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.

• Fever

  Fever and feeling of malaise are the primary signs of neuroblastoma. Children also complain of poor appetite and eventually undergo weight loss. [symptoma.com]

  In children less than 5 years old, with an abdominal mass and/or bone pain, irritability, and a fever from an unknown cause, neuroblastoma should be considered as a possible diagnosis. [ncbi.nlm.nih.gov]

  […] 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]

• Anemia

  She presented with tachypnea, worsening anemia, and oxygen desaturation. Hemothorax was diagnosed based on chest radiography, ultrasonography, and diagnostic thoracic puncture results. [ncbi.nlm.nih.gov]

  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]

  Bone marrow metastases may cause anemia and/or thrombocytopenia. Anemia also occasionally occurs when bleeding into these highly vascular tumors causes a rapid drop in Hb. [merckmanuals.com]

• Weight Loss

  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. [symptoma.com]

  The disease can also be associated with arterial hypertension, fever, and an altered general state (weight loss, pain, irritability, and anemia). [orpha.net]

  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 symptoms will often include tiredness, high temperature (fever), weight loss and loss of appetite. Other symptoms again depend on which part of the body is affected: Bones are the most common place to which a neuroblastoma may spread. [patient.info]

  loss Bone pain When to see a doctor Contact your child's doctor if your child has any signs or symptoms that worry you. [mayoclinic.org]

• Fatigue

  […] swelling, pain, constipation or difficulty urinating if a tumor is present in 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 [curesearch.org]

  Symptoms can include: Unusual lump or mass, typically in the abdomen Swollen abdomen Swelling in the face or throat Chronic fatigue Problems with urination or bowel movements Loss of movement in the hips or extremities Diagnosing Neuroblastoma A physician [uwhealthkids.org]

  This type of treatment can cause side effects, such as skin irritation, diarrhea, and fatigue. Immunotherapy Immunotherapy is also called biologic therapy. [healthline.com]

• Malaise

  Fever and feeling of malaise are the primary signs of neuroblastoma. Children also complain of poor appetite and eventually undergo weight loss. [symptoma.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]

  Symptoms The first symptoms are usually fever, a general sick feeling (malaise), and pain. There may also be loss of appetite, weight loss, and diarrhea. [pennstatehershey.adam.com]

• Respiratory Distress

  After the first cycle of chemotherapy he developed pulmonary hemorrhage and respiratory distress. He required ventilation support and mechanical ventilation was started. Metastatic nodules were determined on second thorax HRCT. [ncbi.nlm.nih.gov]

  Higher thoracic and cervical masses can also lead to Horner’s syndrome (associated with unilateral ptosis, miosis and anhidrosis), superior vena cava syndrome or respiratory distress due to pressure on surrounding structures. [intechopen.com]

  Rarely thoracic masses can present with superior vena cava syndrome or respiratory distress. [cancertherapyadvisor.com]

  Among younger infants, high birth weight, heavier maternal gestational weight gain, maternal hypertension, older maternal age, ultrasound, and respiratory distress were ideas increasing the risk of neuroblastoma development include. [eyewiki.aao.org]

• Diarrhea

  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]

  Some of the symptoms associated with neuroblastoma — such as high blood pressure, rapid heartbeat or diarrhea — are caused by increased catecholamines. [ucsfbenioffchildrens.org]

  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]

  Another rare syndrome causes abdominal swelling and diarrhea. Oct. 09, 2019 [mayoclinic.org]

  Possible short-term effects of radiation include nausea, diarrhea, fatigue, sunburn changes to the skin and hair loss. [eapsa.org]

• Abdominal Mass

  The most frequent manifestations were: fever (25%), abdominal pain (22%), abdominal mass (19%), and bone pain (19%). The mean time from symptom onset to diagnosis was 3.0±4.8 months. The most common location of the tumor was the abdomen (63%). [ncbi.nlm.nih.gov]

  The abdominal mass is irregular, firm, and clearly crosses the midline. An MRI of her head shows potential metastasis to the skull. [step2.medbullets.com]

  In most cases, neuroblastomas stem from the adrenal glands within the abdominal cavity and present as a palpable abdominal mass that can cross the midline. [amboss.com]

• Loss of Appetite

  A 2-year-old boy presented with abdominal pain, nausea, and loss of appetite. Computed tomography revealed a large tumor in the left suprarenal region with massive infiltration into the kidney. [ncbi.nlm.nih.gov]

  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 child may also have loss of appetite, vague aches and pains and sweating, or a lump may be felt or seen. Diagnosis A specimen of urine is collected to test for catecholamine levels. [rch.org.au]

• Abdominal Pain

  A 2-year-old boy presented with abdominal pain, nausea, and loss of appetite. Computed tomography revealed a large tumor in the left suprarenal region with massive infiltration into the kidney. [ncbi.nlm.nih.gov]

  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]

  […] distention abdominal pain hallmark of disease hypsarrythmia (dancing feet) opsoclonus (dancing eyes) Physical exam palpable, firm, and irregular mass crosses midline (vs Wilms' tumor, unilateral, smooth ) may have diastolic hypertension Evaluation Biopsy [step2.medbullets.com]

• Constipation

  Some of the more common symptoms include: Abdominal swelling, pain, constipation or difficulty urinating if a tumor is present in the abdomen A lump or bump in the neck that can sometimes be accompanied by drooping of the eyelid, a small pupil, and lack [curesearch.org]

  At 2 years of age, patient is able to walk with help of leg orthoses, suffers chronic constipation requiring daily medications, and has neurologic bladder necessitating multiple daily catheterizations. [ncbi.nlm.nih.gov]

  […] in the legs and an unsteady walk, with numbness in the lower body, constipation and difficulty passing urine fatigue, loss of energy, pale skin, loss of appetite and weight loss bone pain, a limp and general irritability rarely, jerky eye and muscle [nhs.uk]

  Tumors in the abdomen may push out the abdomen or cause constipation. Anemia (not enough oxygen-carrying red blood cells) may develop if tumors affect the bone marrow. This can cause fatigue. Tumors around the eyes may cause bulging or dark circles. [seattlecca.org]

• Liver Mass

  Computed tomography (CT) scans: Detailed pictures of the chest or abdomen are taken, reconstructed in different views to get a better picture of the liver mass. (See Figure 4). [eapsa.org]

• Hypertension

  However, the presences of hypertension are uncommon. We report the perioperative management of a 15-month-old infant with giant abdominal neuroblastoma who presented severe hypertension. [ncbi.nlm.nih.gov]

  Patients with secreting tumors can present with episodes of flushing, diaphoresis and tachycardia as well as episodes of hypertension. [oncologynurseadvisor.com]

• Chest Pain

  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. [symptoma.com]

  […] signs and symptoms such as: Wheezing Chest pain Changes to the eyes, including drooping eyelids and unequal pupil size Other signs and symptoms that may indicate neuroblastoma include: Lumps of tissue under the skin Eyeballs that seem to protrude from [mayoclinic.org]

  For example, a tumor in the chest area may cause breathing difficulty, chest pain, and trachea compression. If the tumor is located lower in the abdomen, it may cause abdominal pain and bloating. [en.wikipedia.org]

• Flushing

  These may include fast heart beat, high blood pressure, sweating, diarrhea, and flushed skin. [seattlecca.org]

  […] diarrhea → electrolyte imbalances Opsoclonus-myoclonus-ataxia: a paraneoplastic syndrome of unclear etiology involving rapid and multi-directional eye movements, rhythmic jerks of the limbs, and ataxia Hypertension, tachycardia, palpitations, sweating, flushing [amboss.com]

  […] 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 [pennstatehershey.adam.com]

• Petechiae

  Occasionally, pallor (anemia), petechiae (thrombocytopenia), and leukopenia develop due to bone marrow metastases. Other less common sites of metastasis include the skin and brain. Hemorrhage and necrosis into the tumor may occur. [web.archive.org]

  Children with anemia may have pallor, and those with thrombocytopenia may have petechiae. Children occasionally present with focal neurologic deficits or paralysis due to direct extension of the cancer into the spinal canal. [merckmanuals.com]

  […] or lower extremities painless, bluish swellings beneath the skin Less common symptoms include: fatigue a fever shortness of breath a cough high blood pressure diarrhea abnormal bleeding or bruising, including small, flat, red spots on the skin called petechiae [healthline.com]

• Increased Sweating

  The liver may not work properly and this may lead to skin or the whites of the eyes becoming a yellow colour (jaundice). if the neuroblastoma makes high levels of the chemicals called catecholamines then this may cause weight loss, increased sweating, [patient.info]

• Purpura

  These metastases cause bone pain and, possibly, signs of bone marrow failure (i.e., anemia and purpura). The skull is a frequent site of bone metastases, which commonly present as proptosis and periorbital ecchymoses. [aafp.org]

• Bone Pain

  The most frequent metastatic sites are bone marrow, bone, liver and skin. Symptoms of metastasis including bone pain, limp, paralysis, hepatomegaly (Pepper's syndrome), and exophthalmia (Hutchinson's syndrome), indicate metastatic neuroblastoma. [orpha.net]

  The most frequent manifestations were: fever (25%), abdominal pain (22%), abdominal mass (19%), and bone pain (19%). The mean time from symptom onset to diagnosis was 3.0±4.8 months. The most common location of the tumor was the abdomen (63%). [ncbi.nlm.nih.gov]

  […] 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 Difficulty breathing if the tumor is present in the chest Weakness or paralysis if the tumor is near the spinal cord [curesearch.org]

  Many symptoms of neuroblastoma are caused by pressure from the tumor or bone pain if the cancer has spread to the bones. Bone pain may cause the child to limp, refuse to walk, or become unable to walk. [cancer.net]

• Periorbital Ecchymosis

  Periorbital ecchymosis and proptosis may occur with retrobulbar metastasis. Liver metastases, especially in infants, may cause abdominal distention and respiratory problems. [web.archive.org]

  Infiltration of periorbital bones may produce periorbital ecchymosis, ptosis and proptosis. [pedclerk.bsd.uchicago.edu]

  These include bone pain due to widespread bone metastases, periorbital ecchymosis and proptosis due to retrobulbar metastasis, and abdominal distention and respiratory problems due to liver metastases, especially in infants. [merckmanuals.com]

• Miosis

  Presenting features include: Chest radiograph findings, often incidental Tracheal deviation with resulting stridor Superior Vena cava syndrome Cervical involvement (5%) produces the following symptoms: Horner’s syndrome (ptosis, miosis, anhydrosis) Tracheal [pedclerk.bsd.uchicago.edu]

  Tumors in the neck or upper chest may cause Horner syndrome (ptosis, miosis, anhidrosis). They may also present with paraneoplastic syndromes, such as cerebellar ataxia, opsoclonus-myoclonus, watery diarrhea, or hypertension. [merckmanuals.com]

  […] 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]

• 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]

• Cerebellar Ataxia

  They may also present with paraneoplastic syndromes (see Overview of Cancer: Paraneoplastic Syndromes ) such as cerebellar ataxia, opsoclonus-myoclonus, watery diarrhea, or hypertension. [web.archive.org]

  They may also present with paraneoplastic syndromes, such as cerebellar ataxia, opsoclonus-myoclonus, watery diarrhea, or hypertension. [merckmanuals.com]

  […] absence of cerebellar ataxia. [intechopen.com]

• Focal Neurological Deficit

  Children occasionally present with focal neurologic deficits or paralysis due to direct extension of the cancer into the spinal canal. [web.archive.org]

  Children occasionally present with focal neurologic deficits or paralysis due to direct extension of the cancer into the spinal canal. Tumors in the neck or upper chest may cause Horner syndrome (ptosis, miosis, anhidrosis). [msdmanuals.com]

  neurologic deficits Spinal ependymomas: Progressive neurologic deficit Physical findings with intracranial ependymomas may include the following: General or focal neurologic signs reflecting the location of the tumor Infratentorial ependymomas: Papilledema [emedicine.medscape.com]

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.

• Hepatocellular Carcinoma

  Abstract Sorafenib is a multikinase inhibitor that is approved for use against renal cell and hepatocellular carcinoma. We found that sorafenib potently induced cell death in human neuroblastoma cells. [ncbi.nlm.nih.gov]

  The most important clinical marker for HBL is serum alpha-fetoprotein (AFP), except in the case of some rare variants of HBL and hepatocellular carcinoma that exhibit lower AFP levels. [2] Medulloblastoma [ edit ] Brain tumors are the most common type [en.wikipedia.org]

  Xenografts of human hepatocellular carcinoma: a useful model for testing drugs. Clin. Cancer Res. 12, 4306–4314 (2006). 118. Huynh, H. et al. [doi.org]

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].

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].

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.

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.

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].

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.

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].

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.

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.