Neuroblastoma - Childhood - Stages and Groups

Approved by the Cancer.Net Editorial Board, 04/2016

ON THIS PAGE: You will learn about how doctors describe neuroblastoma’s growth or spread. This is called the stage. To see other pages, use the menu.

Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and whether it is affecting other parts of the body. Doctors use diagnostic tests to find out the cancer's stage, so staging may not be complete until all of the tests are finished.

Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis, which is the chance of recovery. There are different stage descriptions for different types of cancer. Once a diagnosis of neuroblastoma is confirmed, how much the tumor has grown and spread is evaluated or staged. The tumor’s stage helps your child’s doctor plan treatment.

There are 2 staging systems for neuroblastoma: INSS and INRGSS. Each is described below, followed by an explanation of risk groupings.

International Neuroblastoma Staging System Committee (INSS) system

The following is a brief summary of each INSS stage:

Stage 1: The tumor can be removed completely during surgery. Lymph nodes attached to the tumor removed during surgery may or may not contain cancer, but other lymph nodes near the tumor do not.

Stage 2A: The tumor is located only in the area it started and cannot be completely removed during surgery. Nearby lymph nodes do not contain cancer.

Stage 2B: The tumor is located only in the area where it started and may or may not be completely removed during surgery, but nearby lymph nodes do contain cancer.

Stage 3: The tumor cannot be removed with surgery. It has spread to regional lymph nodes (lymph nodes near the tumor) or other areas near the tumor, but not to other parts of the body.

Stage 4: The original tumor has spread to distant lymph nodes (lymph nodes in other parts of the body), bones, bone marrow, liver, skin, and/or other organs, except for those listed in stage 4S, below.

Stage 4S: The original tumor is located only where it started (as in stage 1, 2A, or 2B), and it has spread only to the skin, liver, and/or bone marrow, in infants younger than one. The spread to the bone marrow is minimal, usually less than 10% of cells examined show cancer.

The International Neuroblastoma Risk Group Staging System (INRGSS)

The INRGSS was designed specifically for the International Neuroblastoma Risk Group (INRG) pre-treatment classification system (see Risk groups, below). Unlike the INSS explained above, the INRGSS uses only the results of imaging tests taken before surgery. It does not include surgical results or spread to lymph nodes to determine the stage.  Knowledge regarding the presence or absence of image defined risk factors (IDRF) are required for this staging system.

Stage L1: The tumor is located only in the area where it started; no IDRFs are found on imaging scans, such as CT or MRI.

Stage L2: The tumor has not spread beyond the area where it started and the nearby tissue; IDRFs are found on imaging scans, such as CT or MRI.

Stage M: The tumor has spread to other parts of the body (except stage MS, see below)

Stage MS: The tumor has spread to only the skin, liver, and/or bone marrow (less than 10% bone marrow involvement) in patients younger than 18 months.

Risk groups

Some children are cured with surgery alone or surgery with chemotherapy (see Treatment Options). Others have a very aggressive disease that is difficult to treat. By using a combination of factors, doctors can usually predict how well treatment will work for a neuroblastoma tumor, or if it will come back after treatment.

In the INRG classification system, a combination of clinical, pathologic and genetic markers are used to predict whether the tumor will grow and how it will respond to treatment. These markers are used to define risk. Using the following factors, neuroblastoma is classified into 1 of 4 categories: very low-risk, low-risk, intermediate-risk, or high-risk.

  • The stage of the disease according to the INRG staging system

  • Age at the time of diagnosis

  • Histologic category, such as maturing ganglioneuroma versus ganglioneuroblastoma, intermixed versus ganglioneuroblastoma or nodular versus neuroblastoma

  • Grade or how cells of the tumor are differentiated

  • MYCN gene status

  • Chromosome 11q status

  • Tumor cell ploidy, which is the DNA content of tumor cells

The Children’s Oncology Group (COG) currently uses the following factors to determine risk but will be using the INRG Risk Group definitions in future studies:

  • The stage of the disease according to the INSS system

  • Age at the time of diagnosis

  • MYCN gene status

  • Tumor ploidy; this is only important for children younger than 18 months

  • Tumor histopathology according to the International Neuroblastoma Pathologic Classification (INPC) system

Descriptions of low-risk, intermediate-risk, or high-risk neuroblastoma according to the current COG definitions are listed below.

Low-risk neuroblastoma

  • Stage 1 disease

  • Stage 2A or 2B disease in which more than 50% of the tumor was surgically removed, except for a child with MYCN amplification

  • Stage 4S disease, no MYCN amplification, favorable histopathology, and hyperdiploidy, meaning having extra chromosomes

Intermediate-risk neuroblastoma

  • Stage 2A or 2B disease with no MYCN amplification in which less than 50% of the tumor was removed with surgery

  • Stage 3 disease in children younger than 18 months, no MYCN amplification

  • Stage 3 disease in children older than 18 months, no MYCN amplification, and favorable histopathology

  • Stage 4 disease in children younger than 12 months, no MYCN amplification.

  • Stage 4 disease in children age 12 months to 18 months, no MYCN amplification, hyperdiploidy, and favorable histology.

  • Stage 4S disease, no MYCN amplification, unfavorable histopathology and/or diploidy

High-risk neuroblastoma

  • Stage 2A or 2B disease and MYCN amplification

  • Stage 3 disease and MYCN amplification

  • Stage 3 disease in children age 18 months or older, no MYCN amplification, and unfavorable histopathology

  • Stage 4 disease in children younger than 12 months and MYCN amplification

  • Stage 4 disease in children between 12 months and 18 months old with MYCN amplification, and/or diploidy, and/or unfavorable histology

  • Stage 4 disease in children 18 months or older

  • Stage 4S disease and MYCN amplification

Descriptions of very-low, low-risk, intermediate-risk, or high-risk neuroblastoma according to INRG definitions are listed below:

Very low-risk neuroblastoma

  • Stage L1/L2 with ganglioneuroma maturing or ganglioneuroblastoma intermixed histology

  • Stage L1 with non-amplified MYCN

  • Stage MS in children younger than 18 months of age with no 11q aberration

Low-risk neuroblastoma

  • Stage L2 in children younger than 18 months of age with no11q aberration

  • Stage L2 in children older than 18 months of age with ganglioneuroblastoma nodular or neuroblastoma with differentiating histology and no 11q aberration

  • Stage M in children younger than 18 months without MYCN amplification and hyperdiploidy

Intermediate-risk neuroblastoma

  • Stage L2 in children younger than 18 months without MYCN amplification with 11q aberration

  • Stage L2 in children older than 18 months with ganglioneuroblastoma nodular or neuroblastoma with differentiating histology with 11q aberration

  • Stage L2 in children older than 18 months with ganglioneuroblastoma nodular or neuroblastoma with poorly differentiated or undifferentiated histology

  • Stage M in children younger than 12 months with diploidy

  • Stage M in children 12 months to 18 months with diploidy

High-risk neuroblastoma

  • Stage L1 with MYCN amplification

  • Stage L2 with MYCN amplification

  • Stage M in children younger than 18 months of age with MYCN amplification

  • Stage M in children with older than 18 months

  • Stage MS in children younger than 18 months with 11q aberration

  • Stage MS in children younger than 18 months of age with MYCN amplification

Treatment is tailored according to the risk assigned to the tumor. Most patients with very-low and low-risk disease commonly receive surgery alone. Sometimes, infants with small localized tumor have been successfully watched closely without any surgery, called observation.

Patients with intermediate-risk disease receive surgery and chemotherapy. In the Children’s Oncology Group, the recently completed clinical trial for the intermediate-risk group varied the length of treatment such as the number of cycles of chemotherapy. This resulted due to the presence or absence of tumor genetic changes in chromosomes 1p and 11q, tumor histology, tumor ploidy, stage, and age.

A very intensive approach, often using several types of treatments, is used for patients with high-risk neuroblastoma. More information can be found in the Treatment Options section.

Information about the cancer’s stage and risk group will help the doctor recommend a specific treatment plan. The next section in this guide is Treatment Options. Or, use the menu to choose another section to continue reading this guide.