Transcription

FEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesFEP Medical Policy ManualFEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon CancerSyndromesEffective Policy Date: January 1, 2022Original Policy Date: March 2012Related Policies:2.04.101 - Genetic Testing for Li-Fraumeni Syndrome2.04.53 - Biomarker Testing (Including Liquid Biopsy) for Targeted Treatment and Immunotherapy in Metastatic Colorectal Cancer2.04.88 - Genetic Testing for PTEN Hamartoma Tumor SyndromeGenetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesDescriptionDescriptionGenetic testing is available for both those with and those at risk for various types of hereditary cancer. This review evaluates genetic testing forhereditary colorectal cancer (CRC) and polyposis syndromes, including familial adenomatous polyposis (FAP), Lynch syndrome (formerly known ashereditary nonpolyposis colorectal cancer), MUTYH-associated polyposis (MAP), Lynch syndrome-related endometrial cancer, juvenile polyposissyndrome (JPS), and Peutz-Jeghers syndrome (PJS).OBJECTIVEThe objective of this evidence review is to assess whether the use of genetic testing improves the net health outcome in patients with Lynch syndromeand other inherited colon cancer syndromes. This review does not address individuals without a personal history ofcancer, nor screening or presymptomatic use of genetic tests and services.The policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are notintended to replace or substitute for the independent medical judgment of a practitioner or other health care professional in the treatment of an individual member. TheBlue Cross and Blue Shield Association does not intend by the FEP Medical Policy Manual, or by any particular medical policy, to recommend, advocate, encourage ordiscourage any particular medical technologies. Medical decisions relative to medical technologies are to be made strictly by members/patients in consultation with theirhealth care providers. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that the Blue Cross andBlue Shield Service Benefit Plan covers (or pays for) this service or supply for a particular member.

FEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesPOLICY STATEMENTAPC TestingGenetic testing of the APC gene may be considered medically necessary in the following patients:Patients with a differential diagnosis of attenuated FAP versus MUTYH-associated polyposis (MAP) versus Lynch syndrome. Whether testingbegins with APC variants or screening for mismatch repair (MMR) variants depends on clinical presentation.Genetic testing for APC gene variants is not medically necessary for colorectal cancer (CRC) patients with classical FAP for confirmation of the FAPdiagnosis.MUTYH TestingGenetic testing of the MUTYH gene may be considered medically necessary in the following patients:Patients with a differential diagnosis of attenuated FAP versus MAP versus Lynch syndrome and a negative result for APC gene variants. Afamily history of no parents or children with FAP is consistent with MAP (autosomal recessive).Testing for germline MUTYH gene variants for inherited CRC syndromes is considered investigational in all other situations.MMR Gene TestingGenetic testing of MMR genes (MLH1, MSH2, MSH6, PMS2) may be considered medically necessary in the following patients:Patients with colorectal cancer (CRC) with tumor testing suggesting germline MMR deficiency or meeting clinical criteria for Lynch syndrome(see Policy Guidelines section).Patients with endometrial cancer with tumor testing suggesting germline MMR deficiency or meeting clinical criteria for Lynch syndrome (seePolicy Guidelines section).Patients with a differential diagnosis of attenuated FAP versus MAP versus Lynch syndrome. Whether testing begins with APC variants orscreening for MMR genes depends on clinical presentation.EPCAM TestingGenetic testing of the EPCAM gene may be considered medically necessary when the following criteria (solid bullets) is met:Patients with CRC, for the diagnosis of Lynch syndrome (see Policy Guidelines section) when:Tumor tissue shows lack of MSH2 protein expression by immunohistochemistry and patient is negative for an MSH2 germline variant;ORTumor tissue shows a high level of microsatellite instability and patient is negative for a germline variant in MLH1, MSH2, MSH6, andPMS2BRAF V600E or MLH1 promoter methylationSomatic genetic testing for BRAF V600E or MLH1 promoter methylation may be considered medically necessary to exclude a diagnosis of Lynchsyndrome when the MLH1 protein is not expressed in a CRC tumor on immunohistochemical analysis.Testing for somatic BRAF V600E or MLH1 promoter methylation to exclude a diagnosis of Lynch syndrome is considered investigational in all othersituations.The policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are notintended to replace or substitute for the independent medical judgment of a practitioner or other health care professional in the treatment of an individual member. TheBlue Cross and Blue Shield Association does not intend by the FEP Medical Policy Manual, or by any particular medical policy, to recommend, advocate, encourage ordiscourage any particular medical technologies. Medical decisions relative to medical technologies are to be made strictly by members/patients in consultation with theirhealth care providers. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that the Blue Cross andBlue Shield Service Benefit Plan covers (or pays for) this service or supply for a particular member.

FEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesSMAD4 and BMPR1A TestingGenetic testing of SMAD4 and BMPR1A genes may be considered medically necessary when the following major criteria is met:Patients with a clinical diagnosis of juvenile polyposis syndrome based on the presence of any 1 of the following:at least 5 juvenile polyps in the colonmultiple juvenile polyps found throughout the gastrointestinal tractany number of juvenile polyps in a person with a known family history of juvenile polyps.STK11 TestingGenetic testing for STK11 gene variants may be considered medically necessary when the following criteria is met:Patients with a clinical diagnosis of Peutz-Jeghers syndrome based on the presence of any 2 of the following:presence of 2 or more histologically confirmed Peutz-Jeghers polyps of the gastrointestinal tract.characteristic mucocutaneous pigmentation of the mouth, lips, nose, eyes, genitalia, or fingersfamily history of Peutz-Jeghers syndrome.Other VariantsGenetic testing of all other genes for an inherited CRC syndrome is considered investigational.Genetic CounselingPre- and posttest genetic counseling may be considered medically necessary as an adjunct to the genetic testing itself.POLICY GUIDELINESEvaluation for Lynch SyndromeFor patients with colorectal cancer (CRC) or endometrial cancer being evaluated for Lynch syndrome, the microsatellite instability (MSI) test or theimmunohistochemical (IHC) test with or without BRAF gene variant testing, or methylation testing, should be used as an initial evaluation of tumortissue before mismatch repair (MMR) gene analysis. Both tests are not necessary. Proceeding to MMR gene sequencing would depend on results ofMSI or IHC testing. In particular, IHC testing may help direct which MMR gene likely contains a variant, if any, and may also provide additionalinformation if MMR genetic testing is inconclusive. For further information on tumor tissue test results, interpretation, and additional testing options, seethe NCCN [National Comprehensive Cancer Network] clinical care guidelines on genetic/familial high risk assessment: colorectal.When indicated, genetic sequencing for MMR gene variants should begin with MLH1 and MSH2 genes, unless otherwise directed by the results of IHCtesting. Standard sequencing methods will not detect large deletions or duplications; when MMR gene variants are expected based on IHC or MSIstudies, but none are found by standard sequencing, additional testing for large deletions or duplications is appropriate.The policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are notintended to replace or substitute for the independent medical judgment of a practitioner or other health care professional in the treatment of an individual member. TheBlue Cross and Blue Shield Association does not intend by the FEP Medical Policy Manual, or by any particular medical policy, to recommend, advocate, encourage ordiscourage any particular medical technologies. Medical decisions relative to medical technologies are to be made strictly by members/patients in consultation with theirhealth care providers. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that the Blue Cross andBlue Shield Service Benefit Plan covers (or pays for) this service or supply for a particular member.

FEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesGenetic CounselingExperts recommend formal genetic counseling for patients who are at risk for inherited disorders and who wish to undergo genetic testing. Interpretingthe results of genetic tests and understanding risk factors can be difficult for some patients; genetic counseling helps individuals understand the impactof genetic testing, including the possible effects the test results could have on the individual or their family members. It should be noted that geneticcounseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Further, genetic counseling should beperformed by an individual with experience and expertise in genetic medicine and genetic testing methods.BENEFIT APPLICATIONExperimental or investigational procedures, treatments, drugs, or devices are not covered (See General Exclusion Section of brochure).Screening (other than the preventive services listed in the brochure) is not covered. Please see Section 6 General exclusions.Benefits are available for specialized diagnostic genetic testing when it is medically necessary to diagnose and/or manage a patient's existing medicalcondition. Benefits are not provided for genetic panels when some or all of the tests included in the panel are not covered, are experimental orinvestigational, or are not medically necessary.FDA REGULATORY STATUSThis policy also assumes that the microsatellite instability test or the immunohistochemical test as an initial evaluation for Lynch syndrome is performedas part of the routine pathologic evaluation of the colorectal or endometrial cancer specimen. Thus, this policy deals only with testing for geneticvariants. Proceeding to DNA mismatch repair gene sequencing would depend on the results of microsatellite instability and immunohistochemicaltesting. Microsatellite instability and immunohistochemical testing may also provide additional information when genetic testing for nonpolyposiscolorectal cancer is inconclusive.The complex patient selection criteria requiring a detailed family history are not readily available on claim forms. Also, genetic testing is a multistepprocedure that is currently coded using a series of nonspecific CPT codes. For these reasons, the most efficient application of this policy may be itsuse as a tool for prospective or retrospective review.Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet thegeneral regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Genetic tests reviewed in this evidence review are availableunder the auspices of the CLIA. Laboratories that offer laboratory-developed tests must be licensed by the CLIA for high-complexity testing. To date,the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.RATIONALESummary of EvidenceFor individuals who are suspected of attenuated familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and Lynch syndromewho receive genetic testing for adenomatous polyposis coli (APC), or are at-risk relatives of patients with FAP who receive genetic testing for MUTYHafter a negative APC test result, the evidence includes a TEC Assessment. Relevant outcomes are overall survival (OS), disease-specific survival, andtest accuracy and validity. For patients with an APC variant, enhanced surveillance and/or prophylactic treatment will reduce the future incidence ofcolon cancer and improve health outcomes. A related familial polyposis syndrome, MAP syndrome, is associated with variants in the MUTYH gene.Testing for this genetic variant is necessary when the differential diagnosis includes both FAP and MAP because distinguishing between the 2 leads todifferent management strategies. Depending on the presentation, Lynch syndrome may be part of the same differential diagnosis. The evidence issufficient to determine that the technology results in an improvement in the net health outcome.For individuals who (1) are suspected of attenuated FAP, MAP, and Lynch syndrome, or (2) have colon cancer, or (3) have endometrial cancer meetingclinical criteria for Lynch syndrome, who receive genetic testing for mismatch repair (MMR) genes, the evidence includes an Agency for HealthcareThe policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are notintended to replace or substitute for the independent medical judgment of a practitioner or other health care professional in the treatment of an individual member. TheBlue Cross and Blue Shield Association does not intend by the FEP Medical Policy Manual, or by any particular medical policy, to recommend, advocate, encourage ordiscourage any particular medical technologies. Medical decisions relative to medical technologies are to be made strictly by members/patients in consultation with theirhealth care providers. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that the Blue Cross andBlue Shield Service Benefit Plan covers (or pays for) this service or supply for a particular member.

FEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesResearch and Quality report, a supplemental assessment to that report by the Evaluation of Genomic Applications in Practice and Prevention WorkingGroup, and an Evaluation of Genomic Applications in Practice and Prevention recommendation for genetic testing in colorectal cancer (CRC). Relevantoutcomes are OS, disease-specific survival, and test accuracy and validity. A positive genetic test for a MMR variant can also lead to changes in themanagement of other Lynch syndrome malignancies. The evidence is sufficient to determine that the technology results in an improvement in the nethealth outcome.For individuals who warrant Lynch testing, screen negative on MMR testing, but positive for microsatellite instability (MSI) and lack MSH2 proteinexpression who receive genetic testing for EPCAM variants, the evidence includes variant prevalence studies and case series. Relevant outcomes areOS, disease-specific survival, and test accuracy and validity. Identification of an EPCAM variant could lead to changes in management that improvehealth outcomes. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.For individuals who have CRC in whom MLH1 protein is not expressed on IHC analysis who receive genetic testing for BRAF V600E or MLH1promoter methylation, the evidence includes case series. Relevant outcomes are OS, disease-specific survival, and test accuracy and validity. Studieshave shown, with high sensitivity and specificity, an association between BRAF V600E variant and MLH1 promoter methylation with sporadic CRC.Therefore, this type of testing could eliminate the need for further genetic testing or counseling for Lynch syndrome. The evidence is sufficient todetermine that the technology results in an improvement in the net health outcome.For individuals who (1) are suspected of JPS or PJS or (2) are at-risk relatives of patients suspected of or diagnosed with JPS or PJS who receivegenetic testing for SMAD4, BMPR1A, or STK11 genes, respectively, the evidence includes multiple observational studies. Relevant outcomes are OS,disease-specific survival, and test accuracy and validity. Studies have shown, with high sensitivity and specificity, an association between SMAD4 andBMPR1A and STK11 variants with JPS and PJS, respectively. Direct evidence of clinical utility for genetic testing of JPS or PJS is not available.Genetic testing may have clinical utility by avoiding burdensome and invasive endoscopic examinations, release from intensified screening programsresulting in psychological relief. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.SUPPLEMENTAL INFORMATIONPractice Guidelines and Position StatementsGuidelines or position statements will be considered for inclusion in 'Supplemental Information' if they were issued by, or jointly by, a US professionalsociety, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelinesthat are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.National Comprehensive Cancer NetworkThe NCCN guidelines on high-risk colorectal cancer syndromes (v.1.2021) are summarized in Table 1.77,The policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are notintended to replace or substitute for the independent medical judgment of a practitioner or other health care professional in the treatment of an individual member. TheBlue Cross and Blue Shield Association does not intend by the FEP Medical Policy Manual, or by any particular medical policy, to recommend, advocate, encourage ordiscourage any particular medical technologies. Medical decisions relative to medical technologies are to be made strictly by members/patients in consultation with theirhealth care providers. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that the Blue Cross andBlue Shield Service Benefit Plan covers (or pays for) this service or supply for a particular member.

FEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesTable 1. Criteria for Evaluation of Lynch SyndromeCriteria for the Evaluation of Lynch SyndromeKnown LS variant in the familyAn individual with colorectal or endometrial cancer and any of the following:Diagnosed 50 yAnother synchronous or metachronous LS-related cancera1 first-degree or second-degree relative with LS-relateda cancer diagnosed 50 y 2 first-degree or second-degree relatives with LS-relateda cancers regardless of ageAn individual with colorectal or endometrial cancer at any age with tumor showing evidence of MMR deficiency, either by PCR, NGS, or IHCdiagnosed at any age.bbFamily history of any of the following: 1 first-degree relative with colorectal or endometrial cancer diagnosed 50 y 1 first-degree relative with colorectal or endometrial cancer and another synchronous or metachronous LS-related cancera 2 first-degree or second-degree relatives with LS-related cancer,a including 1 diagnosed 50 y 3 first-degree or second-degree relatives with LS-related cancers,a regardless of ageAn individual with an LS-related cancera or unaffected individual with 5% riskc of having an MMR gene variant based on predictive models(PREMM5, MMRpro, MMRpredict)IHC: immunohistochemisty; LS: Lynch syndrome; MMR: mismatch repair; MSI: microsatellite instability; NGS: next generation sequencing; PCR: polymerase chain reaction.aLS-related cancers include colorectal, endometrial, gastric, ovarian, pancreas, ureter and renal pelvis, brain (usually glioblastoma), biliary tract, small intestinal cancers, as well assebaceous carcinomas, and keratoacanthomas as seen in Muir-Torre syndrome.bTumor screening for MMR deficiency is appropriate for all colorectal and endometrial cancers regardless of age at diagnosis, however, germline genetic testing is generallyreserved for patients with early age at diagnosis; positive family history; or abnormal tumor testing results; MSI or loss of MMR protein expression.cThere are recent data that resulted in a lower threshold of 2.5% for the PREMM5 predictive model risk for having an MMR gene variant. Based on these data, it is reasonable fortesting to be done based on the 2.5% score result and clinical judgment. Of note, with the lower threshold, there is an increase in sensitivity, but a decrease in specificity. It is notknown how this applies to the general population of unaffected individuals.Genetic Testing Recommendations for Lynch SyndromeScreening of the tumor for defective DNA mismatch repair (MMR) using immunohistochemistry (IHC) and/or microsatellite instability (MSI) is used toidentify which patients should undergo mutation testing for Lynch syndrome.27, The NCCN guidelines also indicate BRAF V600E testing or MLH1promoter methylation testing may be used when MLH1 is not expressed in the tumor on IHC analysis to exclude a diagnosis of Lynch syndrome.The NCCN guidelines for colon cancer (v.2.2021) recommend that all newly diagnosed patients with colon cancer be tested for MMR or MSI.26,The NCCN guidelines for uterine neoplasm (v.3.2021) also recommend universal screening for MMR genes.27, Additionally, the NCCN guidelinesrecommend screening for Lynch syndrome in all endometrial cancer patients younger than 50 years.The NCCN guidelines for genetic/familial high-risk assessment: colorectal (v1.2021) recommend genetic testing for at-risk family members of patientswith positive variants in MLH1, MSH2, MSH6, PMS2, and EPCAM. 77, These guidelines also address familial adenomatous polyposis (classical andattenuated) and MUTYH-associated polyposis and are consistent with the information provided in this evidence review.The policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are notintended to replace or substitute for the independent medical judgment of a practitioner or other health care professional in the treatment of an individual member. TheBlue Cross and Blue Shield Association does not intend by the FEP Medical Policy Manual, or by any particular medical policy, to recommend, advocate, encourage ordiscourage any particular medical technologies. Medical decisions relative to medical technologies are to be made strictly by members/patients in consultation with theirhealth care providers. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that the Blue Cross andBlue Shield Service Benefit Plan covers (or pays for) this service or supply for a particular member.

FEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesSurveillance Recommendations for Lynch SyndromeThe NCCN guidelines for colon cancer (v.2.2021)26,and for colorectal cancer (CRC) screening (v.2.2021)78, recommend CRC patients treated withcurative-intent surgery undergo surveillance colonoscopy at 1 year post-surgery and, if normal, again in 3 years, then every 5 years based on findings.The NCCN guidelines on genetic/familial high-risk assessment for CRC indicate for MLH1, MSH2, and EPCAM variant carriers that surveillance withcolonoscopy should begin "at age 20 to 25 years or 2 to 5 years before the earliest colon cancer if it is diagnosed before age 25 years and repeatevery 1 to 2 years."77,MSH6 and PMS2 variant carriers should begin surveillance with colonoscopy "at age 30 to 35 years or 2 to 5 years before the earliest colon cancer if itis diagnosed before age 30 years and repeat every 1 to 2 years"77,.Peutz-Jeghers Syndrome and Juvenile Polyposis SyndromeThere are limited data on the efficacy of various screening modalities in juvenile polyposis syndrome (JPS) and Peutz-Jeghers syndrome (PJS). TheNCCN cancer risk and surveillance 2 category 2A recommendations for these indications are summarized in Tables 2 and 3.77,Table 2. Risk and Surveillance Guidelines for Peutz-Jeghers SyndromeSiteLifetimeRisk, %Breast32 to 54Colon39Colonoscopy every 2 to 3 yLate teensStomach29Upper endoscopy every 2 to 3 yLate teensSmall intestine13Small bowel visualization (CT or MRI enterography orvideo capsule endoscopy baseline at 8 to 10 y withfollow-up interval based on findings but at least by age18, then every 2 to 3 y, though this may be individualized,or with symptoms)8 to 10 yPancreas11 to 36Magnetic resonance cholangiopancreatography withcontrast or endoscopic ultrasound every 1 to 2 h30 to 35 yOvary; Cervix(typically cervicaladenomamalignum)Uterus18 to 2110Ovary (typicallybenign sexcord/Sertoli celltumors)9Lung7 to 17Screening Procedure and IntervalMammogram and breast MRI annuallyClinical breast exam every 6 moPelvic examination and Pap smear annuallyPelvic examination and Pap smear annuallyInitiation Age, y30 y18 to 20 y18 to 20 yProvide education about symptoms and smokingcessationThe policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are notintended to replace or substitute for the independent medical judgment of a practitioner or other health care professional in the treatment of an individual member. TheBlue Cross and Blue Shield Association does not intend by the FEP Medical Policy Manual, or by any particular medical policy, to recommend, advocate, encourage ordiscourage any particular medical technologies. Medical decisions relative to medical technologies are to be made strictly by members/patients in consultation with theirhealth care providers. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that the Blue Cross andBlue Shield Service Benefit Plan covers (or pays for) this service or supply for a particular member.

FEP 2.04.08 Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer SyndromesNo other specific recommendations have beenmadeCT: computed tomography; MRI: magnetic resonance imaging.Table 3. Risk and Surveillance Guidelines for Juvenile Polyposis SyndromeSiteLifetimeRisk, %Screening Procedure and IntervalInitiation Age, yColonup to 50Colonoscopy: Repeat every 2 to 3 years. If polyps are found,repeat at shorter intervals based on polyp size, number, andpathology.a18 yStomachup to 21especially ifmultiplepolypspresentUpper endoscopy: Repeat every 2 to 3 years. If polyps arefound, repeat at shorter intervals based on polyp size,number, and pathology.a18 ySmallintestineRare,undefinedNo recommendations madea Infamilies where a SMAD4 or BMPR1A mutation is not identified, consider extending colonoscopy/upper endoscopy intervals in at-risk individuals who have no polyps from 2 to 3years to 5 years beginning at age 20, and then every 10 years beginning at age 40s,American College of GastroenterologyThe American College of Gastroenterology (2015) issued practice guidelines for the management of patients with hereditary gastrointestinal cancersyndromes.21,For Lynch syndrome, the College recommended:"All newly diagnosed colorectal cancers (CRCs) should be evaluated for mismatch repair deficiency.Analysis may be done by immunohistochemical testing for the MLH1/MSH2/MSH6/PMS2 proteins and/or testing for microsatellite instability. Tumorsthat demonstrate loss of MLH1 should undergo BRAF testing or analysis for MLH1 promoter hypermethylation.Individuals who have a personal history of a tumor showing evidence of mismatch repair deficiency (and no demonstrated BRAF variant orhypermethylation of MLH1), a known family variant associated with LS [Lynch syndrome], or a risk of 5% chance of LS based on risk predictionmodels should undergo genetic evaluation for LS.79,Genetic testing of patients with suspected LS should include germline variant genetic testing for the MLH1, MSH2, MSH6, PMS2, and/or EPCAMgenes or the altered gene(s) indicated by IHC testing.”For adenomatous polyposis syndromes, the College recommended:"Familial adenomatous polyposis (FAP)/MUTYH-associated polyposis/attenuated polyposisIndividuals who have a personal history of 10 cumulative colorectal adenomas, a family history of one of the adenomatous polyposis syndromes, or ahistory of adenomas and FAP-type extracolonic manifestations (duodenal/ampullary adenomas, desmoid tumors, papillary thyroid cancer, congenitalhypertrophy of the retinal pigment epithelium, epidermal cysts, osteomas) should undergo assessment for the adenomatous polyposis syndromes.Genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene variant analysis.”The policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not

Jan 06, 2022 · The policies contained in the FEP Medical Policy Manual are developed to assist in administering contractual benefits and do not constitute medical advice. They are not intended to replace or substitute for the independent medical judgment of a practitioner or other health ca