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| Genetic Test: Germline Mutations of the RET Protooncogene in Medullary Carcinoma of the Thyroid | |
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| Description: |
Medullary carcinoma of the thyroid is an uncommon type of thyroid cancer that arises from the parafollicular or C cells thyroid, which produce the hormone calcitonin. (Papillary thyroid cancer, arising from the glandular cells, is the most common type of thyroid cancer.) Three distinct but related familial cancer syndromes together are responsible for approximately one-fourth of the incidence of medullary carcinoma of the thyroid; the remaining three-fourths are sporadic. The three inherited syndromes include multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid cancer (FMTC). MEN 2A and MEN 2B differ from each other (and from MEN 1) in the spectrum and frequency of accompanying endocrine malignancies and other disorders. In contrast, FMTC is defined as being in a family with the repeated occurrence of medullary thyroid cancer in the absence of other endocrine malignancies or disorders. MEN 2A, MEN 2B, and FMTC are all dominantly inherited. Point mutations of the germline RET gene, located on chromosome 10, are associated with inheritance of MEN 2A, MEN 2B, or FMTC. Medullary thyroid cancer is curable surgically if detected before it has spread to regional lymph nodes. However, lymph node involvement at diagnosis may be found in up to 75% of patients for whom a thyroid nodule is the first sign of disease. Surveillance by annual biochemical monitoring has been used to identify those with the inherited disease before it progresses beyond the earliest stages. The development of invasive medullary thyroid cancer usually is preceded by C-cell hyperplasia, which can be detected by hypersecretion of calcitonin in response to a chemical challenge. Recently, genetic assays for RET mutations have been used as an alternative to annual biochemical testing for C-cell hyperplasia, in patients with a known family history of MEN 2A, 2B, or FMTC. Annual biochemical screening can be stopped in those patients who test negative for mutations. Patients who test positive may undergo immediate thyroidectomy or postpone thyroidectomy until biochemical tests suggest evolving medullary cancer. Genetic assays have also been used to determine if new cases of medullary thyroid cancer without a family history are truly sporadic in origin. A positive test in this setting should initiate evaluation of family members. In addition, a positive test may prompt screening for pheochromocytoma, a component of MEN 2A and 2B, in the affected patient. |
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Policy/ Coverage: |
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Genetic testing for RET proto-oncogene point mutations meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for members with:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Genetic testing for RET proto-oncogene point mutations not meeting the above criteria or for any other circumstance does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, genetic testing for RET proto-oncogene point mutations not meeting the above criteria or for any other circumstance is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
The data provide very strong support for the hypothesis that genetic tests for germline point mutations in the RET gene can identify those with an inherited susceptibility for medullary thyroid cancer earlier and more definitively than is possible with biochemical tests. For example, of 365 asymptomatic family members at risk for the inherited disease, 115 tested positive for RET gene mutations. Evidence of disease was subsequently found in all 115 with mutations and in none of the 250 without mutations. Test results affect patient management by prompting thyroidectomy or continued biochemical monitoring in affected patients, and by prompting discontinuation of monitoring in patients who test negative.
2009 Update
A search of the MEDLINE database was conducted through August 2009. There was no new published information that would prompt a change in the coverage policy.
2014 Update
A literature search was conducted using the MEDLINE database through July 2014. There was no new literature identified that would prompt a change in the coverage statement.
2016 Update
A literature search was conducted using the MEDLINE database through July 2016. There was no new literature identified that would prompt a change in the coverage statement.
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2018. No new literature was identified that would prompt a change in the coverage statement.
2019 Update
A literature search was conducted through July 2019. There was no new information identified that would prompt a change in the coverage statement.
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2020. No new literature was identified that would prompt a change in the coverage statement.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2021. No new literature was identified that would prompt a change in the coverage statement.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2022. No new literature was identified that would prompt a change in the coverage statement.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2023. No new literature was identified that would prompt a change in the coverage statement.
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2024. No new literature was identified that would prompt a change in the coverage statement.
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2025. No new literature was identified that would prompt a change in the coverage statement.
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| CPT/HCPCS: | |
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| References: |
1997 Blue Cross Blue Shield Association Technology Evaluation Center Assessment; Tab 12.
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| Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants. | |
| CPT Codes Copyright © 2026 American Medical Association. | |