widespread neuroblastoma with a favourable prognosis. Lancet 1971; 1:1046.
    7. Buckley SE, Chittenden SJ, Saran FH, Meller ST, Flux GD. Whole-body dosimetry for individualized treatment planning of 131I-MIBG radionuclide therapy for neuroblastoma. J Nucl Med. Sep 2009;50(9):1518-24.
    8. Strother DR, London WB, Schmidt ML, et al. Outcome after surgery alone or with restricted use of chemotherapy for patients with low-risk neuroblastoma: results of Children's Oncology Group study P9641. J Clin Oncol 2012; 30:1842.
    9. Matthay KK, Sather HN, Seeger RC, et al. Excellent outcome of stage II neuroblastoma is independent of residual disease and radiation therapy. J Clin Oncol. Feb 1989;7(2):236-44
    10. Jennings RW, LaQuaglia MP, Leong K, et al. Fetal neuroblastoma: prenatal diagnosis and natural history. J Pediatr Surg 1993; 28:1168.

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    Media References

    1. Neuroblastoma rosettes, Public Domain

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