Molecular Pathology/Molecular Diagnostics/Genetic Testing

Transcription

1 Policy Number GEN RP Approved By UnitedHealthcare Medicare Reimbursement Policy Committee Current Approval Date 01/28/2015 IMPORTANT NOTE ABOUT THIS REIMBURSEMENT POLICY This policy is applicable to UnitedHealthcare Medicare Advantage Plans offered by UnitedHealthcare and its affiliates. You are responsible for submission of accurate claims. This reimbursement policy is intended to ensure that you are reimbursed based on the code or codes that correctly describe the health care services provided. UnitedHealthcare reimbursement policies use Current Procedural Terminology (CPT *), Centers for Medicare and Medicaid Services (CMS), or other coding guidelines. References to CPT or other sources are for definitional purposes only and do not imply any right to reimbursement. This reimbursement policy applies to all health care services billed on CMS 1500 forms and, when specified, to those billed on UB04 forms (CMS 1450). Coding methodology, industry-standard reimbursement logic, regulatory requirements, benefits design and other factors are considered in developing reimbursement policy. This information is intended to serve only as a general resource regarding UnitedHealthcare s reimbursement policy for the services described and is not intended to address every aspect of a reimbursement situation. Accordingly, UnitedHealthcare may use reasonable discretion in interpreting and applying this policy to health care services provided in a particular case. Further, the policy does not address all issues related to reimbursement for health care services provided to UnitedHealthcare enrollees. Other factors affecting reimbursement may supplement, modify or, in some cases, supersede this policy. These factors may include, but are not limited to: legislative mandates, the physician or other provider contracts, and/or the enrollee s benefit coverage documents. Finally, this policy may not be implemented exactly the same way on the different electronic claims processing systems used by UnitedHealthcare due to programming or other constraints; however, UnitedHealthcare strives to minimize these variations. UnitedHealthcare may modify this reimbursement policy at any time by publishing a new version of the policy on this Website. However, the information presented in this policy is accurate and current as of the date of publication. *CPT copyright 2010 (or such other date of publication of CPT) American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association. Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Table of Contents Application...2 Summary...2 Overview...2 Reimbursement Guidelines...6 Documentation Guidelines...7 CPT/HCPCS Codes...7 Modifiers...16 References Included (but not limited to):...16 CMS NCD(s)...16 CMS LCD(s)...17 CMS Article(s)...17 CMS Benefit Policy Manual...17 CMS Claims Processing Manual...17 UnitedHealthcare Medicare Advantage Coverage Summaries...17 UnitedHealthcare Reimbursement Policies...17 UnitedHealthcare Medical Policies...17 Others...17 History...17 Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 1

2 Application This reimbursement policy applies to services reported using the Health Insurance Claim Form CMS-1500 or its electronic equivalent or its successor form, and services reported using facility claim form CMS-1450 or its electronic equivalent or its successor form. This policy applies to all products, all network and non-network physicians, and other health care professionals. The HCPCS/CPT code(s) may be subject to Correct Coding Initiative (CCI) edits. This policy does not take precedence over CCI edits. Please refer to the CCI for correct coding guidelines and specific applicable code combinations prior to billing UnitedHealthcare. It is not enough to link the procedure code to a correct, payable ICD-9-CM diagnosis code. The diagnosis must be present for the procedure to be paid. Compliance with the provisions in this policy is subject to monitoring by pre-payment review and/or post-payment data analysis and subsequent medical review. The effective date of changes/additions/deletions to this policy is the committee meeting date unless otherwise indicated. CPT codes and descriptions are copyright 2010 American Medical Association (or such other date of publication of CPT). All rights reserved. CPT is a registered trademark of the American Medical Association. Applicable FARS/DFARS restrictions apply to Government use. Fee schedules, relative value units, conversion factors, and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein. Current Dental Terminology (CDT), including procedure codes, nomenclature, descriptors, and other data contained therein, is copyright by the American Dental Association, 2002, All rights reserved. CDT is a registered trademark of the American Dental Association. Applicable FARS/DFARS apply. Summary Overview Hereditary Breast and Ovarian Cancer Families can be suspected of having hereditary breast or ovarian cancer based on occurrence at an early age, in multiple generations, often bilaterally, and in a pattern suggesting an autosomal dominant pattern of inheritance. The susceptibility may be transmitted through the maternal or paternal side of the family. Germ-line alterations in two genes, BRCA1 and BRCA2, are associated with an increased risk of breast and ovarian cancer. Alterations in BRCA1 and BRCA2 explain many, but not all, of inherited forms of breast and ovarian cancer. With the identification of BRCA1 and BRCA2, it is now possible to test for abnormalities in the genes to provide information on the future risk of cancer and to make important treatment decisions in affected individuals. Approximately five- to ten-percent of all breast cancers, and a similarly small percentage of ovarian cancers, are attributed to dominantly inherited susceptibility. In patients with breast or ovarian cancer who are from high-risk families without a known BRCA1 or BRCA2 gene, the entire gene must be sequenced to identify possible mutations. In those families with a known BRCA1 or BRCA2 gene mutation, only a single mutation site sequence is required. In the case of individuals with Ashkenazi Jewish ancestry, testing for 3 mutations common in this population may be warranted even after a single mutation has been identified in their family member. (See LCDs for Cancer section for specific coverage guidelines) Oncotype Diagnostic Test for Breast Cancer Prognosis Oncotype DX (trademark) is a patented gene panel test developed for node-negative, estrogen receptor (ER)- positive breast cancer. More recent clinical data supports its use for micro metastases and for 1-3 positive nodes. The assay can be conducted on routine paraffin-embedded breast cancer tissue. Algorithmic weighting of gene expression yields a Recurrence Score (RS) which is strongly correlated with the recurrence of breast cancer and may be used in the decision making for chemotherapy. The test is provided to Medicare beneficiaries throughout the US by the CLIA-regulated laboratory of Genomic Health, Inc. Therefore, when this test is a Part B service, most or all coverage decisions for Medicare beneficiaries are made by the Part B contractor serving Genomic Health, Inc, which is Palmetto GBA. Test results have been incorporated in one version of a nationally recognized multi-variate prognostic model for breast cancer recurrence. (See LCDs for Cancer section for specific coverage guidelines) Mammaprint Test Breast Cancer Prognosis MammaPrint is an FDA cleared in vitro microarray diagnostic test that uses gene expression profiling to analyze the gene activity of the tumor itself. By analyzing the individual activity of the tumor's genes, MammaPrint enables a more accurate prognosis of breast cancer recurrence to assist physicians in dealing Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 2

3 with their patients with breast cancer. MammaPrint, in addition to other tests and clinical factors, helps to classify the tumors into high and low risk for recurrence. Chemotherapy itself has inherent risk of morbidity, particularly in patients with comorbid conditions. When physicians make treatment decisions that chemotherapy can be safely avoided and alternative therapy (hormonal manipulation, radiation therapy) used, there can be patient benefit. (See LCDs for Cancer section for specific coverage guidelines) Breast Cancer Index (BCI) Genetic Assay The BCI assay uses pathologic complete response to interrogate selected proliferation-related and endocrine signaling-related genes, and may identify a subset of postmenopausal women who are at increased risk of late relapses for estrogen receptor positive breast cancer and who may derive a greater benefit from extended hormone therapy. (See LCDs for Cancer section for specific coverage guidelines) Hereditary Colorectal and Endometrial Cancer Syndromes Lynch Syndrome (previously denoted as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome), is an autosomal dominant syndrome that accounts for about 3-5% of colorectal cancer cases. HNPCC syndrome mutations occur in the following genes: hmlh1, hmsh2, hmsh6, PMS2 and EPCAM. Colorectal cancers associated with Lynch syndrome occur at a younger age (average age of onset between years of age) compared with the more common colorectal cancers typically found during the seventh decade of life. Other Lynch syndrome-associated cancers include endometrial, ovarian, gastric, pancreas, ureter and renal pelvis, biliary tract, brain (usually glioblastoma, and small intestine cancers, as well as sebaceous gland adenomas/carcinomas and keratoacanthomas (AKs). Female carriers of a specific Lynch gene mutation have up to a 71% risk of endometrial cancer and 12% risk of ovarian cancer, in addition to the other Lynch syndrome cancer risks. Furthermore, gynecologic cancers may precede colorectal cancer in as many as 50% of female HNPCC gene mutation carriers. Familial Adenomatous Polyposis (FAP) is an autosomal dominant syndrome caused by a germ-line mutation of the APC gene. Characteristically, affected patients develop multiple adenomas diffusely throughout the colon beginning in their teens. Colorectal cancer is inevitable in patients with FAP if colectomy is not performed. The average age at symptomatic diagnosis ranges from 34 to 45 years of age. However, the average age of colonic adenoma appearance is 16 years and of cancer diagnosis is 39 years. The FAP gene mutation occurs in approximately 1/10,000-1/30,000 live births in the United States, affects both sexes equally, and accounts for up to 1% of colorectal cancers. MYH-associated polyposis (MAP) is an autosomal recessive syndrome linked to germ-line mutations of the MYH gene. The full clinical picture of MYH-associated polyposis (MAP) is incompletely understood at this time. Current evidence suggests it is associated with about % of colorectal cancers. (See LCDs for Cancer section for specific coverage guidelines) Therapy-Directing testing Coverage for KRAS testing is limited to use in patients with metastatic colorectal cancer for whom either cetuximab (Erbitux) or panitumumab (Vectibix) therapy is contemplated as being appropriate. Although there remain some unanswered questions concerning the role of personalized medicine, it appears that there is sufficient sensitivity and specificity in the K-RAS testing to allow the decision to be made that use of either of the two drugs noted above would be inappropriate if the KRAS mutation is identified. Coverage for JAK2 testing is appropriate in patients with signs or symptoms suggesting an underlying chronic myeloproliferative disorder, including increased red-cell mass, increased platelets, unexplained persistent peripheral cytopenia to cytosis, unexplained peripheral or hepatic vein thrombosis (Budd-Chiari Syndrome) or bone marrow examination showing features of a chronic myeloproliferative disorder. Documentation must also indicate that the provider anticipates that the test result is likely to be of use in management of the condition. The BCR/ABL fusion gene is the classic mutation seen in Chronic Myelogenous Leukemia (CML) and is also seen in Acute Lymphocytic Leukemia (ALL) and certain other hematologic diseases. Major factors influencing consideration of testing for this gene include some that are too non-specific to support coverage. (See LCDs for Cancer section for specific coverage guidelines) Multiple Myeloma Gene Expression Profile MyPRS is a test for Multiple Myeloma Gene Expression Profile. Multiple myeloma is an incurable malignancy of terminally differentiated antibody secreting plasma cells. The Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 3

4 median overall survival is reported at 3-4 years. Disease sequelae associated with this malignancy includes anemia, immunodeficiency, renal insufficiency/failure, lytic bone lesions and hypercalcemia. The classification of myeloma is inadequate with morphology alone. The Durie-Salmon Staging System was first published in 1975 and predicts tumor mass and estimates survival by using levels of immunoglobin proteins, hemoglobin and calcium, and the number of bone lesions. CMS follows this classification in NCD for Autologous Stem Cell Transplantation and will continued to be followed until changed. Multiple Myeloma Gene Expression Profile (MyPRS) isolates plasma cells from myeloma patients, extracts DNA, which is then subjected to MicroArray testing and application of validated software programs to identifying patterns of genetic abnormalities. Seventy highly predictive genes have been identified and correlated to myeloma early relapse. MyPRS gives a predictive risk signature as high-risk or low-risk at this time. A high risk score predicts a <20% three-year complete remission where as a low-risk predicts a five-year complete remission of > 60%. The predictive value for the stratification of therapeutic interventions allows these patients to be treated in a more personalized manner based on their own genetic profile. However, it would be inappropriate to use this test as a diagnostic tool or as a monitoring device of ongoing therapy. Other testing is available for this function. This test is used only after an initial diagnosis of multiple myeloma has been made and will be available to be used in stratification of therapeutic interventions. The coverage is set to include only two clinical settings: 1. once after initial diagnosis is made (ICD-9-CM ), or 2. If relapse has occurred and a change in the therapeutic modalities is contemplated (203.02) (See LCDs in Cancer section for coverage guidelines) Loss-of-Heterozygosity Based Topographic Genotyping with PathfinderTG Test for pancreatic cyst/mass Combining pathologic study with molecular analyses of microdissected tissue, is claimed to enhance the ability to provide more specific diagnostic information, to help guide treatment decisions. These testing combinations are generally known as topographic genotyping. More specifically, loss-of-heterozygosity based topographic genotyping and other molecular analyses are combined in a patented technology known as PathfinderTG. Recently, a Technology Assessment Report prepared by the Tufts Evidence-Based Practice Center, for the Agency for Healthcare Research and Quality (AHRQ), reviewed the existing scientific literature for PathfinderTG. The Technology Assessments conclusions noted insufficient studies measuring whether the use of PathfinderTG Technology would improve patient relevant clinical outcomes. (See LCD for Pathfinder, Miscellaneous section for coverage guidelines) Circulating Tumor Cell (CTC) Assay CTCs represent the point in the metastatic process of solid tumors when cells from a primary tumor invade, detach, disseminate, colonize and proliferate in a distant site. Detection of elevated CTCs during therapy may be an accurate indication of subsequent rapid disease progression and mortality in breast, colorectal and prostate cancer, noting that FDA labeling includes each of these neoplasms. As a result of limited acceptable study data, CTCs are considered not medically necessary, for all indications. (See LCDs for CTCs for specific coverage guidelines) NRAS Genetic Testing of Tumor Tissue This is genetic testing of tumor tissue for somatic mutations in the NRAS gene. RAS oncogene is a superfamily of signal transduction proteins, which are proteins that communicate signals between the cells. DNA mutations in the RAS family genes turns the signals on permanently such that the cells divide nonstop, leading to cancer. (See LCDs in Cancer section for coverage guidelines) Bladder Tumor Markers Cystoscopy in conjunction with bladder tumor markers is the standard practice to evaluate patients with symptoms suggesting bladder cancer and to monitor treated patients for recurrence or progression. Although cystoscopy is considered the gold standard, studies have shown that up to 20% of tumor can be missed. Urinary cytology has close to a 90%-100% specificity, but only 10%-50% sensitivity for low grade urinary cancer (UC) detection. Due to this deficit, clinicians have sought noninvasive tumor markers detectable in urine. Bladder Tumor Marker tests include: BTA TRAK, Nuclear matrix protein 22 (NMP-22), NMP-22 BladderChek, The UroVysion, BTA (bladder tumor antigen)stat, and The ImmunoCyt. (See LCDs for Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 4

5 Cancer section for coverage guidelines) Molecular Diagnostics: Infectious Disease Testing Molecular diagnostic testing, which includes DNA- or RNA-based analysis, with or without amplification/quantification, provides sensitive, specific and timely identification of diverse biological entities. These include bacterial organisms, fungal organisms and tumors which are encountered for the majority of gynecological and other infectious disease presentations. (See LCDs for Molecular Pathology section for coverage guidelines) Molecular Assays for Prostate Cancer ConfirmMDx assesses the methylation status of 3 biomarkers (GSTP1, RASSF1, APC) associated with prostate cancer. ConfirmMDx is intended for use in patients with high-risk factors such as elevated/rising prostatespecific antigen (PSA) or abnormal digital rectal examination (DRE), with a negative or non-malignant abnormal histopathology finding (e.g., atypical cell or high grade prostate intraepithelial neoplasia (HGPIN)) in the previous biopsy, and is being considered for repeat biopsy. The PROGENSA PCA3 Assay is an FDA-approved, automated molecular test (assay) that helps physicians determine the need for repeat prostate biopsies in men who have had a previous negative biopsy. Prolaris is an RNA based assay measuring the expression of 31 cell cycle progression (CCP) genes and 15 genes that act as internal controls and normalization standards in each patient sample. The assay is performed on formalin fixed paraffin-embedded (FFPE) prostate cancer blocks. The assay results are reported as a numerical score along with accompanying interpretive information. The Decipher prostate cancer assay, a 22-biomarker expression signature using oligonucleotide microarray technology, interrogates 1.4 million RNAs extracted from a formalin-fixed paraffin embedded (FFPE) tissue block of the index lesion (defined by highest tumor stage or histological Gleason grade) from the radical prostectomy specimen. The biomarkers that comprise the Decipher classifier include cell cycle progression, androgen signaling, cell adhesion, tumor cell motility, migration and immune evasion functions. (See LCDs for Cancer for coverage guidelines) AlloMap for Heart Transplant Recipients AlloMap Molecular Expression Testing is a non-invasive gene expression test used to aid in the identification of heart transplant recipients with stable allograft function who have a low probability of moderate/severe acute cellular rejection at the time of testing in conjunction with standard clinical assessment. AlloMap testing measures the expression levels of 20 genes from a blood sample. The combined expression of these genes is represented as an AlloMap test score. AlloMap is performed in the XDx CLIA-certified laboratory and has been commercially available since AlloMap was cleared by the U.S. Food and Drug Administration in 2008 and was CE marked for the European Union in April Use of AlloMap is also included in the International Society of Heart and Lung Transplant (ISHLT) Practice Guidelines, published in August 2010, the worldwide standard for the care of heart transplant patients. Approximately 66% of the United States heart transplant population is covered for AlloMap. (See LCDs for Molecular Pathology section for coverage guidelines) Molecular Pathology Procedures for Human Leukocyte Antigen (HLA) Typing Human Leukocyte Antigen (HLA) typing is performed to assess compatibility of recipients and potential donors as a part of solid organ and hematopoietic stem cell/ bone marrow pretransplant testing. HLA testing is also performed to identify HLA alleles and allele groups (antigen equivalents) associated with specific diseases and individualized responses to drug therapy (e.g., HLA-B*27 and ankylosing spondylitis and HLA-B57:01 and abacavir hypersensitivity), as well as other clinical uses. One or more HLA genes may be tested in specific clinical situations (e.g., HLA A, B, C,-DRB1, and DQB1 for kidney transplantation). Each HLA gene typically has multiple variant alleles or allele groups that can be identified by typing. (See LCDs for Molecular Pathology for coverage guidelines) HLA-B*5701 Testing The Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) is a working group of the Office of AIDS Research Advisory Council (OARAC). The Panel recommends HLA-B*5701 testing prior to initiating abacavir therapy to reduce the risk of hypersensitivity reaction. HLA-B*5701-positive patients should not be prescribed abacavir, and the positive status should be recorded as an abacavir allergy in the patient s medical record. (See LCDs for Molecular Pathology for coverage guidelines) Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 5

6 Cytogenetic Studies Cytogenetics is the study of chromosomes by light or fluorescent microscopy. Cytogenetic testing is used to study an individual's chromosome makeup. Specimens for cytogenetic analysis can be obtained for routine analysis from the peripheral blood, in which case T lymphocytes are examined; from amniotic fluid for culture of amniocytes; from trophoblastic cells from the chorionic villus; from bone marrow; from solid tumors, and from cultured fibroblasts, usually obtained from a skin biopsy. Enough cells must be examined so that the chance of missing a cytogenetically distinct cell line (a situation of mosaicism) is statistically low. (See LCDs for Cytogenetics, Miscellaneous section for coverage guidelines) GeneSight Assay for Refractory Depression GeneSight Psychotropic is a multiplex pharmacogenomic test involving the analysis of fifty alleles (SNPs) from six different genes. The test results in the differentiation of psychoactive drugs that are likely to be effective and well-tolerated by a particular patient versus those that are not. GeneSight testing may only be ordered by licensed psychiatrists contemplating an alteration in neuropsychiatric medication for patients diagnosed with major depressive disorder (MDD) who are suffering with refractory moderate to severe depression (as defined by the 17-item Hamilton Rating Scale for Depression (HAM-D17) score of 14 or greater) after at least one prior neuropsychiatric medication failure. (See LCD for GeneSight in Miscellaneous section for coverage guidelines) CYP2C19, CYP2D6, CYP2C9, and VKORC1 Genetic Testing for Drug Metabolism Genetic alterations or polymorphisms are common in these drug metabolizing enzymes. These polymorphisms can lead to differences in individual drug response secondary to variation in metabolism. Pharmacogenetic testing has been proposed to predict individual response to a variety of drugs. In certain scenarios, an individual patient may benefit from this genetic testing in determining dosage and likely response to specific medications. (See LCDs for Drug Metabolism in Miscellaneous section for coverage guidelines) Assays for Rheumatoid Arthritis The Avise PG Assay, developed to support dose optimization and therapeutic decision making for patients diagnosed with rheumatoid arthritis (RA) on methotrexate ('MTX'). Vectra DA is multi-biomarker blood test to measure rheumatoid arthritis (RA) disease activity. Vectra DA measures 12 key proteins that represent multiple RA biological pathways. It is validated for use in adults diagnosed with RA. (See Article section for coverage guidelines) Reimbursement Guidelines Based on the Centers for Medicare & Medicaid Services (CMS) Program Integrity Manual (100-08), this policy addresses the circumstances under which the item or service is reasonable and necessary under the Social Security Act, 1862(a)(1)(A). For laboratory services, a service can be reasonable and necessary if the service is safe and effective; and appropriate, including the duration and frequency that is considered appropriate for the item or service, in terms of whether it is furnished in accordance with accepted standards of medical practice for the diagnosis of the patient's condition; furnished in a setting appropriate to the patient's medical needs and condition; ordered and furnished by qualified personnel; one that meets, but does not exceed, the patient's medical need; and is at least as beneficial as an existing and available medically appropriate alternative. Compliance with the provisions in this policy is subject to monitoring by post payment data analysis and subsequent medical review. Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states "...no Medicare payment shall be made for items or services which are not reasonable and necessary for the diagnosis and treatment of illness or injury...". Furthermore, it has been longstanding CMS policy that "tests that are performed in the absence of signs, symptoms, complaints, or personal history of disease or injury are not covered unless explicitly authorized by statute". Screening services, such as pre-symptomatic genetic tests and services, are those used to detect an undiagnosed disease or disease predisposition, and as such are not a Medicare benefit and not covered by Medicare. Similarly, Medicare may not reimburse the costs of tests/examinations that assess the risk for and/or of a condition unless the risk assessment clearly and directly effects the management of the patient. However, Medicare does cover a broad range of legislatively mandated preventive services to prevent disease, detect disease early when it is most treatable and curable, and manage disease so that complications can be avoided. These services can be found on the Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 6

7 CMS website at Any preventive services and tests not listed on the CMS Preventive Services webpage are considered non-covered screening (preventive) tests or services which are not a benefit of the Medicare program. Per 42 Code of Federal Regulations (CFR) section (a) states the following requirements: All diagnostic x-rays tests, diagnostic laboratory tests, and other diagnostic tests must be ordered by the physician who is treating the beneficiary, that is, the physician who furnishes a consultation or treats a beneficiary for a specific medical problem and who uses the results in the management of the beneficiary s specific medical problem. Tests not ordered by the physician who is treating the beneficiary are not reasonable and necessary (see (k)(1)). Also, see Medicare Benefit Policy Manual (100-02), Chapter 15, Section 80.6 for related physician order instructions. Laboratory services must meet all applicable requirements of the Clinical Laboratory Improvement Amendments of 1988 (CLIA), as set forth at 42 CFR part 493. Section 1862(a)(1)(A) of the Act provides that Medicare payment may not be made for services that are not reasonable and necessary. Clinical laboratory services must be ordered and used promptly by the physician who is treating the beneficiary as described in 42 CFR (a), or by a qualified nonphysician practitioner, as described in 42 CFR (a)(3). Many applications of the molecular pathology procedures are not covered services given lack of benefit category (preventive service) and/or failure to reach the reasonable and necessary threshold for coverage (based on quality of clinical evidence and strength of recommendation). Furthermore, payment of claims in the past (based on stacking codes) or in the future (based on the new code series) is not a statement of coverage since the service was not audited for compliance with program requirements and documentation supporting the reasonable and necessary testing for the beneficiary. Certain tests and procedures may be subject to prepayment medical review (records requested) and paid claims must be supportable, if selected, for post payment audit by the MAC or other contractors. Tests for diseases or conditions that manifest severe signs or symptoms in newborns and in early childhood or that result in early death (e.g., Canavan disease) could be subject to automatic denials since these tests are not usually relevant to a Medicare beneficiary. Documentation Guidelines Documentation must be adequate to verify that coverage guidelines listed above have been met. Thus, the medical record must contain documentation that the testing is expected to influence treatment of the condition toward which the testing is directed. The laboratory or billing provider must have on file the physician requisition which sets forth the diagnosis or condition (ICD-9-CM code) that warrants the test(s). Examples of documentation requirements of the ordering physician/nonphysician practitioner (NPP) include, but are not limited to, history and physical or exam findings that support the decision making, problems/diagnoses, relevant data (e.g., lab testing, imaging results). Documentation requirements of the performing laboratory (when requested) include, but are not limited to, lab accreditation, test requisition, test record/procedures, reports (preliminary and final), and quality control record. Documentation requirements for lab developed tests/protocols (when requested) include diagnostic test/assay, lab/manufacturer, names of comparable assays/services (if relevant), description of assay, analytical validity evidence, clinical validity evidence, and clinical utility. Providers are required to code to specificity however, if an unlisted CPT code is used the documentation must clearly identify the unique procedure performed. When multiple procedure codes are submitted on a claim (unique and/or unlisted) the documentation supporting each code should be easily identifiable. If on review the contractor cannot link a billed code to the documentation, these services will be denied based on Title XVIII of the Social Security Act, 1833(e). When the documentation does not meet the criteria for the service rendered or the documentation does not establish the medical necessity for the services, such services will be denied as not reasonable and necessary under Section 1862(a)(1)(A) of the Social Security Act. CPT/HCPCS Codes Code Description DMD (dystrophin) (eg, Duchenne/Becker muscular dystrophy) deletion analysis, and duplication analysis, if performed Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 7

8 81200 ASPA (aspartoacylase) (e.g., Canavan disease) gene analysis, common variants (e.g., E285A, Y231X) APC (adenomatous polyposis coli) (eg, familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; full gene sequence APC (adenomatous polyposis coli) (eg, familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; known familial variants APC (adenomatous polyposis coli) (eg, familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; duplication/deletion variants BCKDHB (branched-chain keto acid dehydrogenase E1, beta polypeptide) (e.g., Maple syrup urine disease) gene analysis, common variants (e.g., R183P, G278S, E422X) BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; major breakpoint, qualitative or quantitative BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; minor breakpoint, qualitative or quantitative BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; other breakpoint, qualitative or quantitative BLM (Bloom syndrome, RecQ helicase-like) (e.g., Bloom syndrome) gene analysis, 2281del6ins7 variant BRAF (v-raf murine sarcoma viral oncogene homolog B1) (e.g., colon cancer), gene analysis, V600E variant BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants in BRCA1 (i.e., exon 13 del 3.835kb, exon 13 dup 6kb, exon del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb) BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) gene analysis; 185delAG, 5385insC, 6174delT variants BRCA1, BRCA2 (breast cancer 1 and 2) (e.g., hereditary breast and ovarian cancer) gene analysis; uncommon duplication/deletion variants BRCA1 (breast cancer 1) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants (i.e., exon 13 del 3.835kb, exon 13 dup 6kb, exon del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb) BRCA1 (breast cancer 1) (e.g., hereditary breast and ovarian cancer) gene analysis; known familial variant BRCA2 (breast cancer 2) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis BRCA2 (breast cancer 2) (e.g., hereditary breast and ovarian cancer) gene analysis; known familial variant CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; common variants (e.g., ACMG/ACOG guidelines) CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; known familial variants CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; duplication/deletion variants CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; full gene sequence CFTR (cystic fibrosis transmembrane conductance regulator) (e.g., cystic fibrosis) gene analysis; intron 8 poly-t analysis (e.g., male infertility) Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 8

9 81225 CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (e.g., drug metabolism), gene analysis, common variants (e.g., *2, *3, *4, *8, *17) CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (e.g., drug metabolism), gene analysis, common variants (e.g., *2, *3, *4, *5, *6, *9, *10, *17, *19, *29, *35, *41, *1XN, *2XN, *4XN) CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (e.g., drug metabolism), gene analysis, common variants (e.g., *2, *3, *5, *6) Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number variants (e.g., Bacterial Artificial Chromosome [BAC] or oligo-based comparative genomic hybridization [CGH] microarray analysis) Cytogenomic constitutional (genome-wide) microarray analysis; interrogation of genomic regions for copy number and single nucleotide polymorphism (SNP) variants for chromosomal abnormalities EGFR (epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants (eg, exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q) F2 (prothrombin, coagulation factor II) (e.g., hereditary hypercoagulability) gene analysis, 20210G>A variant F5 (coagulation Factor V) (e.g., hereditary hypercoagulability) gene analysis, Leiden variant FANCC (Fanconi anemia, complementation group C) (e.g., Fanconi anemia, type C) gene analysis, common variant (e.g., IVS4+4A>T) FMR1 (Fragile X mental retardation 1) (e.g., fragile X mental retardation) gene analysis; evaluation to detect abnormal (e.g., expanded) alleles FMR1 (Fragile X mental retardation 1) (e.g., fragile X mental retardation) gene analysis; characterization of alleles (e.g., expanded size and methylation status) FLT3 (fms-related tyrosine kinase 3) (e.g., acute myeloid leukemia), gene analysis, internal tandem duplication (ITD) variants (i.e., exons 14, 15) G6PC (glucose-6-phosphatase, catalytic subunit) (e.g., Glycogen storage disease, Type 1a, von Gierke disease) gene analysis, common variants (e.g., R83C, Q347X) GBA (glucosidase, beta, acid) (e.g., Gaucher disease) gene analysis, common variants (e.g., N370S, 84GG, L444P, IVS2+1G>A) GJB2 (gap junction protein, beta 2, 26kDa, connexin 26) (eg, nonsyndromic hearing loss) gene analysis; full gene sequence GJB2 (gap junction protein, beta 2, 26kDa; connexin 26) (eg, nonsyndromic hearing loss) gene analysis; known familial variants GJB6 (gap junction protein, beta 6, 30kDa, connexin 30) (eg, nonsyndromic hearing loss) gene analysis, common variants (eg, 309kb [del(gjb6-d13s1830)] and 232kb [del(gjb6- D13S1854)]) HEXA (hexosaminidase A [alpha polypeptide]) (e.g., Tay-Sachs disease) gene analysis, common variants (e.g., 1278insTATC, G>C, G269S) HFE (hemochromatosis) (e.g., hereditary hemochromatosis) gene analysis, common variants (e.g., C282Y, H63D) HBA1/HBA2 (alpha globin 1 and alpha globin 2) (e.g., alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis, for common deletions or variant (e.g., Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5, and Constant Spring) IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complexassociated protein) (e.g., familial dysautonomia) gene analysis, common variants (e.g., T>C, R696P) Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 9

10 81261 (Immunoglobulin heavy chain locus) (e.g., leukemias and lymphomas, B-cell), gene rearrangement analysis to detect abnormal clonal population(s); amplified methodology (e.g., polymerase chain reaction) (Immunoglobulin heavy chain locus) (e.g., leukemias and lymphomas, B-cell), gene rearrangement analysis to detect abnormal clonal population(s); direct probe methodology (e.g., Southern blot) (Immunoglobulin heavy chain locus) (e.g., leukemia and lymphoma, B-cell), variable region somatic mutation analysis (Immunoglobulin kappa light chain locus) (e.g., leukemia and lymphoma, B-cell), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (e.g., pre-transplant recipient and donor germline testing, post-transplant nonhematopoietic recipient germline [e.g., buccal swab or other germline tissue sample] and donor testing, twin zygosity testing, or maternal cell contamination of fetal cells) Comparative analysis using Short Tandem Repeat (STR) markers; each additional specimen (e.g., additional cord blood donor, additional fetal samples from different cultures, or additional zygosity in multiple birth pregnancies) (List separately in addition to code for primary procedure) Chimerism (engraftment) analysis, post transplantation specimen (e.g., hematopoietic stem cell), includes comparison to previously performed baseline analyses; without cell selection Chimerism (engraftment) analysis, post transplantation specimen (e.g., hematopoietic stem cell), includes comparison to previously performed baseline analyses; with cell selection (e.g., CD3, CD33), each cell type JAK2 (Janus kinase 2) (e.g., myeloproliferative disorder) gene analysis, p.val617phe (V617F) variant KRAS (v-ki-ras2 Kirsten rat sarcoma viral oncogene) (e.g., carcinoma) gene analysis, variants in codons 12 and Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1, and ANK2); full sequence analysis Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1, and ANK2); known familial sequence variant Long QT syndrome gene analyses (e.g., KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP, SNTA1, and ANK2); duplication/deletion variants MGMT (O-6-methylguanine-DNA methyltransferase) (eg, glioblastoma multiforme), methylation analysis. (New Code for 2014) MLH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; promoter methylation analysis MCOLN1 (mucolipin 1) (e.g., Mucolipidosis, type IV) gene analysis, common variants (e.g., IVS3-2A>G, del6.4kb) MTHFR (5,10-methylenetetrahydrofolate reductase) (e.g., hereditary hypercoagulability) gene analysis, common variants (e.g., 677T, 1298C) MLH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MLH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants MLH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 10

11 81295 MSH2 (muts homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MSH2 (muts homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants MSH2 (muts homolog 2, colon cancer, nonpolyposis type 1) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants MSH6 (muts homolog 6 [E. coli]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MSH6 (muts homolog 6 [E. coli]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants MSH6 (muts homolog 6 [E. coli]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants 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, if performed MECP2 (methyl CpG binding protein 2) (e.g., Rett syndrome) gene analysis; full sequence analysis MECP2 (methyl CpG binding protein 2) (e.g., Rett syndrome) gene analysis; known familial variant MECP2 (methyl CpG binding protein 2) (e.g., Rett syndrome) gene analysis; duplication/deletion variants NPM1 (nucleophosmin) (e.g., acute myeloid leukemia) gene analysis, exon 12 variants PML/RARalpha, (t(15;17)), (promyelocytic leukemia/retinoic acid receptor alpha) (e.g., promyelocytic leukemia) translocation analysis; common breakpoints (e.g., intron 3 and intron 6), qualitative or quantitative PML/RARalpha, (t(15;17)), (promyelocytic leukemia/retinoic acid receptor alpha) (e.g., promyelocytic leukemia) translocation analysis; single breakpoint (e.g., intron 3, intron 6 or exon 6), qualitative or quantitative PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g., hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants PTEN (phosphatase and tensin homolog) (eg, Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; full sequence analysis PTEN (phosphatase and tensin homolog) (eg, Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; known familial variant PTEN (phosphatase and tensin homolog) (eg, Cowden syndrome, PTEN hamartoma tumor syndrome) gene analysis; duplication/deletion variant PMP22 (peripheral myelin protein 22) (eg, Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; duplication/deletion analysis PMP22 (peripheral myelin protein 22) (eg, Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; full sequence analysis PMP22 (peripheral myelin protein 22) (eg, Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies) gene analysis; known familial variant Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 11

12 81330 SMPD1(sphingomyelin phosphodiesterase 1, acid lysosomal) (e.g., Niemann-Pick disease, Type A) gene analysis, common variants (e.g., R496L, L302P, fsp330) SNRPN/UBE3A (small nuclear ribonucleoprotein polypeptide N and ubiquitin protein ligase E3A) (e.g., Prader-Willi syndrome and/or Angelman syndrome), methylation analysis SERPINA1 (serpin peptidase inhibitor, clade A, alpha-1 antiproteinase, antitrypsin, member 1) (e.g., alpha-1-antitrypsin deficiency), gene analysis, common variants (e.g., *S and *Z) TRB@ (T cell antigen receptor, beta) (e.g., leukemia and lymphoma), gene rearrangement analysis to detect abnormal clonal population(s); using amplification methodology (e.g., polymerase chain reaction) TRB@ (T cell antigen receptor, beta) (e.g., leukemia and lymphoma), gene rearrangement analysis to detect abnormal clonal population(s); using direct probe methodology (e.g., Southern blot) TRG@ (T cell antigen receptor, gamma) (e.g., leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide A1) (e.g., irinotecan metabolism), gene analysis, common variants (e.g., *28, *36, *37) VKORC1 (vitamin K epoxide reductase complex, subunit 1) (e.g., warfarin metabolism), gene analysis, common variants (e.g., -1639/3673) HLA Class I and II typing, low resolution (e.g., antigen equivalents); HLA-A, -B, -C, - DRB1/3/4/5, and -DQB HLA Class I and II typing, low resolution (e.g., antigen equivalents); HLA-A, -B, and - DRB1/3/4/5 (e.g., verification typing) HLA Class I typing, low resolution (e.g., antigen equivalents); complete (i.e., HLA-A, -B, and - C) HLA Class I typing, low resolution (e.g., antigen equivalents); one locus (e.g., HLA-A, -B, or - C), each HLA Class I typing, low resolution (e.g., antigen equivalents); one antigen equivalent (e.g., B*27), each HLA Class II typing, low resolution (e.g., antigen equivalents); HLA-DRB1/3/4/5 and -DQB HLA Class II typing, low resolution (e.g., antigen equivalents); one locus (e.g., HLA- DRB1/3/4/5, -DQB1, -DQA1, -DPB1, or -DPA1), each HLA Class II typing, low resolution (e.g., antigen equivalents); one antigen equivalent, each HLA Class I typing, high resolution (i.e., alleles or allele groups); complete (i.e., HLA-A, -B, and -C) HLA Class I typing, high resolution (i.e., alleles or allele groups); complete (i.e., HLA-A, -B, and -C) HLA Class I typing, high resolution (i.e., alleles or allele groups); one locus (e.g., HLA-A, -B, or -C), each HLA Class I typing, high resolution (i.e., alleles or allele groups); one allele or allele group (e.g., B*57:01P), each HLA Class II typing, high resolution (i.e., alleles or allele groups); one locus (e.g., HLA-DRB1, - DRB3, -DRB4, -DRB5, -DQB1, -DQA1, -DPB1, or -DPA1), each HLA Class II typing, high resolution (i.e., alleles or allele groups); one allele or allele group (e.g., HLA-DQB1*06:02P), each Molecular pathology procedure, Level 1 analysis (short description) Molecular pathology procedure, Level 2 analysis (short description) Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 12

13 81402 Molecular pathology procedure, Level 3 analysis (short description) Molecular pathology procedure, Level 4 analysis (short description) Molecular pathology procedure, Level 5 analysis (short description) Molecular pathology procedure, Level 6 analysis (short description) Molecular pathology procedure, Level 7 analysis (short description) Molecular pathology procedure, Level 8 analysis (short description) Molecular pathology procedure, Level 9 analysis (short description) Hereditary colon cancer syndromes (eg, Lynch syndrome, familial adenomatosis polyposis); genomic sequence analysis panel, must include analysis of at least 7 genes, including APC, CHEK2, MLH1, MSH2, MSH6, MUTYH, and PMS Hereditary colon cancer syndromes (eg, Lynch syndrome, familial adenomatosis polyposis); duplication/deletion gene analysis panel, must include analysis of at least 8 genes, including APC, MLH1, MSH2, MSH6, PMS2, EPCAM, CHEK2, and MUTYH Targeted genomic sequence analysis panel, solid organ neoplasm, DNA analysis, 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 Targeted genomic sequence analysis panel, solid organ or hematolymphoid neoplasm, DNA and RNA analysis when performed, 51 or greater genes (eg, ALK, BRAF, CDKN2A, CEBPA, DNMT3A, EGFR, ERBB2, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MLL, NPM1, NRAS, MET, NOTCH1, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed Targeted genomic sequence analysis panel, hematolymphoid neoplasm or disorder, DNA and RNA analysis when performed, 5-50 genes (eg, BRAF, CEBPA, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KRAS, KIT, MLL, NRAS, NPM1, NOTCH1), interrogation for sequence variants, and copy number variants or rearrangements, or isoform expression or mrna expression levels, if performed Unlisted molecular pathology procedure 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 Unlisted chemistry procedure Unlisted hematology and coagulation procedure Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood) Cell enumeration using immunologic selection and identification in fluid specimen (eg, circulating tumor cells in blood); physician interpretation and report, when required Immunoassay for tumor antigen, qualitative or semiquantitative (eg, bladder tumor antigen) Immunoassay for tumor antigen, other antigen, quantitative (eg, CA 50, 72-4, 549), each Nuclear Matrix Protein 22 (NMP22), qualitative Unlisted immunology procedure Adenovirus ag if (short description) Respiratory syncytial ag if (short description) Bartonella DNA amp probe (short description) Lyme dis DNA amp probe (short description) Infectious agent detection by nucleic acid (DNA or RNA); Candida species, direct probe Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 13

14 87481 Infectious agent detection by nucleic acid (DNA or RNA); Candida species, amplified probe Chylmd pneum DNA amp probe (short description) Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia trachomatis, direct probe Infectious agent detection by nucleic acid (DNA or RNA); Chlamydia trachomatis, amplified probe Cytomeg DNA amp probe (short description) Cytomeg DNA quant (short description) Enterovirus probe&revrs trns (short description) Vancomycin DNA amp probe (short description) Influenza DNA amp prob 1+ (short description) Influenza DNA amp probe (short description) Influenza DNA amp prob addl (short description) Infectious agent detection by nucleic acid (DNA or RNA); Gardnerella vaginalis, direct probe Hepatitis B DNA amp probe (short description) Hepatitis B DNA quant (short description) Hepatitis C probe & rvrs trnsc (short description) Hepatitis C revrs trnscrpj (short description) Hepatitis G DNA amp probe (short description) HSV DNA amp probe (short description) Hhv-6 DNA amp probe (short description) Hiv-1 DNA dir probe (short description) Hiv-1 probe&reverse trnscrpj (short description) Hiv-1 quant&revrse trnscrpj (short description) Hiv-2 DNA dir probe (short description) Hiv-2 probe&revrse trnscripj (short description) Hiv-2 quant&revrse trnscripj (short description) Legion pneumo DNA amp prob (short description) Mycobacteria DNA amp probe (short description) M.tuberculo DNA amp probe (short description) M.avium-intra DNA amp prob (short description) M.pneumon DNA amp probe (short description) Infectious agent detection by nucleic acid (DNA or RNA); Neisseria gonorrhoeae, direct probe Infectious agent detection by nucleic acid (DNA or RNA); Neisseria gonorrhoeae, amplified probe Hpv high-risk types (short description) Staph a DNA amp probe (short description) Mr-staph DNA amp probe (short description) Strep A DNA dir probe (short description) Strep B DNA amp probe (short description) Infectious agent detection by nucleic acid (DNA or RNA); Trichomonas vaginalis, direct probe Trichomonas vaginalis amplif (short description) Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 14

15 87797 Detect agent nos DNA dir (short description) Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; amplified probe Unlisted microbiology procedure Genotype DNA HIV reverse t (short description) Genotype DNA/RNA Hep C (short description) Phenotype DNA HIV w/culture (short description) Phenotype DNA HIV w/clt add (short description) Genotype DNA/RNA HIV (short description) Cytopathology, in situ hybridization (eg, FISH), urinary tract specimen with morphometric analysis, 3-5 molecular probes, each specimen; manual Cytopathology, in situ hybridization (eg, FISH), urinary tract specimen with morphometric analysis, 3-5 molecular probes, each specimen; using computer-assisted technology Unlisted cytopathology procedure Tissue culture for non-neoplastic disorders; lymphocyte Tissue culture for non-neoplastic disorders; skin or other solid tissue biopsy Tissue culture for non-neoplastic disorders; amniotic fluid or chorionic villus cells Tissue culture for neoplastic disorders; bone marrow, blood cells Tissue culture for neoplastic disorders; solid tumor Cryopreservation, freezing and storage of cells, each cell line Thawing and expansion of frozen cells, each aliquot Chromosome analysis for breakage syndromes; baseline Sister Chromatid Exchange (SCE), cells Chromosome analysis for breakage syndromes; baseline breakage, score cells, count 20 cells, 2 karyotypes (eg, for ataxia telangiectasia, Fanconi anemia, fragile X) Chromosome analysis for breakage syndromes; score 100 cells, clastogen stress (eg, diepoxybutane, mitomycin C, ionizing radiation, UV radiation) Chromosome analysis; count 5 cells, 1 karyotype, with banding Chromosome analysis; count cells, 2 karyotypes, with banding Chromosome analysis; count 45 cells for mosaicism, 2 karyotypes, with banding Chromosome analysis; analyze cells Chromosome analysis, amniotic fluid or chorionic villus, count 15 cells, 1 karyotype, with banding Chromosome analysis, in situ for amniotic fluid cells, count cells from 6-12 colonies, 1 karyotype, with banding Molecular cytogenetics; DNA probe, each (eg, FISH) Molecular cytogenetics; chromosomal in situ hybridization, analyze 3-5 cells (eg, for derivatives and markers) Molecular cytogenetics; chromosomal in situ hybridization, analyze cells (eg, for microdeletions) Molecular cytogenetics; interphase in situ hybridization, analyze cells Molecular cytogenetics; interphase in situ hybridization, analyze cells Chromosome analysis; additional karyotypes, each study Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 15

16 88283 Chromosome analysis; additional specialized banding technique (eg, NOR, C-banding) Chromosome analysis; additional cells counted, each study Chromosome analysis; additional high resolution study Cytogenetics and molecular cytogenetics, interpretation and report Unlisted cytogenetic study Immunohistochemistry or immunocytochemistry, per specimen; each additional single antibody stain procedure (List separately in addition to code for primary procedure) Immunohistochemistry or immunocytochemistry, per specimen; initial single antibody stain procedure Examination and selection of retrieved archival (ie, previously diagnosed) tissue(s) for molecular analysis (eg, KRAS mutational analysis) In situ hybridization (eg, FISH), each probe Morphometric analysis, in situ hybridization (quantitative or semi-quantitative) each probe; using computer-assisted technology Morphometric analysis, in situ hybridization (quantitative or semi-quantitative) each probe; manual Unlisted surgical pathology procedure Unlisted miscellaneous pathology test Unlisted reproductive medicine laboratory procedure G0452 Molecular pathology procedure; physician interpretation and report S0265 Genetic counseling, under physician supervision, each 15 minutes S3800 Genetic testing for amyotrophic lateral sclerosis (ALS) S3841 Genetic testing for retinoblastoma S3842 Genetic testing for Von Hippel-Lindau disease S3845 Genetic testing for alpha-thalassemia S3846 Genetic testing for hemoglobin E beta-thalassemia S3849 Genetic testing for Niemann-Pick disease S3850 Genetic testing for sickle cell anemia S3852 DNA analysis for APOE epsilon 4 allele for susceptibility to Alzheimer's disease S3853 Genetic testing for myotonic muscular dystrophy S3854 Gene expression profiling panel for use in the management of breast cancer treatment S3861 Genetic testing, sodium channel, voltage-gated, type V, alpha subunit (SCN5A) and variants for suspected Brugada Syndrome S3866 Genetic analysis for a specific gene mutation for hypertrophic cardiomyopathy (HCM) in an individual with a known HCM mutation in the family S3870 Comparative Genomic Hybrization (CGH) microarray testing for developmental delay, autism spectrum disorder and/or mental retardation Modifiers Code Description TC Technical component References Included (but not limited to): CMS NCD(s) NCD Cytogenetic Studies Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 16

17 Reference NCD: NCD Human Tumor Stem Cell Drug Sensitivity Assays CMS LCD(s) Numerous LCDs CMS Article(s) Numerous articles CMS Benefit Policy Manual Chapter 15; Clinical Laboratory Services CMS Claims Processing Manual Chapter 12; 60 Payment for Pathology Services Chapter 16; 10 Laboratory Services General Explanation of Payment; 40 & 40.7 Billing for Clinical Laboratory Tests/Billing for Noncovered Clinical Laboratory Tests UnitedHealthcare Medicare Advantage Coverage Summaries Genetic Testing Laboratory Tests and Services UnitedHealthcare Reimbursement Policies Corus CAD (Coronary Artery Disease) Laboratory Services UnitedHealthcare Medical Policies Chemosensitivity and Chemoresistance Assays in Cancer Gene Expression Tests Genetic Testing for Hereditary Breast and/or Ovarian Cancer Syndrome (HBOC) Others 2015 CMS Clinical Laboratory Fee Schedule (CLFS) Final Recommendation, CMS Website MolDx Covered Tests (M00023), Palmetto Website MolDx Excluded Tests (M00105, v2), Palmetto Website History Date Revisions 12/29/2015 Administrative udpates 10/30/2015 Administrative udpates 09/09/2015 Semi-annual review of policy with announcement at MRPC 06/25/2015 Administrative udpates 03/02/2015 Administrative udpates 01/28/2015 Annual Review for MRP Committee presentation and approval ChemoFx (NCD 190.7), Heartsbreath (NCD ), Sweat Test (NCD 190.5) removed from policy as these topics are addressed via NCD policies This policy will be reviewed every 6 months 04/23/2014 Merged NCD Cytogenetic Studies into this policy; NCD to be archived 01/22/2014 Adding CPT Code 81287; New Code for /01/2013 Adding additional new 2013 CPT Codes to list above 04/24/2013 Administrative udpates 04/08/2013 Administrative udpates 02/27/2013 Annual Review for MRP Committee presentation and approval 02/26/2013 Administrative udpates 08/15/2012 Administrative udpates 12/09/2012 Updated list of modifiers with Expiration date of 12/31/2012 Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 17

18 04/11/2012 Updates approved by Committee 04/02/2012 Updated policy with ChemoFx, Heartsbreath coverage information 01/25/2012 Policy Approved 12/15/2011 Policy Created Proprietary information of UnitedHealthcare. Copyright 2016 United HealthCare Services, Inc. Page 18