What are the other Names for this Condition? (Also known as/Synonyms)

• Primary Neuroblastoma of Neck

What is Primary Cervical Neuroblastoma? (Definition/Background Information)

• Primary Cervical Neuroblastoma is a very rare form of malignancy that arises in the cervical or neck region. The tumor is mostly seen in young children including infants
• However, in order to diagnose Primary Cervical Neuroblastoma of Kidney, metastasis from other sites to the cervical region, such as from the abdomen or chest cavity, should be excluded
• In general, neuroblastoma is a malignant tumor that is most commonly found in children. It develops from immature nerve cells of the sympathetic nervous system
• The adrenal glands are the most common sites for a neuroblastoma. While, only 1-5% of the cases involve the neck region, neuroblastomas can arise from other parts of the body too
• The risk factors for tumor development are not well-established, but may include certain genetic disorders (such as Beckwith-Weidemann and DiGeorge syndromes) and a positive family history. The cause of Primary Cervical Neuroblastoma is believed to be due to genetic factors and several abnormalities have been noted
• The symptoms associated with Primary Cervical Neuroblastoma can vary from one individual to another. Fatigue, loss of appetite, changes in bowel habits, breathing and swallowing difficulties may be observed. Additionally, the presence of a lump in the affected area may be noted
• Surgery, chemotherapy, and/or radiotherapy are the options used to treat the tumor. Factors such as the histological type, cytogenetic and molecular features of the tumor, the child’s age, and whether the tumor has spread to other areas, are factors that help decide the best course of treatment to be followed
• The prognosis is generally favorable when neuroblastomas are detected early and treated appropriately, in cases of small-sized localized tumors with a favorable tumor biology. In most cases, the prognosis of Primary Cervical Neuroblastoma is guarded

Who gets Primary Cervical Neuroblastoma? (Age and Sex Distribution)

• Primary Cervical Neuroblastoma is observed in young and old children, including in infants
• The tumor may be observed in young and old adults too, but is rare
• No specific gender, racial, or ethnic group preference is noted

What are the Risk Factors for Primary Cervical Neuroblastoma? (Predisposing Factors)

No clearly established risk factors are noted for Primary Cervical Neuroblastoma. However, in general, the following factors may predispose an individual to neuroblastoma development:

• Children with a family history of neuroblastoma may have a higher risk of developing this malignant tumor. Although, a vast majority of children who develop the tumor, do not have a family history of the same
• Association with certain genetic disorders including:
  • Neurofibromatosis type 1 (NF1)
  • Beckwith-Weidemann syndrome
  • DiGeorge syndrome
  • Hirschsprung disease
  • Hypoventilation syndrome

The potential risk factors (not definitely proven though) for neuroblastoma include:

• Exposure to certain chemicals in industries: Researchers believe that the exposure of either parent to occupational chemicals from the electronics industry, farming, or other industries may play a role in its development
• Excessive alcohol consumption
• Smoking
• Infections during early childhood
• Use of certain drugs, medicines during pregnancy
• Hormone use and fertility drugs
• Hair dye application in expectant mothers

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Primary Cervical Neuroblastoma? (Etiology)

Currently, scientists do not know the definitive factor(s) causing Primary Cervical Neuroblastoma. It is thought to occur spontaneously due to certain genetic mutations (chromosomal abnormalities).

• Deletions in chromosomes 1 and 11 affecting the KIF1B gene (tumor suppressor gene) have been noted. The genes affected in deletion of chromosome 11 has not yet been characterized
• Amplification of MYCN gene is mostly seen in high-risk tumors
• ALK gene mutations have been implicated in both the sporadic and inherited forms of neuroblastoma
• PHOX2B gene mutations are rarely noted in familial neuroblastoma
• Some tumors, have specific single nucleotide polymorphisms (SNPs, types of genomic variables), that may be either associated with low-risk or high-risk neuroblastomas

Neuroblastoma starts to form at the embryonic stage of immature nerve cells, called neuroblasts, which are found in tissues.

• Normally, during the developmental process, neuroblasts mature into functioning nerve cells and are typically fully-developed by birth
• However, in the case of neuroblastoma, the immature neuroblasts do not develop into nerve cells. Instead, they divide and multiply uncontrollably, leading to the formation of a tumor mass (neuroblastoma)

What are the Signs and Symptoms of Primary Cervical Neuroblastoma?

The signs and symptoms of Primary Cervical Neuroblastoma vary from one individual to another and is based on the extent of spread to other areas of the body. The symptoms also arise because of the growing tumor pressing on the adjoining or surrounding tissues. The initial symptoms observed are irritability, loss of appetite, and fatigue.

The common signs and symptoms of Primary Cervical Neuroblastoma include:

• An unusual lump in the neck
• Swallowing and breathing difficulty; choking sensation in very young children
• Neck pain
• Cough, noisy breathing
• Changes in bowel habits, including diarrhea or constipation
• Paralysis or inability to move a body part
• Drooping eyelids, unequal pupil size
• Bulging eyes (proptosis)
• Fever
• Easy bruising
• Bone pain or soreness
• Paleness
• Swelling in the legs

Older children are more often diagnosed with neuroblastoma arising from the retroperitoneal and pelvic region, while more infants are diagnosed with tumors that arise in the neck and chest region.

How is Primary Cervical Neuroblastoma Diagnosed?

Before diagnosing an individual with Primary Cervical Neuroblastoma, a physician will first review the individual’s medical history including family history, and conduct a thorough physical examination. Additional tests may be performed to help confirm the diagnosis and to determine the location and size of a tumor. These may include:

• Urine and blood tests: These tests may provide information on the causes of the symptoms experienced by the individual. Blood and urine tests can detect high levels of homovanillic acid (HVA) and vanillylmandelic acid (VMA), both catecholamine metabolites, made by the neuroblastoma cells. Lab tests may also show decreased sodium levels (hyponatremia)
• Imaging tests: Imaging tests help in detecting a mass, which may suggest the presence of a tumor. These tests include X-ray, computerized tomography (CT), positron emission tomography (PET), ultrasound, and magnetic resonance imaging (MRI) scans of the head and neck region. Imaging tests are also helpful to determine the spread of the tumor, which can help determine the best course of treatment to be followed. Rarely, neuroblastoma is detected prenatally through a fetal ultrasound
• Iodine-123 metaiodobenzylguanidine scan (123-I-MIBG): In a MIBG scan, a radioactive substance is injected into blood, which will then bind to the neuroblastoma cells. This test helps in determining whether the tumor has spread to other regions of the body or not
• Tissue biopsy: If a mass is found, the physician may have a sample of the tissue removed and sent to the laboratory for a histopathological examination. A pathologist will examine the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and together with microscope findings, the pathologist arrives at a definitive diagnosis
• The pathologist may also request cytogenetic and molecular studies to determine genetic features of the cancerous cells, which is crucial in developing the most appropriate treatment plan for the affected individual
• Bone marrow biopsy: It may be helpful in determining tumor staging

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Primary Cervical Neuroblastoma?

The possible complications from Primary Cervical Neuroblastoma include:

• Metastasis (spread) of the tumor to other areas of the body, such as the bones, lymph nodes, liver, orbit, and skin, leading to functional and or anatomical derangement of the affected organ
  • Children with cancer spread generally show anemia, high blood pressure, and fever
  • In adolescents, bone marrow metastasis is uncommon (unlike in young children), while spread of malignancy to the brain and lung is more common (which is generally not seen in young children though)
• Spinal cord compression: As the tumor grows, it can press upon the spinal cord leading to paralysis of the arms/legs and pain
• Some tumors can secrete vasoactive intestinal peptide (VIP) hormone causing severe (watery) diarrhea that is also noted with chemotherapy
• Tumors in the neck can cause Horner’s syndrome that consists of contracted pupil (myosis), drooping eyelid (ptosis), decreased sweating (anhidrosis), depression of eye ball (or enophthalmos, which occurs due to compression of nerves)
• Side effects of chemotherapy and/or radiotherapy

Neuroblastomas may have the ability to secrete hormones, which can affect distant ‘normal’ body tissues and cause symptoms. This can lead to a condition known as paraneoplastic syndrome. Paraneoplastic symptoms are rare in children; but, it can result in permanent neurological damage.

The symptoms of paraneoplastic syndromes include:

• High blood pressure and/or rapid heartbeat
• Reddening of the skin
• Sweating
• A rare paraneoplastic syndrome that affects children with neuroblastoma is called opsoclonus-myoclonus-ataxia. It is characterized by rapid eye movement (dancing eyes) and difficulty in coordination (dancing feet). Tumors associated with opsoclonus/myoclonus syndrome are known to have favorable prognosis

How is Primary Cervical Neuroblastoma Treated?

Once a diagnosis of neuroblastoma has been established, the extent to which the tumor has spread is assessed, known as staging. The system used to stage neuroblastoma is the International Neuroblastoma Staging System (INSS), which is as follows:

• Stage 1: Localized tumor confined to the area of origin
• Stage 2A: Unilateral tumor with incomplete gross resection; identifiable ipsilateral and contralateral lymph node negative for tumor
• Stage 2B: Unilateral tumor with complete or incomplete gross resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor
• Stage 3: Tumor infiltrating across midline with or without regional lymph node involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement
• Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S
• Stage 4S: Age <1-year-old with localized primary tumor as defined in Stage 1 or 2, with dissemination limited to liver, skin, or bone marrow (less than 10% of nucleated bone marrow cells are tumors)

The majority of Primary Cervical Neuroblastoma cases require some form of treatment. The type of treatment required is dependent on several factors, which include:

• The child’s age
• Stage of cancer (whether the tumor has spread to other areas of the body)
• Microscopic and genetic characteristics of the tumor

With this information, the healthcare provider may be able to classify the cancer as low-risk, intermediate-risk, or high-risk. The combination of treatment options is determined by the risk category and may include:

Surgery:

• Surgery can be used to remove the tumor. The size and location of the tumor can influence whether the tumor can be removed completely
• In low-risk patients, surgery may be the only treatment method needed
• Surgically removing tumors in close proximity to vital organs, such as the lungs, may be associated with complications

In individuals categorized as intermediate-risk, additional treatment options, including chemotherapy may be necessary following the removal of tumor.

In individuals categorized as high-risk, the treatment options, such as chemotherapy, radiation therapy, stem cell transplantation, biological therapy, and immunotherapy, may be necessary following the surgical removal of tumor.

Chemotherapy:

• Chemotherapy uses drugs to kill cancer cells or prevent their further growth
• While chemotherapy is utilized to target cancerous cells, it can also cause damage to healthy, normal cells in the body, resulting in side effects

Radiation therapy:

• Radiation therapy uses high-energy waves, such as X-rays, to kill the cancer cells
• This type of treatment may be beneficial for children with low-risk and intermediate-risk neuroblastoma, especially if surgery and chemotherapy have not proved to be helpful
• For high-risk neuroblastoma, radiation therapy may be used following surgery and chemotherapy, to prevent the cancer from returning

Autologous stem cell transplant:

• This type of treatment, along with intensive chemotherapy, may be useful with high-risk neuroblastomas
• In this procedure, the individual’s blood stem cells are collected and stored. Following this, high doses of chemotherapy drugs are then administered to destroy the cancerous cells
• After the chemotherapy treatment, the stored stem cells are then injected into the child to allow the formation of new blood cells

Immunotherapy:

• Immunotherapy drugs are used to enhance the body’s immune system and its ability to defend against cancerous cells
• Individual’s with high-risk conditions may undergo immunotherapy to increase the immune system’s fight against the neuroblastoma cells

Note:

• Newer therapies include biological therapy (using isotretinoin) and antibody therapy (using cytokine proteins) have been used in the treatment
• ALK kinase inhibitors are helpful in treating recurrent tumors and those tumors that do not respond to treatment (refractory neuroblastoma)
• Treatment may be undertaken for symptoms, such as spinal cord compression (causing paralysis) and severe diarrhea
• Appropriate therapy is necessary following surgery, to recover from neurological symptoms caused by the tumor

Observation: In some rare cases, neuroblastoma may disappear on its own, without any treatment. Therefore, sometimes, the physicians may use what is known as “watchful waiting” before planning appropriate treatment options.

How can Primary Cervical Neuroblastoma be Prevented?

Current medical research has not established a method of preventing Primary Cervical Neuroblastoma.

• Cancer screenings are important tests in that they can detect cancer in its earliest stages, which would help optimize treatment efforts. Nevertheless, currently, there are no standardized screening tests for neuroblastomas
• Regular medical screening at periodic intervals with blood tests, imaging scans, and physical examinations, are mandatory for those who have already had the tumor removed or destroyed. This is because neuroblastomas have a high metastasizing (spreading capacity) potential and the possibility of recurrence

In general, preventive methods for cancers include reducing contributory risk factors, such as:

• Smoking
• Unhealthy diet and lifestyle
• Obesity
• Exposure to toxins
• Unnecessary medication

What is the Prognosis of Primary Cervical Neuroblastoma? (Outcomes/Resolutions)

The prognosis for Primary Cervical Neuroblastoma can vary from one child to another and is dependent on a set of several factors that include:

• Age of the child
• Location of the tumor
• The physical and genetic characteristics of the tumor cells (including histological type of tumor)
• Stage of the tumor: With lower-stage tumors, when the tumor is confined to the site of origin, the prognosis is usually better with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
• Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
• Involvement of the regional lymph nodes (in children older than 12 months)

Often times, there is a favorable response to treatment, if the cancer has not already spread. Children diagnosed before the age of 12 months, most of the times, see a more successful outcome. However, the prognosis of Primary Cervical Neuroblastoma is mostly guarded.

As with any tumor, it is important to have follow-up appointments with a physician to monitor for any returning tumors. Close monitoring in children after surgery, to watch out for long-term treatment side effects (such as from chemotherapy) is essential and is recommended.

Additional and Relevant Useful Information for Primary Cervical Neuroblastoma:

Please visit our Cancer & Benign Tumors Health Center for more physician-approved health information:

http://www.dovemed.com/diseases-conditions/cancer/