Highmark Commercial Medical Policy - Pennsylvania

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Medical Policy: L-178-004
Topic: Peutz-Jeghers Syndrome Testing
Section: Laboratory
Effective Date: November 13, 2017
Issue Date: November 13, 2017
Last Reviewed: June 2017

Peutz-Jeghers syndrome (PJS) is a genetic disorder characterized by of the development of polyps (hamartomas) in the gastrointestinal (GI) tract, most commonly the small intestine.

PJS is caused by mutations in the STK11 gene; STK11 is a tumor suppressor gene. Mutations in STK11 cause cells to grow and divide uncontrollably, leading to the development of polyps and an increased risk for cancer.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

STK11 (LKB1) gene testing may be considered medically necessary for individuals with a suspected or known clinical diagnosis of PJS, or a known family history of a STK11 (LKB1) mutation.

Testing is indicated for individuals whose medical and/or family history is consistent with ANY of the following:

  • A relative with a known deleterious STK11 (LKB1) gene mutation; or
  • A clinical diagnosis of PJS based on as least TWO of the following features:
    • At least TWO PJS-type hamartomatous polyps of the gastrointestinal tract; or
    • Mucocutaneous hyperpigmentation of the mouth, lips, nose, eyes, genitalia, or fingers; or
    • A family history of PJS.
Procedure Codes
81403, 81404, 81405

Professional Statements and Societal Positions

Evidence-based guidelines for the diagnosis and management of PJS were published in 2010. These guidelines outline clinical diagnostic criteria for PJS, and surveillance recommendations, but do not specifically address the utility of genetic testing.

  • A clinical diagnosis of PJS may be made in an affected person when ONE of the following is present (directly quoted):
    • Two (2) or more histologically confirmed PJ polyps
    • Any number of PJ polyps detected in one individual who has a family history of PJS in close relative(s)
    • Characteristic mucocutaneous pigmentation in an individual who has a family history of PJS in close relative(s)
    • Any number of PJS polyps in an individual who also has characteristic mucocutaneous pigmentation.
  • "No clear genotype-phenotype correlation has been demonstrated in PJS, and no clear differences found between cases with STK11 mutation and in those in whom no mutation has been detected."

The National Comprehensive Cancer Network (2016) guidelines outline similar clinical diagnostic criteria and provide some guidance on surveillance, but do not address the use of genetic testing.

  • "A clinical diagnosis of PJS can be made when an individual has two (2) or more of the following features:
    • Two (2) or more Peutz-Jeghers-type hamartomatous polyps of the small intestine
    • Mucocutaneous hyperpigmentation of the mouth, lips, nose, eyes, genitalia, or fingers
    • Family history of PJS".
  • "The majority of cases occur due to mutations in the STK11 (LKB1) gene and clinical genetic testing is available."
  • Screening procedures and intervals are outlined for breast, colon, stomach, pancreatic, small intestine, cervical, ovarian, uterine, and testicular cancers.

Clinical diagnostic criteria have been validated by genetic testing in one series of 71 patients. Of 56 patients who met clinical criteria for PJS, 94% had an STK11 mutation found by a combination of sequencing and deletion/duplication analysis. Twelve patients had only a "presumptive diagnosis" of PJS based on the presence of hyperpigmentation or isolated PJS polyps, with no known family history. No STK11 mutations were found in those 12 patients.

A 2016 expert-authored review states:

  • "Testing of at-risk asymptomatic adults for Peutz-Jeghers syndrome is available after the disease causing STK11 mutation has been identified in an affected family member."
  • "Testing for the disease-causing mutation in the absence of definite symptoms of the disease is predictive testing. At-risk asymptomatic adult family members may seek molecular genetic testing in order to make personal decisions regarding medical surveillance, reproduction, financial matters, and career planning."
  • "Because early detection of at-risk individuals who have an STK11 mutation affects medical management, particularly surveillance, testing of at-risk individuals during childhood is beneficial."

The American Society of Clinical Oncologists (ASCO) position statement on genetic testing (originally published 1996; revised/affirmed in 2003, 2008, 2010 and 2015) outlines general recommendations for genetic testing for hereditary cancer syndromes and specifically addresses issues around genetic testing in at-risk children:

  • "Indications for Genetic Testing: ASCO recommends that genetic testing be offered when 1) the individual has personal or family history features suggestive of a genetic cancer susceptibility condition, 2) the test can be adequately interpreted, and 3) the results will aid in diagnosis or influence the medical or surgical management of the patient or family members at hereditary risk of cancer."
  • "Special Issues in Testing Children for Cancer Susceptibility: ASCO recommends that the decision to offer testing to potentially affected children should take into account the availability of evidence-based risk-reduction strategies and the probability of developing a malignancy during childhood. Where risk-reduction strategies are available or cancer predominantly develops in childhood, ASCO believes that the scope of parental authority encompasses the right to decide for or against testing."
  • "Tests for high-penetrance mutations in appropriate populations have clinical utility, meaning that they inform clinical decision making and facilitate the prevention or amelioration of adverse health outcomes."

Place of Service: Outpatient

PJS testing is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of business

Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.


Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

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    • Qualified sign language interpreters
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If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

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