Humana Code Compendium (Laboratory) Form

Table of Contents

• 0035U Prion Disease Detection Using Real-Time Quaking-Induced Conversion of Cerebrospinal Fluid
• 0107U Clostridioides Difficile Toxins A/B Antigen Detection by Immunoassay Intrinsic IDx Test
• 0251U Hepcidin Neurofilament Chain for Neuronal Light Assays Damage
• 0361U, 83520 Alpha-Synuclein Protein Testing
• 0393U Perfluoroalkyl Substances Testing
• 0394U Folate Receptor Antibody Testing
• ower ae seer' Digitization of Glass Microscope Slides (Whole Slide Imaging)
• 81283 IFNL3 (Interferon, Lambda 3) Gene Analysis
• 03810, 0382U, Direct-to-Consumer Laboratory Testing

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 2 of 33

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Prion Disease Detection Using Real-Time Quaking-Induced Conversion of Cerebrospinal Fluid Section

Effective Date: 04/27/2023
Revision Date: 04/27/2023
Review Date: 04/27/2023

Change Summary: Updated References

Description

Not Covered

Prion diseases or transmissible spongiform encephalopathies are a family of rare, neurodegenerative disorders that affect both humans and animals. In humans, the identified disease names in this family are Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI) and kuru. CJD and vCJD are the more prevalent types.

The abnormal prions (pathogenic agents) induce abnormal folding of specific cellular proteins that are most abundantly found in the brain. This abnormal folding leads to the characteristic symptoms of the disease and leads to brain damage. These diseases are characterized with rapid progressive mental deterioration, behavior abnormalities, and neurological deficits which become fatal.

There are other methods for detecting prion disease, with the gold standard being brain biopsy. Less invasive testing techniques have been proposed, namely for CJD and vCJD, including searching for the presence of 14-3-3 protein in cerebrospinal fluid (CSF) (which is a marker for CJD) and DNA extracted from the blood or other tissues, however sensitivity can be low. The National Prion Disease Pathology Surveillance Center has introduced a real-time quaking-induced conversion (RT-QuIC) test of CSF to detect the abnormal prion proteins to purportedly allow for improved sensitivity, leading to more definitive diagnosis.

Coverage Determination

Humana members may NOT be eligible under the Plan for prion disease detection using real-time quaking-induced conversion (RT-QuIC) of CSF. This technology is considered experimental/investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 3 of 33

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

References

1. Centers for Disease Control and Prevention (CDC). CDC’s diagnostic criteria for Creutzfeldt-Jakob disease (CJD), 2018. https://www.cdc.gov. Published January 24, 2019. Accessed March 27, 2023.
2. Foutz A, Appleby BS, Hamlin C, et al.

2. Diagnostic and prognostic value of human prion detection in cerebrospinal fluid. Ann Neurol. 2017;81(1):79-92.
3. Green, AJE. RT-QuIC: a new test for sporadic CJD. Pract Neurol. 2019;19:49-55.
4. Merck Manual: Professional Version. Creutzfeldt-Jakob disease (CJD). https://www.merckmanuals.com. Updated July 2020. Accessed March 26, 2023.
5. UpToDate, Inc. Creutzfeldt-Jakob disease. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.
6. UpToDate, Inc. Diseases of the central nervous system caused by prions. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.
7. UpToDate, Inc. Variant Creutzfeldt-Jakob disease. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.
8. Zerr, I. Laboratory diagnosis of Creutzfeldt–Jakob disease. N Engl J Med. 2022;386:1345-1350. https://www.nejm.org. Accessed March 25, 2023.

Clostridioides Difficile Toxins A/B Antigen Detection by Immunoassay Section

Effective Date: 04/27/2023
Section Revision Date: 04/27/2023
Section Review Date: 04/27/2023

Change Summary: Updated References

Description

Not Covered

Clostridioides (formerly Clostridium) difficile (C. difficile) is a spore-forming, anaerobic, gram positive, toxin-producing bacterium. C. difficile infection (CDI) is transmitted through the fecal/oral route and is the most common cause of antibiotic-associated diarrhea and nosocomial infection in the United States. The diagnosis of C. difficile infection should be suspected in an individual with acute diarrhea (greater or equal to 3 loose stools in 24 hours) with no apparent explanation (eg, laxative use) and have risk factors such as recent antibiotic use, hospitalization, immunocompromised status or advanced age.

Laboratory tests for CDI rely on the detection of free toxin or molecular detection of toxin genes. Nucleic acid amplification tests (NAATs) (including polymerase chain reaction [PCR]) are the preferred method for laboratory diagnosis, either alone or as part of an algorithm with initial enzyme immunoassay (EIA) screening for glutamate dehydrogenase (GDH) antigen and toxins A (TcdA) and B (TcdB).

The Singulex Clarity C. diff toxins A/B assay is a rapid, microparticle-based, automated assay that detects C. difficile TcdA and TcdB in stool by using single- photon fluorescence detection for analyte measurement and is purported to have greater sensitivity and may be used as a standalone test.

Coverage Determination

Humana members may NOT be eligible under the Plan for Singulex Clarity C. diff toxins A/B assay. This technology is considered experimental/ investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

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References

1. American College of Gastroenterology (ACG). ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. https://gi.org. Published May 18, 2021. Accessed March 26, 2023.
2. American Gastroenterological Association (AGA). Clinical Practice Update. Management of Clostridium difficile infection in inflammatory bowel disease: expert review from the clinical practice updates committee of the AGA Institute. https://www.gastro.org. Published February 1, 2017. Accessed March 26, 2023.
3. Guh AY, Kutty PK. Clostridioides difficile infection. Ann Intern Med. 2018;169(7):49-64. https://annals.org.

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7. Hansen G, Young S, Wu, AH, et al. Ultrasensitive detection of Clostridioides difficile toxins A and B by use of automated single-molecule counting technology. J Clin Microbiol. 56(11):908-918. https://jcm.asm.org. Accessed March 25, 2023.
8. Infectious Diseases Society of America (IDSA). IDSA Guideline. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. https://www.idsociety.org. Published June 28, 2018. Accessed March 27, 2023.
9. Infectious Diseases Society of America (IDSA). IDSA Guideline. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). https://www.idsociety.org. Published April 1, 2017. Accessed March 27, 2023.
10. Merck Manual: Professional Version. Clostridioides (formerly Clostridium) difficile – induced diarrhea. https://www.merckmanuals.com. Updated May 2021. Accessed March 26, 2023.
11. Testing.com: for health professionals. Clostridium difficile and C. diff toxin testing. https://www.testing.com. Updated November 9, 2021. Accessed March 27, 2023.
12. UpToDate, Inc. Clostridioides (formerly Clostridium) difficile infection in adults: clinical manifestations and diagnosis. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.
13. UpToDate, Inc. Clostridioides (formerly Clostridium) difficile infection in adults: epidemiology, microbiology, and pathophysiology. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.
14. UpToDate, Inc. Clostridioides (formerly Clostridium) difficile infection in children: clinical features and diagnosis. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.

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Intrinsic Hepcidin IDx Test Section

Effective Date: 04/27/2023
Section Revision Date: 04/27/2023
Section Review Date: 04/27/2023
Change Summary: Updated References

Description

0251UHepcidin-25, enzyme-linked immunosorbent assay (ELISA), serum or plasmaNot Covered

Hepcidin is a 25-amino acid peptide hormone that regulates dietary iron absorption from the duodenum, controls recycling of senescent erythrocyte iron by macrophages and manages iron transport from hepatocytes into plasma. Hepcidin is positively regulated by plasma iron and IL-6 (inflammation, infection) and is suppressed by erythropoiesis via erythroferrone. Abnormally low serum hepcidin is associated with iron deficiency anemia (IDA) and hereditary hemochromatosis. High serum hepcidin may lead to iron sequestration and to anemia of inflammation (anemia of chronic disease) observed in chronic kidney disease (CKD), rheumatoid arthritis (RA), various cancers and iron refractory iron deficiency anemia (IRIDA). Hepcidin levels are currently under investigation for predicting response to oral iron therapy.

Coverage Determination

Humana members may NOT be eligible under the Plan for hepcidin testing.

This is considered experimental/investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

References

1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Research Update. Story of discovery: erythroferrone – new regulator of iron balance. https://www.niddk.nih.gov. Updated June 19, 2016. Accessed March 26, 2023.
2. UpToDate, Inc. Anemia of chronic disease/anemia of inflammation. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.

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UpToDate, Inc. Regulation of iron balance. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.

Neurofilament Light Chain Assays for Neuronal Damage Section

Effective Date: 06/22/2023
Section Revision Date: 06/22/2023
Section Review Date: 04/27/2023
Change Summary: Updated Coverage Determination, Coverage Limitations, Provider Claims Codes

Description

0361U Neurofilament light chain, digital immunoassay, wae plasma, quantitativeNot Covered

Neurofilaments are cytoskeletal proteins that are encoded by the NEFL gene and are found in the axonal interior of healthy, myelinated neurons in both the central and peripheral nervous systems. They comprise 85 percent of neuronal structural proteins and determine axonal diameter. There are several different types of neurofilaments, including heavy chain, medium chain and light chain. Neurofilament light chain assays have been proposed as a biomarker to assess for neuronal damage in neurodegenerative diseases or concussion.

Coverage Determination

Humana members may be eligible under the Plan for serum neurofilament light chain testing for neuronal damage when treatment for amyotrophic lateral sclerosis (ALS) with Qalsody (togersen) is being considered.
For information regarding Qalsody, please refer to Qalsody (togersen) Pharmacy Coverage Policy.

Coverage Limitations

Humana members may NOT be eligible under the Plan for serum neurofilament light chain testing for neuronal damage for any indications other than those listed above. This is considered experimental/investigational as it is not identified as widely used and generally accepted for any other proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

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References

1. American Association for Clinical Chemistry. Serum free light chains: optimal testing recommendations. https://www.aacc.org. Updated June 2020. Accessed March 27, 2023.
2. Hayes, Inc. Precision Medicine Research Brief. Neurofilament light chain assay for Alzheimer disease. https://evidence.hayesinc.com. Published February 8, 2023. Accessed March 25, 2023.
3. UpToDate, Inc. Clinical presentation, course, and prognosis of multiple sclerosis in adults. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.
4. UpToDate, Inc. Syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL). https://www.uptodate.com.

Alpha-Synuclein Protein Testing Section

Effective Date: 06/22/2023
Section Revision Date: N/A
Section Review Date: 06/22/2023
Change Summary: New Policy

Description

Not Covered

Alpha-synuclein (α-syn) is protein that is abundant in the central nervous system (CNS) and accounts for approximately 1 percent of total CNS protein. Aggregates of α-syn are a prominent finding in Parkinson disease and several other neurodegenerative disorders (eg, dementia with Lewy bodies, multiple system atrophy) known as synucleinopathies. The physiologic role of α-syn is not fully understood, although it appears to be involved in synaptic function and plasticity.³ Testing of cerebral spinal fluid (CSF) has been proposed to detect misfolded α-syn protein aggregates which are thought to be associated with the onset of synucleinopathies.

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 9 of 33

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Humana members may NOT be eligible under the Plan for alpha-synuclein (α-syn) protein testing. This technology is considered experimental/investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

References

1. American Academy of Neurology (AAN). Practice guideline update summary: mild cognitive impairment. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. https://www.aan.com. Published January 16, 2018. Accessed June 17, 2023.
2. National Center for Biotechnology Information (NCBI). Genetic Testing Registry. Parkinson disease overview. https://www.ncbi.nlm.nih.gov. Published May 25, 2004. Updated July 25, 2019. Accessed June 17, 2023.
3. UpToDate, Inc. Epidemiology, pathogenesis, and genetics of Parkinson disease. https://www.uptodate.com. Updated May 2023. Accessed June 17, 2023.
4. UpToDate, Inc. Epidemiology, pathology, and pathogenesis of dementia with Lewy bodies. https://www.uptodate.com. Updated May 2023. Accessed June 17, 2023.

Per- and Polyfluoroalkyl Substances Testing Section

Effective Date: 06/22/2023
Section Revision Date: N/A
Section Review Date: 06/22/2023
Change Summary: New Policy

Description

0394U Perfluoroalkyl substances (PFAS) (eg, perfluorooctanoic acid), 16 PFAS compounds by liquid chromatography-tandem mass spectrometry (LC-MS/MS), plasma
Not Covered

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 10 of 33

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals that have been in use since the 1940s. PFAS are found in a wide array of consumer and industrial products such as nonstick cookware, carpet, stain resistant treatments for clothing, aqueous film-forming foam concentrate (AFFF) firefighting foam, nonstick packaging and various industrial processes. Due to widespread use and persistence in the environment, most people in the United States have been exposed to PFAS.

The US Environmental Protection Agency (EPA) is currently partnering with other agencies to limit human exposure to potentially harmful levels of PFAS in the environment, and researchers are developing standards for human health toxicity reference values for specific PFAS where sufficient scientific data exist.⁴ Although PFAS testing in the environment (food, soil, water) is common practice, measurement of exposure in humans is only recommended currently as part of a scientific investigation or health study, due to limited correlations of measured levels and risk of adverse outcomes.

Coverage Determination

Humana members may NOT be eligible under the Plan for per- and polyfluoroalkyl substances testing. This is considered experimental/investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). An overview of the science and guidance for clinicians on per- and polyfluoroalkyl substances (PFAS). https://www.atsdr.cdc.gov. Updated December 6, 2019. Accessed June 19, 2023.
2. Agency for Toxic Substances and Disease Registry (ATSDR). Per- and polyfluoroalkyl substances (PFAS) and your health. PFAS blood testing. https://www.atsdr.cdc.gov. Updated November 1, 2022. Accessed June 19, 2023.
3. UpToDate, Inc. Occupational and environmental risks to reproduction in females: specific exposures and impact. https://www.uptodate.com. Updated May 2023. Accessed June 19, 2023.

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UpToDate, Inc. Overview of occupational and environmental risks to reproduction in females. https://www.uptodate.com. Updated May 2023. Accessed June 19, 2023.

US Environmental Protection Agency (EPA). Research on Per- and Polyfluoroalkyl Substances (PFAS). https://www.epa.gov. Updated May 26, 2023. Accessed June 19, 2023.

US Food & Drug Administration (FDA). Per- and Polyfluoroalkyl Substances (PFAS). https://www.fda.gov. Updated May 31, 2023. Accessed June 19, 2023.

Folate Receptor Antibody Testing Section

Effective Date: 06/22/2023
Section Revision Date: N/A
Section Review Date: 06/22/2023
Change Summary: New Policy

Description

Cerebral folate deficiency is a disorder that develops from a shortage of folate (vitamin B9) in the brain and is characterized by below normal levels of the active metabolite of folate (5-methyltetrahydrofolate [5MTHF]) in the central nervous system (CNS), despite normal levels of folate metabolites in the blood. Folic acid delivery to the brain is essential for optimal development and function of the brain. Folate receptor protein alpha (FRA, FRα) is responsible for transporting folic acid and 5MTHF into the brain, ovaries and placenta. Recently, autoantibodies have been identified which attach to FRα, making it dysfunctional. Folate receptor antibody testing has been proposed to help aid in the diagnosis of several disorders including autism spectrum disorders, cerebral folate deficiency, infertility, mitochondrial diseases and neural tube defects.

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 12 of 33

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Humana members may NOT be eligible under the Plan for folate receptor antibody testing. This technology is considered experimental/investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

References

1. American Academy of Child and Adolescent Psychiatry (AACAP). Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. https://www.aacap.org. Published February 2014. Accessed June 19, 2023.
2. American Academy of Pediatrics (AAP). Clinical Report. Identification, evaluation and management of children with autism spectrum disorders. https://www.aap.org. Published January 2020. Accessed June 19, 2023.
3. UpToDate, Inc. Autism spectrum disorder in children and adolescents: evaluation and diagnosis. https://www.uptodate.com. Updated May 2023. Accessed June 19, 2023.
4. UpToDate, Inc. Clinical manifestations and diagnosis of vitamin B12 and folate deficiency. https://www.uptodate.com. Updated May 2023. Accessed June 19, 2023.
5. UpToDate, Inc. Mitochondrial disorders: treatment. https://www.uptodate.com. Updated May 2023. Accessed June 19, 2023.

Digitization of Glass Microscope Slides (Whole Slide Imaging)

Digitization of Glass Microscope Slides (Whole Slide Imaging) Section

Effective Date: 12/24/2023
Section Revision Date: 12/14/2023
Section Review Date: 04/27/2023

Change Summary: Updated Description, Provider Claims Codes

Considered integral to the primary procedure and not separately reimbursable

Description

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 13 of 33

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Digitization of glass microscope slides for immunohistochemistry or immunocytochemistry, per specimen, initial single antibody stain procedure (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for immunohistochemistry or immunocytochemistry, per specimen, each additional single antibody stain procedure (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for immunohistochemistry or immunocytochemistry, per specimen, each multiplex antibody stain procedure (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for morphometric analysis, tumor immunohistochemistry (eg, Her-2/neu, estrogen receptor/progesterone receptor), quantitative or semiquantitative, per specimen, each single antibody stain procedure, manual (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for cytopathology, fluids, washings, or brushings, except cervical or vaginal; smears with interpretation (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for cytopathology, fluids, washings, or brushings, except cervical or vaginal; simple filter method with interpretation (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for cytopathology, concentration technique, smears, and interpretation (eg, Saccomanno technique)

Considered integral to the primary procedure and not separately reimbursable
Considered integral to the primary procedure and not separately reimbursable
Considered integral to the primary procedure and not

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to the primary procedure and not separately reimbursable

Digitization of glass microscope slides for cytopathology, smears, any other source; preparation, screening and interpretation (List separately in addition to code for primary procedure) Digitization of glass microscope slides for cytopathology, smears, any other source; extended study involving over 5 slides and/or multiple stains (List separately in addition to code for primary procedure) Digitization of glass microscope slides for cytopathology, evaluation of fine needle aspirate; immediate cytohistologic study to determine adequacy for diagnosis, first evaluation episode, each site (List separately in addition to code for primary procedure) Digitization of glass microscope slides for cytopathology, evaluation of fine needle aspirate; immediate cytohistologic study to determine adequacy for diagnosis, each separate additional evaluation episode, same site (ListConsidered integral to the primary procedure and not separately reimbursable0836T

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Considered integral to the primary procedure and not separately reimbursable Considered integral to the primary procedure and not separately reimbursable Considered integral to the primary procedure and not separately reimbursable Considered integral to the primary procedure and not separately reimbursable Considered integral to the primary procedure and not separately reimbursable Considered integral to the primary procedure and not separately reimbursable Considered integral to the primary procedure and not separately reimbursable Considered integral to the primary procedure and not

Digitization of glass microscope slides for consultation, comprehensive, with review of records and specimens, with report on referred material (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for pathology consultation during surgery; first tissue block, with frozen section(s), single specimen (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for pathology consultation during surgery; each additional tissue block with frozen section(s) (List separately in addition to code for primary procedure)
Digitization of glass microscope slides for pathology consultation during surgery; cytologic examination (eg, touch preparation, squash preparation), initial site (List separately in addition to code for primary procedure)

Digitization of glass microscope slides for pathology consultation during surgery; cytologic examination (eg, touch preparation, squash 0844T

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0851T Digitization of glass microscope slides for morphometric analysis, in situ hybridization (quantitative or semiquantitative), manual, per specimen; initial single probe stain procedure (List separately in addition to code for primary procedure)

Considered integral to the primary procedure and not separately reimbursable

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Digital pathology is an image-based environment that enables the acquisition, management and interpretation of pathology information generated from digitized glass microscope slides. Glass microscope slides are scanned by clinical staff and captured images (either real-time or stored on a computer server or a cloud-based digital image archival and communication system) are used for digital examination for pathologic diagnosis. Digitization of glass microscope slides enable remote examination by the pathologist and/or in conjunction with artificial intelligence (AI) algorithms.

Digitization of glass microscope slides (whole slide imaging) is considered integral to the primary procedure and not separately reimbursable.

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

References

1. College of American Pathologists. Validating whole slide imaging for diagnostic purposes in pathology: 2021 guideline update. https://www.cap.org. Published December 2013. Updated May 2021. Accessed March 27, 2023.
2. Kumar N, Gupta R, Gupta S. Whole slide imaging (WSI) in pathology: current perspectives and future directions. J Digit Imaging. 2022;33(4):1034-1040. URL. Accessed March 25, 2023.

IFNL3 (Interferon, Lambda 3) Gene Analysis Section

Effective Date: 04/27/2023
Section Revision Date: 04/27/2023
Section Review Date: 04/27/2023

Change Summary: Updated References

Description

81283 IFNL3 (interferon, lambda 3) (eg, drug response), gene analysis, rs12979860 variant
Not Covered

The IFNL3 (interferon, lambda-3) gene, formerly known as IL28B (interleukin-28B), encodes a cytokine related to type I interferons and interleukin-10. Cytokines are released in the presence of viruses, bacteria or tumor cells.

Description

IFNL3 polymorphisms may indicate either a favorable or unfavorable response to treatment of Hepatitis C virus (HCV) genotype 1, the most common type of HCV in the United States, when pegylated interferon-alfa and ribavirin containing treatment regimens are used. Testing is not recommended in clinical practice at this time because the results do not change current HCV treatment recommendations.

Coverage Determination

Humana members may NOT be eligible under the Plan for IFNL3 (interferon, lambda 3) gene analysis. This is considered experimental/ investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

References

1. American Association for the Study of Liver Diseases (AASLD). Hepatitis C guidance 2019 update: American Association for the Study of Liver Diseases – Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. https://www.aasld.org. Published February 2020. Accessed March 26, 2023.
2. Hayes, Inc. Genetic Test Evaluation (GTE) Report (ARCHIVED). Interleukin 28B (IL28B) testing to predict response to treatment of hepatitis C virus (HCV) infection. https://evidence.hayesinc.com. Published February 28, 2013. Updated February 13, 2015. Accessed March 25, 2023.
3. Merck Manual: Professional Version. Hepatitis C, chronic. https://www.merckmanuals.com. Updated August 2022. Accessed March 26, 2023.
4. UpToDate, Inc. Predictors of response to antiviral therapy for chronic hepatitis C virus infection. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.

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Direct-to-Consumer Laboratory Testing Section

Effective Date: 04/27/2023
Section Revision Date: 04/27/2023
Section Review Date: 04/27/2023

Change Summary: Updated Description, Provider Claims Codes, References

Description

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Direct-to-consumer (DTC) laboratory tests, including DTC genetic tests, are test kits sold directly to an individual through the internet or retail stores rather than at a physician’s office without a written order or prescription from a healthcare practitioner. DTC tests may also be referred to as direct-access or at-home testing. After the kit is purchased, the sample (eg, blood, saliva, stool, urine) is collected and placed inside a container to return by mail to the lab. Results may be provided within weeks via a website, mail or telephone.

The use of DTC testing carries significant risks if test results are utilized without referring to a physician or other healthcare provider, including a genetic counselor for genetic testing. Questions have also been raised regarding the reliability and reproducibility of these services. An example of a DTC laboratory test is a self-collected, blood spot collection test. An example of DTC genetic testing is 23andMe Personal Genome Service (PGS) Genetic Health Risk Report.

Coverage Determination

Any federal or state mandates for DTC testing take precedence over this medical coverage policy.

For information regarding DTC SARS-CoV-2 viral diagnostic testing, please refer to Severe Acute Respiratory Syndrome Coronavirus 2 Viral Testing Medical Coverage Policy.

Humana members may NOT be eligible under the Plan for DTC laboratory tests. Although they may be prescribed by a health care practitioner, DTC laboratory tests are available without a written order or prescription and may be obtained over-the-counter (OTC) and are therefore generally excluded by certificate. In the absence of a certificate exclusion for OTC items, these lab tests are considered not medically necessary as defined in the member’s individual certificate. Please refer to the member’s individual certificate for the specific definition.

Humana members may NOT be eligible under the Plan for confirmatory genetic testing based solely on DTC genetic testing results. This is considered experimental/investigational as it is not identified as widely used and generally accepted for the proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

References

1. American Academy of Pediatrics (AAP). Policy Statement. Ethical and policy issues in genetic testing and screening of children. https://www.aap.org. Published February 2013. Accessed March 27, 2023.
2. American College of Medical Genetics and Genomics (ACMG). ACMG Statement. Direct-to-consumer genetic testing: a revised position statement of the American College of Medical Genetics and Genomics. https://www.acmg.net. Published February 2016. Accessed March 26, 2023.
3. American College of Medical Genetics and Genomics (ACMG). ACMG Statement. Direct-to-consumer prenatal testing for multigenic or polygenic disorders: a position statement of the American College of Medical Genetics and Genomics. https://www.acmg.net. Published June 28, 2021. Accessed March 26, 2023.
4. American College of Obstetricians and Gynecologists (ACOG). Committee Opinion. Consumer testing for disease risk. https://www.acog.org. Published January 2021. Accessed March 27, 2023.
5. Association for Molecular Pathology (AMP).

5. Association for Molecular Pathology position statement: consumer genomic testing. https://www.amp.org. Published June 2019. Accessed March 26, 2023.
6. Gray SW, Gollust SE, Carere DA, et al. Personal genomic testing for cancer risk: results from the impact of personal genomics study. J Clin Oncol. 2017;35(6):636-644. https://www.ncbi.nlm.nih.gov/pmc. Accessed March 25, 2023.
7. Hayes, Inc. GTE Synopsis. Health + Ancestry (23andMe). https://evidence.hayesinc.com. Published April 27, 2017. Accessed March 25, 2023.
8. National Cancer Institute (NCI). Cancer genetics risk assessment and counseling (PDQ) – health professional version. https://www.cancer.gov. Published June 13, 2022. Accessed March 27, 2023.

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

10. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. https://www.nccn.org. Published February 13, 2023. Accessed March 27, 2023.
11. National Society of Genetic Counselors (NSGC). At-home genetic testing position statement. https://nsgc.org. Published June 24, 2019. Accessed March 27, 2023.
12. Tandy-Connor S, et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med. 2018;20(12):1515-1521. Accessed March 25, 2023.
13. UpToDate, Inc. Disorders of tyrosine metabolism. https://www.uptodate.com. Updated February 2023. Accessed March 28, 2023.
14. UpToDate, Inc. Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.
15. UpToDate, Inc. Overview of maple syrup urine disease. https://www.uptodate.com. Updated February 2023. Accessed March 28, 2023.
16. UpToDate, Inc. Overview of phenylketonuria. https://www.uptodate.com. Updated February 2023. Accessed March 28, 2023.
17. UpToDate, Inc. Personalized medicine. https://www.uptodate.com. Updated February 2023. Accessed March 26, 2023.
18. US Food & Drug Administration (FDA). Direct-to-consumer tests with marketing authorization. https://www.fda.gov. Updated December 20, 2019. Accessed March 26, 2023.
19. US Food & Drug Administration (FDA). FDA Statement. Statement from FDA Commissioner Scott Gottlieb, M.D., on implementation of agency’s streamlined development and review pathway for consumer tests that evaluate genetic health risks. https://www.fda.gov. Published November 6, 2017. Accessed June 20, 2022.
20. Provider Claims Codes
21. Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes.

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure.

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0755T Digitization of glass microscope slide for level VI, surgical pathology, gross and microscopic examination (List separately in addition to code for primary procedure) Always considered integral to the primary procedure and not separately reimbursable

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Digitization of glass microscope slides for morphometric analysis, tumor immunohistochemistry (eg, Her-2/neu, estrogen receptor/progesterone receptor), quantitative or semiquantitative, per specimen, each single antibody stain procedure, manual (List separately in addition to code for primary procedure) Always considered integral to the primary procedure and not separately reimbursable

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

separately reimbursable New Code Effective 01/01/2024

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Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 29 of 33

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 30 of 33

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 31 of 33Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 32 of 33Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

HCPCS Code(s) S3650 Saliva test, hormone level; during menopause Not Covered

Code Compendium (Laboratory) Policy Number: HUM-0576-014 Page: 33 of 33

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

S3652 Saliva test, hormone level; to assess preterm labor risk Not Covered