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

• Neuroblastoma of Adrenal Gland

What is Adrenal Gland Neuroblastoma? (Definition/Background Information)

• Adrenal Gland Neuroblastoma is a rare and aggressive form of cancer. It is considered to be a type of small blue cell tumor. The tumor is mostly seen in infants and young children
• The adrenal glands are the most common sites for a neuroblastoma. Nearly 40% of the cases involve these glands, which are located on top of the kidneys. Neuroblastomas can arise from other parts of the body too
• Neuroblastoma is a malignant tumor that is most commonly found in infants and young children. It develops from immature nerve cells of the sympathetic nervous system
• 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 Adrenal Gland Neuroblastoma is believed to be due to genetic mutations and several genetic abnormalities have been noted
• The signs and symptoms of Neuroblastoma of Adrenal Gland may include blood in urine, a lump on the side of the abdomen, flank pain, unexplained fever, and unexplained weight loss. It can give rise to complication such as the spread of cancer to other parts of the body (metastasis)
• The treatment options include surgery, radiation therapy, chemotherapy, and targeted drug therapy. A healthcare provider decides on the treatment based on the risk category and stage of the malignancy
• The prognosis of Adrenal Gland Neuroblastoma depends on the size of the tumor and whether it is localized in the adrenal gland or has metastasized (if it is in its early or advanced stage, at the time of diagnosis). In general, the prognosis is assessed on a case-by-case basis

Who gets Adrenal Gland Neuroblastoma? (Age and Sex Distribution)

• Adrenal Gland 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 Adrenal Gland Neuroblastoma? (Predisposing Factors)

No clearly established risk factors are noted for Adrenal Gland 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 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 Adrenal Gland Neuroblastoma? (Etiology)

Currently, scientists do not know the definitive factor(s) causing Adrenal Gland Neuroblastoma. It is thought to occur spontaneously due to certain genetic mutations (chromosomal abnormalities). In general, neuroblastoma tumor can be sporadic, due to the presence of random mutations, or familial.

• Deletions in chromosomes 1 and 11 affecting the KIF1B gene (tumor suppressor gene) have been noted. The genes affected in tumor involving 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 Adrenal Gland Neuroblastoma?

The signs and symptoms associated with Adrenal Gland Neuroblastoma depend 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, weight loss, and fatigue.

The most common signs and symptoms of Adrenal Gland Neuroblastoma include:

• Blood in the urine (hematuria)
• Fatigue due to anemia
• A visible lump may be seen on the side of the abdomen
• Fluid accumulation in the lower legs (pedal edema)
• Abdominal pain and flank pain
• Night sweats, unexplained fever
• Generalized weakness and pain in the body
• Abnormal liver function test
• Bleeding can occur within large tumors; hemorrhage within the tumors can lead to tissue death (or infarction)
• Small-sized tumors may be asymptomatic; many tumors are not known to present any significant signs and symptoms

The secretions of catecholamines from the tumor causes a variety of symptoms including:

• Increased blood pressure (hypertension)
• Increased heart rate
• Flushing of skin
• Uncontrolled sweating

The signs and symptoms may depend on the size of the adrenal gland tumor. The combination of signs and symptoms may also vary from individual to individual.

How is Adrenal Gland Neuroblastoma Diagnosed?

A healthcare provider might employ one or several of the following tools to diagnose Adrenal Gland Neuroblastoma tumors:

• Evaluation of the patient’s personal and family medical history
• A complete physical examination
• Blood tests such as complete blood count (CBC), serum calcium, serum albumin, liver function test (LFT), etc. Lab tests may show increased urine catecholamines
• Urine analysis such as albumin levels
• Plain X-ray of the abdomen
• Ultrasound scan of the abdomen
• Computed tomography (CT) scans of the abdomen
• Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans may help differentiate benign and malignant tumors by detecting areas of metastasis (if any)

Although the above modalities can be used to make the initial diagnosis, a tissue biopsy of the tumor may be required to make a definitive diagnosis to begin treatment.

• The tissue for diagnosis can be procured in multiple different ways, and they include:
  • Fine needle aspiration (FNA) biopsy of the tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
  • Core biopsy of the tumor
  • Open biopsy of the tumor
• A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
• Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
• Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely electron microscopic studies to assist in the diagnosis

Note: Radiological imaging studies may show calcification.

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 Adrenal Gland Neuroblastoma?

The possible complications associated with Adrenal Gland Neuroblastoma include:

• The rarity of the condition may cause a delayed diagnosis leading to metastasis
• Metastasis: The cancer can spread to other areas of the body, such as to the bones, liver, skin, and around the orbit. This can also result in associated symptoms such as bone pain (if bone is involved), blue skin rashes (if skin is involved), etc.
• Recurrence of the tumor due to its partial or incomplete surgical removal
• Complications due to surgery
• Side effects of chemotherapy (such as toxicity) and radiation

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. The symptoms of paraneoplastic syndromes include:

• High blood pressure and/or rapid heartbeat
• Reddening of the skin
• Sweating
• Permanent neurologic symptoms
• 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 Adrenal Gland 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 neuroblastoma cases require some form of treatment. The type of treatment required is dependent on several factors, which include:

• The age of the individual
• 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. The treatment measures for Adrenal Gland Neuroblastoma may include the following:

• Surgery:
  • In majority of individuals, surgical resection of the tumor with clear margins is performed, especially if the tumor is confined to the adrenal gland. In some cases, due to location of the tumor, a complete surgical removal may be difficult
  • Several different surgical procedures may be available, such as partial/radical nephrectomy or laparoscopic surgery, depending on the type, size, and location of the tumor
  • In low-risk patients, surgery may be the only treatment method needed
  • Postoperative care is important: One must maintain minimum activity levels, until the surgical wound heals

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
• Newer therapies include biological therapy (using isotretinoin) and antibody therapy (using cytokine proteins) have been used in treating the tumor
• ALK kinase inhibitors are helpful in treating recurrent tumors and those tumors that do not respond to treatment (refractory neuroblastoma)

A long-term follow-up is required, because there is a risk of recurrence of the tumor at the site of surgery or metastasis in distant sites.

How can Adrenal Gland Neuroblastoma be Prevented?

Current medical research has not established a method of preventing Adrenal Gland 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 Adrenal Gland Neuroblastoma? (Outcomes/Resolutions)

The prognosis of Adrenal Gland Neuroblastoma depends on the age of the individual, the size of the tumor, their localization and spread. In general, the prognosis is poor, since the tumors are aggressive malignancies.

• Typically, the prognosis also depends upon a set of several factors, which include:
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually better with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The physical and genetic characteristics of the tumor cells 
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
• When Adrenal Gland Neuroblastoma is diagnosed in the early stages, the possibility of survival increases and the prognosis is considered good with treatment
• In cases where the cancer has spread to other parts of the body, the possibility of prolonged survival following diagnosis is limited

As with any tumor, it is important to have follow-up appointments with a physician to monitor for any returning tumors.

Additional and Relevant Useful Information for Adrenal Gland Neuroblastoma:

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

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