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The rules say that plans must pay for a medical service or item if regular Medicare would pay for it in this case. 
You can find this rule at 42 Code of Federal Regulations (CFR) Section 422.101. 
 
The rules state that molecular pathology procedures have broad clinical and research applications. The 
following examples of applications may not be relevant to a Medicare beneficiary or may not meet a Medicare 
benefit category and/or reasonable and necessary threshold for coverage. Such examples include Genetic 
Testing and Genetic Counseling (when applicable) for: 
 
- Disease Risk, 
- Carrier Screening, 
- Hereditary Cancer Syndromes, 
- Gene Expression Profiling for certain cancers, 
- Prenatal Diagnostic testing, 
- Diagnosis and Monitoring Non-Cancer Indications, and 
- Several Pharmacogenomic applications. 
 
This Local Coverage Determination (LCD) addresses the circumstances under which the item or service may 
be reasonable and necessary. For laboratory services, a service may be reasonable and necessary if the service 
is safe and effective; and appropriate, including the duration and frequency that is considered appropriate for 
the item or service, in terms of whether it is furnished in accordance with accepted standards of medical 
practice for the diagnosis of the patient's condition; furnished in a setting appropriate to the patient's medical 
needs and condition; ordered and furnished by qualified personnel; one that meets, but does not exceed, the 
patient's medical need; and is at least as beneficial as an existing and available medically appropriate 
alternative. 
 
Many applications of the molecular pathology procedures are not covered services given lack of benefit 
category (e.g., preventive service or screening for a genetic abnormality in the absence of a suspicion of 
disease) and/or failure to the reasonable and necessary threshold for coverage (e.g., based on quality of clinical 
evidence and strength of recommendation or when the results would not reasonably be used in the management 
of a beneficiary). Furthermore, payment of claims in the past (based on stacking codes) or in the future (based 
on the new code series) is not a statement of coverage since the service may not have been audited for 
compliance with program requirements and documentation supporting the reasonable and necessary testing for the beneficiary. Certain molecular pathology procedures may be subject to prepayment medical review (records 
requested) and paid claims must be supportable, if selected, for post payment audit by the MAC or other 
contractors. Molecular pathology tests for diseases or conditions that manifest severe signs or symptoms in 
newborns and in early childhood or that result in early death (e.g., Canavan disease) could be subject to 
automatic denials since these tests are not usually relevant to a Medicare beneficiary. 
 
This LCD gives general guidance to the medically reasonable and necessary applications of the Molecular 
Pathology Procedures and Genomic Sequencing Procedures, described in Current Procedural Terminology 
(CPT). Coding guidance is provided in Molecular Pathology Procedures Article A56199, attached below.   
 
Indications: 
Molecular pathology procedures (Tier1 and Tier 2) may be eligible for coverage when ALL of the following 
criteria are met: 
- Alternative laboratory or clinical tests to definitively diagnose the disorder/identify the condition are 
unavailable or results are clearly equivocal; AND 
- Availability of a clinically valid test, based on published peer reviewed medical literature; AND 
- Testing assay(s) are Food and Drug Administration (FDA) approved/cleared or if LDT (lab developed 
test) or LDT protocol or FDA modified test(s) the laboratory documentation should support assay(s) of 
analytical validity and clinical utility; AND 
- Results of the testing must directly impact treatment or management of the Medicare beneficiary; AND 
- For testing panels, including but not limited to, multiple genes or multiple conditions, and in cases 
where a tiered approach/method is clinically available, testing would be covered ONLY for the number 
of genes or test that are reasonable and necessary to obtain necessary information for therapeutic 
decision making; AND 
- Individual has not previously received genetic testing for the disease/condition. (In general, diagnostic 
genetic testing for a disease should be performed once in a lifetime.) Exceptions include clinical 
scenarios whereby repeat testing of somatically acquired mutations (for example, pre- and post- 
therapy) may be required to inform appropriate therapeutic decision-making. 
 Limitations: 
- Any procedures required prior to cell lysis should be reported separately and utilization must be clearly 
supported based on the application and clinical utility. Such claims may be subject to prepayment 
medical review. 
- The medically necessary interpretation and report of a molecular pathology test, written by a 
pathologist, which is above and beyond the report of standard laboratory results may not be reported by 
Non- physician practitioners (e.g., PhD, scientists etc.); only physicians are eligible to report this 
service. 
- Testing for quality assurance component of the service is not separately billable. 
Indications and Limitations of Coverage 
ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) (eg, acquired imatinib tyrosine kinase inhibitor 
resistance), gene analysis, variants in the kinase domain is considered medically necessary in patients with 
acute lymphoblasic leukemia (ALL) and chronic myeloid leukemia (CML) to guide therapeutic decision 
making. 
ATP7B is considered medically necessary in patients with symptoms of Wilson's disease to guide therapeutic 
decision making. BCR/ABL is indicated in patients with suspected CML with either persistent, unexplained leukocytosis or 
thrombocytosis. BCR/ABL is considered medically necessary in the evaluation of individuals with chronic 
myelogenous leukemia or BCR-ABL positive acute lymphoblastic leukemia to evaluate treated individuals 
who manifest suboptimal response to initial tyrosine kinase inhibitor therapy or loss of response to tyrosine 
kinase inhibitor therapy. 
BLM (Bloom syndrome, RecQ helicase-like)(e.g. Bloom syndrome) gene analysis, 2281 del6ins7 variant is 
considered medically necessary for a beneficiary who may have Bloom syndrome to confirm diagnosis and 
guide medical decision-making. 
BRAF gene analysis is considered medically necessary for patients who have malignant melanoma, non-small 
cell lung cancer, hairy cell leukemia, or metastatic colorectal cancer when needed to determine if a Medicare 
covered therapy is a reasonable option given the individual's specific clinical presentation. 
BRCA1 and BRCA2 genetic testing is considered medically necessary for a beneficiary with a current 
diagnosis or a personal history of a cancer associated with the BRCA mutation who meets one or more of the 
criteria found in the most recent version of the NCCN guidelines for Genetic/Familial High-Risk Assessment: 
Breast and Ovarian or other evidence based guideline addressing genetic testing, and the results will be used to 
benefit the individual tested in terms of potential to guide therapeutic decision making. 
Cardiology (heart transplant), mRNA, gene expression profiling by real-time quantitative PCR of 20 genes 
(11 content and 9 housekeeping), utilizing subtraction of peripheral blood, algorithm reported as rejection risk 
score is considered medically necessary for heart transplant patients to guide therapeutic decision-making. 
CEBPA (CCAAT/enhancer binding protein [C/EBP], alpha) (eg, acute myeloid leukemia), full gene sequence 
is considered medically necessary in patients with acute myelogenous leukemia (AML) to guide therapeutic 
decision making. 
CALR (calreticulin) (e.g., myeloproliferative disorders), gene analysis, common variants in exon 9 is 
considered medically necessary in the initial diagnostic work-up of BCR-ABL negative, JAK2-negative adults 
with clinical, laboratory, or pathological findings suggesting polycythemia vera (PV), essential 
thrombocythemia (ET) or primary myelofibrosis (PMF). 
CCND1/IGH (BCL1/IgH, t)(e.g., mantle cell lymphoma) translocation analysis, major breakpoint, qualitative 
and quantitative, if performed is considered medical necessary for patients who have non- Hodgkin's 
lymphoma to guide therapeutic decision-making. 
CFTR (cystic fibrosis transmembrane conductance regulator) (e.g. Cystic fibrosis) gene analysis, common 
variants (e.g. ACMG/ACOG guidelines) is considered medically necessary for a beneficiary who has or may 
have cystic fibrosis to guide therapeutic decision-making. 
Chimerism analysis to identify appropriate donors and monitor engraftment success or disease reoccurrence is 
considered medically necessary. 
CYP2C6 19-cytochrome P450 CYP2C6 19-cytochrome P450 Based on the FDA's Black Box warning for 
clopidogrel, the effectiveness of clopidogrel is dependent on its activation to an active metabolite by the 
cytochrome P450 (CYP) system, principally CYP2C19. CYP2C619 genotyping may be medically necessary 
once per lifetime to identify individuals: 
- Who are poor metabolizers of clopidogrel, so that alternative treatment or treatment strategies can be 
considered - Who are poor metabolizers of clopidogrel with acute coronary syndrome or who are undergoing 
percutaneous coronary intervention 
CYP2C9 (cytochrome P450, family 2, subfamily D polypeptide 9) (e.g., drug metabolism), gene analysis, is 
only considered medically necessary for individuals who have relapsing forms of multiple sclerosis, and 
require CYP2C9 genotyping for dosing in accordance with the FDA prescribing information for Mayzent. 
CYP2C9 testing must include the *1, *2, and *3 alleles that are necessary to safely dose the FDA-approved 
drug Mayzent. 
CYP2D6 (cytochrome P450, family 2, subfamily D polypeptide 6) (e.g., drug metabolism), gene analysis, is 
only considered medically necessary for individuals with Huntington's disease for whom doses of 
tetrabenazine greater than 50 mg per day are being considered, and for testing prior to the initiation of 
Cerdelga
TM
 (eliglustat) for Gaucher's disease. 
EGFR (epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants (eg, 
exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q) [when specified as EGFR mutation analysis 
testing] EGFR testing is considered medically necessary as a technique to predict treatment response for 
individuals with non-small cell lung cancer undergoing treatment with EGFR tyrosine kinase inhibitor (TKI) 
therapy (for example, erlotinib [Tarceva ], gefitinib [Iressa ], or afatinib [Gilotrif ]). 
F2 gene (prothrombin coagulation factor II) and F5 gene (coagulation factor V) The F2 and F5 genetic tests are 
not considered to be clinically efficacious; therefore, testing is not medically necessary. 
FLT3 is considered medically necessary in patients with acute myeloid leukemia (AML) to guide therapeutic 
decision making. 
Gene Testing for Warfarin Response Pharmacogenomic Testing for Warfarin Response, gene testing 
on CYP2C9 and/or VKORC1 see NCD 90.1 for coverage information. 
HFE (hemochromatosis)(hereditary hemochrosis) gene analysis, common variants (e.g. C282Y, H63D) is 
considered medically necessary in patients with iron overload of uncertain etiology (e.g. when the test is used 
to avoid liver biopsy in someone when the ferritin and the transferrin saturation are elevated greater than 45%). 
The genotyping of patients with iron overload of uncertain etiology is allowed only once per lifetime. 

You can find this rule at the Medicare Local Coverage Determination (LCD) L35000: Molecular Pathology 
Procedures. 
 
If you want to read these Medicare rules, you can go to this website www.medicareappeal.com. 
 
The Plan contract says that the Plan covers items and services in accordance with Medicare rules.