LETTER OF MEDICAL NECESSITY FOR LI-FRAUMENI SYNDROME GENETIC TESTING (TP53
ANALYSIS)
Date:
Date of service/claim
To:
Utilization Review Department
Insurance Company Name, Address, City, State
Re:
Patient Name, DOB, ID #
ICD-9 Codes: (quick reference as suggestions: 174.9 malignant neoplasm of female breast,
unspecified; 233.0 carcinoma in situ of breast; V10.3 personal history of breast cancer; V10.85 personal
history of malignant neoplasm of brain; V16.3 family history of breast cancer; V16.9 family history of
unspecified malignant neoplasm)
This letter is in regards to my patient and your subscriber, First, Last Name to request full coverage
of medically-indicated genetic testing for Li-Fraumeni syndrome to be performed by Ambry
Genetics Corporation.
Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome that can affect children and
adults. While many different types of cancers can occur in individuals with LFS, the most common
include: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumors (e.g.
astrocytomas, glioblastomas, medulloblastomas, choroid plexus carcinomas), adrenocortical
carcinoma, and leukemias.1,2,3 These are often diagnosed in childhood or young adulthood, and
multiple primary cancers can occur throughout one’s lifetime.2 Those with LFS have up to a 50%
risk of developing any associated cancers by age 30, and a lifetime risk of up to 90%.3,4
At least 70% of those clinically diagnosed with LFS has an identifiable mutation in the TP53 gene.2
While having a family history of LFS-associated cancers increases the chance of having a mutation
in TP53, up to 20% of individuals has a de novo (brand-new) mutation in TP53; therefore, a negative
family history of LFS-associated cancers does not rule out a TP53 mutation in an individual.
Significant aspects of my patient’s personal and/or family medical history that suggest a
reasonable probability of LFS are below:



Based on the above, LFS is suspected in my patient and I am requesting coverage for this test (TP53
analysis). According to National Comprehensive Cancer Network (NCCN) published
guidelines germline genetic for TP53 genetic testing is warranted.5
This genetic testing will help estimate my patient’s risk to develop cancer, and will directly
impact my patient’s medical management. If a mutation is identified, we will adjust medical care
to reduce my patient’s risk of developing (and potentially dying of) an advanced stage cancer. An
aggressive approach following established screening and management guidelines is indicated in
individuals that carry a TP53 mutation. Guidelines suggest the following screening options:


Careful dermatologic and neurologic assessments with annual examinations
For breast cancer: breast self-examinations, clinical breast examinations,
mammogram, ultrasound, MRI, consideration of prophylactic mastectomies, and/or
chemoprevention to reduce a woman’s risk of developing breast cancer



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Avoidance of radiation treatment when possible
Consideration of MRI-based screening/technologies
For colorectal cancer: consideration of colonoscopy
Other:______________________________________________________________
Due to the significant cancer risks associated with TP53 mutations and the interventions available
to reduce these risks, this genetic testing is medically indicated. As such, I am requesting
coverage for this testing as medically necessary care and affirm that my patient/patient’s
family has provided informed consent for genetic testing.
A positive test result would confirm a genetic diagnosis and/or risk in my patient, and would
ensure my patient is being managed appropriately. I am specifying Ambry Genetics Corporation
because this laboratory has highly-sensitive and cost-effective testing for LFS, along with a large
database of previously tested patients to ensure highly validated, accurate, and informative test
interpretation.
I recommend that you support this request for coverage of diagnostic genetic testing for LFS in my
patient. Genetic testing can take up to several weeks to complete, and the laboratory will not bill
until testing is concluded. Therefore, we are requesting that authorization be valid for 3 months.
Thank you for your time, and please don’t hesitate to contact me with any questions.
Sincerely,
Ordering Clinician Name (Signature Provided on Test Requisition Form)
(MD/DO, Clinical Nurse Specialist, Nurse-Midwives, Nurse Practitioner, Physician Assistant, Genetic
Counselor*)
*Authorized clinician requirements vary by state
Test Details
CPT codes:
81405x1, 81479x1
Laboratory:
Ambry Genetics Corporation (TIN 33-0892453 / NPI 1861568784), a CAPaccredited and CLIA-certified laboratory located at 15 Argonaut, Aliso Viejo, CA
92656
References:
1.
2.
3.
4.
5.
Gonzalez KD, et al. Beyond Li-Fraumeni syndrome: clinical characteristics of families with p53 germline
mutations. J Clin Oncol. 2009; 27(8): 1250-1256.
Schneider K, et al. Li-Fraumeni Syndrome. January 19, 1999 (updated April 11, 2013). In: Pagon RA, Adam MP,
Ardinger HH, et al., editors. GeneReviews®. Seattle, WA: University of Washington, Seattle; 1993-2014.
Birch JM, et al. Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni
families. Cancer Research. 1994; 54: 1298-1304.
Olivier M, et al. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53
genotype. Cancer Research. 2003; 63: 6643-6650.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/Familial High-Risk Assessment:
Breast and Ovarian. Version 2.2014, 09/23/2014.