Pathology/Lab Coding Alert

Don’t lose pay for separate RNA, DNA testing.

With more RNA testing working its way into genomic sequencing procedures (GSP), you need to get familiar with CPT^® 2023 changes that impact how you report and get paid for the tests.

Read on to learn about new and revised codes that you need to know if your lab performs any GSP and Other Molecular Multianalyte Assays in that pathology section of the revised 2023 code book.

Background: The codes in the GSP section describe tests to investigate the genetic basis of disease for either germline (heritable) conditions, or diseases due to somatic-cell genetic changes (not inherited), such as some cancers. Each test looks at a large swath of genetic material related to a specific condition, typically a large group of genes, an exome (all protein coding genes) or genome (all genes).

Terminology: To understand these tests, you must remember that genes are made up of DNA that exists in chromosomes. Some genes contain code that is “transcribed” into messenger RNA (mRNA), a short-lived molecule that “translates” into the production of a chemical (such as a protein) that has a function in the body. Other genes regulate when and how mRNA is transcribed from DNA, and the entire process is called “gene expression.” GSP testing may focus on any of the elements in this process.

See How Lab Method Impacts GSP Coding

Labs typically perform GSP tests using newer lab methods that allow simultaneous, rapid sequencing of huge amounts of genetic material. You may see the methods referred to as next generation sequencing (NGS) or massively parallel sequencing (MPS).

However, using an older method such as polymerase chain reaction (PCR) or microarrays doesn’t rule out reporting a GSP code. CPT^® instruction states, “These codes should be used when the components of the descriptor(s) are fulfilled regardless of the technique used to provide the analysis, unless specifically noted in the code descriptor.”

Don’t miss: The GSP introduction maintains that the “typical” method for these codes is NGS or MPS, but CPT^® 2023 adds the phrase “although others may be employed.” The phrase reinforces the instruction about using methods such as PCR, but also allows for using the codes to describe developing lab methods.

Caveat: When CPT^® provides codes for tests that offer similar information using different lab methods, you’ll find text notes to direct you to the appropriate code.

For instance: Genome-wide evaluations for constitutional chromosomal abnormalities may use procedures other than sequencing, and text notes help you choose between similar codes by different methods such as GSP code 81425 (Genome (eg, unexplained constitutional or heritable disorder or syndrome); sequence analysis) and Tier 1 Molecular Pathology code 81228 (Cytogenomic (genome-wide) analysis for constitutional chromosomal abnormalities; interrogation of genomic regions for copy number variants, comparative genomic hybridization [CGH] microarray analysis) and other codes in that family (81229, 81349).

Focus on DNA or RNA Testing

CPT^® 2023 revises three codes and adds three new codes as a “child” code under each to allow labs to distinguish whether they’re performing RNA or DNA sequencing or both.

Here are the changes:

• 81445 (Targeted genomic sequence analysis panel, solid organ neoplasm, DNA analysis, and RNA analysis when performed, 5-50 genes (eg, ALK, BRAF, CDKN2A, EGFR, ERBB2, KIT, KRAS, MET, NRAS, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed; DNA analysis or combined DNA and RNA analysis): Revised code (, )
• 81449 (… RNA analysis) New code under 81445
• 81450 (Targeted genomic sequence analysis panel, hematolymphoid neoplasm or disorder, DNA analysis, and RNA analysis when performed, 5-50 genes (eg, BRAF, CEBPA, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MLL, NOTCH1, NPM1, NRAS), interrogation for sequence variants, and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed; DNA analysis or combined DNA and RNA analysis): Revised code (, )
• 81451 (… RNA analysis): New code under 81450
• 81455 (Targeted genomic sequence analysis panel, solid organ or hematolymphoid neoplasm or disorder, DNA analysis, and RNA analysis when performed, 51 or greater genes (eg, ALK, BRAF, CDKN2A, CEBPA, DNMT3A, EGFR, ERBB2, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MET, MLL, NOTCH1, NPM1, NRAS, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed; DNA analysis or combined DNA and RNA analysis): Revised (strikethrough deleted, underline added)
• 81456 (… RNA analysis): New code under 81455

“In addition to pathology exam of bone marrow or tumor tissue specimens, clinicians may order one of these tests to evaluate alterations in 51 or more genes that could impact treatment decisions for certain solid organ or hematolymphoid cancers,” says R.M. Stainton Jr., MD, president of Doctors’ Anatomic Pathology Services in Jonesboro, Arkansas.

Background: The original codes 81445, 81450, and 81455 included only DNA analysis. With the advent of new lab test methods, some labs began adding RNA analysis, and CPT^® revised the codes to add “and RNA analysis when performed” to the code descriptors.

Now: Because labs may now perform DNA and RNA analysis in a single procedure, or may perform one or the other or both as distinct procedures, CPT^® revised the codes yet again. The revised codes 81445, 81450, and 81455 are now parent codes and include other minor revisions such as correcting alphabetical order of the listed genes.

Plus: By adding three new “child” codes (81449, 81451, 81456), you now have a way to separately report a stand-alone RNA test, explained Jan A. Nowak MD, PhD, FCAP, representing The College of American Pathologists in his presentation at the Clinical Laboratory Fee Schedule (CLFS) annual meeting for the new CPT^® 2023 codes.

Guidelines: The GSP introduction section and text notes following codes 81445-81456 explains how you should report DNA and/or RNA testing for somatic alterations in neoplasms:

• If the lab uses a combined method (one procedure) for both DNA and RNA analysis, you should report one of the parent codes.
• If the lab performs only DNA testing, report one of the parent codes.
• “For targeted genomic sequence DNA analysis and RNA analysis performed separately rather than via a combined method, report 81445, 81450, or 81455 for the DNA analysis and report 81449, 81451, or 81456 for the RNA analysis,” according to new language in the introduction and a new text note following these codes.
• If the lab performs just RNA testing, report one of the child codes.

Don’t miss: If you fail to document that the lab performed separate procedures for a DNA and RNA analysis, coders might report the work using just the parent code (for combined DNA and RNA analysis) and neglect to additionally report a separate RNA child code. That could cost your lab significant pay. For instance, 81455 and 81456 each pay $2919.60 on the 2023 CLFS, so reporting this wrong could cut your pay in half.