CPT 81504, 86849 - Multiple myeloma, Microarray based Gene testing

Coding   Code Description CPT

81479 Unlisted molecular pathology procedure

81504 Oncology (tissue of origin), microarray gene expression profiling of >2000 genes, utilizing formalin-fixed paraffin embedded tissue, algorithm reported as tissue similarity scores

81599 Unlisted multianalyte assay with algorithmic analysis (MAAA)

86849 Unlisted immunology procedure





Microarray-Based Gene Expression Profile Testing for Multiple Myeloma Risk Stratification


Introduction 

Multiple myeloma is a cancer that forms in a type of white blood cell called a plasma cell. Doctors aren’t sure what causes multiple myeloma. Abnormal changes (mutations) in genes have been found in the plasma cells of people who have multiple myeloma. Not everyone with multiple myeloma has the same genetic changes in their plasma cells, and some genetic changes seem to make the cancer more deadly than others. It has been suggested that a type of testing called “microarray-based gene expression profiling” can be used to try to determine the prognosis of an individual’s multiple myeloma. Not enough good quality medical studies have been done to show that this type of testing is reliable and helpful in taking care of multiple myeloma patients. For this reason, microarray-based gene expression profiling is still considered to be unproven (investigational). 

Note:   The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a service may be covered. 

Policy Coverage Criteria 

Testing Investigational
Microarray-based gene expression profile testing

Microarray-based gene expression profile testing for multiple myeloma is considered investigational for all indications. 
Note: Commercially available tests include MyPRS™/MyPRS Plus™ GEP70 test. 
See Related Information for a key to acronyms used in this policy.




Related Information 

Acronym Key

CRAB: This stands for the four clinical features of multiple myeloma: calcium elevation; renal insufficiency; anemia; and, bone disease.

DSS: This stands for Durie-Salmon Staging System. One of the two validated clinical system used to assess prognosis in newly diagnosed multiple myeloma patients. The DSS estimates the clinical stage (stage range is 1-3) of disease by assessing multiple myeloma cell numbers, clinical, laboratory and imaging studies. The DSS is primarily focused on tumor mass, rather than tumor behavior. (See ISS system)

GEP: This stands for gene expression profile. GEP testing measures the activity of messenger RNA (mRNA) in a tissue or bodily fluid at a single point, reflecting an individual’s current disease state or the likelihood of developing a disease. GEP tests are not “genetic” tests.

ISS: This stands for the International Staging System. One of the two validated clinical systems used to assess prognosis in patients newly diagnosed with multiple myeloma. The ISS divides myeloma into 3 stages based on levels of serum albumin and ß2-microglobulin in the blood. The ISS is considered valuable to permit comparison of outcomes across clinical trials, but can only be useful if diagnosis has already been made. (See DSS system).

MGUS: This stands for monoclonal gammopathy of undetermined significance. MGUS is a generally benign condition, with a transformation rate to symptomatic plasma cell disorders (like multiple myeloma) of about 1% to 2% annually.


MolDx: ResponseDX Tissue of Origin® Billing and Coding Guidelines

Tissue of Origin®, a microarray-based gene expression assay designed to determine the similarity of unknown or unresolved tumors to cancers from 1 of 15 known tumors of origin, has been assigned a unique identifier.

To bill for Tissue of Origin services, please provide the following claim information:

• Enter “1” in the Days/Unit field

• Select the appropriate ICD-10-CM diagnosis.

• Enter DEX Z-Code™ identifier adjacent to the CPT code in the comment/narrative field for the following

Part B claim field/types:

◦ Loop 2400 or SV101-7 for the 5010A1 837P

◦ Box 19 for paper claim


• Enter DEX Z-Code™ identifier adjacent to the CPT code in the comment/narrative field for the following Part A claim field/types:
◦ Line SV202-7 for 837I electronic claim
◦ Block 80 for the UB04 claim form



Group 1 Codes:
ICD-10 Codes that are covered Information Table

Code Description
C18.1 Malignant neoplasm of appendix
C18.9 Malignant neoplasm of colon, unspecified
C22.0 Liver cell carcinoma
C22.2 Hepatoblastoma
C22.3 Angiosarcoma of liver
C22.4 Other sarcomas of liver
C22.7 Other specified carcinomas of liver
C22.8 Malignant neoplasm of liver, primary, unspecified as to type
C22.9 Malignant neoplasm of liver, not specified as primary or secondary
C25.2 Malignant neoplasm of tail of pancreas
C25.7 Malignant neoplasm of other parts of pancreas
C25.8 Malignant neoplasm of overlapping sites of pancreas
C25.9 Malignant neoplasm of pancreas, unspecified
C33 Malignant neoplasm of trachea
C34.00 Malignant neoplasm of unspecified main bronchus
C34.01 Malignant neoplasm of right main bronchus
C34.02 Malignant neoplasm of left main bronchus
C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.11 Malignant neoplasm of upper lobe, right bronchus or lung
C34.12 Malignant neoplasm of upper lobe, left bronchus or lung
C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung
C34.31 Malignant neoplasm of lower lobe, right bronchus or lung
C34.32 Malignant neoplasm of lower lobe, left bronchus or lung
C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus and lung
C34.81 Malignant neoplasm of overlapping sites of right bronchus and lung
C34.92 Malignant neoplasm of unspecified part of left bronchus or lung
C43.51 Malignant melanoma of anal skin
C43.52 Malignant melanoma of skin of breast
C43.59 Malignant melanoma of other part of trunk
C45.9 Mesothelioma, unspecified
C47.0 Malignant neoplasm of peripheral nerves of head, face and neck
C47.9 Malignant neoplasm of peripheral nerves and autonomic nervous system, unspecified
C48.0 Malignant neoplasm of retroperitoneum
C49.0 Malignant neoplasm of connective and soft tissue of head, face and neck
C49.9 Malignant neoplasm of connective and soft tissue, unspecified
C50.411 Malignant neoplasm of upper-outer quadrant of right female breast
C50.419 Malignant neoplasm of upper-outer quadrant of unspecified female breast
C50.511 Malignant neoplasm of lower-outer quadrant of right female breast
C50.512 Malignant neoplasm of lower-outer quadrant of left female breast
C50.519 Malignant neoplasm of lower-outer quadrant of unspecified female breast
C50.811 Malignant neoplasm of overlapping sites of right female breast
C50.812 Malignant neoplasm of overlapping sites of left female breast
C50.819 Malignant neoplasm of overlapping sites of unspecified female breast
C50.911 Malignant neoplasm of unspecified site of right female breast
C50.912 Malignant neoplasm of unspecified site of left female breast
C50.919 Malignant neoplasm of unspecified site of unspecified female breast
C56.1 Malignant neoplasm of right ovary
C56.2 Malignant neoplasm of left ovary
C56.9 Malignant neoplasm of unspecified ovary
C61 Malignant neoplasm of prostate
C64.1 Malignant neoplasm of right kidney, except renal pelvis



Microarray-based Gene Expression Testing for Cancers of Unknown Primary

Policy Guidelines


Cancers of unknown primary (CUP) represent 3% to 4% of cancers diagnosed in the United States. These cancers are heterogeneous and many accompanied by poor prognoses. A detailed history and physical combined with imaging and tissue pathology can identify some, but not all, primary sources of secondary tumors. It is suggested that identifying the likely primary source with gene expression profiling to direct treatment accordingly may improve health outcomes.

For individuals who have a CUP who receive gene expression profiling, the evidence includes studies of clinical validity, and limited evidence on potential clinical utility. Relevant outcomes are overall survival, disease-specific survival, test validity, and quality of life. Of the 3 commercially available tests reviewed, one has been cleared by the Food and Drug Administration (Tissue of Origin). For these tests, the clinical validity is the ability of a test to determine the site of origin. Using different reference standards (known tumor type, reference diagnosis, a primary tumor identified during follow-up, immunohistochemical analysis) for the tissue of origin, the tests have reported sensitivities or concordances generally high (eg, 80% to 90% or more). However, evidence for clinical validity does not support potential benefit. There is limited indirect evidence from nonrandomized studies on clinical utility, and all studies had significant limitations. Benefit would be most convincingly demonstrated through a marker strategy-designed trial randomizing patients with a CUP to treatment based on expression profiling results or to usual care. The evidence is insufficient to determine the effects of the technology on health outcomes.



Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes: 81479, 81504, 81540, G0452

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.