Neuroblastoma

What is Neuroblastoma?

Neuroblastoma (NB) is a common kind of tumor found in children, appearing outside their brain. It is known as an embryonal neuroendocrine tumor, meaning it comes from early nerve cells called neural crest progenitor cells. Because of this type, it can develop anywhere in the sympathetic nervous system, which includes various glands in the body like the superior cervical, paraspinal, and celiac ganglia, with most of them found in the adrenal glands. People may experience different symptoms depending on the tumor, varying from a benign well-felt mass with swelling to serious illness from extensive tumor spread. Even though more people are surviving for five years without the disease progressing, studies show that survival rates can differ significantly between those with less harmful low-risk types and those with high-risk types where little progress has been made. Therefore, there’s a strong need to create specialized treatments specifically for managing the high-risk types intensively.

What Causes Neuroblastoma?

We still don’t fully understand what causes certain key gene mutations that lead to neuroblastoma, a type of cancer that often affects children. Researchers believe that certain factors during conception and pregnancy might increase the risk, but they are still studying this topic.

Neuroblastoma can develop sporadically, meaning it happens without a clear cause, or it can be inherited, passed down from parents to their children. Most inherited cases of neuroblastoma come from certain mutations in the ALK or PHOX2B genes. However, some inherited cases of neuroblastoma follow an autosomal dominant pattern, which means that only one copy of the altered gene in each cell is sufficient to cause the disorder.

Even though 15% of sporadic cases of neuroblastoma come from mutations in a gene called ALK, more commonly, changes in genes called BARD1, LIN28B, or FLJ22536 are responsible. Other genetic changes, such as loss of specific parts of chromosomes 1 and 11, or too many copies of part of chromosome 17, may also play a role in neuroblastoma.

Of particular note is the MYCN gene. When too many copies of this gene are present—a condition called MYCN amplification—it can worsen the prognosis of neuroblastoma patients. This happens in around 25% of all cases. Additionally, having too many copies of part of chromosome 17 and loss of parts of chromosome 1 are often associated with MYCN amplification.

Risk Factors and Frequency for Neuroblastoma

Neuroblastoma is a very common type of cancer in infants, typically diagnosed around 17 months of age. It’s the leading type of tumor in the sympathetic nervous system, accounting for 97% of all cases. Sadly, it’s responsible for about 15% of cancer-related deaths in children.

• Each year in the United States, about 650 new cases of neuroblastoma are diagnosed. This is equivalent to roughly 10.2 cases for every million children, or 65 cases per million infants.
• These rates have hardly changed over time.
• While we have seen some improvement in the five-year survival rate from 1975 to 2005, this doesn’t hold true for all subgroups of patients.

Signs and Symptoms of Neuroblastoma

Neuroblastoma is a type of cancer that comes from early forms of nerve cells found in an embryo or fetus. Given the widespread regions originally inhabited by these types of cells, neuroblastoma can appear in various parts of the body including the neck, chest, abdomen, or pelvis. The most common place it starts is in the adrenal glands, small glands on top of each kidney. In this case, patients often report a solid mass in their abdomen.

Depending upon where the disease is located, different symptoms can be noticed. If the disease involves the upper neck area, patients might exhibit symptoms including drooping upper eyelid, small pupil, and decreased sweating on the same side of the face (Horner syndrome). In cases where the spinal cord is involved, patients may experience issues such as cord compression, which leads to loss of feeling or moving parts of the body, or paralysis. The behavior of tumor can be highly unpredictable, varying from spontaneously shrinking to spreading quickly throughout the body.

Unfortunately, in many cases, the disease has already spread at the time of diagnosis, frequently involving structures such as bones and bone marrow, followed by lymph nodes, and in rarer cases, lungs. Patients may experience non-specific symptoms like fever, weight loss, and fatigue. The signs and symptoms can range from feeling a mass without any other symptoms to severe illness, and these depend on factors linked with patient’s outlook.

Some other presentations of the disease include rare cases of high blood pressure (usually due to compression of the kidney artery), chronic diarrhea (caused by secretion of intestinal hormones), bone pain and limping (in case the bones are involved), symptoms due to chest tumors (Horner syndrome), and unusual cases of quick, involuntary muscle jerking (myoclonus) and rapid, uncontrolled eye movement (opsoclonus).

• Solid mass in the abdomen
• Horner syndrome (when disease involves upper neck area)
• Issues like paralysis or loss of feeling (when disease involves spinal cord)
• Problems like fever, weight loss, and fatigue (when disease has spread)
• High blood pressure (usually caused by kidney artery compression)
• Chronic diarrhea (caused by secretion of intestinal hormones)
• Bone pain and limping (when bones are involved)
• Myoclonus and opsoclonus (unusual cases)

Testing for Neuroblastoma

Diagnosing certain medical conditions, such as neuroblastoma, requires multiple steps. Starting with a careful gathering of your medical history and a physical exam, doctors can then turn to a number of laboratory tests. This could include a complete blood count (CBC), checks on your kidney and liver health, and electrolyte and LDH (lactate dehydrogenase) measurements.

In order to confirm a diagnosis of neuroblastoma, a tissue sample must be examined under a microscope. You might hear your doctor talk about ‘small blue cell tumours’. This refers to the appearance of cells from a neuroblastoma when they are displayed under a microscope – they are small, round, and blue. When a tumour is confirmed to be present, a closer look at its DNA can tell doctors more about what particular kind of neuroblastoma it is.

Regularly, neuroblastomas produce certain chemicals called catecholamines. Your doctor can look for breakdown products of these chemicals in your urine to help confirm the diagnosis. Most neuroblastomas will produce these breakdown products.

Overall, the aim of these tests is to build up a picture of how far the disease has spread in your body. From there, the best treatment plan can be decided.

Once the diagnosis is confirmed, imaging studies can help determine how far the disease has spread. MRI scans are typically the first imaging tests used due to their high resolution, which helps plan any surgical procedures required. Other imaging techniques include mIBG scans, which take advantage of the neuroblastoma cells’ activity to accurately highlight the reach of the disease’s spread.

Unfortunately, neuroblastoma can often spread to the bones. Therefore, a sample of your bone marrow, the spongy tissue inside your bones, may also be examined. Besides, additional imaging studies, such as CT scans of your abdomen and chest and skeletal surveys, might be recommended to look for other signs of disease throughout your body.

If symptoms suggest that the nervous system might be involved, an MRI of the spine might be performed. Some neuroblastomas can also cause heart-related problems, so tests like ECG (an electrical recording of the heart) and echocardiogram (an ultrasound of the heart) might be performed. If the treatment plan involves certain medications, such as cisplatin, that might affect your hearing, a baseline hearing test might be performed.

Treatment Options for Neuroblastoma

Treatment options for neuroblastoma, a type of cancer, vary based on where the tumor is located, how advanced it is, and its grade. These options can include simple monitoring, surgery, chemotherapy, radiation therapy, stem cell transplantation, and immunotherapy.

In low-risk cases, the tumors are localized, meaning they haven’t spread to other parts of the body. Sometimes, these small tumors may even shrink on their own, especially in infants. Instead of surgery, doctors may simply monitor the tumor’s growth through regular imaging tests, usually performed every six to twelve weeks.

For larger localized tumors, typically in patients older than infancy, surgery may be necessary. However, for patients under 18 months old, an observational approach is currently being studied internationally. Children who have symptoms might be given moderate chemotherapy, without needing either surgery or radiation therapy.

Intermediate-risk patients usually have localized metastasis, meaning their cancer has spread to nearby areas like the lymph nodes or marrow. In these cases, treatment tends to involve chemotherapy and, if possible, surgery.

The highest risk cases are those in which the cancer has spread to more distant areas of the body, like the bone marrow, bones, lungs, and liver. Treatment for these patients is usually more aggressive and involves a series of steps: first, induction chemotherapy to reduce tumor size at all locations; second, maximally invasive surgery to remove the tumor; third, another intense form of chemotherapy followed by stem-cell transplantation. After this, patients are usually given a combination of maintenance chemotherapy and immunotherapy.

One drug that’s used as an immunotherapy treatment is dinutuximab, a monoclonal antibody that attaches to a carbohydrate molecule found on many neuroblastoma cells. Using dinutuximab has been shown to improve the two-year survival rate of high-risk patients from 46% to 66%.

Overall, surgery is a central part of the treatment plan for neuroblastoma. In situations where the disease is still localized, surgery alone can potentially result in a cure. Sometimes, surgery is done after chemotherapy to remove any remaining tumor. And, in some cases, surgery might be performed simply to confirm a diagnosis.

What else can Neuroblastoma be?

When doctors are considering a diagnosis, they could be looking at many different conditions. Some of these could include:

• Dermoid cyst
• Ewings sarcoma
• Germ cell tumour
• Hepatoblastoma
• Infantile fibromatosis
• Infections
• Lymphoma
• Rhabdomyosarcoma
• Small round cell sarcoma
• Wilm’s syndrome