Centene Cytogenetic Testing Coverage Update

Coverage Criteria for Cytogenetic Testing

inv-01: Tumor Specific ALK Gene Rearrangement (FISH and PCR) — somatic ALK rearrangement analysis (88271, 88274, 88275, 88291) in solid tumors is considered medically necessary when:

Somatic ALK rearrangement analysis (88271, 88274, 88275, 88291) in solid tumors is considered medically necessary when:

ALK coverage: The member/enrollee has a diagnosis of or is in the initial work up stage for one of: advanced or metastatic lung adenocarcinoma; advanced or metastatic large cell lung carcinoma; advanced or metastatic squamous cell lung carcinoma; advanced or metastatic non-small cell lung cancer (NSCLC) not otherwise specified (NOS); or anaplastic thyroid carcinoma.

Supports use of CPT codes 88271, 88274, 88275, 88291 for these indications.

inv-02: Tumor Specific BCR/ABL Gene Rearrangement (FISH and PCR) — somatic BCR/ABL1 rearrangement analysis via FISH or PCR in peripheral blood or bone marrow

Somatic BCR/ABL1 rearrangement analysis via FISH (88271, 88274, 88275, 88291) or PCR (81479) in peripheral blood or bone marrow is considered medically necessary when:

BCR/ABL coverage: Covered when the member/enrollee is suspected to have a myeloproliferative neoplasm (polycythemia vera, essential thrombocythemia, primary myelofibrosis, or chronic myeloid leukemia), OR is undergoing diagnostic workup for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or chronic myelogenous leukemia (CML).

Specifies specimen types: peripheral blood or bone marrow; CPT examples: 88271, 88274, 88275, 88291, 81479.

inv-03: Bladder Cancer Diagnostic and Recurrence FISH Tests — bladder cancer diagnostic and recurrence FISH tests (88120, 88121):

Bladder cancer diagnostic and recurrence FISH tests (88120, 88121):

Bladder FISH investigational: Bladder cancer diagnostic and recurrence FISH tests (88120, 88121) for screening, diagnosis, and monitoring of bladder cancer are considered investigational.

Investigational designation indicates these tests are not medically necessary under this policy.

inv-04: CLL/SLL FISH Panel Analysis — CLL/SLL FISH panel analysis (88271, 88274, 88275, 88291) in peripheral blood or bone marrow is medically necessary when:

CLL/SLL FISH panel analysis (88271, 88274, 88275, 88291) in peripheral blood or bone marrow is medically necessary when:

CLL/SLL panel coverage: Covered when the panel includes analysis for +12, del(11q), del(13q), and del(17p), AND the member/enrollee is undergoing initial diagnostic workup for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Both specified panel composition and clinical context are required; specimen types: peripheral blood or bone marrow.

inv-05: Multiple Myeloma FISH Panel Analysis — multiple myeloma FISH panel analysis (88271, 88274, 88275, 88291) of bone marrow is medically necessary when:

Multiple myeloma FISH panel analysis (88271, 88274, 88275, 88291) of bone marrow is medically necessary when:

Multiple myeloma panel coverage: Covered when the panel includes analysis for del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, and del(1p), AND the member/enrollee is undergoing initial diagnostic workup for multiple myeloma.

Specimen specified as bone marrow; CPTs: 88271, 88274, 88275, 88291.

inv-07: Multiple Myeloma FISH Panel - Medically Necessary — covered when ALL of the following are met

Covered when ALL of the following are met

Multiple Myeloma FISH Panel: Panel includes analysis for del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, del(1p).

CPTs commonly used: 88271, 88274, 88275, 88291.

Multiple Myeloma clinical context: Member/enrollee is undergoing initial diagnostic workup for multiple myeloma.

Both panel completeness and diagnostic context are required for coverage.

inv-06: Tumor Specific ERBB2 (HER2) ISH Testing — somatic ERBB2 (HER2) amplification analysis via ISH (88360, 88377) in solid tumors is medically necessary when:

Somatic ERBB2 (HER2) amplification analysis via ISH (88360, 88377) in solid tumors is considered medically necessary when:

HER2 ISH coverage: Covered when the member/enrollee has any of: recurrent or newly diagnosed stage I–IV invasive breast cancer; inoperable locally advanced, recurrent, or metastatic gastric cancer when trastuzumab (or FDA-equivalent) is being considered; suspected or proven metastatic synchronous colorectal cancer or documented metachronous metastases; suspected or proven metastatic esophageal and/or esophagogastric junction adenocarcinoma; or recurrent, unresectable, or metastatic salivary gland tumors.

CPTs: 88360, 88377.

inv-08: Tumor-Specific ERBB2 (HER2) Amplification - Medically Necessary — covered when ANY of the following tumor indications are present

Covered when ANY of the following tumor indications are present

ERBB2 (HER2) ISH/CISH Indications: Recurrent or newly diagnosed stage I–IV invasive breast cancer; inoperable locally advanced, recurrent, or metastatic gastric cancer when trastuzumab is being considered; suspected or proven metastatic synchronous colorectal cancer or documented metachronous metastases; suspected or proven metastatic esophageal and/or esophagogastric junction adenocarcinoma; recurrent, unresectable, or metastatic salivary gland tumors.

CPTs: 88360, 88377.

inv-09: NTRK Fusion Analysis Panel - Medically Necessary — covered when ANY of the following tumor indications are present

Covered when ANY of the following tumor indications are present

NTRK Fusion Analysis Indications: Member/enrollee is undergoing initial diagnostic workup for or has a diagnosis of advanced/metastatic lung adenocarcinoma, large cell lung carcinoma, squamous cell lung carcinoma, NSCLC NOS, unknown primary, advanced/metastatic colorectal cancer, cervical sarcoma, recurrent/progressive/metastatic vulvar cancer, recurrent/metastatic endometrial carcinoma or uterine sarcoma, recurrent unresectable or stage IV invasive breast cancer, unresectable locally advanced/recurrent/metastatic gastric or esophageal cancer, anaplastic thyroid carcinoma (or certain recurrent/advanced thyroid carcinomas), acute lymphoblastic leukemia (ALL), or soft tissue sarcoma.

CPTs: 81191–81194; methods include FISH or IHC.

inv-10: Tumor PD-L1 Protein Expression Analysis - Medically Necessary — covered when ANY of the following tumor indications are present

Covered when ANY of the following tumor indications are present

PD-L1 IHC Indications: The member/enrollee has a diagnosis of or is in the initial work up stage for advanced or metastatic lung adenocarcinoma, large cell lung carcinoma, squamous cell lung carcinoma, NSCLC NOS; locally advanced or metastatic bladder cancer; recurrent, progressive, or metastatic cervical cancer; recurrent or stage IV triple negative breast cancer; suspected or proven metastatic esophageal and/or esophagogastric junction adenocarcinoma; suspected or proven metastatic gastric adenocarcinoma; recurrent/unresectable/oligometastatic/metastatic nasopharyngeal cancer; or recurrent, progressive, or metastatic vulvar cancer.

CPTs: 88341, 88342, 88360, 88361. PD-L1 IHC is often adjunct to comprehensive molecular profiling.

inv-11: PML/RARA Gene Rearrangement - Medically Necessary — covered when ALL of the following are met

Covered when ALL of the following are met

PML/RARA Rearrangement Testing: PML/RARA rearrangement analysis via FISH (or PCR) in peripheral blood or bone marrow for suspected or diagnosed acute promyelocytic leukemia (APL) as part of the AML workup.

CPTs: 88271, 88274, 88275, 88291; NCCN recommends testing all patients with AML for prognostically relevant markers including PML-RARA.

inv-12: Tumor ROS1 Gene Rearrangement - Medically Necessary — covered when ANY of the following tumor indications are present

Covered when ANY of the following tumor indications are present

ROS1 Rearrangement Testing: Somatic ROS1 rearrangement analysis via FISH in members/enrollees with advanced or metastatic lung adenocarcinoma, large cell lung carcinoma, squamous cell lung carcinoma, or NSCLC not otherwise specified (NOS).

CPTs: 88271, 88274.

Bladder cancer diagnostic and recurrence fluorescent in situ hybridization (FISH) tests (CPT codes 88120, 88121) are designated investigational and are not included in the policy's medically necessary test categories.

Guideline sources do not support replacing cystoscopic surveillance with urine-based FISH testing. The NCCN does not currently recommend bladder FISH tests (e.g., UroVysion) for routine surveillance, and the American Urological Association/Society of Urologic Oncology explicitly state that urinary biomarkers should not replace cystoscopy in surveillance of non–muscle-invasive bladder cancer and should not be routinely used for surveillance of low‑risk disease; biomarkers may be used selectively (for example, to assess response to intravesical BCG or to adjudicate equivocal cytology).

If state Medicaid coverage provisions conflict with this clinical policy, the applicable state Medicaid coverage provisions take precedence. Providers should consult the state Medicaid manual for any state‑specific coverage rules before applying this policy.

Covered Indications (Tumor- and Disease-specific)

inv-43: Somatic ALK rearrangement testing in advanced/metastatic lung cancers and anaplastic thyroid carcinoma

ALK lung/thyroid indications: Somatic ALK rearrangement testing is indicated for advanced/metastatic lung adenocarcinoma, large cell, squamous cell, NSCLC NOS, and anaplastic thyroid carcinoma as part of initial diagnostic or staging evaluation.

Aligns with CPT group 88271, 88274, 88275, 88291.

inv-44: BCR/ABL1 rearrangement testing for suspected myeloproliferative neoplasms or diagnostic workup of ALL, AML, CML

BCR/ABL myeloid/lymphoid indications: BCR/ABL1 rearrangement testing is indicated when a myeloproliferative neoplasm is suspected (polycythemia vera, essential thrombocythemia, primary myelofibrosis, CML) or during diagnostic workup for ALL, AML, or CML.

Specimens: peripheral blood or bone marrow; methods: FISH or PCR (CPTs: 88271, 88274, 88275, 88291, 81479).

inv-45: CLL/SLL FISH panel with specified probes during initial diagnostic workup

CLL/SLL panel components: Initial diagnostic workup for CLL/SLL with a FISH panel that includes +12, del(11q), del(13q), and del(17p) is covered.

Specimen: peripheral blood or bone marrow; CPTs: 88271, 88274, 88275, 88291.

inv-46: Multiple myeloma FISH panel with specified probes on bone marrow during initial diagnostic workup

Multiple myeloma panel components: Initial diagnostic workup for multiple myeloma with a bone marrow FISH panel that includes del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, and del(1p) is covered.

CPTs: 88271, 88274, 88275, 88291.

inv-47: ERBB2 (HER2) ISH testing in specified solid tumor indications including breast, gastric, colorectal metastases, esophageal/gastroesophageal junction, and certain salivary tumors

HER2 ISH tumor list: ERBB2 (HER2) ISH testing is indicated in breast (recurrent or newly diagnosed stage I–IV invasive), inoperable locally advanced/recurrent/metastatic gastric cancer when trastuzumab is being considered, metastatic colorectal disease, metastatic esophageal/esophagogastric junction adenocarcinoma, and recurrent/unresectable/metastatic salivary gland tumors.

CPTs: 88360, 88377.

inv-48: Tumor- or disease-specific testing as listed (multiple myeloma FISH panel, ERBB2/HER2 ISH, NTRK fusion analysis, PD-L1 IHC, PML/RARA rearrangement, ROS1 rearrangement).

Tumor- or disease-specific testing listed in this policy includes: multiple myeloma FISH panel; ERBB2 (HER2) ISH; NTRK fusion analysis; PD-L1 IHC; PML/RARA rearrangement testing; and ROS1 rearrangement testing.

Each test has indication-specific coverage criteria and associated CPT examples as listed in the policy.

Provider Responsibilities and Billing Actions

Prior Authorization

Prior Authorization May Be Required

Prior authorization may be required for listed CPT codes. Verify payer-specific prior authorization requirements before ordering cytogenetic or molecular tests; failure to obtain required prior authorization may result in claim denial or delayed services.

Affected CPT examples: 88271, 88274, 88275, 88291, 88360, 88377, 88120, 88121, 81191-81194, 81479

Prior Authorization

Prior Authorization — Tumor ISH/Fusion Testing

Prior authorization is required per payer process when requesting somatic ERBB2 (HER2) ISH testing (88360, 88377) or NTRK fusion analysis (e.g., 81191–81194) for tumor-directed therapy selection. Confirm authorization pathways when testing may influence targeted therapy (e.g., trastuzumab) or access to drug-specific coverage.

Examples: ERBB2 (HER2) ISH — CPT 88360, 88377; NTRK fusion testing — CPT 81191, 81192, 81193, 81194

Documentation Required

Panel Completeness Required for Multiple Myeloma FISH

For Multiple Myeloma FISH panel analysis to be considered medically necessary, the panel performed must include the specified component analyses. Failure to perform the complete panel (del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, del(1p), etc.) may affect coverage determinations.

Required panel components: del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, del(1p)
Common CPTs for panel: 88271, 88274, 88275, 88291

Note

Coverage Documents and Legal Compliance

Providers must follow the terms, conditions, exclusions and limitations in members' coverage documents (e.g., evidence of coverage, certificate of coverage, policy or contract). Coverage decisions and administration of benefits are subject to plan-level rules, state and federal requirements, and the Health Plan's administrative policies and procedures.

Coverage is subject to the member's benefit document and applicable law
The Health Plan may change, amend, or withdraw clinical policies and may have additional administrative requirements

Documentation Required

Coding and Documentation Guidance

Submit accurate coding and supporting documentation with all test requests and claims. Providers should reference current CPT guidance and include clinical documentation demonstrating the diagnosis or clinical scenario that matches the indication for testing. Incomplete or inconsistent documentation may lead to denial or requests for additional information.

Reference current CPT manuals and payer coding guidance
Include diagnosis, staging, prior treatments, and rationale linking test to management decision

Documentation Required

Match Test to Documented Clinical Indication

Match each requested test to a documented clinical indication in the medical record. Clinical documentation must support the specific indication listed in the policy (for example, initial diagnostic workup for multiple myeloma, specific advanced/metastatic solid tumor types for NTRK or ERBB2 testing). Tests ordered without an appropriate documented indication risk denial.

Examples: Multiple myeloma panel — documentation of initial diagnostic workup; ERBB2 ISH — recurrent or newly diagnosed invasive breast cancer or other listed indications
Ensure notes, imaging, pathology reports, and treatment plans support the test order

Note

Provider Responsibilities and Coverage Documents

Providers are expected to exercise professional medical judgment in delivering care and to meet administrative responsibilities for prior authorization, documentation, and billing. Providers remain responsible for complying with plan-level administrative processes and for retaining appropriate documentation when submitting claims.

Providers are independent contractors and responsible for medical advice and treatment decisions
Follow Health Plan prior authorization and submission processes to avoid payment issues

Note

Not Specified

No additional provider action specified in this section.

Step Therapy

Step therapy: No step therapy specifics are provided in this section. When step therapy rules exist for targeted therapies tied to test results, follow plan-specific step therapy requirements and prior authorization processes.

If plan-level step therapy applies to drug access based on test results, obtain required prior authorization and document test-driven medical necessity

Key Definitions

Somatic mutation (definition and relevance)

DefinitionSomatic oncogenic mutations (driver mutations) are genetic changes in tumor cells that can direct targeted therapy and influence prognosis.

Clinical relevanceIdentify actionable targets to guide targeted therapy selection and inform prognosis and treatment response in subsets of cancers.

Specimen sourcesTesting may be performed on tumor tissue, or for hematologic malignancies on blood or bone marrow; liquid biopsy addressed in related policies.

Role in diagnosisMolecular analysis can aid in making a diagnosis of a specific type of malignancy in both solid and hematologic tumors.

Cytogenetic analysis (definition and methods)

DefinitionCytogenetic analysis comprises testing methods such as FISH, CISH, and PCR used to detect chromosomal rearrangements, amplifications, deletions, and gene fusions in tumors or hematologic specimens.

Common methodsFluorescent in situ hybridization (FISH), chromogenic in situ hybridization (CISH), and polymerase chain reaction (PCR).

Detected abnormalitiesChromosomal rearrangements, gene amplifications, deletions, and gene fusions relevant to tumor classification and therapy selection.

Specimen considerationsPerformed on tumor tissue for solid tumors or on peripheral blood/bone marrow for hematologic malignancies; alternative specimens (e.g., liquid biopsy) are covered in related policies.

Advanced cancer (definition)

DefinitionAdvanced cancer is cancer that is unlikely to be cured or controlled with treatment and may have spread to nearby tissue, lymph nodes, or distant sites.

Clinical implicationsTreatment may be palliative — intended to shrink tumor, slow growth of cancer cells, or relieve symptoms rather than cure.

Staging contextIncludes cancers described as advanced or metastatic in policy indications for tumor-specific testing (e.g., ALK, NTRK, ROS1).

NCCN guideline references (policy sources)

Primary source setNational Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (multiple disease-specific guidelines).

Examples citedNCCN guidelines referenced include NSCLC, colon, cervical, thyroid, gastric, esophageal, AML, MPN, CML, ALL, pediatric ALL, CLL/SLL, and breast cancer guidelines.

Purpose of referencesNCCN disease-specific recommendations inform testing indications and selection of cytogenetic/molecular assays across tumor types in this policy.

OpenPayer

Oncology: Cytogenetic Testing (FISH, CISH, PCR) - Coverage Criteria

Coverage Criteria for Cytogenetic Testing

Covered Indications (Tumor- and Disease-specific)

Procedure and Billing Codes

Provider Responsibilities and Billing Actions

Not Covered / Investigational

Background and Rationale

Key Definitions

88271	Cytogenetic analysis (various FISH-related)
88274	Cytogenetic analysis (FISH)
88275	Cytogenetic analysis (FISH)
88291	Cytogenetic analysis (FISH interpretation)
81479	Unlisted molecular pathology procedure (used for some PCR tests)

88360	In situ hybridization (e.g., HER2 ISH)
88377	Interpretation and report of ISH

81191	NGS fusion analysis (example panel codes listed)
81192	NGS fusion analysis
81193	NGS fusion analysis
81194	NGS fusion analysis

88120	Urine cytology (used for bladder FISH context)
88121	Cytopathology, excluding exfoliative

88271	FISH testing - cytogenetic procedures (multiple myeloma panel listed)
88274	FISH testing - probe-based
88275	FISH testing - other
88291	Interpretation and report

88360	In situ hybridization (e.g., ISH, CISH) ERBB2 (HER2)
88377	Interpretation and report for ISH

81191	NTRK1 FISH/IHC/fusion analysis
81192	NTRK2 fusion analysis
81193	NTRK3 fusion analysis
81194	NTRK panel

88341	Immunohistochemistry (IHC), first antibody
88342	IHC, each additional antibody
88360	In situ hybridization (also listed with PD-L1 note)
88361	In situ hybridization, each additional

88271	FISH testing (PML/RARA qualitative FISH)
88274	FISH testing - probe-based
88275	FISH testing - other
88291	Interpretation and report

88271	FISH testing (ROS1 rearrangement)
88274	FISH testing - probe-based