Proposed LCD - Molecular Pathology Procedures (DL35000)

TRB@ (T CELL antigen receptor, BETA) (e.g., leukemia and lymphoma), gene rearrangement analysis to detect abnormal cloning population(s); using amplification methodology is considered necessary to guide therapeutic decision-making for individuals with acute lymphoid leukemia, aplastic anemia, and T cell prolymphocytic leukemia.TRG@ (T CELL antigen receptor, GAMMA ) (e.g., leukemia and lymphoma), gene rearrangement analysis , evaluation to detect abnormal cloning population(s) are considered medically necessary to guide therapeutic decision-making for individuals with acute lymphoid leukemia, aplastic anemia, and T cell prolymphocytic leukemia and mastocytosis.Tier 2 Covered Gene/Gene CombinationsLimited coverage may be provided for specific genes reported below:ACEATP7B (ATPase, Cu++ transporting, beta polypeptide)CCND1/IGHCBFB-MYH11CDKN2A (cyclin-dependent kinase inhibitor 2A)E2A/PBX1EML4-ALKETV6-RUNX1EWSR1/ERGEWSR1/FLI1EWSR1/WT1F11coagulation factor XIF13BF5F7F8 (coagulation factor VIII)FGBFIP1L1-PDGFRFOXO1/PAX3FOXO1/PAX7MEN1 (multiple endocrine neoplasia 1) (eg, multiple endocrine neoplasia type 1, Wermer syndrome), duplication/deletionMEN1 (multiple endocrine neoplasia 1) (eg, multiple endocrine neoplasia type 1, Wermer syndrome), full gene sequenceMUTYH (mutY homolog [E.coli])NPM/ALKPAX8/PPARGPRSS1 (protease, serine, 1 [trypsin 1])RARS (SF3B1RUNX1/RUNX1T1TP53 (tumor protein 53) (e.g. tumor samples), targeted sequence analysis of 2-5 exonsTP53 (tumor protein 53) (e.g. Li-Fraumeni syndrome, tumor samples), full gene sequence or targeted sequence analysis of >5 exonsVHL (von Hippel-Lindau tumor suppressor)Tier 2 Individual Review Codes/Gene CombinationsAny genetic test reported with a Tier 2 CPT code, not listed above or below, is subject to individual review.Tier 2 Non-covered Codes/Gene CombinationsThe following individual Tier 2 genetic tests are unlikely to impact therapeutic decision-making, directly impact treatment, outcome and/or clinical management in the care of the beneficiary and will be denied as not medically necessary (Please note that this list of non-covered genes is not exhaustive, and the fact that a specific gene is not mentioned does not mean it is covered. In addition, many genes have several names that are used. The most common names have been used in this policy):ABCC8ACADMACADS (acyl-CoA dehydrogenase)ACADVL (acyl-CoA dehydrogenase, very long chain)ADRB2AGTR1AIRE (APSI)AKT1ANG (angiogenin, ribonuclease, RNase A family, 5)APOEAQP2 (aquaporin 2 [collecting duct])AR (androgen receptor)ARX (aristaless related homeobox)ATN1BTD (biotinidase)C9orf72CASR (CAR, EIG8, extracellular calcium-sensing receptor, FHH, FIH, GPRC2A, HHC, HHC1, NSHPT, PCAR1)CAV3 (caveolin 3) (eg, CAV3-related distal myopathy, limb-girdle muscular dystrophy type 1C), full gene sequenceCBS (cystathionine-beta-synthase)CCR5CDKL5 (cyclin-dependent kinase-like 5)CFH/ARMS2Chromosome 18q-CLRN1CLRN1 (clarin 1)CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1)CYP21A2 (cytochrome P450, family 21, subfamily A, polypeptide2)CYP21A2DEK/NUP214DLAT (dihydrolipoamide S-acetyltransferase)DLD (dihydrolipoamide dehydrogenase)DMPK (dystrophia myotonica-protein kinase (DM gene and DM1)DMPK (dystrophia myotonica-protein kinase)DYT1 (TOR1A)EGR2 (early growth response 2) (eg, Charcot-Marie-Tooth)F8 (coagulation factor VIII)F8 (coagulation factor VIII)FGFR2 (fibroblast growth factor receptor 2) (2 EXONS)FGFR3FGFR3FGFR3 (fibroblast growth factor receptor 3) (4 EXONS)FGFR3 (fibroblast growth factor receptor 3) one exonFKRP (Fukutin related protein)FOXG1 (forkhead box G1)FSHMD1A (facioscapulohumeral muscular dystrophy 1A)FSHMD1A (facioscapulohumeral muscular dystrophy 1A)FXN (frataxin)GALT (galactose-1-phosphate uridylyltransferase)GALT (galactose-1-phosphate uridylyltransferase)GJB1 (gap junction protein, beta 1) (eg, Charcot-Marie-Tooth X-linked), full gene sequenceH19HADHA (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase [trifunctional protein] alpha subunit)HAX1 (HAX1_HUMAN, HCLS1- associated protein X-1, HCLSBP1, HS1-associating protein X-1, HS1 binding protein, HS1-binding protein 1, HS1BP1, HSP1BP-1)HEXA (hexosaminidase A, alpha polypeptide)HNF1B (HNF1 homeobox B)HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog Costello syndrome)HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog)HTT (huntingtin)IL28BIVDKCNJ10 (potassium inwardly-rectifying channel, subfamily J, member 10)KCNQ10T1 (KCNQ1 overlapping transcript 1)KIF6Level 8 Molecular Pathology ProceduresLevel 9 Molecular Pathology ProceduresLMNA (lamin A/C)LPA intron 25 genotypeMEFV (Mediterranean fever) (eg, familial Mediterranean fever)MEG3/DLK1MEK1MLL/AFFMPZ (myelin protein zero)MT-ATP6MT-ND4, MT-ND6MT-ND5 mitochondrially encoded tRNA leucine 1 [UUA/G] mitochondrially encoded NADH dehydrogenase 5)MT-RNR1 (mitochondrially encoded 12S RNA)MT-RNR1 (mitochondrially encoded 12S RNA)MT-TK (mitochondrially encoded tRNA lysine)MT-TL1MT-TS1MT-TS1 (mitochondrially encoded tRNA serine 1)MUTYH (mutY homolog [E. coli])NF2 (neurofibromin 2 [merlin])NSD1 (nuclear receptor binding SET domain protein 1)PAH (phenylalanine hydroxylase)PAX2 (paired box 2)PDHA1 (pyruvate dehydrogenase [lipoamide] alpha1)PIK3C, PI3Ks, PI(3)Ks, PI-3KsPOLG (polymerase [DNA directed], gamma)PRKAG2 (protein kinase, AMP-activated, gamma 2 non-catalytic subunit)PRSS1 (protease, serine, 1 [trypsin 1])PTPN11 (protein tyrosine phosphatase, non-receptor type 11)RET (ret-proto-oncogene) (eg, Hirschsprung disease), full gene sequenceSCA1SDA2SLC25A4 (solute carrier family 25 [mitochondrial carrier; adenine nucleotide translocation]SLC9A6 (solute carrier family 9 [sodium/hydrogen exchanger] member 6)SMN1SMN1 (survival of motor neuron 1, telomeric)SMN1/SMN2 (survival of motor neuron 1, telomeric/survival of motor neuron 2, centromeric)SOS1 (son of sevenless homolog 1)SPG4TAZ (tafazzin)TOR1ATRDTSC1 (tuberous sclerosis 1)TSC2 (tuberous sclerosis 2)UBE3A (ubiquitin protein ligase)UPD (Uniparental disomy)VEGFR2 (CD309, FLK1, VEGFR)VWF (von Willebrand factor)General InformationAssociated InformationN/ASources of InformationAgency for Healthcare Research and Quality (AHRQ). Update for horizon scans of genetic tests currently available for clinical use in cancers. 2011. Tufts Evidence-based Practice Center.American Medical Association. Current procedural terminology (CPT) professional edition 2013.Centers for Disease Control and Prevention (CDC). Genomic testing: Genomic tests by level of evidence. 2013. http://www.cdc.gov/genomics/gtesting/Current Procedural Terminology (CPT), 2015 American Medical Association.Hampel H, Frankel WL, Martin E, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer).New England Journal of Medicine.2005;352(18):1851-60.LCDs and policies from other Medicare contractors and private insurersLoupakis, F, Ruzzo A, Cremolini C, et al. KRAS codon 61, 146, and BRAF mutations predict resistance to cetuximab and irinotecan in KRAS codon 12 and 13, wild type metastatic colorectal cancer.BR J Cancer, 2009.101(4):p.715-721.Schmeler KM, Lynch HT, Chen L, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in Lynch syndrome.New England Journal of Medicine.2006;354(3):261-269.Secretarys Advisory Committee on Genetics, Health, and Society. U.S. system of oversight of genetic testing: A response to the charge of the secretary of health and human services.Department of Health and Human Services.2008. http://www4.od.nih.gov/oba/sacghs/reports/SACGHS_oversight_report.pdfU.S. Preventive Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: Recommendation statement. 2005. http://www.uspreventiveservicestaskforce.org/uspstf05/brcagen/brcagenrs.htm.Vaughn, CP, Zobell SD, Furtado LV, et al. Frequency of KRAS, BRAF, and NRAS Mutations in Colorectal Cancer.Genes Chromosomes Cancer, 2011, 50(5): p. 307-312.Mesa R, Jamieson C, Bhatia R, et al. Myeloproliferative Neoplasms. NCCN Clinical Practice Guidelines in Oncology. 2017;Version 2.2018.BibliographyNCCN Clinical Practice Guidelines in Oncology: Chronic Myeloid Leukemia Version 3.2018. 2018.NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia Version 1.2018. 2018.NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms Version 2.2018. 2018.NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes Version 2.2018. 2018.NCCN Clinical Practice Guidelines in Oncology: Central Nervous System Cancers NCCN V1.2018. 2018.NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas Version 3.2018. 2018.NCCN Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia Version 1.2018. 2018.