CurrentCapital BluecrossPolicy MP 2.274

GENETIC TESTING FOR LI-FRAUMENI SYNDROME

Defines medical necessity criteria for germline TP53 testing (including targeted familial variant testing) to diagnose Li-Fraumeni syndrome and specifies not medically necessary indications and coding guidance for Capital Blue Cross products (with product variations and exclusions noted).

Policy Summary

PayerCapital Bluecross

PolicyGENETIC TESTING FOR LI-FRAUMENI SYNDROME

Policy CodePolicy MP 2.274

Change TypeAdministrative updates; diagnosis codes added

Effective Date10/01/2025

Next Review Date

Key ActionProvider must document that the individual meets Classic or Chompret criteria, has breast cancer diagnosed <31 years, has pediatric hypodiploid ALL, or is an at-risk relative of a proband with a known TP53 pathogenic variant to support medical necessity for testing.

POLICY UPDATE CHANGES

Added new DX codes C50.A-C50.A2 on 09/02/2025.

Removed Benefit Variations section and updated Disclaimer on 09/11/2025.

Effective date set to 10/01/2025.

4Primary covered indications listed

1Targeted familial testing indication

multipleICD-10 breast malignancy codes referenced

Coverage Summary

Overview: This policy defines medical necessity criteria for germline TP53 genetic testing to diagnose Li‑Fraumeni syndrome and for targeted familial variant testing in at‑risk relatives. It applies to Capital Blue Cross products with program‑specific benefit variations and coding guidance.

Medical-Necessity Criteria

Medically necessary: Diagnostic germline TP53 testing

Genetic testing for TP53 may be considered medically necessary to confirm a diagnosis of Li-Fraumeni syndrome when ANY of the following are met:

ANY of the following

Classic LFS: Individual meets Classic clinical diagnostic criteria for Li-Fraumeni syndromeproband sarcoma < 45 years; relative ages per Classic criteria
Classic LFS requires ALL of: proband with sarcoma before 45 years; first-degree relative with any cancer before 45; first- or second-degree relative with any cancer before 45 or a sarcoma at any age
Chompret criteria (2015): Individual meets Chompret clinical diagnostic criteria for Li-Fraumeni syndromeproband tumor < 46 years; relative < 56 years where specified
Chompret criteria (2015) include several pathways e.g., proband with LFS-spectrum tumor before 46 AND at least one first- or second-degree relative with LFS tumor before 56 or multiple tumors; proband with multiple tumors (2 in LFS spectrum, first before 46); patient with adrenocortical carcinoma, embryonal/anaplastic rhabdomyosarcoma, or choroid plexus tumor irrespective of family history; female proband with breast cancer before 31
Early-onset breast cancer: Individual with early-onset breast cancerage of diagnosis < 31 years
Pediatric hypodiploid ALL: Individual with pediatric hypodiploid acute lymphoblastic leukemiapediatric definition ≤18 years (AYA patients treated in pediatric settings may be up to age 30)
See Policy Guidelines: 'pediatric' includes age ≤18 years and AYA patients >18 treated in pediatric oncology settings (could include patients up to age 30)

The nodes array contains the top-level 'any' operator with four leaf criteria: Classic LFS, Chompret criteria (2015), early-onset breast cancer (age <31), and pediatric hypodiploid ALL (pediatric per guidelines).

Medically necessary: Targeted familial variant testing

Targeted TP53 familial variant testing is medically necessary when ALL of the following are met:

Asymptomatic at-risk relative of a proband with a known TP53 pathogenic variant

Testing is targeted to the known familial pathogenic variant

Not medically necessary

Germline TP53 testing is considered not medically necessary when NONE of the above criteria are met:

Testing for a germline TP53 variant for all other indications not specified above

Genetic testing for a germline TP53 variant is considered not medically necessary for all other indications (see Policy Guidelines).

Coding

Covered / medically necessary procedure codes (examples listed)CPT|HCPCS|mixedCovered

81351	TP53 (genetic testing) — listed in policy as covered when medically necessary
81352	Associated procedure code listed in coding section
81353	Associated procedure code listed in coding section
81479	Unlisted molecular pathology procedure — listed in coding section

Diagnosis / ICD-10 codes added/ referencedICD-10

C50.011	Malignant neoplasm of nipple and areola, right female breast
C50.012	Malignant neoplasm of nipple and areola, left female breast
C50.111	Malignant neoplasm of central portion of right female breast
C50.112	Malignant neoplasm of central portion of left female breast
C50.211	Malignant neoplasm of upper-inner quadrant of right female breast
C50.212	Malignant neoplasm of upper-inner quadrant of left female breast
C50.311	Malignant neoplasm of lower-inner quadrant of right female breast
C50.312	Malignant neoplasm of lower-inner quadrant of left female breast
C50.411	Malignant neoplasm of upper-outer quadrant of right female breast
C50.412	Malignant neoplasm of upper-outer quadrant of left female breast

1–10 of 23

1/3

Billing Rule

Coding accuracy and claim determination

Listing codes in the coding section does not guarantee coverage. Payment and coding determination are subject to the member's benefit program, eligibility on the date of service, and a medical necessity determination.

81351
81352
81353
81479
Note: Listing codes does not guarantee coverage; payment subject to member benefit program and medical necessity.

Provider Actions

Documentation Required

Document clinical criteria or known familial variant

Providers must document that the individual meets Classic or Chompret clinical diagnostic criteria for Li-Fraumeni syndrome, or has early-onset breast cancer diagnosed before age 31 years, or has pediatric hypodiploid acute lymphoblastic leukemia, or is an asymptomatic at-risk relative of a proband with a known TP53 pathogenic variant to support medical necessity for germline TP53 testing.

81351
81352
81353
81479

Prior Authorization

Prior authorization may be required per product

Policy applies to certain Capital Blue Cross programs and products and benefit variations exist. Providers should verify product-specific preauthorization requirements and member benefit information to determine coverage and any prior authorization requirements.

Applies to certain Capital Blue Cross products; verify product-specific preauthorization and member benefits.

Background

Background: Li‑Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant cancer predisposition syndrome caused by germline pathogenic variants in the TP53 gene. Core LFS‑associated tumors include bone and soft tissue sarcomas, premenopausal breast cancer, certain brain/CNS tumors, adrenocortical carcinoma, and pediatric hypodiploid acute lymphoblastic leukemia. Germline TP53 testing confirms the diagnosis of LFS, establishes genetic status in asymptomatic relatives, and informs surveillance and risk‑reduction strategies (for example, consideration of bilateral mastectomy and avoidance of radiotherapy in variant carriers).

Definitions: Classic LFS — proband with a sarcoma before 45 years; a first‑degree relative with any cancer before 45 years; and a first‑ or second‑degree relative with any cancer before 45 years or a sarcoma at any age. Chompret criteria (2015) — includes patients such as a proband with an LFS‑spectrum tumor before 46 years plus a first‑ or second‑degree relative with an LFS tumor before 56 years or multiple tumors; a proband with multiple LFS tumors (2) with the first before 46 years; certain tumor types (adrenocortical carcinoma, embryonal/anaplastic rhabdomyosarcoma, choroid plexus tumor) irrespective of family history; or a female proband with breast cancer before 31 years. Targeted familial variant testing — testing only for the known familial TP53 pathogenic variant in an asymptomatic at‑risk relative of a proband.

Evidence (compact)

Clinical sensitivity in suspected LFS50% to 80%

Frequency of TP53 alterations in low hypodiploid ALLUpwards of 90% with nearly half suspected germline

Penetrance by age 70Approximately 80% lifetime risk

OpenPayer