CurrentCentenePolicy N/A

Cg Onc Cytogenetics 2025.1

Defines medical necessity criteria for tumor-specific cytogenetic and protein expression tests (e.g., ALK, ROS1, RET, ERBB2/HER2, PD-L1, NTRK, PML/RARA, FOLR1, bladder FISH, CLL/SLL and multiple myeloma FISH panels) including required indications, specimen types, and frequency limits for select tests.

Policy Summary

PayerCentene

PolicyCg Onc Cytogenetics 2025.1

Policy CodePolicy N/A

Change TypeCriteria expansion, coding updates, and editorial edits

Effective Date

Next Review Date

Key ActionProviders must document the specific diagnosis/indication (cancer type and stage, prior workup, prior treatment status) when ordering cytogenetic tests and follow frequency and coding guidance in the policy.

SourceLink

POLICY UPDATE CHANGES

Tumor Specific RET Gene Rearrangement Tests (FISH) and related criteria were added.

Multiple tumor-specific criteria were expanded and wording updated to align with NCCN guidance (NTRK, ROS1, ALK, PD-L1, ERBB2/HER2 and others).

Bladder Cancer Diagnostic and Recurrence FISH Tests coverage changed from non-covered to covered per CMS LCD guidance.

Policy reference table coding updated (removed CPT 88275 and 88291; added CPT 81315, 81316 and 88273; other coding/reference edits).

Editorial and terminology updates throughout the policy (e.g., 'coverage criteria' replaced with 'criteria', other minor clarifications).

13Tumor-specific test categories listed

Coverage Summary

Scope: Defines medical necessity criteria for tumor-specific cytogenetic and protein expression testing (FISH/IHC/ISH) across multiple assays (e.g., ALK, ROS1, RET, ERBB2/HER2, PD-L1, NTRK, PML/RARA, FOLR1, bladder FISH, CLL/SLL and multiple myeloma FISH panels) including required indications, acceptable specimen types, and frequency limits for select tests. Policy subject: Oncology cytogenetic testing (FISH/IHC/ISH) — tumor-specific assays. Coverage stance: covered_with_criteria.

Specimen types noted: testing may be performed on tumor tissue for solid tumors and on blood or bone marrow for hematologic malignancies; ctDNA/CTC (liquid biopsy) testing is addressed in related policies. Bladder FISH tests' coverage status was updated from non-covered to covered in alignment with CMS LCD guidance, with specified frequency limits.

Quick facts — tumor-specific cytogenetic testing

Tumor-specific test categories listed13

Representative CPT codes shown (approx)~20

Bladder FISH frequency tiers4

Bladder FISH frequency — years 1-2<= 4 tests/year

Bladder FISH frequency — year 3<= 3 tests/year

Bladder FISH frequency — year 4<= 2 tests/year

Bladder FISH frequency — years 5-15<= 1 test/year

Medical Necessity Criteria (by test / criteria group)

Tumor Specific ALK Gene Rearrangement (Qualitative FISH and PCR) Tests

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

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Coding (Representative CPT groups)

ALK gene rearrangement common CPT codesCPTCovered

88271	FISH, single probe or break apart
88274	FISH, probe and interpretation (per probe)

Bladder cancer FISHCPT

88120	FISH, bladder, quantitative
88121	FISH, bladder, interpretation/reporting

CLL/SLL FISH panelCPTCovered

88271	FISH probe analysis
88274	FISH probe (per probe)
88275	FISH, add-on or panel code
88291	Interpretation and report

ERBB2 (HER2) testing codesCPTCovered

88377	In situ hybridization (e.g., FISH) for HER2
88360	IHC single or multiplex stains with interpretation

Multiple myeloma FISH panelCPTCovered

88237	Chromosome analysis, bone marrow (karyotype)
88271	FISH probe analysis
88275	FISH panel/add-on
88291	Interpretation and report

NTRK fusion panelCPTCovered

81191	NGS, fusion panel, tier 1
81192	NGS, fusion panel, tier 2
81193	NGS, fusion analysis, add-on
81194	NGS, fusion analysis, add-on

PD-L1 protein analysisCPTCovered

88341	Immunohistochemistry, per specimen
88342	IHC, each additional marker
88360	IHC single or multiplex stains with interpretation
88361	IHC, per slide, add-on

FOLR1 IHCCPTCovered

88360

IHC single or multiplex stains with interpretation

PML/RARA and other leukemia FISH/PCRCPTCovered

81315	Molecular pathology procedure, gene rearrangement
81316	Molecular pathology procedure, gene rearrangement
88271	FISH probe analysis
88274	FISH probe (per probe)
88275	FISH panel/add-on
88291	Interpretation and report

RET gene rearrangement FISHCPTCovered

88374	In situ hybridization, each probe
88377	In situ hybridization (e.g., FISH), each probe
88271	FISH probe analysis
88275	FISH panel/add-on
88291	Interpretation and report

ROS1 gene rearrangement FISHCPTCovered

88271	FISH probe analysis
88274	FISH probe (per probe)

Codes removed from Policy Reference TableCPT

88275	CPT removed from reference table per revisions
88291	CPT removed from reference table per revisions

Codes added to Policy Reference TableCPT

81315	Added under PML/RARA Gene Rearrangement (Qualitative FISH and PCR)
81316	Added under PML/RARA Gene Rearrangement (Qualitative FISH and PCR)
88273	Added to Multiple Myeloma FISH Panel Analysis (replaced 88274)

Tumor-specific RET Gene Rearrangement (FISH) - related codes (policy references)mixed

No codes listed

Provider Actions and Billing Rules

Documentation Required

Indication documentation required

Providers must document the specific diagnosis/indication that meets the medical necessity criteria when ordering cytogenetic tests. This includes the tumor type and clinical context (e.g., initial diagnostic workup, recurrent, locally advanced, metastatic) and any relevant staging information to demonstrate the indication meets the policy criteria.

Billing Rule

Bladder FISH frequency limits

Bladder FISH tests (CPT 88120, 88121) have defined frequency limits for monitoring after treatment: up to 4 tests per year during years 1–2 after diagnosis; up to 3 tests in year 3; up to 2 tests in year 4; and up to 1 test annually for up to 15 years. Per the CMS LCD, one repeat FISH within 1 year may be reasonable for high‑risk persistent hematuria after a negative comprehensive workup.

Affected codes: 88120, 88121
Frequency thresholds: <=4/year (years 1-2); <=3/year (year 3); <=2/year (year 4); <=1/year (years 5-15)

Background, Evidence, and Definitions

Background: Cytogenetic analysis of solid tumors and hematologic malignancies is used for tumor classification, prognostication, and targeted therapy selection. Testing can be performed on tumor tissue, peripheral blood, or bone marrow depending on the malignancy type. For solid tumors, molecular analysis can be performed on the tumor or via circulating tumor DNA or circulating tumor cells — see the Oncology: Circulating Tumor DNA and Circulating Tumor Cells (Liquid Biopsy) policy for related criteria. CMS LCD guidance (L33420) informs utilization and coverage expectations for bladder FISH testing.

Source	Details
Guideline references	NCCN guidelines across tumor types cited in support of testing recommendations (multiple 2024/2025 guideline references; examples in policy references list).
CMS LCD	CMS LCD 'Lab: Bladder/Urothelial Tumor Markers' (MolDX L33420) referenced for bladder FISH utilization and coverage conditions, including frequency limits and validated assay guidance.
NCCN versions cited	Numerous NCCN guideline versions across tumor types (e.g., NSCLC v7.2024, Gastric v2.2024, Vaginal v1.2025) listed in policy references.
CMS LCD	L33420 referenced specifically for bladder tumor markers (see MolDX LCD and related Billing & Coding Article A53095).

Definitions: Advanced cancer — Cancer that is unlikely to be cured or controlled with treatment; the cancer may have spread to nearby tissue, lymph nodes, or distant parts of the body. Treatment may be palliative, to shrink the tumor, slow growth, or relieve symptoms.

Medicare Determinations and Local Coverage Documents

Name	Type / Number
Lab: Bladder/Urothelial Tumor Markers	LCD
MolDX: Lab: Bladder/Urothelial Tumor Markers	L33420, LCD
MolDX: Billing and Coding: Lab: Bladder/Urothelial Tumor Markers	A53095, Article

Revision History

10/23editorial

Throughout policy: replaced 'coverage criteria' with 'criteria' (editorial/terminology change).

10/23coding_revision_non_material

Policy Reference Table coding updated: removed CPT 88275 and 88291; added Tumor Specific RET Gene Rearrangement entries and related content (coding/reference table edits).

10/23material_added

Tumor Specific RET Gene Rearrangement Tests (FISH) and related criteria were added (new RET FISH testing entries and indications).