LETTER OF MEDICAL NECESSITY FOR PTEN HAMARTOMA TUMOR 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:
This letter is in regards to my patient and your subscriber, First, Last Name to request full coverage
of medically-indicated genetic testing for PTEN hamartoma tumor syndrome (PHTS) to be
performed by Ambry Genetics Corporation.
PHTS is a complex group of genetic disorders that can present as distinct syndromes, including:
Bannayan-Riley-Ruvalcaba syndrome (BRRS), autism with macrocephaly, Proteus syndrome (PS),
and Cowden syndrome (CS). The PHTS group predisposes individuals to develop benign and
malignant tumors, and other features that can include: dermatologic growths, macrocephaly,
intellectual disability, autism spectrum disorders (ASD), hamartomatous intestinal polyposis,
pigmented penile macules, limb/tissue overgrowth, congenital malformations, distinctive facial
features, and increased lifetime risks for breast, uterine, and endometrial cancers.1,2 While each
syndrome in this group can be considered separate conditions, there is considerable clinical
overlap between them. Genetically, they are all related to mutations in the PTEN gene.
Significant aspects of my patient’s personal and/or family medical history that suggest a
reasonable probability of PHTS are below:
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Based on the above, PHTS is suspected in my patient and I am requesting coverage for this test that
analyzes the PTEN gene. This gene is responsible for ~90% of CS, 65% of BRRS, and 20% of PS.1
Furthermore, gross deletions (identifiable by this test) have been found in 10% of BRRS and/or CSlike syndrome.1,4 Mutations have also been reported in 5% of patients with ASD and another 12% of
patients with developmental delay or intellectual disability.5 According to National
Comprehensive Cancer Network (NCCN) guidelines and American College of Medical
Genetics (ACMG) recommendations, germline genetic testing is warranted.3,6
Due to the clinical overlap between the PHTS disorders, those with BRRS and PS should follow
established screening and management guidelines for CS. This genetic testing will help offer
anticipatory guidance and assess my patient’s risk to develop cancer and other health
concerns. It will directly impact my patient’s medical management. If a mutation is identified,
we will adjust care to reduce my patient’s risk of developing an advanced stage cancer. Guidelines
suggest the following screening and/or prevention options:
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For female breast cancer, starting at age 30: 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)
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Consideration of neurologic exam in those diagnosed during childhood
Colonoscopy every 5 years, starting at age 35
Renal imaging, starting at age 40
Additional screening based on family history
Medical care will also be adjusted accordingly to address non-cancer medical concerns (such as
congenital malformations and autism spectrum disorders). Due to the medical 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/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 PHTS, 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 PHTS 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.
5.
6.
Eng C. PTEN Hamartoma Tumor Syndrome (PHTS). November 29, 2001 (updated January 23, 2014). In: Pagon
RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®. Seattle, WA: Univ. of Washington, Seattle; 1993-2014.
Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Gen. 2000;37:828-830.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/Familial High-Risk Assessment:
Breast and Ovarian. Version 2.2014, 09/23/2014.
Zhou XP, et al. Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba
syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am
J Hum Genet. 2003;73(2):404-11.
Varga EA, et al. The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders,
developmental delay, and macrocephaly. Gene in Med. 2009;11:111-117.
Schaefer GB and Mendelsohn NJ; ACMG Professional Practice and Guidelines Committee. Clinical genetics
evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med.
2013;15(5):399-407.