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

• Primary Renal Neuroblastoma

What is Primary Neuroblastoma of Kidney? (Definition/Background Information)

• Primary Neuroblastoma of Kidney is a very rare and aggressive kidney cancer. It is considered to be a type of small blue cell tumor. The tumor is mostly seen in older children, teens, and young adults
• However, in order to diagnose Primary Neuroblastoma of Kidney, metastasis from other sites to the kidney, such as from the adrenal glands or retroperitoneum, should be excluded
• 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. Neuroblastomas most commonly originate in the adrenal glands, which are located on top of the kidneys. They 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 Neuroblastoma of Kidney is believed to be due to genetic mutations and several genetic abnormalities have been noted
• The signs and symptoms of Primary Neuroblastoma of Kidney 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 (whether low-risk or high-risk) and stage of the malignancy
• The prognosis of Primary Neuroblastoma of Kidney depends on the age of the individual and whether it is localized in the kidney or has metastasized (if it is in its early or advanced stage, at the time of diagnosis). The prognosis of the tumor is assessed on a case-by-case basis

Who gets Primary Neuroblastoma of Kidney? (Age and Sex Distribution)

• Primary Neuroblastoma of Kidney is an extremely rare malignancy that is observed in children, adolescents, young and old adults
• No specific gender, racial, or ethnic group preference is noted

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

No clearly established risk factors are noted for Primary Neuroblastoma of Kidney. 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 health care provider.

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

Currently, scientists do not know the definitive factor(s) causing Primary Neuroblastoma of Kidney. 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 deletion of chromosome 11 has not yet been characterized
• Extra copies of N-myc gene: When the kidney is involved, fewer cases are reported with N-myc gene amplification
• ALK gene mutations have been implicated in both the sporadic and inherited forms of neuroblastoma
• PHOX2B gene mutations are rarely noted in familial neuroblastoma

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 Neuroblastoma of Kidney?

The signs and symptoms associated with Primary Neuroblastoma of Kidney 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 Primary Neuroblastoma of Kidney include:

• Blood in the urine (hematuria)
• Fatigue due to anemia
• A visible lump may be seen on the side of the abdomen; some tumors are known to grow up to 10 cm in size
• 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

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 kidney tumor. The combination of signs and symptoms may also vary from individual to individual.

How is Primary Neuroblastoma of Kidney Diagnosed?

A healthcare provider might employ one or several of the following tools to diagnose Primary Neuroblastoma of Kidney 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 blood serum catecholamines and 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 kidneys
• 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
• The differential diagnosis of Primary Neuroblastoma of Kidney includes the following:
  • Metastasis of neuroblastoma to the retroperitoneal region or adrenal glands
  • Wilms tumor

Note:

• Radiological imaging studies may show calcification
• Based on histology, the tumor may be differentiated, poorly-differentiated, or undifferentiated. It may also have favorable or unfavorable pathology

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 Neuroblastoma of Kidney?

The possible complications associated with Primary Neuroblastoma of Kidney 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. Involvement of the bone marrow is not typically noted
• 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 Primary Neuroblastoma of Kidney 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 Primary Neuroblastoma of Kidney 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 kidney. 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 Primary Neuroblastoma of Kidney be Prevented?

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

• 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 kidney 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 Neuroblastoma of Kidney? (Outcomes/Resolutions)

The prognosis of Primary Neuroblastoma of Kidney depends on the age of the individual, the size of the tumor, their localization, and spread. In general, the prognosis is guarded.

• 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 to 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 Primary Neuroblastoma of Kidney is diagnosed in the early stages, the possibility of survival increases and the prognosis is considered good with treatment
• Tumors that are differentiated and with favorable histology have a much better prognosis than those that are undifferentiated/poorly-differentiated and having unfavorable histology
• 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. 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 Neuroblastoma of Kidney:

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

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