Blue Cross of Idaho Logo

Express Sign-on

Thank you for registering with Blue Cross of Idaho

If you are an Individual or Family Member, please register here.

If you are a Medicare Advantage or Medicare Supplement member, please register here.

MP 2.04.05 Genetic Testing for Germline Mutations of the RET Proto-Oncogene in Medullary Carcinoma of the Thyroid

Medical Policy
Original Policy Date
Last Review Status/Date
Reviewed by consensus/2:2003
Return to Medical Policy Index


Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.


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 3 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.


Genetic testing for RET proto-oncogene point mutations may be considered medically necessary in the following situations:

  1. Among symptomatic members of families with defined RET gene mutations;
  2. Among members of families known to be affected by inherited medullary thyroid cancer, but not previously evaluated for RET mutations; and
  3. Among patients with sporadic medullary thyroid cancer.

Policy Guidelines

Genetic testing for germline mutations associated with medullary carcinoma of the thyroid are done in a limited number of either reference laboratories or laboratories associated with academic medical centers. There is no one single CPT code used to describe this multistep test. The following series of CPT codes have been used.

83890: Molecular diagnostics; molecular isolation or extraction
83894: Molecular diagnostics; separation
83898: Molecular diagnostics; amplification, e.g., polymerase chain reaction
83912: Molecular diagnostics; interpretation and report

CPT codes 83890-83898 describe the preparation of DNA for analysis. Prior to 1999, there were no specific CPT codes describing the actual analysis of DNA. In 1999, a series of CPT codes were introduced to describe the various techniques; i.e., single strand conformation polymorphisms, heteroduplex, denaturing gradient gel electrophoresis (all CPT code 83903); mutation identification by sequencing (83904), mutation identification by allele specific transcription (83905) or translation (83906). The exact methodology used will depend on the clinical situation.

In July 2003, a HCPCS code specific to this test issued (S3840).

Benefit Application

BlueCard/National Account Issues

Specific benefit language regarding genetic testing as screening test in unaffected family members may be applicable. It is recommended that the most efficient implementation strategy for this policy would be its use as a tool for retrospective review and post pay audit to identify provider or institution outliers.


The above policy is based on a 1997 TEC Assessment. The assessment concluded that 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.


1997 TEC Assessment; Tab 12







Molecular diagnostics; molecular isolation or extraction, each nucleic acid type (ie. DNA or RNA)



Molecular diagnostics; separation, each nucleic acid preparation



Molecular diagnostics; amplification, e.g., polymerase chain reaction 



Mutation scanning or identification (New 1999 CPT codes) 



Molecular diagnostics; interpretation and report 

ICD-9 Procedure 

No Code 

ICD-9 Diagnosis 


Malignant neoplasm of thyroid gland 



Secondary malignant neoplasm of other specified sites (includes thyroid gland) 



Carcinoma in situ of other specified sites (includes thyroid gland) 



Personal history of malignant neoplasm of thyroid 



Family history of malignant neoplasm 



DNA analysis for germline mutations of the RET proto-oncogene for susceptibility to multiple endocrine neoplasia type 2 

Type of Service 


Place of Service 



Genetic testing, medullary thyroid cancer
Medullary thyroid cancer
RET proto-oncogene
Thyroid cancer, medullary

Policy History

Date Action Reason
11/1/97 Add to Pathology/Laboratory section New policy
11/15/98 Coding update 99 CPT Coding Release
07/12/02 Replace policy Policy reviewed by consensus; new review date only
07/17/03 Replace policy Policy no longer scheduled for review; S code added


Search for Policies

Policy Feedback

Resource Center

Find a Provider Find a Pharmacy Medicare Medicare Formulary