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Molecular Testing for Neurofibroma

Last updated March 24, 2017

Molecular Testing for Neurofibroma is a genetic test that is helpful in aiding a diagnosis of neurofibroma.


What are other Names for this Test? (Equivalent Terms)

  • Gene Mutation Analysis for Neurofibroma
  • Test for Molecular Diagnosis of Neurofibroma

What is Molecular Testing for Neurofibroma? (Background Information)

  • Molecular Testing for Neurofibroma is a genetic test that is helpful in aiding a diagnosis of neurofibroma. The lab test results may also be subsequently useful in taking appropriate treatment decisions
  • A neurofibroma is a type of peripheral nerve sheath tumor (PNST). This tumor may arise from the nerves underneath the skin surface, or from nerves deep within the body
  • The risk factors for the development of neurofibroma is unknown in many cases. In some cases, multiple tumors may indicate the presence of neurofibromatosis type 1 (NF-1); solitary tumors are not associated with this genetic disorder
  • Neurofibromas usually manifest in young men and women. They do not present any significant signs and symptoms in many cases. However, the tumors may involve the spinal nerves, cranial nerves, or small nerves of the skin causing associated signs and symptoms

The cause of neurofibroma is due to genetic mutations.

  • Currently, studies indicate defects in the following gene: NF1 gene
  • Additionally, the following chromosomal aberration is noted:
    • Mutations in chromosome 17 due to loss of 17q (long arm); this is observed frequently
    • Mutations in chromosome 19 due to loss of 19p and 19q (on short arm and long arm respectively)
    • Mutations in chromosome 22 due to loss of 22q (long arm)
  • In some forms of neurofibroma (such as the localized intraneural and plexiform types), frequently, deletion in 9p is noted. It is also sometimes associated with abnormalities in the following genes:
    • CDKN2A
    • CDKN2B
    • MTAP

The above genetic abnormalities can be detected using molecular studies, which may play a significant role in identifying the tumor type, and in some cases, helping the healthcare provider take appropriate treatment decisions.

The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization technique, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for neurofibroma may vary from one laboratory to another. 

Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the Molecular Testing for Neurofibroma Test?

Molecular Testing for Neurofibroma is undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis of neurofibroma
  • To distinguish other tumors/conditions that have similar histological features, when examined by a pathologist under the microscope
  • To help in determining treatment options
  • To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)

How is the Specimen Collected for Molecular Testing for Neurofibroma?

Following is the specimen collection process for Molecular Testing for Neurofibroma:

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Fresh tumor tissue during biopsy
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility

Note:

  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tumor specimen over time

Cost of Molecular Testing for Neurofibroma:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)

What is the Significance of the Molecular Testing for Neurofibroma Result?

The significance of Molecular Testing for Neurofibroma is explained:

  • Presence of a positive test result helps aid, and in some cases, confirm the diagnosis of neurofibroma
  • The result can help exclude other tumors with similar histological features
  • It can help determine the prognosis of the patient
  • In some cases, the test results may help in taking treatment decisions

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test
  • Additional mutations are still being discovered in many of these tumors. This may further contribute towards tumor diagnosis and treatment. Please consult with your healthcare provider for any information updates

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

What are some Useful Resources for Additional Information?

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/neurofibroma-skin/

Please visit our Laboratory Procedures Center for more physician-approved health information:

http://www.dovemed.com/common-procedures/procedures-laboratory/

References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 03/07/2017)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 03/07/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 03/07/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 03/07/2017)

http://www.abta.org/brain-tumor-information/types-of-tumors/neurofibroma.html?referrer=https://www.google.co.in/ (accessed on 03/07/2017)

http://www.dermnetnz.org/topics/neurofibromatosis/ (accessed on 03/07/2017)

https://nfcenter.wustl.edu/what-is-nf/neurofibromatosis-type-1/nerve-tumors/ (accessed on 03/07/2017)

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Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)

Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)

Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17

Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524

Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368

Antonescu, C. R., Brems, H., Legius, E., & Woodruff, J. M. (2013). Neurofibroma (including variants).

Kacerovska, D., Michal, M., Kuroda, N., Tanaka, A., Sima, R., Denisjuk, N., ... & Kazakov, D. V. (2013). Hybrid peripheral nerve sheath tumors, including a malignant variant in type 1 neurofibromatosis. The American Journal of Dermatopathology, 35(6), 641-649.

Morais, P., Ferreira, O., Bettencourt, H., & Azevedo, F. (2010). Segmental neurofibromatosis: a rare variant of a common genodermatosis. Acta Dermatoven APA, 19(3).

Hummel, T. R., Jessen, W. J., Miller, S. J., Kluwe, L., Mautner, V. F., Wallace, M. R., ... & Schorry, E. K. (2010). Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. Clinical Cancer Research, 16(20), 5048-5057.

Rojnueangnit, K., Xie, J., Gomes, A., Sharp, A., Callens, T., Chen, Y., ... & Babovic‐Vuksanovic, D. (2015). High incidence of Noonan syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p. Arg1809: genotype–phenotype correlation. Human mutation, 36(11), 1052-1063.

Jouhilahti, E. M., Peltonen, S., Heape, A. M., & Peltonen, J. (2011). The pathoetiology of neurofibromatosis 1. The American journal of pathology, 178(5), 1932-1939.

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Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: March 24, 2017
Last updated: March 24, 2017