Diagnosis of neuroblastoma

Summary

Various diagnostics tests are used for the detection of neuroblastoma (NBL) tumor size, location and the spread of cancer. The diagnostics tests used for NBL include CT scan, MRI imaging, Bone scan, PET scan, mIBG Scan, Blood tests, Biomarker detection, Urine tests, and Bone marrow aspiration/biopsy.

Introduction

Doctors perform various tests to diagnose neuroblastoma (NBL). The doctors can also refer for diagnostic tests to determine if cancer has spread to other regions of the body, also referred to as metastasis. Imaging tests show pictures of the inside of the body, which can be used to detect tumor size, location and the spread of cancer. Diagnostics tests may also be performed to determine the best treatment options for the patients.

CT/Magnetic Resonance Imaging (MRI)

CT and MRI are the primary anatomical imaging techniques used to evaluate neuroblastoma. They play an important role in staging and surgical planning, identifying primary tumors and assessing vascular entry, invasion of adjacent organs/structures, and regional lymphadenopathy​1​. MRI is the preferred method for evaluating tumors that have spread to the spinal cord​2​.

MRI can detect bone marrow metastases, but false positives have been reported after treatment​3​. Cortical bone metastases can be detected by both CT and MRI, but the detection area is limited to the scan area.

Bone Scan

The Tc-methylene diphosphonate bone scan is a traditional test used to evaluate cortical bone metastasis of neuroblastoma. Bone scans are still standard for diagnosis as well as cancer staging. Bone scans can differentiate between cortical bone and bone marrow metastases, which is essential for identifying stages in 18-month-old patients.

NBL metastases can have a symmetrical effect on long bone metaphyses and are difficult to detect during bone scans. Bone scans may be positive after injury even if there is no tumor involvement.

FDG positron emission tomography (PET) scan

The use of fluorodeoxyglucose (FDG) positron emission tomography (PET) in pediatric oncology is increasing, with recent studies elucidating a role in neuroblastoma. A PET scan is a method of imaging the organs and tissues inside the body. A small amount of radioactive material is injected into the patient’s body. This substance is mainly absorbed by the organs and tissues that consume the most energy. Cancer cells absorb more radioactive material as it actively uses energy.

mIBG Scan

Metaiodobenzylguanidine (mIBG) scans may play a prognostic role in diagnosing response to chemotherapy in children one year of age and older with metastatic disease. A positive MIBG scan after induction chemotherapy or immediately before myeloablative therapy indicates an increased risk of recurrence and may serve as a prognostic factor​4​. MIBG scan is the most sensitive study for detecting bone damage and unexpected recurrence in high-risk patients​5​.

Biomarker testing of the tumor/genetic tests

The doctor may recommend laboratory testing of a tumor sample to look for genes, proteins, and other tumor-related factors. DNA testing of neuroblastoma cells is used to detect changes in the oncogenic MYCN, a gene responsible for cell growth. Ten or more copies of the gene are associated with rapidly growing and spreading tumors, making treatment more difficult. The unamplified MYCN gene is associated with less aggressive tumors that grow and spread slowly. Additional tests, such as DNA sequencing tests, may be performed to determine if there are ALK gene mutations that may be associated with the risk of NBL​6​.

Blood tests and urine tests

  • Complete blood counts (CBC) can be performed to determine if the child has signs of anaemia, indicated by low red blood cells level in the blood. Additional blood tests may be performed to check for kidneys and liver. A blood clotting test may also be recommended.
  • Urinary catecholamine metabolites are found in more than 85% of patients with NBL. The body breaks down catecholamine molecules into smaller pieces called metabolites, which are then excreted in the urine. The two most commonly measured catecholamine metabolites are vanillylmandelic acid (VMA) and homovanillic acid (HVA). A urine sample may be collected for the presence of these metabolites​7​.

Bone marrow aspiration and biopsy

Bone marrow aspiration is performed with a needle to remove a sample of bodily fluid. Bone marrow aspiration can be examined under a microscope for the presence of cancer cells. A common bone marrow aspiration and biopsy site is the pelvic bone located in the lower abdomen. Doctors use anaesthesia to numb the area and sedate the child before performing this procedure in many centres.

References

  1. 1.
    Siegel M, Ishwaran H, Fletcher B, et al. Staging of neuroblastoma at imaging: report of the radiology diagnostic oncology group. Radiology. 2002;223(1):168-175. doi:10.1148/radiol.2231010841
  2. 2.
    Slovis T, Meza M, Cushing B, et al. Thoracic neuroblastoma: what is the best imaging modality for evaluating extent of disease? Pediatr Radiol. 1997;27(3):273-275. doi:10.1007/s002470050123
  3. 3.
    Lebtahi N, Gudinchet F, Nenadov-Beck M, Beck D, Bischof D. Evaluating bone marrow metastasis of neuroblastoma with iodine-123-MIBG scintigraphy and MRI. J Nucl Med. 1997;38(9):1389-1392. https://www.ncbi.nlm.nih.gov/pubmed/9293795
  4. 4.
    Sharp S, Gelfand M, Shulkin B. Pediatrics: diagnosis of neuroblastoma. Semin Nucl Med. 2011;41(5):345-353. doi:10.1053/j.semnuclmed.2011.05.001
  5. 5.
    Brodeur G, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993;11(8):1466-1477. doi:10.1200/JCO.1993.11.8.1466
  6. 6.
    Zhu S, Lee J, Guo F, et al. Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell. 2012;21(3):362-373. doi:10.1016/j.ccr.2012.02.010
  7. 7.
    Berthold F, Hunneman D, Harms D, Käser H, Zieschang J. Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma. Eur J Cancer. 1992;28A(12):1950-1954. doi:10.1016/0959-8049(92)90234-s