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Neuroblastoma

Neuroblastic Tumor

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].

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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.

Fever
  • This case report depicts a 3-year-old girl who presented with a recurring fever, runny nose, and a positive test for rhinovirus suggesting a simple case of the common cold. Further investigation, however, revealed stage 4 neuroblastoma.[ncbi.nlm.nih.gov]
  • Fever and feeling of malaise are the primary signs of neuroblastoma. Children also complain of poor appetite and eventually undergo weight loss.[symptoma.com]
  • We recommend sequencing NBAS in cases of recurrent hepatitis in infancy of unknown cause, especially in individuals with fever-associated hepatic dysfunction.[ncbi.nlm.nih.gov]
  • 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]
  • 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]
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]
  • We uncovered a novel heterozygous germline missense mutation p.F58L (c.172T C) in the anaplastic lymphoma kinase (ALK) gene and one novel heterozygous rearrangement Q418Hfs(*)11 (c.1254_1264delins TTACTTAGTACAAGAACTG) in the Fanconi anemia gene FANCD2[ncbi.nlm.nih.gov]
  • Because anemia progressed at the end of the operation, transfusion of red cell component was initiated. Ten minutes later, he suddenly developed hypoxemia, tachypnea, and tachycardia.[ncbi.nlm.nih.gov]
  • Embryonal tumors in patients with DNA repair defects such as Fanconi anemia (FA) often have a poor prognosis, because of lack of therapeutic options.[ncbi.nlm.nih.gov]
  • 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]
Fatigue
  • This type of treatment can cause side effects, such as skin irritation, diarrhea, and fatigue. Immunotherapy Immunotherapy is also called biologic therapy.[healthline.com]
  • 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]
  • 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]
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]
  • 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]
  • Generally, symptoms include abdominal pain, emesis, weight loss, anorexia, fatigue, and bone pain. Hypertension is an uncommon sign of the disease and is generally caused by renal artery compression, not catecholamine excess.[emedicine.medscape.com]
  • 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]
  • The disease can also be associated with arterial hypertension, fever, and an altered general state (weight loss, pain, irritability, and anemia).[orpha.net]
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]
  • The first symptoms are usually fever, a general sick feeling ( malaise ), and pain. There may also be loss of appetite, weight loss, and diarrhea.[nlm.nih.gov]
  • 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]
  • 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]
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]
  • Another rare syndrome causes abdominal swelling and diarrhea. Nov. 28, 2018[mayoclinic.org]
  • Some of the symptoms associated with neuroblastoma — such as high blood pressure, rapid heartbeat or diarrhea — are caused by increased catecholamines.[ucsfbenioffchildrens.org]
  • Possible short-term effects of radiation include nausea, diarrhea, fatigue, sunburn changes to the skin and hair loss.[eapsa.org]
Abdominal Mass
  • We present a rare case of perinatal intrarenal neuroblastoma in a neonate who presented with an incidentally detected abdominal mass. These tumors cause diagnostic and therapeutic dilemma because of its uncommon location.[ncbi.nlm.nih.gov]
  • Neonatal evaluation confirmed the etiology of the abdominal mass to be liver metastasis from neuroblastoma. The child died on the 46th day. 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:502-506, 2017.[ncbi.nlm.nih.gov]
  • 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 abdominal mass is irregular, firm, and clearly crosses the midline. An MRI of her head shows potential metastasis to the skull.[step2.medbullets.com]
  • The most common symptoms are abdominal pain, discomfort, and fullness due to an abdominal mass. Some children present with bone pain from widespread bony metastases. Periorbital ecchymosis and proptosis may occur with retrobulbar metastasis.[web.archive.org]
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]
  • We report a case of 23-year-old man who presented with complaints of progressive abdominal distension for the past 3 months along with the loss of appetite and weight and had a large solid cystic mass in the left half of the abdominal cavity revealed[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]
Constipation
  • 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]
  • 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]
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]
  • A 5-year-old boy with chemoresistant neuroblastoma treated with bevacizumab plus radioimmunotherapy developed acute abdominal pain. Computed tomography scan showed free abdominal air and pneumatosis coli.[ncbi.nlm.nih.gov]
  • 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 most common symptoms are abdominal pain, discomfort, and fullness due to an abdominal mass. Some children present with bone pain from widespread bony metastases. Periorbital ecchymosis and proptosis may occur with retrobulbar metastasis.[web.archive.org]
  • […] origin anywhere along sympathetic chain Genetics associated with amplification of N-Myc oncogene Associated conditions sometimes (2-3%) seen with opsoclonus myoclonus ataxia syndrome with or without ataxia Presentation Symptoms abdominal distention abdominal[step2.medbullets.com]
Cheilitis
  • Grade 3 or 4 toxic effects, including elevations in aminotransferase levels (2 percent of patients), renal effects (2 percent), gastrointestinal effects (2 percent), skin effects (cheilitis, dryness, and rash; 2 percent), infection (12 percent), and hypercalcemia[doi.org]
Hypertension
  • Hypertension resolved immediately after complete surgical resection of the tumor with an uneventful follow-up (24 months at the present time).[ncbi.nlm.nih.gov]
  • 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]
  • The clinical picture of adult renal NB is that of a 44-year-old woman, presenting with an abdominal or renal mass about 13cm in size, accompanied by hypertension, hematuria, or pain.[ncbi.nlm.nih.gov]
  • Author information 1 Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan. 2 Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan[ncbi.nlm.nih.gov]
Chest Pain
  • 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]
  • 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 the sockets (proptosis) Dark circles, similar[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]
Thrombosis
  • CONCLUSION: We cannot rule out the possibility that a clotting defect, commonly observed in disseminated malignancies such as a metastatic neuroblastoma may be associated with the etiology of the gastroschisis, as this defect may result from a thrombosis[ncbi.nlm.nih.gov]
Bone Pain
  • 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]
  • 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]
  • Symptoms of metastasis including bone pain, limp, paralysis, hepatomegaly (Pepper's syndrome), and exophthalmia (Hutchinson's syndrome), indicate metastatic neuroblastoma.[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]
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]
  • […] 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]
  • In addition, neuroblastoma tumors can release hormones that may cause other signs and symptoms such as high blood pressure, rapid heartbeat, flushing of the skin, and sweating.[ghr.nlm.nih.gov]
  • . – Catecholamine excess syndrome: Symptoms include flushing, sweating, tachycardia, headache and hypertension. What other disease/condition shares some of these symptoms? Neuroblastoma has a broad oncologic differential diagnosis.[cancertherapyadvisor.com]
Ptosis
  • A 3-month-old male developed intermittent left upper eyelid ptosis at the age of 1 month that was gradually increasing in frequency and duration.[ncbi.nlm.nih.gov]
  • Infiltration of periorbital bones may produce periorbital ecchymosis, ptosis and proptosis.[pedclerk.bsd.uchicago.edu]
  • […] 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. If there is suspicion of neuroblastoma, the patient should be referred to an oncologist for further work up.[eyewiki.aao.org]
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]
  • […] 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]
  • Signs of radiculopathy include weakness, numbness, tingling, etc. primarily in a dermatome distribution. [2] Visual Changes : The patient may present with drooping eyelids (ptosis) and decreased pupil size (miosis) due to pressure on Cranial Nerve III[physio-pedia.com]
  • […] lymphangiectasia.[ 51 ] Vasoactive intestinal peptide secretion may also occur upon chemotherapeutic treatment, and tumor resection reduces vasoactive intestinal peptide secretion.[ 52 ] Presence of Horner syndrome: Horner syndrome is characterized by miosis[web.archive.org]
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]
Facial Numbness
  • A 39-year-old man presented with 1 month of decreased vision, left facial numbness, and swelling. Physical examination demonstrated left-sided exophthalmos and blindness. He had also lost his sense of smell.[emedicine.medscape.com]
Testicular Mass
  • Neuroblastoma should be considered in the differential diagnosis of testicular mass and work-up for neuroblastoma should be done before orchiectomy.[ncbi.nlm.nih.gov]
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]
  • ataxia or opsoclonus/myoclonus, occur rarely in children with neuroblastoma.[ 55 ] Opsoclonus/myoclonus syndrome can be associated with pervasive and permanent neurologic and cognitive deficits, including psychomotor retardation.[web.archive.org]
  • ataxia or opsoclonus/myoclonus, occur rarely in children with neuroblastoma.[ 68 ] Of young children presenting with opsoclonus/myoclonus syndrome, about one-half are found to have neuroblastoma.[ 69, 70 ] The incidence in the United Kingdom is estimated[cancer.gov]

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.

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].

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.

References

Article

  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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Last updated: 2019-07-11 22:12