LETTER OF MEDICAL NECESSITY FOR COWDEN SYNDROME GENETIC TESTING (PTEN–RELATED
DISORDERS)
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; 179 malignant neoplasm of uterus, unspecified; 193 malignant neoplasm of thyroid gland;
V10.3 personal history of breast cancer; 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 Cowden syndrome to be performed by Ambry Genetics
Corporation.
Cowden syndrome (CS) is a complex genetic disorder that predisposes individuals to develop
benign and malignant tumors, particularly in the breast, thyroid, and endometrium. Mucocutaneous
findings, colonic polyps, and macrocephaly are typically also present in the majority of those with
CS.1,2 Those diagnosed with CS have an estimated lifetime risk between of up to 85% to develop
female breast cancer, ~35% for thyroid cancer, and ~28% to develop endometrial (uterine)
cancer,2 although one publication suggests these risks may be even higher.3
CS is a part of a broader syndrome called PTEN hamartoma tumor syndrome (PHTS), all caused by
mutations in the PTEN gene. These include Bannayan-Riley-Ruvalcaba syndrome and Proteus
syndrome. The PTEN gene is responsible for ~90% of CS. There is considerable overlap of clinical
features between the PHTS disorders, and they do not always present as discrete syndromes in
families with a mutation in the PTEN gene. Therefore, molecular testing can be helpful in
confirming a diagnosis or identifying at-risk relatives.
Significant aspects of my patient’s personal and/or family medical history that suggest a
reasonable probability of CS (and, therefore, PHTS) are below:
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Based on the above information, CS is suspected in my patient and I am requesting coverage for this
test, which includes sequence and deletion/duplication analysis of the PTEN gene (responsible for
85% of CS). According to National Comprehensive Cancer Network (NCCN) guidelines,
germline genetic testing is warranted.4
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 PTEN mutation. Guidelines suggest the following screening and/or
prevention options:
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For breast cancer: breast self-examinations, clinical breast examinations,
mammogram, ultrasound, MRI, consideration of prophylactic mastectomies, and/or
chemoprevention
Consideration of hysterectomy
Annual thyroid ultrasound and dermatologic exam (including children)
Colonoscopy every 5 years, starting at 35 years of age
Additional screening based on family history
Due to the cancer risks associated with PTEN mutations and interventions available to reduce these
risks, this genetic testing is medically indicated. As such, I am ordering this testing as medically
necessary and affirm that my patient 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 CS, 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 CS 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 the 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:
81321x1, 81323x1
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.
Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet.
2000;37:828-830.
Hobert JA and Eng C. PTEN hamartoma tumor syndrome: an overview. Genet Med. 2009
Oct;11(10):687-94.
Tan MH, et al. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer
Res. 2012 Jan 15;18(2):400-7.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/Familial High-Risk
Assessment: Breast and Ovarian. Version 2.2014, 09/23/2014.