Proposed LCD - Molecular Pathology Procedures (DL35000)

Disease Association:Standard of care testing to diagnose certain HLA related diseases/conditions when the testing is supported by the clinical literature and is informative for the direct management of a patient bearing a certain allele(s). It is not expected that more than one test would be required in a given beneficiarys lifetime. Possible covered indications when standard laboratory testing (tissue typing) not adequate:HLA-B*27 for the diagnosis of certain cases of symptomatic patients with presumed ankylosing spondylitis or related inflammatory disease. HLA-B*27 is covered for ankylosing spondylitis in cases where other methods of diagnosis would not be appropriate or have yielded inconclusive results (NCD 190.1).In the work-up of certain patients with an unclear diagnosis of celiac disease and gluten hypersensitivity usually related to ambiguous standard laboratory results and/or inconsistent biopsy results (e.g., HLA-DQ2 by HLA-DQB1*02 and of DQ8 by HLA-DQB1*0302).Pharmacogenetics:Standard of care testing to diagnose certain HLA related drug hypersensitivity reactions when the testing is supported by the clinical literature and is informative for the direct management of a patient bearing a certain allele(s) associated to fatal skin drug reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis). It is not expected that more than one test would be required in a given beneficiarys lifetime. Possible covered indications:HLA B*5701 when testing performed prior to the initiation of an abacavir-containing regime in the treatment of HIV Infection.HLA-B*1502 when genotyping may be useful for risk stratification when the testing is performed prior to the initiation of carbamazepine therapy in the treatment of patients at high risk of having this allele. HLA-B*1502 occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians.Identification of HLA compatible platelets for transfusion when standard typing is not adequate.HUMAN PLATELET ANTIGEN 1-15as genotyping for human platelet antigens is important for identifying woman at risk for neonatal alloimmune thrombocytopenia (NAIT). Post-transfusion purpura is an immune reaction against human platelet antigens, often occurring when a woman is sensitized during pregnancy, then subsequently receives a transfusion. There are few Medicare beneficiaries for whom this testing will be clinically actionable.IGH@ (Immunoglobulin heavy chain locus) is considered medically necessary for acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and lymphoma, B-cell to guide therapeutic decision making.JAK2 V617Fgenotyping is considered medically necessary in the initial diagnostic work-up of BCR-ABL negative, JAK2-negative adults with clinical, laboratory, or pathological findings suggesting myeloproliferative neoplasm (MPN) (polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF)) or a myelodysplastic syndrome (MDS). Note: JAK2 (exons 12 and 13) (reported with 81403) is medically necessary in individuals for whom PV is a strong consideration.JAK2(Janus kinase 2) (eg, myeloproliferative disorder), exon 12 sequence and exon 13 sequence is considered medically necessary in the initial work-up of BCR-ABL and JAK2 (V617F variant) negative adults with clinical, laboratory, or pathological findings suggesting polycythemia vera.KIT(v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (eg, gastrointestinal stromal tumor [GIST], acute myeloid leukemia, melanoma), gene analysis, targeted sequence analysis (eg, exons 8, 11, 13, 17, 18) is considered medically necessary in patients who have GIST, acute myeloid leukemia (AML) or melanoma to guide therapeutic decision making.KIT(v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (eg, mastocytosis), gene analysis, D816 variant(s) is considered medically necessary in patients who have mastocytosis to guide therapeutic decision making.KRASgene analysis, variants in codons 12 and 13, is considered medically necessary in patients with colorectal cancer or non-small cell lung cancer when needed to determine if a Medicare covered therapy is a reasonable option given the individual's specific clinical presentation.KRAS(Kirsten rat sarcoma viral oncogene homolog) (e.g., carcinoma) gene analysis; additional variant(s) (e.g., codon 61, codon 146) is considered medically necessary in patients with colorectal cancer or non-small cell lung cancer when needed to determine if a Medicare covered therapy is a reasonable option given the individual's specific clinical presentation.MEN1(multiple endocrine neoplasia 1) (eg, multiple endocrine neoplasia type 1, Wermer syndrome), duplication/deletion and CPT code 81405 MEN1 (multiple endocrine neoplasia 1) e.g. multiple endocrine neoplasia type 1, Wermer syndrome), duplication/deletion analysis) are considered medically necessary in patients with multiple endocrine neoplasia to guide therapeutic decision-making.METproto-oncogene, receptor tyrosine kinase, is considered medically necessary in patients with non-small cell lung cancer when needed to determine if a Medicare covered therapy is a reasonable option given the individuals specific clinical presentation.MGMT(O-6-methylguanine-DNA methyltransferase) (e.g., glioblastoma multiforme), methylation analysis) is considered medically necessary in patients with malignant brain neoplasm to guide therapeutic decision making.MPL(myeloproliferative leukemia virus oncogene, thrombopoietin receptor, TPOR) (eg, myeloproliferative disorder), common variants (eg, W515A, W515K, W515L, W515R) is considered medically necessary in the initial work-up of BCR-ABL negative, JAK2 negative, and CALR negative adults with clinical, laboratory, or pathological findings suggesting thrombocytosis, essential thrombocythemia (ET), or primary myelofibrosis (PMF).MPL(myeloproliferative leukemia virus oncogene, thrombopoietin receptor, TPOR) (eg, myeloproliferative disorder), exon 10 sequence is considered medically necessary in the initial work-up of BCR-ABL negative, JAK2 negative, and CALR negative adults with clinical, laboratory, or pathological findings suggesting thrombocytosis, essential thrombocythemia (ET), or primary myelofibrosis (PMF).MTHFR(5,10-methyenetetrahydrofolate reductase) (e.g. hereditary hypercoaguability), gene analysis, common variants(e.g., EG, 677T, 1298C) is not considered to be clinically efficacious; therefore, testing is not medically necessary.Microsatellite instability analysis(e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) of markers for mismatch repair deficiency (e.g. BAT25, BAT26), includes comparison of neoplastic and normal tissue and is considered medically necessary in individuals who have colorectal cancer (CRC) diagnosed at less than or equal to 70 years of age, and those greater than 70 years who meet the revised Bethesda Lynch Syndrome (LS) guidelines to guide therapeutic decision-making. Despite the high penetrance of CRC and endometrial cancer and recommendations of consideration for screening unaffected first-degree relatives following diagnosis of an LS proband, testing of genetic carriers who are unaffected with a Lynch- related cancer is not a Medicare benefit, and is statutorily excluded from coverage.MSI testing is also required by FDA for the clinical use of Keytruda (pembrolizumab) in a restricted population of patients. These are patients who have unresectable or metastatic solid tumors who have progressed following prior treatment and have no satisfactory alternative options. When Keytruda (pembrolizumab) is a potential clinically appropriate therapeutic choice, MSI testing is medically necessary in these patients. Because this is a wide-ranging population of advanced cancer patients, ICD-10 specificity is impractical, therefore use an ICD-10 appropriate for the tumor type and location.MYD88genetic test is considered medically necessary in patients with Marginal Zone Lymphoma (MZL), Waldenstroms Macroglobulinemia (WM) and Lymphoplasmacytic Lymphoma (LPL) to guide therapeutic decision-making.NPM1 (nucleophosmin) is considered medically necessary in patients with acute myeloid leukemia (AML) to guide therapeutic decision making.NRAS(neuroblastoma RAS viral [v-ras] oncogene homolog) (e.g., colorectal carcinoma), gene analysis, variants in exon 2 (e.g., codons 12 and 13) and exon 3 (e.g., codon 61) is considered medically necessary in patients with colorectal cancer when needed to determine if a Medicare covered therapy is a reasonable option given the individual's specific clinical presentation.Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 21 genes, utilizing formalin-fixed paraffin embedded tissue, algorithm reported as recurrence score is considered medically necessary to guide therapeutic decision-making in patients with the following findings:estrogen-receptor positive, node-negative carcinoma of the breastestrogen-receptor positive micrometastases of carcinoma of the breast, andestrogen-receptor positive breast carcinoma with 1-3 positive nodes.PDGFRA(platelet-derived growth factor receptor, alpha polypeptide) (e.g., gastrointestinal stromal tumor [GIST]), gene analysis, targeted sequence analysis (eg, exons 12, 18) is considered medically necessary in patients with PDGFRA-associated chronic eosinophilic leukemia or GIST caused by mutations in the PDGFRA gene to guide therapeutic decision making.PML/RARALPHA, (T(15;17)), (PROMYELOCYTIC LEUKEMIA/RETINOIC ACID RECEPTOR ALPHA) (EG, PROMYELOCYTIC LEUKEMIA) TRANSLOCATION ANALYSIS; COMMON BREAKPOINTS (EG, INTRON 3 AND INTRON 6), QUALITATIVE OR QUANTITATIVE is considered medically necessary in patients with promyelocytic leukemia.Prosigna Breast Cancer Prognostic Gene Signature Assayis considered medically necessary in patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:A prognostic indicator for distant recurrence-free survival at 10 years in post- menopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors.A prognostic indicator for distant recurrence-free survival at 10 years in post- menopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 positive nodes}, Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with 4 or more positive nodesRARS(SF3B1 mutation) is considered medically necessary in patients with Myelodysplastic Syndrome to guide therapeutic decision-making.RET(ret-proto-oncogene) is considered medically necessary in patients with medullary CA of thyroid, multiple endocrine neoplasia, pheochromocytoma, and parathyroid tumors) to guide therapeutic decision making.ROSproto-oncogene 1, receptor tyrosine kinase, is considered medically necessary in patients with non-small cell lung cancer when needed to determine if a Medicare covered therapy is a reasonable option given the individuals specific clinical presentation.SERPINA1(serpin peptidase inhibitor, clade A, alpha-1- antiproteinase, antitrypsin, member 1) (e.g., antitrypsin deficiency), gene analysis, common variants (e.g. *S and *Z) is considered medically necessary for patients who have antitrypsin deficiency to guide therapeutic decision-making.Targeted genomic sequence analysis panel, solid organ neoplasm, DNA analysis, and RNA analysis when performed, 5-50 genes (EG, ALK, BRAF, CDKN2A, EGFR, ERBB2, KIT, KRAS, NRAS, MET, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed is considered not medically necessary except when used to guide treatment decision making in individuals with non-small cell lung cancer (please refer to LCD L37810).TP53(tumor protein 53) (e.g. tumor samples), targeted sequence analysis of 2-5 exons, and CPT code 81405 TP53 (tumor protein 53) (e.g. Li-Fraumeni syndrome, tumor samples), full gene sequence or targeted sequence analysis of >5 exons are considered medically necessary in individuals who have Acute Myelogenous Leukemia, chronic lymphocytic leukemia (CLL), or Myelodysplastic Disease to guide therapeutic decision-making.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.