What are other Names for this Test? (Equivalent Terms)
- Gene Mutation Analysis for Malignant Peripheral Nerve Sheath Tumor
- Molecular Testing for MPNST
- Test for Molecular Diagnosis of Malignant Peripheral Nerve Sheath Tumor
What is Molecular Testing for Malignant Peripheral Nerve Sheath Tumor? (Background Information)
- Molecular Testing for Malignant Peripheral Nerve Sheath Tumor is a genetic test that is helpful in aiding a diagnosis of malignant peripheral nerve sheath tumor. The lab test results may also be subsequently useful in taking appropriate treatment decisions
- Malignant peripheral nerve sheath tumor (MPNST) is a type of soft tissue sarcoma (a malignant type of tumor). Approximately, 5% of soft tissue sarcomas are MPNSTs
- These tumors can occur in individuals with a history of neurofibromatosis type 1 (NF1, a genetic disorder affecting the skin and other body systems), or without NF1. About 65% of the individuals with MPSNT may be diagnosed with NF1
- Malignant peripheral nerve sheath tumors typically occur in older adults, when there is no history of neurofibromatosis type 1. If it develops against a background of NF1, it usually occurs earlier
The cause of malignant peripheral nerve sheath tumor is due to genetic mutations. Currently, studies indicate defects in the following genes:
- NF1: The mutation in the NF1 gene may either be germline (involving all cells in the body) or somatic (not always involving all cells in the body). Germline mutations usually occur during fetal development, or are inherited from parents
Additionally, the following chromosomal aberrations are noted:
- Loss of chromosome 17 material in the long arm (17q loss)
- Loss of chromosome 9 material in the short arm (9p loss)
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 malignant peripheral nerve sheath tumor 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 Malignant Peripheral Nerve Sheath Tumor Test?
Molecular Testing for Malignant Peripheral Nerve Sheath Tumor is undertaken in the following situations:
- To assist (and in some cases, confirm) the initial diagnosis of malignant peripheral nerve sheath tumor
- 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 Malignant Peripheral Nerve Sheath Tumor?
Following is the specimen collection process for Molecular Testing for Malignant Peripheral Nerve Sheath Tumor:
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 required:
- 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
- Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
- Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
- 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 Malignant Peripheral Nerve Sheath Tumor:
- 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 Malignant Peripheral Nerve Sheath Tumor Result?
The significance of Molecular Testing for Malignant Peripheral Nerve Sheath Tumor is explained:
- Presence of a positive test result helps aid, and in some cases, confirm the diagnosis of malignant peripheral nerve sheath tumor
- 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:
Please visit our Laboratory Procedures Center for more physician-approved health information:
References and Information Sources used for the Article:
https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 02/17/2017)
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 02/17/2017)
http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 02/17/2017)
http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 02/17/2017)
http://sarcomahelp.org/mpnst.html (accessed on 02/17/2017)
https://rarediseases.info.nih.gov/diseases/10872/malignant-peripheral-nerve-sheath-tumor (accessed on 02/17/2017)
http://www.nature.com/modpathol/journal/v13/n11/full/3880230a.html (accessed on 02/17/2017)
Helpful Peer-Reviewed Medical Articles:
Carrano, A. V., et al. Measurement and purification of human chromosomes by flow cytometry and sorting. Proceedings of the National Academy of Sciences 76, 1382–1384 (1979)
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
Farid, M., Demicco, E. G., Garcia, R., Ahn, L., Merola, P. R., Cioffi, A., & Maki, R. G. (2014). Malignant peripheral nerve sheath tumors. The oncologist, 19(2), 193-201.
Margaritescu, I., Chirita, A. D., & Vasilescu, F. (2015). Malignant Peripheral Nerve Sheath Tumor. In Rare Malignant Skin Tumors (pp. 257-260). Springer New York.
James, A. W., Shurell, E., Singh, A., Dry, S. M., & Eilber, F. C. (2016). Malignant Peripheral Nerve Sheath Tumor. Surgical oncology clinics of North America, 25(4), 789-802.
Stucky, C. C. H., Johnson, K. N., Gray, R. J., Pockaj, B. A., Ocal, I. T., Rose, P. S., & Wasif, N. (2012). Malignant peripheral nerve sheath tumors (MPNST): the Mayo Clinic experience. Annals of surgical oncology, 19(3), 878-885.
Rahrmann, E. P., Watson, A. L., Keng, V. W., Choi, K., Moriarity, B. S., Beckmann, D. A., ... & Wallace, M. R. (2013). Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and genetic pathways driving tumorigenesis. Nature genetics, 45(7), 756.
Kroep, J. R., Ouali, M., Gelderblom, H., Le Cesne, A., Dekker, T. J. A., Van Glabbeke, M., ... & Hohenberger, P. (2011). First-line chemotherapy for malignant peripheral nerve sheath tumor (MPNST) versus other histological soft tissue sarcoma subtypes and as a prognostic factor for MPNST: an EORTC soft tissue and bone sarcoma group study. Annals of Oncology, 22(1), 207-214.
Benz, M. R., Czernin, J., Dry, S. M., Tap, W. D., Allen‐Auerbach, M. S., Elashoff, D., ... & Eilber, F. C. (2010). Quantitative F18‐fluorodeoxyglucose positron emission tomography accurately characterizes peripheral nerve sheath tumors as malignant or benign. Cancer, 116(2), 451-458.
Carter, J. M., O'hara, C., Dundas, G., Gilchrist, D., Collins, M. S., Eaton, K., ... & Folpe, A. L. (2012). Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with “neuroblastoma-like” schwannomatosis and a novel germline SMARCB1 mutation. The American journal of surgical pathology, 36(1), 154.
Feber, A., Wilson, G. A., Zhang, L., Presneau, N., Idowu, B., Down, T. A., ... & Schiza, V. (2011). Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors. Genome research, 21(4), 515-524.