Pathology/Lab Coding Alert

Prepare for 25 added and 2 deleted codes beginning Oct. 1, 2025.

The AMA has announced updates to the CPT^® Proprietary Laboratory Analyses (PLA) codes, with changes taking effect on Oct. 1, 2025. These changes reflect the rapid growth of proprietary laboratory diagnostics, particularly in the areas of oncology, infectious disease, and transplant monitoring.

In this quarterly update, the code set will add 25 PLA codes (0575U to 0599U), while deleting two (0450U and 0451U). Keeping up with these changes is important because CPT^® guidelines state, “When a PLA code is available to report a given proprietary laboratory service, that PLA code takes precedence.” In other words, when there’s a PLA code for a test, you must report that PLA code. You should not use any other CPT^® code for that test.

Watch Oncology Code Expansion

The October release adds several PLA codes targeting cancer diagnosis, prognosis, and treatment planning:

• 0577U (Oncology (ovarian), serum, analysis of 39 glycoproteins …) measures 39 glycoproteins in blood with liquid chromatography tandem mass spectrometry (LC-MS/MS) to calculate malignancy likelihood in ovarian tissue (Test Name: GlycoKnow^TM Ovarian; Lab/Manufacturer: InterVenn Biosciences).
• 0578U (Oncology (cutaneous melanoma), RNA, gene expression profiling by realtime qPCR of 10 genes …) is a real-time quantitative polymerase chain reaction (qPCR) analysis of 10 genes from melanoma tissue to predict lymph node metastasis and recurrence risk (Test Name: Merlin^TM Test; Lab/Manufacturer: SkylineDx USA).
• 0585U (Targeted genomic sequence analysis panel, solid organ neoplasm, circulating cell-free DNA (cfDNA) analysis from plasma of 521 genes …) uses cfDNA analysis of 521 genes to identify mutations in solid organ cancers (Test Name: Labcorp^® Plasma Complete^TM; Lab/Manufacturer: Labcorp).
• 0586U (Oncology, mRNA, gene expression profiling of 216 genes …) involves mRNA expression profiling of 204 cancer-related genes (and 12 housekeeping genes) for clinical information and therapy guidance (Test Name: RNA Salah Targeted Expression Panel; Lab/Manufacturer: Moffitt Cancer Center Advanced Diagnostics Laboratory).
• 0591U (Oncology (prostate cancer), biochemical analysis of 3 proteins (total PSA, free PSA, and HE4), plasma, serum …) combines blood biomarkers (total prostate-specific antigen [PSA], free PSA, HE4) with digital rectal exam results to produce a probability score for aggressive prostate cancer (Test Name: MiCheck^® Prostate; Lab/Manufacturer: Minomic^®, Inc).
• 0592U (Oncology (hematolymphoid neoplasms), DNA, targeted genomic sequence of 417 genes …) involves targeted genomic sequencing, using formalin-fixed paraffin-embedded (FFPE) lymphoma tissue. The test detects mutations, fusions, and rearrangements in 417 genes, which may help guide treatment decisions (Test Name: Aventa Lymphoma; Lab/Manufacturer: Aventa Genomics).
• 0597U (Oncology (breast), RNA expression profiling of 329 genes …) analyzes 329 genes and 20 proteins from preserved breast cancer tissue to calculate tumor recurrence risk (Test Name: AidaBreast^TM; Lab/Manufacturer: Prelude Corporation).
• 0599U (Oncology (pancreatic cancer), multiplex immunoassay … serum …) measures five biomarkers for pancreatic cancer to report positive or negative results (Test Name: PancreaSure^TM; Lab/Manufacturer: Immunovia, Inc).

These codes reflect how PLA testing is moving toward highly specific, multimarker algorithms that inform clinical decisions.

Follow Infectious Disease Advances

Several codes focus on improving detection speed and pathogen specificity:

• 0580U (Borrelia burgdorferi, antibody detection of 24 recombinant protein groups …) immunoassay detects IgG antibodies against 24 Borrelia burgdorferi proteins. Clinicians may order this test to support the diagnosis of Lyme disease (Test Name: iDart™ Lyme IgG ImmunoBlot Kit; Lab/Manufacturer: ID-FISH Technology).

• 0590U (Infectious disease (bacterial and fungal), DNA of 44 organisms …) identifies DNA from 34 bacterial and 10 fungal urinary pathogens (Test Name: Biotia ID™ Urine NGS Assay; Lab/Manufacturer: Biotia Inc).
• 0593U (Infectious disease (genitourinary pathogens), DNA, 46 targets …) detects DNA from 28 UTI-causing organisms and 18 antibiotic resistance genes (Test Name: Taq Array Card Urinary Tract Infection PCR Panel; Lab/Manufacturer: SoftCell Laboratories LLC, Doc Lab Inc).
• 0594U (Infectious disease (sepsis), semiquantitative measurement of pancreatic stone protein concentration …) measures pancreatic stone protein (PSP) and applies an algorithm to estimate sepsis risk (Test Name: IVD Capsule PSP — Rapid Sepsis Test; Lab/Manufacturer: Abionic SA).

0595U (Infectious disease (tropical fever pathogens), vectorborne and zoonotic pathogens …) is a real-time polymerase chain reaction (RT-PCR) test for viruses, bacteria, and parasites causing tropical fevers (Test Name: Biofire^® Filmarray^® Tropical Fever Panel; Lab/Manufacturer: bioMérieux).

These entries emphasize multitarget panels and tests that provide results fast enough to guide early treatment.

Track Liver Transplant and Liver Disease Monitoring Codes

Two new codes relate to transplant rejection surveillance and chronic liver disease management:

• 0575U (Transplantation medicine (liver allograft rejection), miRNA gene expression profiling by RT-PCR of 4 genes …) analyzes microRNA patterns in blood using RT-PCR to assess risk of transplanted liver rejection (Test Name: HepatoTrack™; Lab/Manufacturer: LuminoDx Laboratory).
• 0576U (Transplantation medicine (liver allograft rejection), quantitative donor-derived cell-free DNA) combines cfDNA analysis (via next-generation sequencing) and mRNA profiling of 56 genes (via multiplex PCR) to generate a rejection risk score (Test Name: OmniGraf^®; Lab/Manufacturer: Eurofins Transplant Genomics, LLC).

These tests offer precise, algorithm-based insights that complement standard liver function tests.

Monitor Kidney Testing Change

The update adds a code related to kidney disease:

• 0579U (Nephrology (diabetic chronic kidney disease), enzymelinked immunosorbent assay (ELISA) of apolipoprotein A4 (APOA4) …) combines plasma protein levels (APOA4, CD5L) with patient age and estimated glomerular filtration rate to provide a risk score for kidney function decline (Test Name: Promarker^®D; Lab/Manufacturer: Proteomics International Pty Ltd).

Such risk assessment tools are becoming more common in chronic disease management.

Recognize Neurological Testing Additions

Neurology sees important PLA growth:

• 0584U (Neurology (prion disease), cerebrospinal fluid, detection of prion protein by quakinginduced conformational conversion, qualitative …) detects abnormal prion proteins for diagnosing Creutzfeldt-Jakob disease and related prion disorders. This code has the same descriptor as existing code 0035U, which represents real-time quaking-induced conversion for prion detection (RT-QuIC) from the National Prion Disease Pathology Surveillance Center. Apply the correct code based on the specific test performed (Test Name: RT-QuIC Prion, CSF; Lab/Manufacturer: Mayo Clinic).
• 0596U (Neurology (Alzheimer disease), plasma, 3 distinct isoform-specific peptides …) measures APOE protein forms in blood to report genotype, which is relevant to Alzheimer’s risk (Test Name: Precivity-ApoE™; Lab/Manufacturer: C2N Diagnostics).

Such specialized diagnostics can influence patient care in conditions with limited treatment windows.

Track Whole Genome Sequencing Codes

Two related codes support rapid genetic diagnosis:

• 0582U (Rare diseases (constitutional disease/hereditary disorders), rapid whole genome DNA sequencing for single-nucleotide variants …) sequences a patient’s entire genome to detect single-nucleotide variants (SNVs), insertions/deletions (indels), and copy number variations (CNVs) (Test Name: Rapid Whole Genome Sequencing; Lab/Manufacturer: Mayo Clinic).

• +0583U (Rare diseases (constitutional disease/hereditary disorders), rapid whole genome DNA sequencing for single-nucleotide variants … List separately in addition to code for primary procedure) is an add-on code to 0582U that describes sequencing a relative’s genome to aid interpretation of variants in the proband (primary patient) (Test Name: Rapid Whole Genome Sequencing Family Member Comparator; Lab/Manufacturer: Mayo Clinic).

These codes capture the expanding use of comprehensive genomics as a diagnostic tool for rare diseases.

Add Environmental and Drug Safety Codes

There are also new PLA codes that address broader clinical and public health needs:

• 0587U (Therapeutic drug monitoring, 60-150 drugs and metabolites …) measures 60 to 150 drugs and metabolites in urine or saliva, integrating results into an adverse event risk score (Test Name: SafeDrugs; Lab/Manufacturer: Astraeus Lab, LLC, Quantlio Technologies).
• 0589U (Perfluoroalkyl substances (PFAS) (eg, perfluorooctanoic acid, perfluorooctane sulfonic acid …) quantifies 24 perfluoroalkyl and polyfluoroalkyl substances in blood to assess environmental exposure to forever chemicals (Test Name: PFAS (Forever Chemicals) Panel 2-24 PFAS; Lab/Manufacturer: Quest Diagnostics^®).

Note Other Specialized Additions

The update also adds new codes related to transplant, immune profiling, and gastroenterology:

• 0581U (Transplantation medicine, antibody to non-human leukocyte antigens (nonHLA), blood specimen …) detects 39 non-human leukocyte antigens (non-HLA) antibodies in transplant patients, which may affect graft outcomes (Test Name: Autoantibody to Human Leukocyte Antigen (Non-HLA); Lab/Manufacturer: Mayo Clinic).
• 0588U (Infectious disease (bacterial or viral), 32 genes (29 informative and 3 housekeeping), immune response mRNA …) uses gene expression profiling to determine likelihood of bacterial versus viral infection and illness severity in acute infection and sepsis cases (Test Name: TriVerity™; Lab/Manufacturer: Inflammatix^TM, Inc).

• 0598U (Gastroenterology (irritable bowel syndrome), IgG antibodies to 18 food items by microarray-based immunoassay …) is an IgG antibody test for 18 foods to guide irritable bowel syndrome (IBS) dietary management (Test Name: inFoods^® IBS; Lab/Manufacturer: Ethos Laboratories, Biomerica).

Avoid the Deleted PLA Codes

Effective Oct. 1, 2025, CPT^® will delete two related codes:

• 0450U (Oncology (multiple myeloma), liquid chromatography with tandem mass spectrometry (LC-MS/MS), monoclonal paraprotein sequencing analysis, serum, results reported as baseline presence or absence of detectable clonotypic peptide) (Test Name: M-inSight^® Patient Definition Assay; Lab/Manufacturer: Corgenix Clinical Laboratory, Sebia).
• 0451U (Oncology (multiple myeloma), LC-MS/MS, peptide ion quantification, serum, results compared with baseline to determine monoclonal paraprotein abundance) (Test Name: M-inSight^® Patient Follow-Up Assessment; Lab/Manufacturer: Corgenix Clinical Laboratory, Sebia).

Go here for the full list of PLA updates.

Deborah Marsh, JD, MA, CPC, CHONC, Senior Development Editor, AAPC