Pathology billing - Medicare payment guidelines

Payment for Pathology Services


A.Payment for Professional Component (PC) Services
Payment may be made under the physician fee schedule for the professional component of physician laboratory or physician pathology services furnished to hospital inpatients or outpatients by hospital physicians or by independent laboratories, if they qualify as the
re-assignee for the physician service.

B.Payment for Technical Component (TC) Services

1.General Rule

Payment is not made under the physician fee schedule for TC services furnished in institutional settings where the TC service is bundled into the facility payment, e.g., hospital inpatient and outpatient settings. Payment is made under the physician fee schedule for TC services furnished in institutional settings where the TC service is not bundled into the facility payment, e.g., an ambulatory surgery center (ASC).

Payment may be made under the physician fee schedule for the TC of physician pathology services furnished by an independent laboratory, or a hospital if it is acting as an independent laboratory, to non-hospital patients. The physician fee schedule identifies physician laboratory or physician pathology services that have a TC service.

2.TC Services Furnished by Independent Laboratories to Hospital Inpatients and Outpatients

*For services furnished on or after July 1, 2012, an independent laboratory may not bill the Medicare contractor (and the Medicare contractor may not pay) for the TC of a physician pathology service furnished to a hospital inpatient or outpatient.

*For services furnished prior to July 1, 2012, payment may be made under the fee schedule, as noted below, for the (TC) of pathology services furnished by an independent laboratory to hospital inpatients or outpatients.

CMS published a final regulation in 1999 that would no longer allow independent laboratories to bill under the physician fee schedule for the TC of physician pathology services. The implementation of this regulation was delayed by Section 542 of the Benefits and Improvement and Protection Act of 2000 (BIPA). Section 542 allows the Medicare carrier to continue to pay for the TC of physician pathology services when an independent laboratory furnishes this service to an inpatient or outpatient of a covered hospital. This provision is applicable to TC services furnished January 1, 2001 through June 30, 2012.

For this provision, a covered hospital is a hospital that had an arrangement with an independent laboratory that was in effect as of July 22, 1999, under which a laboratory furnished the TC of physician pathology services to fee-for-service Medicare beneficiaries who were hospital inpatients or outpatients, and submitted claims for payment for the TC to a carrier. The TC could have been submitted separately or combined with the professional component and reported as a combined service.

The term, fee-for-service Medicare beneficiary, means an individual who:

*Is entitled to benefits under Part A or enrolled under Part B of title XVIII or both; and

*Is not enrolled in any of the following: A Medicare + Choice plan under Part C of such title; a plan offered by an eligible organization under §1876 of the Social Security Act; a program of all-inclusive care for the elderly under
§1894; or a social health maintenance organization demonstration project established under Section 4108 of the Omnibus Budget Reconciliation Act of 1987.

In implementing Section 542, the contractors should consider as independent laboratories those entities that it has previously recognized as independent laboratories.

An independent laboratory that has acquired another independent laboratory that had an arrangement of July 22, 1999, with a covered hospital, can bill the TC of physician pathology services for that hospital’s inpatients and outpatients under the physician fee schedule.

An independent laboratory that furnishes the TC of physician pathology services to inpatients or outpatients of a hospital that is not a covered hospital may not bill the carrier for the TC of physician pathology services during the time §542 is in effect.

If the arrangement between the independent laboratory and the covered hospital limited the provision of TC physician pathology services to certain situations or at particular times, then the independent laboratory can bill the carrier only for these limited services.

The contractor shall require independent laboratories that had an arrangement, on or prior to July 22, 1999 with a covered hospital, to bill for the technical component of physician pathology services to provide a copy of this agreement, or other documentation

substantiating that an arrangement was in effect between the hospital and the independent laboratory as of this date. The independent laboratory must submit this documentation for each covered hospital that the independent laboratory services.

C.Physician Laboratory and Pathology Services

Physician laboratory and pathology services are limited to:

*Surgical pathology services;

*Specific cytopathology, hematology and blood banking services that have been identified to require performance by a physician and are listed below;

*Clinical consultation services that meet the requirements in subsection 3 below; and

*Clinical laboratory interpretation services that meet the requirements and which are specifically listed in subsection 4 below.

1.Surgical Pathology Services

Surgical pathology services include the gross and microscopic examination of organ tissue performed by a physician, except for autopsies, which are not covered by Medicare.

Depending upon circumstances and the billing entity, the contractors may pay professional component, technical component or both.

2.Specific Hematology, Cytopathology and Blood Banking Services

Cytopathology services include the examination of cells from fluids, washings, brushings or smears, but generally excluding hematology. Examining cervical and vaginal smears are the most common service in cytopathology. Cervical and vaginal smears do not require interpretation by a physician unless the results are or appear to be abnormal. In such cases, a physician personally conducts a separate microscopic evaluation to determine the nature of an abnormality. This microscopic evaluation ordinarily does require performance by a physician. When medically necessary and when furnished by a physician, it is paid under the fee schedule.

For services furnished prior to January 1, 1999, contractors pay separately under the physician fee schedule for the interpretation of an abnormal pap smear furnished to a hospital inpatient by a physician. They must pay under the clinical laboratory fee schedule for pap smears furnished in all other situations. This policy also applies to screening pap smears requiring a physician interpretation. For services furnished on or after January 1, 1999, contractors allow separate payment for a physician’s interpretation of a pap smear to any patient (i.e., hospital or non-hospital) as long as: (1) the

laboratory’s screening personnel suspect an abnormality; and (2) the physician reviews and interprets the pap smear.

This policy also applies to screening pap smears requiring a physician interpretation and described in the National Coverage Determination Manual and Chapter 18. These services are reported under codes P3000 or P3001.

Physician hematology services include microscopic evaluation of bone marrow aspirations and biopsies. It also includes those limited number of peripheral blood smears which need to be referred to a physician to evaluate the nature of an apparent abnormality identified by the technologist. These codes include 85060, 38220, 85097, and 38221.

Contractors pay the PC for the interpretation of an abnormal blood smear (code 85060) furnished to a hospital inpatient by a hospital physician or an independent laboratory. For other hematology codes, payment may be made for the PC component if the service is furnished to a patient by a hospital physician or independent laboratory. In addition, payment may be made for these services furnished to patients by an independent laboratory.

Blood banking services of hematologists and pathologists are paid under the physician fee schedule when analyses are performed on donor and/or patient blood to determine compatible donor units for transfusion where cross matching is difficult or where contamination with transmissible disease of donor is suspected.

The blood banking codes are 86077, 86078, and 86079 and represent professional component only services.

3.Clinical Consultation Services

Clinical consultations are paid under the physician fee schedule only if they:

a.Are requested by the patient’s attending physician;

b.Relate to a test result that lies outside the clinically significant normal or expected range in view of the condition of the patient;

c.Result in a written narrative report included in the patient’s medical record; and

d.Require the exercise of medical judgment by the consultant physician.

Clinical consultations are professional component services only, i.e., there is no TC service. The clinical consultation codes are 80500 and 80502.

Routine conversations held between a laboratory director and an attending physician about test orders or results do not qualify as consultations unless all four requirements are met. Laboratory personnel, including the director, may from time to time contact attending physicians to report test results or to suggest additional testing or be contacted by attending physicians on similar matters. These contacts do not constitute clinical consultations. However, if in the course of such a contact, the attending physician requests a consultation from the pathologist, and if that consultation meets the other criteria and is properly documented, it is paid under the fee schedule.

EXAMPLE: A pathologist telephones a surgeon about a patient’s suitability for surgery based on the results of clinical laboratory test results. During the course of their conversation, the surgeon asks the pathologist whether, based on test results, patient history and medical records, the patient is a candidate for surgery. The surgeon’s request requires the pathologist to render a medical judgment and provide a consultation. The pathologist follows up his/her oral advice with a written report and the surgeon notes in the patient’s medical record that he/she requested a consultation. This consultation is paid under the fee schedule.

In any case, if the information could ordinarily be furnished by a nonphysician laboratory specialist, the service of the physician is not a consultation payable under the fee schedule.

See the Program Integrity Manual for guidelines for related data analysis to identify inappropriate patterns of billing for consultations.

4.Clinical Laboratory Interpretation Services

Only clinical laboratory interpretation services, which meet the criteria in subsections C.3.a, c, and d, are billable under the physician fee schedule. These codes have a PC/TC indicator of “6” on the Medicare Physician Fee Schedule database. These services are reported under the clinical laboratory code with modifier 26. These services can be paid under the physician fee schedule if they are furnished to a patient by a hospital pathologist or an independent laboratory. Note that a hospital’s standing order policy can be used as a substitute for the individual request by the patient’s attending physician.

Contractors are not allowed to revise CMS’s list to accommodate local medical practice. The CMS periodically reviews this list and adds or deletes clinical laboratory codes as warranted.

D.Global Billing

Billing globally for services that are split into separate PC and TC services is only possible when the PC and TC are furnished by the same physician or supplier entity. For example, where the PC and the TC of a diagnostic service are provided in the same service location, this is reflected as the address entered into Item 32 on CMS Form 1500, which provides the ZIP Code to pay the right locality/GPCI. In this case, the physician/entity may bill globally. However, if the PC and the TC are each provided in different service locations (enrolled practice locations), the PC and the TC must be separately billed.


Merely applying the same place of service (POS) code to the PC and the TC does not permit global billing for any diagnostic procedure.

Medicaid Laboratory Billing Guide

LABORATORY

MDHHS follows Medicare’s current OPPS coverage policies as closely as possible and appropriate. In those instances where program differences require coverage disparity, the differences will be reflected through the application of the MDHHS specific status indicator. Procedure codes associated with the identified services will appear on the MDHHS OPPS Wraparound Code List available on the MDHHS website. (Refer to the Directory Appendix for website information.)


MDHHS policy covers hospitals for medically necessary laboratory tests when:

* Performed in a laboratory certified by the Clinical Laboratory Improvement Amendments (CLIA);

* Needed to diagnose a specific condition, illness, or injury; and

* Ordered by physicians (MD or DO), podiatrists, dentists, nurse practitioners, or nurse-midwives.

MDHHS requires medical record documentation of medical necessity. An explanation of the laboratory testing method or the results of diagnostic tests, whether normal or abnormal, is not considered documentation of medical necessity. For approval of payment, the laboratory procedure(s) must be specific and appropriate to the beneficiary's documented condition and diagnosis.

Reimbursement to the inpatient hospital is through the DRG payment. Reimbursement for outpatient services is billed using the appropriate HCPCS code and includes the collection of the specimen(s), the analysis, and the lab test results. MDHHS performs pre- and/or postpayment reviews to monitor laboratory procedures for medical necessity and appropriate practitioner
orders. Outpatient hospitals are subject to corrective action, including the recovery of funds, for laboratory services not specifically ordered by a practitioner.


MDHHS does not cover:

* Screening or routine laboratory testing, except as specified for EPSDT Program or by Medicaid policy;

* "Profiles", "batteries" or "panels" of tests that include tests not necessary for the diagnosis or treatment of the beneficiary's specific condition; or

* Multiple laboratory tests performed as a part of the beneficiary evaluation if the history and physical examination do not suggest the need for the tests.

Services performed by an outpatient hospital laboratory or its employees may not be billed to, or by, the ordering practitioner.

PREGNANCY-RELATED LABORATORY SERVICES

The obstetric profile must be ordered by the attending practitioner and billed as an allinclusive panel of tests for required prenatal laboratory services. It must include the following:

* Blood count, complete (CBC), automated and automated differential WBC count, or Blood count, complete (CBC), automated and appropriate manual differential WBC count

* Hepatitis B surface antigen (HBaAg)

* Antibody, rubella

* Syphilis test, qualitative (e.g., VDRL, RPR, ART)

* Antibody screen, RBC, each serum technique

* Blood typing, ABO

* Blood typing, Rh(D)

Only AMA-approved organ- or disease-oriented panels may be billed. All tests within the panel must be medically necessary. Unless the complete panel is ordered and performed, bill as individual tests.

Testing for HIV is covered separately when determined to be medically necessary and ordered by the practitioner.

Only practitioners should order the serum or urine HCG qualitative method when the beneficiary requires preliminary pregnancy testing.

Nurse-midwives may order only the laboratory tests listed below. Hospitals are not reimbursed for any other tests ordered by a nurse-midwife.

* Acetone and diabetic acid (ketone bodies); qualitative; semi-quantitative

* Albumin; qualitative, semi-quantitative, quantitative (such as Esbach)

* Antibody titer Rh system; albumin, saline and/or AHG technique

* Blood count; RBC, WBC, Hemoglobin, Hematocrit, indices (MCV, MCH, MCHC)

* Blood typing; ABO, Rh(D), RBC antibody screening

* Culture, presumptive (screening), for Neisseria gonorrhea, Candida, Hemophilus, or beta hemolytic Streptococcus group A, etc.

* Culture, urine, definitive; with or without colony count

* Cytopathology, vaginal and/or cervical smears (e.g., Papanicolaou type) screening (cytopathological examination for malignancy, microbial flora, inflammatory features and hormonal evaluation)

* Glucose; qualitative, quantitative, timed specimen, tolerance

* Hemoglobin, electrophoretic separation; qualitative

* Hepatitis B test

* Human immunodeficiency virus detection

* Pregnancy test

* Prenatal laboratory services; routine (Obstetric panel)

* Quantitative sediment analysis and quantitative protein (Addis count); 12- or 24-hour specimen Reticulocyte count, manual

* Rubella test; titer

* Sickle cell slide test

* Skin test, tuberculosis, tine test

* Susceptibility (sensitivity) for aerobes by Kirby-Bauer procedure for specific pathogens, using 10-12 discs per pathogen; also for susceptibility (sensitivity) for anaerobes by generally accepted standard techniques using 5-12 discs per pathogen (specify number of pathogens)

* Syphilis testing, flocculation or precipitin (VDRL, RPR, etc.); qualitative

* Trepanema antibodies, fluorescent, absorbed (FTA-abs)

* Urinalysis, complete (physical appearance, pH, specific gravity, microscopic examination, qualitative chemistry with or without semi-quantitative confirmation)

* Wet mount, smear, tissue; direct microscopic examination


BLOOD HANDLING

MDHHS reimburses for blood handling only when a beneficiary is referred to an outpatient hospital for the sole purpose of drawing, packaging and mailing a blood sample to MDHHS for HIV-1 viral load analysis and/or CD4/CD8 enumeration. The State provides specimen containers and mailin  kits for the analysis. (Requests for supplies and samples for analysis should be sent to the MDHHS Blood Lead Laboratory. Refer to the Directory Appendix for contact information.)


HEMATOLOGY STUDIES

A complete blood count (CBC) with white blood cell (WBC) differential includes the RBC and WBC count, Hgb, Hct, MCH, MCHC, MCV, RBC morphology, platelet estimate, and WBC differential only. If automated instrumentation yields additional test parameters, the results are not reimbursable unless medically necessary and specifically ordered by a practitioner.


MICROBIOLOGY STUDIES

MDHHS coverage and reimbursement for gram fluorescent/acid fast is included in the reimbursement for microbiology when performed on the same DOS for the same beneficiary.


PAP SMEAR

Pap smear screening by a technologist under the supervision of a pathologist is a covered service. If a suspect smear requires additional interpretation by a pathologist, this service is also covered. Only one Papanicolaou test within a 12-month period is covered for each beneficiary, unless medical necessity or history of abnormal findings requires additional studies.


SUBSTANCE ABUSE

For direct-billed laboratory services ordered by an approved CA, the referring provider NPI number must be appropriately reported on the appropriate paper or electronic claim format.


CREATININE BLOOD TESTS

Calculate and report the Glomerular Filtration Rate (eGFR) for tests processed for beneficiaries in outpatient settings and for beneficiaries 18 years of age and older. The eGFR test results must report two values on the lab report for beneficiaries: one for American and one for non-African-American, or one value if race is available and able to be used in calculating the value.

CLIA: SPECIAL ALERT ON LIVE BLOOD CELL ANALYSIS (LBA) UNDER CLIA

[Alternative - Non-Traditional Laboratory Testing]

Live Blood Cell Analysis (LBA) is a test which is used for the purpose of providing information for the diagnosis, prevention, or treatment of any disease or impairment of, or assessment of the health of human beings. LBA is also known as Hemaview, Free Radical Blood Screening, or Nutritional Blood Analysis. LBA is not a Provider-Performed Microscopic Procedure (PPMP) test. It is also a non-covered Medicare service.

In January 1996, the Centers for Disease Control (CDC), determined that the LBA test procedure automatically defaulted to high complexity because it had not been categorized by CDC. In addition, the Centers for Medicare & Medicaid Services (previously the Health Care Financing Administration) Office of General Counsel (OGC) determined in August 1997, that LBA was subject to all CLIA requirements for high complexity testing1 (i.e. patient test management, proficiency testing, quality control, personnel and quality assurance). Therefore, any facility performing this procedure must be certified by CLIA and hold a valid registration certificate,Certificate of Compliance, or Certificate of Accreditation. Failure to comply with any of the CLIA requirements will result in enforcement actions and/or sanctions being taken.

LBA is performed by placing a drop of blood from the patient's fingertip on a microscope slide under a glass coverslip to keep it from drying. In some cases, a powder has been developed that, when sprinkled on the blood, forms a type of "coverslip”. The slide is then viewed at high magnification with a dark-field microscope that forwards the image to a television monitor. The results are then used for prescribing nutritional supplements.

Other examples of Alternative Testing (Non-Traditional Laboratory Testing) that are subject to CLIA:
1. Biological Terrain Assessment (BTA): BTA is a computerized analysis of blood, urine, and saliva specimens used to recommend nutritional programs, vitamin and mineral supplements, homeopathic products, and/or herbs. Analysis is determined through pH determinations which are the portion of the test that is legitimate.

2. Thromboelastograph: This is a valid test which has been categorized by the CDC as either moderate or high complexity, depending on whether the instrument prints the test results. The test is performed by a perfusionist in the operating room or sometimes in blood gas laboratories.

3. Dental sensitivity testing: This test determines whether a person is sensitive to materials in fillings. If sensitive, all fillings can be removed and replaced. All reviewing agencies could not determine whether the method was valid.

4. Cytotoxic Testing (Food Allergy Testing); also called Brian’s Test or Leukocyte Antigen Testing: Cytotoxic testing involves taking about 10 cc of blood from a patient. Microscopic slides are coated with the dried extract of a particular food. White blood cells (WBCs/leukocytes) are then mixed with plasma and sterile water and placed on the coated microscopic slides. The reaction of the cells to the extracts is then examined under a microscope. If the cells collapse, disintegrate, or change shape, the patient is supposedly allergic to that particular food. This evidence of food allergy is then used to explain a variety of symptoms. To correct this condition, the clinic offers a personalized diet program which includes vitamin and mineral supplements.

Laboratory Registry

Once a year the Centers for Medicare & Medicaid Services (CMS) makes available to physicians and to the general public specific information (including information provided to CMS by the Office of the Inspector General) that is useful in evaluating the performance of laboratories. The Clinical Laboratory Improvement Amendments of 1988 (CLIA) and implementing regulations at 42 CFR 493.1850 require that this listing include the following:

A list of laboratories that have been convicted, under Federal or State laws relating to fraud and abuse, false billing, or kickbacks.

A list of laboratories that have had their CLIA certificates suspended, limited, or revoked, and the reasons for the adverse actions.

A list of persons who have been convicted of violating CLIA requirements, as specified in section 353(1) of the Public Health Service Act (PHS Act), together with circumstances of each case and the penalties imposed.

A list of laboratories on which alternative sanctions have been imposed, showing—
    the effective date of the sanctions;
    the reason for imposing them;
    any corrective action taken by the laboratory;
    if the laboratory has achieved compliance, the verified date of compliance.

A list of laboratories whose accreditation has been withdrawn or revoked and the reasons for the withdrawal or revocation.
All appeals and hearing decisions.
A list of laboratories against which CMS has brought suit under Section 493.1846 and the reasons for those actions.
A list of laboratories that have been excluded from participation in Medicare or Medicaid and the reasons for exclusion.
Civil settlements reached with clinical laboratories are also noted.

The Laboratory Registry is compiled for the calendar year preceding the date the information is made available and also contains corrections of any erroneous statements of information that appeared in the previous registry. A final section includes other specific information that may be useful in evaluating the performance of laboratories, as specified in 42 CFR 493.1850(a). It also includes information provided by CLIA exempt states.

In house laboratory CPT code list

All In-Office Laboratory Testing and Procedures: 

  Marked with *, **, ***, ****, and ***** will be limited to one procedure within the same family of asterisks, per visit.

Example: All laboratory testing/procedure codes that are marked with one * will only be allowed to have one laboratory test/procedure performed, per visit, out of all of the codes designated with the single *.

  Marked with the # symbol will only be considered for reimbursement if the member has an infertility benefit and the provider has the appropriate specialty. Refer to the policy titled Infertility Diagnosis and Treatment for additional information related to infertility coverage.


CPT Code Description

Primary Care Physicians and Specialists

80305 Drug test(s), presumptive, any number of drug classes, any number of devices or procedures (e.g., immunoassay); capable of being read by direct optical observation only (e.g., dipsticks, cups, cards, cartridges) includes sample validation when
performed, per date of service

80306 Drug test(s), presumptive, any number of drug classes, any number of devices or procedures (e.g., immunoassay); read by instrument assisted direct optical observation (e.g., dipsticks, cups, cards, cartridges), includes sample validation when
performed, per date of service


81000* Urinalysis, non-automated, with microscopy

81001* Urinalysis, automated, with microscopy

81002* Urinalysis, non-automated, without microscopy

81003* Urinalysis, automated, without microscopy

81025 Urine pregnancy test, by visual color comparison methods

 82270***** Blood, occult, by peroxidase activity (e.g., guaiac), qualitative; feces, consecutive collected specimens with single determination, for colorectal neoplasm screening (i.e., patient was provided three cards or single triple card for consecutive collection)


CPT Code Description

Hematologists/Oncologists/Pediatric Hematologists

85097 Bone marrow; smear interpretation only, with or without differential cell count

86077 Blood bank physician services; difficult cross-match and/or evaluation of irregular antibody(s), interpretation and written report

86078 Blood bank physician services; investigation of transfusion reaction, including suspicion of transmissible disease, interpretation and written report

86079 Blood bank physician services; authorization for deviation from standard bloodbanking procedures, with written report

86927-86999 Transfusion medicine Ophthalmologists and Connecticut CLIA Certified Optometrists

Note: Connecticut optometrists may be reimbursed for CPT code 83861 in the office if they are CLIA Certified (Clinical Laboratory Improvement Amendments of 1988 (CLIA)). If no CLIA certification is on file, the service is not eligible for reimbursement.

83861 Microfluidic analysis utilizing an integrated collection and analysis device, tear osmolarity

Ophthalmologists and Optometrists

83516 Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; qualitative or semiquantitative, multiple step method

87809 Infectious agent antigen detection by immunoassay with direct optical observation; adenovirus

Pulmonologists 82803 Gases, blood, any combination of pH, pCO2, pO2, CO2, HCO3 (including calculated O2 saturation)
Rheumatologists

89060 Crystal Identification by light microscopy with or without polarizing lens analysis; tissue or any body fluid (except urine) Urologists

 89264# Sperm identification from testis tissue, fresh or cryopreserved

89300 Semen analysis; presence and/or motility of sperm including Huhner test (post coital)

89310 Semen analysis; motility and count (not including Huhner test)

89320 Semen analysis; volume, count, motility and differential

89321 Semen analysis; sperm presence and motility of sperm, if performed

89322 Semen analysis; volume, count, motility, and differential using strict morphologic criteria (e.g., Kruger)



REIMBURSEMENT GUIDELINES

In-Office Laboratory Testing and Procedures

Reimbursement of network physicians for the performance of in-office laboratory testing/procedures is limited to those codes listed on the in-office laboratory testing and procedures list. Reimbursement for some of the Laboratory testing/procedures is limited to certain physician specialties. Refer to the Applicable Codes section below for a list of specific CPT codes.



  Marked with a # symbol, will only be considered for reimbursement if the member has an infertility benefit and the provider has the appropriate specialty. Refer to the policy titled Infertility Diagnosis and Treatment for additional information related to infertility coverage.

Specimen Handling and Venipuncture CODE 36415

When specimen handling and venipuncture codes are billed;

With a laboratory/procedure code on the in-office laboratory testing and procedures list, only the laboratory testing/procedure and venipuncture codes will be considered for reimbursement. Note: The laboratory testing/procedure code will only be considered for reimbursement if the code is listed in the Applicable Codes section of the policy and the provider has the appropriate specialty, if required.

  Without a laboratory testing/procedure code on the in-office laboratory testing and procedures list or with other non-laboratory testing/procedure services, the specimen handling and venipuncture codes will be considered for reimbursement.

cpt code 88341, 88342, 88360, 88331, 88332

Procedure code and Description

88312 SPECIAL STAIN INCLUDING INTERPRETATION AND REPORT; GROUP I FOR MICROORGANISMS (EG, ACID FAST, METHENAMINE SILVER)

88313 SPECIAL STAIN INCLUDING INTERPRETATION AND REPORT; GROUP II, ALL OTHER (EG, IRON, TRICHROME), EXCEPT STAIN FOR MICROORGANISMS, STAINS FOR ENZYME CONSTITUENTS, OR IMMUNOCYTOCHEMISTRY AND IMMUNOHISTOCHEMISTRY

88341 IMMUNOHISTOCHEMISTRY OR IMMUNOCYTOCHEMISTRY, PER SPECIMEN; EACH ADDITIONAL SINGLE ANTIBODY STAIN PROCEDURE (LIST SEPARATELY IN ADDITION TO CODE FOR PRIMARY PROCEDURE)

88342 IMMUNOHISTOCHEMISTRY OR IMMUNOCYTOCHEMISTRY, PER SPECIMEN; INITIAL SINGLE ANTIBODY STAIN PROCEDURE

88344 IMMUNOHISTOCHEMISTRY OR IMMUNOCYTOCHEMISTRY, PER SPECIMEN; EACH MULTIPLEX ANTIBODY STAIN PROCEDURE

88360 MORPHOMETRIC ANALYSIS, TUMOR IMMUNOHISTOCHEMISTRY (EG, HER-2/NEU, ESTROGEN RECEPTOR/PROGESTERONE RECEPTOR), QUANTITATIVE OR SEMIQUANTITATIVE, PER SPECIMEN, EACH SINGLE ANTIBODY STAIN PROCEDURE; MANUAL

88361 MORPHOMETRIC ANALYSIS, TUMOR IMMUNOHISTOCHEMISTRY (EG, HER-2/NEU, ESTROGEN RECEPTOR/PROGESTERONE RECEPTOR), QUANTITATIVE OR SEMIQUANTITATIVE, PER SPECIMEN, EACH SINGLE ANTIBODY STAIN PROCEDURE; USING COMPUTER-ASSISTED TECHNOLOGY


• 88331- Pathology consultation during surgery; first tissue block, with frozen section(s), single specimen

• 88332- Pathology consultation during surgery; each additional tissue block with frozen section(s) (list separately in addition to code for primary procedure)

Coverage Guidance
Coverage Indications, Limitations, and/or Medical Necessity

This policy does not designate specific special histochemical stains (aka special stains) and/or immunohistochemical (IHC) stains that should be used in the differential diagnosis of tissues or neoplasms because this information is readily available in text books and various scientific publications. This policy identifies the medically necessary criteria for the use of special stains and/or IHC stains and addresses, based on claims review, the scenarios that may be driving medically unnecessary over-utilization or incorrect billing of these services including:
Reflex templates or pre-orders for special stains and/or IHC stains prior to review of the routine hematoxylin and eosin (H&E) stain by the pathologist; or

Use of special stains and/or IHC stains without clinical evidence that the stain is actionable or provides the treating physician with information that changes patient management, or

Use of added stains when the diagnosis is already known based on morphologic evaluation of the primary stain.


Background

Routine hematoxylin and eosin (H&E) staining is the corner stone of tissue-based microscopic diagnosis. Thin sections of tissue are stained with H&E to visualize the tissue morphology. Hematoxylin dye stains the cell nuclei blue and the eosin dye stains other structures pink/red. H&E staining provides excellent detail required for tissue-based diagnosis and is NOT a separately billable service, as reimbursement for pathology services includes routine H&E staining. At least one lab has touted “acid hematoxylin” as a special stain for purposes of billing Medicare and private payers. Given that all hematoxylin stains are acidic and that this stain has never been recognized by the Biological Stain Commission, it is incorrect coding to present claims for this stain as a special stain. Hematoxylin and eosin (H&E) staining is included in the billing CPT code and is not a separately billable service.

Special stains are called “special” because they are dyes used to stain particular tissues, structures or pathogens such as bacteria that may not be visible by routine H&E staining. Special stains can identify whether a substance is present or absent, where the substance is located in the tissue specimen, and frequently, how many or how much of a substance is present. There are special stains to identify bacteria, yeast and fungi; for connective tissue, muscle, collagen, lipid and fibrin; for nuclei acids; and multi-purpose stains to identify basement membranes, mucins, and various other cellular constituents. Two major AMA CPT coding categories for special stains are recognized: One is specifically for microorganisms; the second code is for all other purposes (not microorganisms) and specifically excludes detection of enzyme constituents.

IHC is a powerful tool for identifying substances and cells in tissue sections using the specificity of antigen-antibody reactions, where the antibody is linked to a colored indicator (stain) that can be seen with a microscope. More than 400 distinct antibody targets are currently available with varying sensitivity and specificity for a given target. A major use of IHC is to identify poorly differentiated malignant neoplasms (tumors) such as a carcinoma, lymphoma, melanoma and sarcoma. Some IHC stains are useful in determining the primary site of a metastatic neoplasm, and others are used to guide specific therapies (e.g., Her2 IHC to determine potential response to trastuzumab).

Medical Necessity of Services Performed

There are many different relationships that exist in providing the provision of pathology services in the United States. Some physicians, groups, laboratories and hospitals submit global claims for the services described in this policy. In other instances, there are separate individuals or entities providing the professional (-26) and the technical services (-TC). It is the obligation of each billing party to recognize that they are responsible for the medical necessity of the charges submitted. For example, when a physician or physician group bills for the professional component of services described in this policy and another entity bills for the technical services, it is the obligation of each entity to independently assure the medical necessity of the services rendered and billed.

Special Stains/IHC Medical Necessity

The IOM, Benefit Policy Manual (CPT15, §80.6.5) specifies “…there may be additional tests, such as special stains, that the pathologist may need to perform, even though they have not been specifically requested by the treating physician/practitioner. The pathologist may perform such additional tests under the following circumstances:
Services are medically necessary so that a complete and accurate diagnosis can be reported to the treating physician/practitioner;

Results of the tests are communicated to and are used by the treating physician/practitioner in the treatment of the beneficiary; and

Pathologist documents in his/her report why additional testing was done.”


The above citation means that reflex templates or pre-orders for special stains and/or IHC stains prior to review of the routine hematoxylin and eosin (H&E) stain by the pathologist are not reasonable and necessary. A pathologist must first review the H&E stain prior to ordering special stains or IHC.

Exceptions do exist and are recognized standards of care in the practice of pathology. These exceptions include but are not limited to renal, liver, and neuromuscular biopsies, and for the suspicion of an infectious disease, particularly in an immune compromised patient. In certain clearly defined circumstances, it may be reasonable to perform some IHC on sentinel lymph nodes when the frozen sections show they are free of tumor.

The medical necessity for the special stain or IHC studies, and the results of the stain or IHC, must be documented in the surgical pathology report.

IHC for Breast Pathology

The clinical care of patients with breast cancer depends upon the accurate diagnosis and the assessment of biomarkers. Hormone receptor assays and Her2 testing are recommended on all primary invasive breast cancers, and on recurrent or metastatic cancers. At the current time, there is no recommendation for Her2 testing on in situ breast lesions outside of a clinical trial. While there are a number of promising additional biomarkers, such as Ki-67, PI3K and gene expression assays, the College of American Pathologists (CAP), the American Society of Clinical Oncologists (ASCO) and the National Comprehensive Cancer Network (NCCN) have not recognized these markers in patient treatment pathways.

Estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (Her2) are well-established prognostic markers in invasive breast cancer management. The triple negative breast carcinoma subtype (ER-/PR-/Her2-) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women.

Ki-67 expression is a biomarker for proliferation and has been associated with response to therapy, but methods of measurement are controversial. In December, 2013, the CAP reported that there is “a lack of consensus on scoring, definition of low versus high expression, an appropriate cut point for positivity, or which part of the tumor should be scored (e.g., leading edge, hot spots, overall average). There is also paucity of data on the effects of pre-analytical variables (e.g., ischemic time, length of fixation, antigen retrieval) on Ki-67 staining. For these reasons, routine testing of breast cancers for Ki-67 expression is not currently recommended by either ASCO or the NCCN." Consequently, Ki-67 is not reasonable and necessary for breast cancer and will not be covered by Medicare.

The clinical utility of testing for hormone receptors in in-situ breast cancer differs from those of invasive disease. Guidelines and the peer reviewed literature support the use of ER testing for in-situ breast neoplasia and PR testing only when the ER status is negative (Lester, personal communication). Clinical guidelines have not been established for the use of Her2 or other biomarkers in patients with non-invasive breast neoplasia.

In the absence of professional guidelines based on proven scientific literature, standing orders from clinicians for such tests as Ki-67 and EGFR on every breast cancer are not reasonable and necessary, and are not a covered Medicine service.

In addition, basal phenotype markers (e.g., IHC for CK5) are not routinely necessary. Neither are IHC stains such as E-cadherin, p27, or high molecular weight cytokeratin to distinguish ductal from lobular differentiation necessary on every breast case, nor are myoepithelial cell markers such as p63 or smooth muscle myosin heavy chain necessary on every case.

Special Stains and/or IHC for GI Pathology

Pathologists are often called upon to microscopically diagnose abnormalities seen on endoscopic exam of the esophagus, stomach, duodenum and colon. Biopsy specimens constitute an important diagnostic patient service. Most normal and abnormal conditions of these organs can be detected by the use of routine H&E stain.

Ordering special stains or IHC stains prior to review of the routine H&E stain is not reasonable and necessary. For most esophageal, gastric and duodenal specimens, it is not reasonable or necessary to perform special stains such as alcian blue – periodic acid Schiff (AB-PAS), or other mucin stains, such as diastase – PAS (D-PAS), or IHC stains such CDX-2 to determine if clinically meaningful intestinal metaplasia is present. In addition, it is not usually reasonable and necessary to perform special stains or IHC to determine the presence of H. pylori organisms.

Other examples of special stains or IHC that are not reasonable and necessary on every specimen include:

Esophagus – fungal stains, trichrome, DPAS, CDX-2 or other mucin stains

Gastric – AB-PAS, D-PAS, CDX-2 or other mucin stains, or special stains or IHC for H. pylori, or neuroendocrine markers such as synaptophysin or chromogranin

Duodenum – AB-PAS, D-PAS, CD3, and trichrome, or other mucin stains

Colon – CD3, p53 trichrome

Hyperplastic polyps – Ki67, CK20, p53, CEA, BRAF

Tubular or tubulovillous adenoma – Ki-67, CK20, CEA, p53, MMR


If special stains or IHC are needed in addition to the routine H&E for gastric specimens, specific documentation to justify the medical necessity for the stain is required in the pathology report. Cases that may require special stains or IHC include but are not limited to the following:

Detection of H pylori in an appropriate milieu when organisms are not seen on H&E stained slides;

Evaluating atrophic gastritis for evidence of autoimmune etiology and for enterochromaffin-like (ECL) cell hyperplasia/carcinoid tumor

Characterizing a carcinoma, lymphoma, melanoma or sarcoma

Defining a GIST tumor and to distinguish it from mimics

Ki-67 by IHC in the differential diagnosis of certain neuroendocrine tumors of the gut


Scientific data demonstrates that the combined number of gastric biopsies requiring special stains or IHC is roughly 20% of biopsies received and examined in a pathology practice. GI specialty practices with a large GI referral base or GI consultant pathologists may sometimes exceed this relative number of special stains/IHC, but one would not expect to see routine high utilization of special stains or IHC.

Over-utilization of special stains has also been observed with duodenal biopsies where CD3 and AB/D-PAS are reportedly used to help exclude intraepithelial lymphocytosis and gastric metaplasia. Both of these conditions, if present, are easily recognizable on H&E morphology. Mucin stains such as AB-PAS or DPAS would be reasonable and necessary in limited circumstances, and rarely is CD3 warranted on duodenal biopsies which show villous architectural abnormalities.

Architectural and histologic features define colonic polyps including hyperplastic, inflammatory, and adenomatous lesions. Special stains and/or IHC stains are not reasonable and necessary for colon polyps despite text books noting, for example, thickened subepithelial collagen demonstrated by trichrome or collagen staining in hyperplastic polyps, or carcinoembryonic antigen (CEA) overexpression in hyperplastic polyps. While the information is of academic interest, special stains are not reasonable and necessary to make the diagnosis of various colonic polyps.

Lynch Syndrome tumor screening for DNA mismatch repair (MLH1, MSH2, MSH6 and PMS2) by qualitative IHC and/or microsatellite instability (MSI) is considered medically necessary and covered by Medicare for the following indications:

All individuals with colorectal cancer diagnosed at age =70 years of age, and those > 70 years of age who meet the revised Bethesda guidelines OR

Individuals with endometrial cancer


No definitive algorithm for LS screening has been recommended. However, if IHC is done first and is abnormal, MSI testing is not warranted. If IHC is normal, MSI may be warranted. IHC testing Lynch syndrome is qualitative and does not require the use of tumor morphometry.

Special Stains and/or IHC for Prostate Pathology

The accuracy of the pathologic diagnosis of prostate cancer is critical for optimal patient care. The diagnosis can usually be made on morphologic features such as growth pattern, nuclear atypia and the absence of basal cells. However, it may be difficult to reach a firm diagnosis by routine H&E stain for small foci of cancer in needle biopsies because many benign conditions can mimic prostate cancer.

The immunohistochemical diagnosis of prostate cancer largely depends on panels of markers because no absolutely specific and sensitive marker for prostate cancer has yet been identified. These panels usually include at least one basal cell marker, such as high-molecular-weight cytokeratin (HMWCK) or p63, and the prostate cancer-specific marker, alpha-methyl-CoA-Racemase (AMACR). Although AMACR is considered a useful IHC marker for prostate cancer, because of non-standardized immunostaining protocols, interpretation criteria and heterogeneous staining pattern, there is wide variation in the sensitivity and specificity of AMACR immunoreactivity in prostate biopsies. Furthermore, because AMACR expression has been demonstrated in high-grade PIN, atypical adenomatous hyperplasia/adenosis and nephrogenic adenoma, it is recommended that AMACR is best restricted to the evaluation of morphologically highly suspicious foci in which negative immunoreactivity of basal cell markers alone is insufficient to establish a diagnosis of cancer.

PTEN and MYC may provide some prognostic information but neither is part of any standard treatment protocol and neither should be routinely performed. ERG is another IHC that is more likely to be positive in cancer than in benign tissue, but it does not add information to conventional PIN4 testing. Similarly, neuroendocrine markers, such as IHC for synaptophysin, may be indicated in cases of recurrent/metastatic prostate carcinoma that have undergone small cell transformation after hormone therapy. The latter marker is only necessary for high grade, undifferentiated tumors and should not be used routinely.

PIN4 is an IHC cocktail of CK5/14, p63 and P504S that is used primarily to differentiate normal and neoplastic epithelial tissues. In prostate tissue, CK5 and CK14 are detected in basal cells of normal glands and prostatic intraepithelial neoplasia (PIN) which is a precursor lesion to prostatic adenocarcinoma. However, expression of CK5 and CK14 is not identified in invasive prostatic adenocarcinoma. P63 is detected in nuclei of basal epithelium in normal prostate glands, but is not expressed in malignant prostate tumors. Because P504S (aka AMACR) is not specific for prostatic adenocarcinoma, the use of PIN4 is best restricted to evaluation of morphologically highly suspicious foci.

It is not reasonable and necessary to bill for IHC testing (either single antibody or antibody cocktails) on cases with morphologically negative cores. It is not reasonable and necessary to bill for IHC testing in a negative or a suspicious core biopsy when obvious prostate cancer is present in other cores. While the pathologist may choose to confirm a suspicious focus in one or more cores in a case where the diagnosis of cancer has already been made, it is not a Medicare covered service because it provides no additional actionable information to the treating physician.

Prostate cases that may require reasonable and necessary IHC staining include but are not limited to the following:
Indeterminate/suspicious focus and no other cores are positive for cancer;

Single worrisome core with minimal percent tumor (roughly <5 p="">
Worrisome core(s) contralateral to a positive core(s);

o In a multi-part biopsy with Gleason 3+3=6 cancer in 1 part, and atypical small acinar proliferation (ASAP) suspicious for Gleason 3+3=6 cancer in other part(s); the number of positive biopsy sites and % core involvement of these sites can affect therapeutic choices for active surveillance (AS), focal therapy or surgery;
o In a multi-part biopsy with 4+3=7 or 4+4=8 cancer in 1 part, and ASAP suspicious for the same grade cancer in other part(s); workup is justified since the extent of high grade cancer affects treatments;

Identify tumor invasion of adjacent structures;

Determine origin of undifferentiated/poorly differentiated neoplasm, such as bladder vs prostate;

Other unexpected results when specific cell stains would be necessary


Prostate cases when IHC workup is Not Reasonable and Necessary include the following:
In a multi-part biopsy with = 3+4=7 cancer in 1 part, and ASAP suspicious for 3+3=6 cancer in other part(s), because stains are unlikely to change treatment; or


In a multi-part biopsy with = 4+3=7 cancer in 1 part, and "atypical cribriform lesson" (ACL) suspicious for intra-ductal carcinoma versus invasive, Gleason pattern 4 cancer in other part(s), because intra-ductal carcinoma is almost always closely associated with invasive high-grade cancer.


The International Society of Pathology (ISUP) recommendations state that at the current time, there are no prognostic IHC or molecular studies that are recommended to be routinely performed on biopsy or resection specimens.

The surgical pathology report is expected to designate the specific block(s) upon which IHC testing is performed, the reason for IHC testing, the specific markers, and whether single antibody(ies) or a cocktail of antibodies is utilized. A statement alone in the pathology report that states “IHC confirms the diagnosis” will not be covered as reasonable and necessary.

Special Stains and/or IHC for Lung Cancer

The diagnostic challenge of a lung biopsy can often prompt the need for additional stains to define the neoplasm. Two important considerations need to be considered in this regard:
The diagnosis of squamous cell cancer can often be made without the use of any special stains, and

The diagnosis of non-small cell carcinoma often requires additional stains but it is essential that tumor tissue be carefully triaged to allow the patient’s sample to be tested for molecular markers (EGFR, ALK, and others) when clinically indicated.


Experts in pulmonary pathology recommend starting the evaluation of non-small cell carcinomas with a combination of TTF-1 and p40 or p63 IHCs. Often these two stains are all that are needed to come to a reasonable diagnosis and retain enough tumor sample to complete molecular studies. In rare patients, a few additional IHCs or mucin stains may be needed.

Ki-67/MIB-1

Ki-67 and MIB-1 monoclonal antibodies are directed against different epitopes of the same proliferation-related antigen. These stains are used to determine the proliferative rate of a tumor. Ki-67 antigen or protein (hereafter Ki-67) is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0). By measuring the amount of tumor cells expressing Ki-67, an estimate of DNA synthesis can be determined which has been found comparable to a mitotic count performed on a standard H&E slide. Furthermore, Ki-67/MIB-1 antibodies have suffered from a lack of international standardization which has limited their clinical usefulness. This is noted above in the discussion of breast cancers.

Classification of lung neuroendocrine (NE) tumors is a step-wise process with four tumor categories being identified by morphology, namely:
Typical carcinoid (TC),

Atypical carcinoid (AC),

Large cell NE carcinoma, and

Small cell lung carcinoma (SCLC).


Ki-67 has potential usefulness in a narrow range of pathologic lung cases. Namely, it allows better classification of atypical and typical lung carcinoid tumors, and in pulmonary neuroendocrine tumors with extensive crush artifact. (As noted above, Ki-67 may be useful in the classification of some gut neuroendocrine tumors.)

Ki-67 by IHC has clinical utility in the workup of lymphomas. Ki-67 has several established applications including:

Final confirmation for the diagnosis of any low-grade lymphoma. A number of publications show a worse prognosis for follicular lymphomas which appear to be grade 1 or 2 but demonstrate high Ki-67 labeling. Similarly, small lymphocytic lymphomas/CLL with a high proliferative rate (“prolymphocytic progression”) may be best detected with Ki-67.

Distinguishing higher versus lower grade mantle cell lymphoma. A small percentage of cases behave as low grade rather than intermediate grade, and Ki-67 is the most accurate means to detect this subgroup. In addition, distinguishing the highly aggressive blastoid variant is aided by Ki-67 IHC testing.

Recognizing Burkitt and Burkitt-like grouping as distinct from diffuse large B-cell type. One of the most important qualifying criteria is Ki-67 labeling at greater than 90%.

Plasma cell myeloma proliferative rate has long been established as one of the most accurate prognostic markers.


IHC for Chemosensitivity and Resistance Tumor Profiling

ER, PR, and Her2 hormonal receptor status have demonstrated clinical utility in invasive breast cancer, as well as ER, and PR when appropriate, for in-situ breast cancer. ER and PR are performed by IHC specifically for tamoxifen therapy. Her2 testing has proven clinical utility in esophago-gastric and gastric cancers to determine response to trastuzumab. ER, PR and Her2 testing for the purpose of identifying patients likely to respond to hormonal therapy, biologics or chemotherapy is a covered Medicare service when medically necessary for breast and gastric adenocarcinoma.

Similarly, the efficacy of imatinib, a CD117 inhibitor, is determined by the mutation status of CD117 expression (c-KIT mutation). CD117 by IHC has a proven clinical benefit in gastrointestinal stromal tumors (GIST), some advanced dermatofibrosarcoma protuberans (DFSP), some lymphoblastic and myeloid leukemias, and mast cell tumors, and is a covered Medicare service when medically necessary.

However, IHC testing as above is distinctly different from chemotherapy sensitivity and/or resistance testing profiles offered by some labs to assist physicians in their selection of specific chemotherapeutic agents based on IHC antigen or protein expression in individual tumors. The goal stated by these profiles is to select a drug or combination of drugs from a panel of drugs to which a tumor has greater expression, and to avoid drugs to which the tumor has less expression.

Neither the ASCO nor the NCCN has endorsed chemosensitivity tumor profile testing by IHC. ASCO has stated, "the use of CSRA's (chemosensitivity and resistance assays) to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting." While the NCCN's Guidelines for Ovarian Cancer (V3.2014) states "chemosensitivity/resistance and/or other biomarker assays are being used in some NCCN member institutions for decisions related to future chemotherapy in situations where there are multiple equivalent chemotherapy options available. The current level of evidence is not sufficient (Category 3) to supplant standard of care chemotherapy." The NCCN panel also stated that in vitro chemosensitivity testing is choose a chemotherapy regimen for recurrent disease should not be recommended due to lack of demonstrated efficacy. Such IHC panels include but are not limited to the following biomarkers for specific drugs:
ALK for crixotinib, penetrexed

Androgen receptor (AR) for goserelin, leuprolide, gonadorelin, flutamide, bicalutamide, abiraterone;

Androgen receptor for bicalutamide, flutamide, abiraterone and enzalutamide;

AREG for cetuximab, panitumumab

BRAF for venurafenib and dabrafenib

BRCA1 for cisplatin, carboplatin

cKIT for sorafenib, sunitinib, imatinib

cMET for erlotinib, gefitinib

EGFR for gefitinib, panitumumab, erlotinib, cetuximab, FOLFIRIEGFRVIII

EGFRvIII, GNA11, GNAQ, IDH2 – for clinical trials

ER and PR for tamoxifen, gefitinib, toremifene, fulvestrant, letrozole, anastrozole, exemestrane, megestrol acetate, erlotinib, panitumumab, medroxyprogesterone;

ERCC1 for oxaliplatin, cisplatin, carboplatin, CAPOX, FOLFOX

EREG for cetuximab, panitumumab

Her2 (ErbB2), PGP and TOP2A (topoisomerase IIA) for doxorubincin, liposomal-doxorubicin, epirubicin;

Her2 or labatinib; epirubicin, pertuzumab, trastuzumab, liposomal doxorubicin, doxorubicin,

KRAS for panitumumab, cetruximab, gefitinib, erlotinib, sorafenib

MGMT for temozolomide and dacarbazine

MRP1 for vinorelbine, vincrisxtine, doxorfubicin, epirubicin, vinblastine, methotrexate

NRAS for cetuximab, panitumumab

PDGFRA for imatinib

PGP (aka MDR1 and ABCB1) for doxorubicin, vincristine, vinblastine, eptoposide, liposomal doxorubicin, paclitaxel , docetaxel, vinorelbine, epirubicin;

PIK3CA for lapatinib, panitumumab, trastuzumab, cetuximab, temsirolimus

PTEN for getitinib, cetuximab, erlotinib, trastuszumab, panitumumab, everolimus, temsirolimus

RET for vandetanib

ROS1 for crizotinib

RRM1 for gemcitabine;

SPARC (monoclonal and polyclonal) for nab-paclitaxel;

TLE3, TUBB3 for docetaxel, paclitaxel;

TOPO1 for irinotecan, topotecan, FOLFIRI;

TS (thymidylate synthase or TYMS) for fluorouracil, capecitabine and pemetrexed


Chemosensitivity profile tumor panels, regardless of whether it is performed by IHC or chromogenic in-situ hybridization (CISH), is not reasonable and necessary for the reasons cited above, and is not a Medicare covered service.

Note, some of these markers are legitimate biomarkers for specified drugs when performed by mutation analysis or FISH testing.

IHC for Cervical/Gyn/Bladder/Kidney Tumors

A variety of IHC stains have found limited use in cervical, gynecologic, and urologic tumor settings. In unusual cases of cervical dysplasia, markers or surrogate markers for HPV may be useful where the diagnosis on conventional H&E stain cannot be made with certainty. These markers are clearly not reasonable and necessary on all biopsies. Claims data indicate combinations of gram stain, PAS, Ki-67, p16 and ProExC stains on all cervical biopsies from select pathology practices, and combinations of p53, Ki-67, CD20 and CD44 on bladder biopsies from select pathology practices.

Similarly, it is rare to need stains to prove that an endometrial or ovarian cancer is a serous cancer or that a kidney neoplasm is an oncocytoma or an eosinophilic or chromophobic renal cell cancer. The use of IHC stains in these circumstances requires adequate documentation in the pathology report, such as “Because the differential histologic diagnosis is between an endometrioid carcinoma and a serous carcinoma, I performed an xxx stain. The controls worked appropriately and the results were positive indicating the tumor is a yyy.”

IHC for Skin & Cutaneous/Soft Tissue/CNS & Peripheral Nervous System Lesions

It is well recognized that most skin lesions are diagnosed with routine H&E slides. That is the case for most melanomas and other pigmented lesions as well. A minority of skin lesions require immunostains (e.g., atypical fibroxanthomas, Merkel cell lesions, lymphomas). Most common skin lesions (e.g., seborrheic keratosis) do not require IHC stains. Use of IHC morphometric codes for skin lesions is incorrect coding.

Similarly, most soft tissue lesions do not require IHC stains or other “special” stains. Soft tissue masses may require stains (e.g., smooth muscle differentiation in a malignant mass) but the most do not.

Many CNS and peripheral nervous system lesions are readily diagnosed with routine stains. It is unusual for a meningioma to require an IHC. The primary role of IHC for CNS and peripheral nervous system lesions is to differentiate primary from metastatic lesions.

IHC for Bone Marrow Samples

Most bone marrow samples are diagnosed with the use of Wright’s stained smears and the use of H&E stained slides with an iron stain supplementing the battery. The use of IHC stains may assist in the interpretation of cases where flow cytometry (FC) does not fit with the routine slide interpretation, when flow cytometry was not obtained or for the evaluation of cell types that are not detected or significantly underrepresented in FC studies, such as large lymphocytes, plasma cells and Reed-Sternberg cells. IHC stains are generally not needed to confirm the results of FC and cytogenetic studies. When medically indicated, justification for the use of both methods must be stated in the pathology report and billed accordingly.



Bill Type Codes:

Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims.
N/A

Revenue Codes:

Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory. Unless specified in the policy, services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes.

N/A

Coding for pathology consultation during surgery with frozen section(s) Current Procedural Terminology (CPT) ® codes 88331 and 88332

First Coast Services Options, Inc. (First Coast) has performed data analysis and medical Review for several codes in which Florida providers have utilization higher than their peers across the Nation. The two codes that Florida providers are driving the nation’s utilization are pathology CPT® codes 88331(Pathology consultation during surgery; first tissue block, with frozen section(s), single specimen) and 88332 (Pathology consultation during surgery; each additional tissue block with frozen section(s). Review of medical records has identified issues with how the codes are being billed and how the code descriptors are being interpreted. The purpose of this article is to provide a clear understanding on the code descriptors and billing related to CPT® codes 88331 and 88332.



First Coast instructions for billing and coding to the above codes:

When a patient has a biopsy or surgery, the surgeon or dermatologist removes the diseased tissue for examination. This specimen is referred to as a "tissue block." After the initial tissue block or blocks, depending on the number of sites excised, are collected by the surgeon or dermatologist, the block(s) are then sent to the lab. At this point, the pathologist will slice the initial” tissue block” into as many samples as the pathologist requires for slide preparation. The question of whether it is the surgeon/dermatologist or pathologist who determines how many tissue blocks will be examined has been the question presented to First Coast and the below scenarios will provide guidance on this topic.

Scenario 1

A patient is in the office presenting with a lesion on the right forearm; the area is now referred as the site. The dermatologist removes one tissue block from the site (the lesion on the forearm). After the first tissue block or specimen is removed, the dermatologist removes another tissue block from the same site to check the margins and make sure the area is free of cancer. The two tissue blocks from the same site are sent to the pathologist. Once the pathologist receives the specimens, he/she then sections the two tissue blocks making 13 frozen sections on the first block and two frozen sections on the second block. How should this be billed using the CPT® codes listed above?

• Response: Correct billing would be 88331- 1 unit and 88332- 1 unit.

• Rationale: The laboratory received two tissue blocks for examination; the numbers of frozen sections or slides made from the initial two tissue blocks submitted are not billed. The billing units for these codes are defined by the tissue blocks removed by the dermatologist.


Scenario 2

A patient is in the office presenting with a lesion on the right forearm, left forearm and right cheek. The dermatologist removes one tissue block from the lesion on the right forearm. After the first lesion was removed, the dermatologist then removes another block from the same site to ensure the margins are clear and the area is free of cancer. Also, one block is removed from the left forearm and one block from the right cheek. The four tissue blocks are sent to the pathologist. Once the pathologist receives the specimens, he/she cuts 13 frozen sections on the first block from the right forearm, cuts two frozen sections on the second block from the right forearm, cuts two frozen sections on the block from the left forearm, and cuts three frozen sections on the block from the right cheek. How should this be billed using the CPT® codes listed above?

• Response: Correct billing would be: 88331, 88332, 88331 59 and 88331 59

• Rational: The laboratory received four tissue blocks; the numbers of frozen sections or slides made from the initial four tissue blocks submitted are not billed. The billing units of these codes are defined by the tissue blocks removed by the dermatologist.
If the surgeon takes a block from different sites, each site should be billed with CPT® code 88331. If the surgeon decides to take another block from the same site, the code billed should be 88332.

The number of blocks will be determined by the physician who performed the procedure (surgeon or dermatologist).

CPT 81479, 81211 - Molecular pathology procedure

Procedure Code and Description

81211 BRCA1, BRCA2 (BREAST CANCER 1 AND 2) (EG, HEREDITARY BREAST AND OVARIAN CANCER) GENE ANALYSIS; FULL SEQUENCE ANALYSIS AND COMMON DUPLICATION/DELETION VARIANTS IN BRCA1 (IE, EXON 13 DEL 3.835KB, EXON 13 DUP 6KB, EXON 14-20 DEL 26KB, EXON 22 DEL 510BP, EXON 8-9 DEL 7.1KB)

81479 UNLISTED MOLECULAR PATHOLOGY PROCEDURE


Genetic Testing, BRCA 1 & 2

CPT/HCPCS CODES 81162, 81211, 81212, 81213, 81214, 81215, 81216, 81217

CRITERIA FOR BRCA 1 AND 2 COMPREHENSIVE SEQUENCE ANALYSIS, FOUNDER MUTATIONS MUST MEET ALL OF THE FOLLOWING:

1. The results of the genetic testing will directly impact surveillance or treatment of the member.
2. One of the following criteria is met:
a. Three or more close relatives1 (including the member) on the same side of the family  have breast (either invasive or non-invasive) or ovarian cancer (includes epithelial ovarian/fallopian tube/primary peritoneal cancers), irrespective of the age at diagnosis.
b. There are fewer than three close relatives on the same side of the family with breast or ovarian cancer, but any of the following are present:
1) The member or a close relative was diagnosed with breast cancer at = 45 years of age;
2) A close relative has been identified with a detectable BRCA 1 or 2 mutation;
3) The member or a close relative was diagnosed with breast cancer = 50 years of age and one of the following:
a) = 1 close relative was diagnosed with breast cancer at any age;
b) = 1 close relative with pancreatic cancer;
c) = 1 close relative with prostate cancer (Gleason score = 7);
d) two primary breast cancers (including bilateral disease or two or more separate primary tumors in the same breast);
e) there is an unknown or limited family history. 2
4) The member was diagnosed with breast cancer at any age and one of the following:

a) = 1 close relative was diagnosed with breast cancer = 50 years of age;

b) = 2 close relatives with breast cancer at any age;

c) = 2 close blood relatives with pancreatic cancer and/or aggressive prostate cancer (Gleason score = 7) at any age.

5) The member or a close relative was diagnosed with triple negative breast cancer = 60 years of age. 3

6) The member or a close relative was diagnosed with ovarian cancer, fallopian tube or primary peritoneal cancer at any age.

7) The member or a close relative with breast cancer is male.

8) The member or a close relative was diagnosed with breast cancer at any age and is at increased risk for specific mutation(s) due to ethnic background (for instance: Ashkenazi Jewish descent).4

c. The member or a close relative was diagnosed with pancreatic cancer at any age with = 1 close relative with ovarian cancer at any age or breast cancer = 50 or two relatives with breast, pancreatic or prostate cancer (Gleason score = 7) at any age.

d. The member or a close relative was diagnosed with prostate cancer (Gleason score =7) at any age with = 1 close relative with ovarian cancer at any age or breast cancer = 50 or two close relatives with breast, pancreatic or prostate cancer (Gleason score = 7) at any age.

e. A third-degree relative has breast and/or ovarian cancer (including fallopian tube or primary peritoneal cancer) and who has = two close relatives with breast cancer (at least one with breast cancer = 50) and/or ovarian cancer.

1 A close relative is defined as a 1st, 2nd or 3rd degree relative (a parent, full sibling, half sibling, child, grandparent, great-grandparent, grandchild, aunt, great aunt, uncle, great uncle, nephew, niece, or first cousin).

2 A limited family history is defined as fewer than two first- or second-degree female relatives or female relatives surviving beyond 45 years in either lineage (maternal and paternal). 3 Breast cancer that is negative for Estrogen receptor (ER), Progesterone receptor (PR)  and HER2.

4 Authorization will initially be for the mutation(s) specific for the ethnic group in question (Multisite 3 BRACAnalysis® or equivalent testing for Founder Mutations). If the initial screening is negative, the member should be authorized for additional genetic testing (ComprehensiveSequence Analysis) only if he/she meets the remainder of the criteria.

Coverage Indications, Limitations, and/or Medical Necessity


This LCD provides limited coverage for the GeneSight® Psychotropic (AssureRx Health, Inc, Mason, OH) gene panel. GeneSight® testing may only be ordered by licensed psychiatristsor or neuropsychiatrists contemplating an alteration in neuropsychiatric medication for patients diagnosed with major depressive disorder (MDD) (in accordance with DSM IV/V criteria) 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.

Background

GeneSight® Psychotropic is a multiplex pharmacogenomic test involving the analysis of fifty alleles (SNPs) from six different genes and a clinical outcomes-based decision support modeling tool that weights the influence of the various alleles/SNPs with respect to thirty-two different psychotropic pharmaceutical agents. 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. In multiple prospective clinical studies, the use of GeneSight® to guide neuropsychiatric pharmaceutical selection and prescription has demonstrated an increased patient response to treatment from 60% to 250% (as measured by the standardized 17-item Hamilton Rating Scale for Depression or HAM-17; response is defined as = 50% reduction in HAM-D17 score) versus unguided, empirical treatment (or treatment as usual).

GeneSight® has particular relevance for Medicare beneficiaries, 26% of whom experience a mental disorder each year. Additionally, six out of ten disabled Medicare beneficiaries (~3.7 million) under age 65, representing roughly 17% of all beneficiaries, have a diagnosis of mental disorder. Furthermore, the American Psychiatric Association (APA) recognizes depression as the most common mental disorder in people aged 65 and older. It frequently appears as a co-morbid symptom to other conditions and can even mimic the symptoms of dementia. As a group, seniors generally take more medications than other age groups, increasing their risk of drug-drug interactions and adverse drug events (ADEs).

The GeneSight® report segments and displays these psychotropic medications into three “traffic light” categories or “bins” - green, yellow and red. Based on the patient’s genetic make-up and the drug’s metabolic and therapeutic pathways, the green bin identifies drugs that will likely be well tolerated and efficacious for the tested patient; the yellow bin identifies drugs with an intermediate effect; and the red bin identifies drugs likely to be poorly tolerated and/or ineffective. The report also identifies common drug-drug interactions that are similarly influenced by the patient’s genetic composition.

Pine Rest Study 

The Pine Rest study was a prospective, patient- and rater-blinded, randomized controlled trial evaluating the clinical impact of GeneSight® on antidepressant selection and treatment outcomes in depressed outpatients (GeneSight®, N=25 vs treatment as usual (TAU), N=24). Patients were assessed for symptom improvement, remission and response from baseline (week 0) and at 2, 4, and 8 weeks, using the HAM-D17 rating.

Subjects in the GeneSight® arm had a greater average decrease in the 17-item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline at 8 weeks (p = 0.30) and a higher response rate (p = 0.055) and significantly higher remission rate (p = 0.012) at any time point. Response rates in the GeneSight®-guided arm were 73% higher compared to the unguided TAU arm. Retrospective analysis of the TAU subjects at the end of the study after un-blinding and stratifying by GeneSight® results proved the clinical validity of GeneSight®, with 30% of subjects unknowingly on red bin medications showing a significant worsening of depressive symptoms in contrast to significant improvements in depressive symptoms experienced by 30% of subjects unknowingly on green bin medications (p = 0.07). Additionally, surveys from the treating clinicians revealed that the GeneSight® composite report had a significant influence on treatment decisions for 65% of the GeneSight® subjects.

Hamm Study

The Hamm Clinic prospective cohort study with two arms (GeneSight® (n = 22) vs. TAU (n = 22)) enrolled adult patients with a primary diagnosis of major depressive disorder utilizing DSM-IV criteria for depression not otherwise specified. GeneSight® subjects achieved greater reductions in depression symptoms between the baseline and the week 8 visits compared to TAU subjects using the Quick Inventory of Depressive Symptomatology – Clinician version (QIDS-C16) (p = 0.0024) and HAM-D17 (p = 0.042) ratings. Both the response and remission rate were more than doubled in the GeneSight® arm compared to the TAU arm. Upon unblinding the TAU group at the end of 8 weeks, TAU subjects were being prescribed significantly more red and yellow bin medications and less green bin medications compared to the GeneSight® guided subjects (p = 0.02).

La Crosse

In the La Crosse prospective cohort study (GeneSight® (n = 72) vs. TAU (n = 93)) at the Franciscan Skemp Hospital in La Crosse, Wisconsin, patients with a primary diagnosis of MDD or depression not otherwise specified with a minimum score of 14 on HAM-D17 were enrolled. Diagnosis was confirmed by checking the diagnosis reported in the physician clinical notes in the electronic medical record (EMR). Samples were collected at baseline in both arms, while only the physicians in the GeneSight® arm were provided with test results to inform treatment decisions. In addition to the prospective comparisons, retrospective analysis in the TAU subjects at the end of the study was implemented after un-blinding the GeneSight® results to test for clinical validity.

A greater reduction in depression scores from baseline to the week 8 visit was observed in the GeneSight® arm for all three measures of depression: QIDS-C16 (p < 0.0001), HAM-D17 (p < 0.0001), and PHQ-9 (p < 0.0001). In all measures, a faster reduction of symptoms was observed in the GeneSight® arm subjects compared to the TAU arm subjects (QIDS-C16 and HAM-D17 (p < 0.0001), PHQ-9 (p = 0.002)). The GeneSight® arm had a significantly higher remission rate based on the QIDS-C16 score (p = 0.03), and significantly higher response rates based on QIDS-C16 (p = 0.005), HAM-D17 (p = 0.03), and PHQ-9 (p = 0.01).

Physicians changed medications more often for subjects in the GeneSight®-guided group (57.9%) than the unguided group (25.9%) (p = 0.0007). Of the 15 GeneSight®-guided subjects classified in the red bin category at baseline, fourteen (93.3%) experienced a medication change or dose adjustment during the eight week study period, compared with 8 out of 18 subjects in the unguided group (44.4%) in the red bin category (p = 0.002). A significant association between bin status and outcome was observed within the unguided group (p = 0.028). Subjects classified in the red bin category had less improvement (11%) eight than those classified in the green or yellow categories (31.9%, p = 0.047), further demonstrating the deleterious effects of red bin medications on patient outcomes.

Dayton Study

This retrospective study, in collaboration with Union Health Services (UHS, a staff model HMO located in Chicago, Illinois), examined healthcare utilization in relation to medication categories (binning) using GeneSight®. Ninety-six patients previously diagnosed with a depressive disorder or anxiety disorder and treated with one of the medications included in the GeneSight® panel were included in the study. The GeneSight® bin assignments of patient psychiatric medications were compared to the medical records for patient medication prescriptions, healthcare utilization, medical absence days, and disability claims for the previous 12 months.

Subjects whose medication regimen included a medication in the GeneSight® red bin (“use with caution and more frequent monitoring”) had 69% more total healthcare visits (p = 0.005), 67% more general medical visits (p = 0.02), greater than 3-fold more medical absence days (p = 0.06), and greater than 4-fold more disability claims (p = 0.004) than subjects taking drugs in the green (“use as directed”) or yellow bin (“use with caution”). The mean healthcare utilization cost calculated for red bin subjects during the previous 12 month period was higher at $8,627, compared to $3,453 calculated for green bin subjects (p = 0.024) and $3,426 for yellow bin subjects (p = 0.027), yielding an average annual increase in healthcare cost of $5,188 for subjects on GeneSight® red bin medications.

Meta-analysis of GeneSight® Prospective 2-Armed Studies

In a meta-analysis of three prospective, 2-armed clinical trials (Pine Rest, Hamm, and La Crosse), use of the test to aid in therapeutic selection has improved patient responses to treatment by 73% on average, which is consistent with the results from each study individually, and is highly significant (p=0.004). These findings support the value of the GeneSight® test in improving patient outcomes.

Documentation Requirements

Documentation supporting the medical need for these tests, including substantiating documentation for the ICD-9 code(s) submitted, must be maintained in the patient’s medical record. In order to be considered medically necessary, the patient must have failed or currently be failing on at least one neuropsychiatric medication, and the healthcare provider must be contemplating an alteration in neuropsychiatric medication treatment. Prior medication failure and intent to alter medication course consistent with the test results must be documented in the patient’s medical record and noted with the test requisition.


Billing/Coding/Physician Documentation Information 

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable codes: Effective in 2013, if the specific analyte is listed in codes 81200-81355 or 81400-81408, that CPT code would be reported. If the specific analyte is not listed in the more specific CPT

codes, unlisted code 81479 would be reported.

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

ICD-10 Codes that Support Medical Necessity


ICD-10 CODE DESCRIPTION

F32.1 Major depressive disorder, single episode, moderate
F32.2 Major depressive disorder, single episode, severe without psychotic features
F32.3 Major depressive disorder, single episode, severe with psychotic features
F32.4 Major depressive disorder, single episode, in partial remission
F32.9 Major depressive disorder, single episode, unspecified
F33.1 Major depressive disorder, recurrent, moderate
F33.2 Major depressive disorder, recurrent severe without psychotic features
F33.3 Major depressive disorder, recurrent, severe with psychotic symptoms
F33.40 Major depressive disorder, recurrent, in remission, unspecified
F33.41 Major depressive disorder, recurrent, in partial remission
F33.9 Major depressive disorder, recurrent, unspecified

Coverage for BRCA1 and BRCA 2 Testing


Coverage Indications, Limitations, and/or Medical Necessity


Germline genetic testing of BRCA1 and BRCA2 is available to identify individuals at increased risk for breast and ovarian cancers, as individuals with an inherited cancer syndrome may benefit from screening and prevention strategies to reduce their risk. The prevalence of BRCA mutations in the population is estimated between 1 in 300 and 1 in 800; however, specific mutations known as founder mutations occur more often in populations founded by a small ancestral group, including Ashkenazi (Eastern European) Jews, French Canadians, and Icelanders. The prevalence of BRCA mutations in the Ashkenazi Jewish population is approximately 1 in 40. Three recurrent BRCA1 and BRCA2 mutations have been identified in Ashkenazi Jewish individuals (i.e., a genetically distinct population of Jewish people of eastern and central European ancestry) and make up the vast majority of BRCA mutations that occur in this population. Rearrangements, such as large genomic alterations including translocations, inversions, large deletions and insertions are believed to be responsible for 12% to 18% of BRCA1 inactivating mutations but are less common in BRCA2 and in individuals of Ashkenazi Jewish descent. The NCCN guidelines note that comprehensive genetic testing includes full sequencing of BRCA1/BRCA2 and the detection of large genomic rearrangements. The NCCN recommends that since certain large genomic rearrangements are not detectable by a primary sequencing assay, additional testing may be needed in some cases.

Evidence in the published, peer-reviewed scientific literature indicates that BRCA1 and BRCA2 genetic testing is appropriate for a specific subset of adult individuals who have been identified to be at high risk for hereditary breast and ovarian cancers. Furthermore, several specialty organizations, including NCCN, American College of Medical Genetics (ACMG), and American Society of Clinical Oncology (ASCO), have issued statements recognizing the role of pre- and post-test genetic counseling and BRCA testing in the management of at risk patients. The U.S. Preventive Services Task Force (USPSTF) has published recommendations regarding genetic risk assessment, genetic counseling and BRCA mutation testing for breast and ovarian cancer susceptibility. Based on this USPSTF recommendation, the Patient Protection and Affordable Care Act (ACA) requires that private group and individual health plans provide coverage for genetic counseling and, if appropriate, genetic testing for women at risk for hereditary breast ovarian cancer syndrome (HBOC) as a preventive service with no out of pocket expense.

Olaparib is a poly ADP-ribose polymerase (PARP) inhibitor inhibitor approved by the FDA as monotherapy in patients with ovarian cancer, with deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation who have been treated with three or more prior lines of chemotherapy. Testing of ovarian cancer patients in this clinical scenario is indicated to guide treatment.

Mutations in the BRCA1 and BRCA2 genes are passed down in families through an autosomal dominant inheritance pattern meaning that the associated cancer predisposition can be inherited through either the mother’s or father’s side of the family and transmitted by a male or female. When a parent carries a BRCA mutation, there is a 50% chance of passing down the gene mutation with every pregnancy. Although the risk of inheriting the predisposition from a parent who carries a mutation is 50%, not everyone with an inherited mutation will develop cancer. The likelihood that a woman with a mutation will develop a related cancer (i.e., penetrance of a BRCA mutation) is estimated between 41% and 90% and is much lower for men. The risk of developing cancer depends on numerous variables, including the penetrance of the specific mutation, the genetic makeup of the individual, environmental risk factors, the gender of the individual and their age.

Several national evidence based and expert opinion guidelines and accrediting bodies recommend that genetic testing should be undertaken only in conjunction with independent pre-test genetic counseling services in order to assist patients in complex clinical decision-making. Post genetic testing counseling is also strongly recommended. The NCCN guidelines [2015] state that genetic counseling is a critical component of the cancer risk assessment process. In addition, the guidelines state that pretest counseling should include a discussion of why the test is being offered and how test results may impact medical management, cancer risks associated with the genes being tested, the significance of possible test results for the individual and family, the likelihood of a positive result, technical aspects and accuracy of the test, and economic considerations. Per the guidelines, posttest counseling includes disclosure of results, discussion of the significance of the results for the individual and relevant family members, a discussion of the impact of the results on psychosocial aspects and on the medical management of the individual, and how and where the patient will receive followup care and access to additional resources.

Medicare is a defined benefit program and requires that testing is only performed on patients with signs and symptoms of disease. Testing of unaffected individuals or family members is not a covered Medicare services. However, once a mutation is identified in the family, Medicare eligible relatives with signs and symptoms of breast cancer are typically tested for that specific mutation only. For patients of Ashkenazi Jewish descent, initial testing is generally done for the three specific mutations that account for most hereditary breast and ovarian cancer in that population: 185delAG and 5382insC (also called 5385insC) in the BRCA1 gene and 6174delT in the BRCA2 gene. If the test results are negative, full analysis of the BRCA1 and BRCA2 genes is only considered if testing criteria for non Jewish individuals are met. Nonetheless, Medicare does not cover testing for patients without signs and symptoms of breast or ovarian cancer.

While not required for payment, NCCN Guidelines recommend referral to a cancer genetics professional with expertise and experience in cancer genetics prior to genetic testing and after genetic testing. Examples of cancer genetics professionals with expertise and experience in cancer genetics include: an American Board of Medical Genetics or American Board of Genetic Counseling certified or board eligible Clinical Geneticist, Medical Geneticist or Genetic Counselor not employed by a commercial genetic testing laboratory (excludes individuals employed by or contracted with a laboratory that is part of an Integrated Health System which routinely delivers health care services beyond just the laboratory test itself as these individuals are also considered inter dependent); medical oncologist, obstetrician-gynecologist or other physician trained in medical cancer genetics, a genetic nurse credentialed as either a Genetic Clinical Nurse (GCN) or an Advanced Practice Nurse in Genetics (APGN) by either the Genetic Nursing Credentialing Commission (GNCC) or the American Nurses Credentialing Center (ANCC) who is not employed by a commercial genetic testing laboratory (excludes individuals employed by or contracted with a laboratory that is part of an Integrated Health System which routinely delivers health care services beyond just the laboratory test itself as these individuals are also considered inter dependent).

Indications

This is a limited coverage policy for BRCA 1 and BRCA 2 genetic testing. BRCA 1 and BRCA 2 genetic testing has been found to be reasonable and necessary in the following instances.

Personal History of Female Breast Cancer

BRCA1 and BRCA2 genetic testing for susceptibility to breast or ovarian cancer is covered in adults [by full sequence analysis and duplication/deletion analysis of common variants (CPT codes 81211 and 81213) as medically reasonable and necessary when there is a personal history of breast cancer (invasive breast cancer or ductal carcinoma in situ) and ANY of the following indications:

Diagnosed at age 60 or younger with a triple negative breast cancer (estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative);
Diagnosed at age 50 or younger with a limited family history (e.g., fewer than two first- or second degree female relatives or female relatives surviving beyond 45 years in the relevant maternal and/or paternal lineage);
Diagnosed at any age and there are at least two close blood relatives* with breast cancer at any age;
Diagnosed at any age with at least one close blood relative* with breast cancer at age 50 or younger;
Diagnosed at any age and there are at least two close blood relatives* with pancreatic cancer or prostate cancer with Gleason score >7 at any age;
Diagnosed at any age with at least one close blood relative* with epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer;
Close male blood relative* with breast cancer;
Individual of Ashkenazi Jewish descent begin testing with Ashkenazi Jewish founder specific mutations (a gene mutation observed with high frequency in a group that is or was geographically or culturally isolated, in which one or more of the ancestors was a carrier of the mutant gene) (CPT code 81212). If negative, complete analysis (CPT 81211 and 81213) may be considered if ancestry also includes non-Ashkenazi Jewish relatives or other criteria for BRCA1/BRCA2 genetic testing are met.

*NCCN defines blood relative as first- (parents, siblings and children), second- (grandparents, aunts, uncles, nieces and nephews, grandchildren and half-siblings), and third degree-relatives (great grandparents, great aunts, great uncles, great grandchildren and first cousins) on same side of family. Genetic testing for a known mutation in a family is a covered service for individuals with signs and/or symptoms of breast cancer. Testing of an unaffected Medicare eligible individual or family member is not a covered Medicare service.

Personal History of Other Cancer

BRCA1 and BRCA2 genetic testing for susceptibility to breast or ovarian cancer is covered in adults [by full sequence analysis and duplication/deletion analysis of common variants (CPT codes 81211) and uncommon duplication/deletion analysis (CPT 81213)] as medically necessary when there is a personal history of ANY of the following indications:

Personal history of epithelial ovarian, fallopian tube, or primary peritoneal cancer;
Personal history of male breast cancer;
Personal history of pancreatic cancer or prostate cancer with Gleason score =7 at any age, =1 close blood relatives* with breast (=50 y), invasive ovarian, pancreatic cancer, or prostate cancer with Gleason score=7 at any age;
Personal history of pancreatic cancer at any age with Ashkenazi Jewish ancestry (Begin testing with Ashkenazi Jewish founder specific mutations [CPT code 81212]. If negative, complete analysis (CPT 81211 and 81213) should be performed. Complete analysis (CPT 81211 and 81213) may be considered if ancestry also includes non-Ashkenazi Jewish relatives and other criteria for BRCA1/BRCA2 genetic testing are met.

Genetic testing for a known mutation in a family is a covered service for individuals with signs and/or symptoms of another inheritable cancer. Testing of an unaffected Medicare eligible individual or family member is not a covered Medicare service.

Multigene Panels

BRCA1 and BRCA2 genetic testing for susceptibility to breast or ovarian cancer with multi-gene next –generation sequencing (NGS) panels is covered as medically necessary when ALL of the following criteria are met:

Pre-test genetic counseling by a cancer genetics professional independent of the laboratory has been performed and post-test genetic counseling by a cancer genetics professional independent of the laboratory is planned;
All genes in the panel are relevant to the personal and family history for the individual being tested (large panels with genes that are not relevant to the individual’s personal and family history are not reasonable and necessary);
Criteria listed under Section 1, Personal history of female breast cancer and/or Section 2 Personal history of other cancer are met.
Individual also meets criteria for at least ONE other hereditary cancer syndrome for which NCCN guidelines provide clear testing criteria and management recommendations, including but not limited to Li-Fraumeni Syndrome, Cowden Syndrome, or Lynch Syndrome.


Limitations

Any test must also meet:

Availability of a clinically valid test, based on published peer reviewed medical literature; AND
Testing assay(s) are Food and Drug Administration (FDA) approved/cleared or if LDT (lab developed test) or LDT protocol or FDA modified test(s) the laboratory documentation should support assay(s) analytical validity and clinical utility.

BRCA1/BRCA2 genetic testing for susceptibility to breast or ovarian cancer is not covered for any other indication including any of the following because it is considered not medically reasonable and necessary for these indications:

Genetic screening in the general population. Such testing is considered screening and is excluded by Medicare statute. An ABN must be obtained for BRCA 1 and BRCA 2 testing for individuals without signs and symptoms of breast, ovarian or other hereditary cancer syndromes as indicated in this policy.
Testing of individuals with no personal history of breast, ovarian, fallopian tube, primary peritoneal, pancreatic, or prostate cancer. Such testing is considered screening and is excluded by Medicare statute.
An ABN must be obtained for BRCA 1 and BRCA 2 testing for individuals without signs and symptoms of breast, ovarian or other hereditary cancer syndromes as indicated in this policy.
Testing of individuals under 18 years of age.

Generic (not disease specific) genomic sequence panels (NGS comprehensive definitive cancer testing panel/s) of 51 or greater genes are non-covered at this time (specific testing of 51 or greater genes as expressed by disease specific coding, e.g. Prosigna breast cancer assay, can be medically necessary).


CPT/HCPCS Codes

Group 1 Paragraph: N/A

Group 1 Codes:
cpt 81211 BRCA1, BRCA2 (BREAST CANCER 1 AND 2) (EG, HEREDITARY BREAST AND OVARIAN CANCER) GENE ANALYSIS; FULL SEQUENCE ANALYSIS AND COMMON DUPLICATION/DELETION VARIANTS IN BRCA1 (IE, EXON 13 DEL 3.835KB, EXON 13 DUP 6KB, EXON 14-20 DEL 26KB, EXON 22 DEL 510BP, EXON 8-9 DEL 7.1KB)

81212 BRCA1, BRCA2 (BREAST CANCER 1 AND 2) (EG, HEREDITARY BREAST AND OVARIAN CANCER) GENE ANALYSIS; 185DELAG, 5385INSC, 6174DELT VARIANTS
81213 BRCA1, BRCA2 (BREAST CANCER 1 AND 2) (EG, HEREDITARY BREAST AND OVARIAN CANCER) GENE ANALYSIS; UNCOMMON DUPLICATION/DELETION VARIANTS

81214 BRCA1 (BREAST CANCER 1) (EG, HEREDITARY BREAST AND OVARIAN CANCER) GENE ANALYSIS; FULL SEQUENCE ANALYSIS AND COMMON DUPLICATION/DELETION VARIANTS (IE, EXON 13 DEL 3.835KB, EXON 13 DUP 6KB, EXON 14-20 DEL 26KB, EXON 22 DEL 510BP, EXON 8-9 DEL 7.1KB)

81215 BRCA1 (BREAST CANCER 1) (EG, HEREDITARY BREAST AND OVARIAN CANCER) GENE ANALYSIS; KNOWN FAMILIAL VARIANT

81216 BRCA2 (BREAST CANCER 2) (EG, HEREDITARY BREAST AND OVARIAN CANCER) GENE ANALYSIS; FULL SEQUENCE ANALYSIS

81217 BRCA2 (BREAST CANCER 2) (EG, HEREDITARY BREAST AND OVARIAN CANCER) GENE ANALYSIS; KNOWN FAMILIAL VARIANT

81445 TARGETED GENOMIC SEQUENCE ANALYSIS PANEL, SOLID ORGAN NEOPLASM, DNA ANALYSIS, AND RNA ANALYSIS WHEN PERFORMED, 5-50 GENES (EG, ALK, BRAF, CDKN2A, EGFR, ERBB2, KIT, KRAS, NRAS, MET, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), INTERROGATION FOR SEQUENCE VARIANTS AND COPY NUMBER VARIANTS OR REARRANGEMENTS, IF PERFORMED
81455 TARGETED GENOMIC SEQUENCE ANALYSIS PANEL, SOLID ORGAN OR HEMATOLYMPHOID NEOPLASM, DNA ANALYSIS, 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
81479 UNLISTED MOLECULAR PATHOLOGY PROCEDURE





ICD-10 Codes that Support Medical Necessity

Group 1Codes

ICD-10 CODE DESCRIPTION

C25.4 Malignant neoplasm of endocrine pancreas

C25.7 Malignant neoplasm of other parts of pancreas

C25.8 Malignant neoplasm of overlapping sites of pancreas

C25.9 Malignant neoplasm of pancreas, unspecified

C50.011 Malignant neoplasm of nipple and areola, right female breast

C50.012 Malignant neoplasm of nipple and areola, left female breast

C50.019 Malignant neoplasm of nipple and areola, unspecified female breast

C50.021 Malignant neoplasm of nipple and areola, right male breast

C50.022 Malignant neoplasm of nipple and areola, left male breast

C50.029 Malignant neoplasm of nipple and areola, unspecified male breast

C50.111 Malignant neoplasm of central portion of right female breast

C50.112 Malignant neoplasm of central portion of left female breast

C50.119 Malignant neoplasm of central portion of unspecified female breast


C50.121 Malignant neoplasm of central portion of right male breast

C50.122 Malignant neoplasm of central portion of left male breast

C50.129 Malignant neoplasm of central portion of unspecified male breast
C50.211 Malignant neoplasm of upper-inner quadrant of right female breast

C50.212 Malignant neoplasm of upper-inner quadrant of left female breast

C50.219 Malignant neoplasm of upper-inner quadrant of unspecified female breast


C50.221 Malignant neoplasm of upper-inner quadrant of right male breast

C50.222 Malignant neoplasm of upper-inner quadrant of left male breast

C50.229 Malignant neoplasm of upper-inner quadrant of unspecified male breast

C50.311 Malignant neoplasm of lower-inner quadrant of right female breast

C50.312 Malignant neoplasm of lower-inner quadrant of left female breast

C50.319 Malignant neoplasm of lower-inner quadrant of unspecified female breast

C50.321 Malignant neoplasm of lower-inner quadrant of right male breast

C50.322 Malignant neoplasm of lower-inner quadrant of left male breast

C50.329 Malignant neoplasm of lower-inner quadrant of unspecified male breast

C50.411 Malignant neoplasm of upper-outer quadrant of right female breast

C50.412 Malignant neoplasm of upper-outer quadrant of left female breast

C50.419 Malignant neoplasm of upper-outer quadrant of unspecified female breast

C50.421 Malignant neoplasm of upper-outer quadrant of right male breast

C50.422 Malignant neoplasm of upper-outer quadrant of left male breast

C50.429 Malignant neoplasm of upper-outer quadrant of unspecified male breast

C50.511 Malignant neoplasm of lower-outer quadrant of right female breast

C50.512 Malignant neoplasm of lower-outer quadrant of left female breast

C50.519 Malignant neoplasm of lower-outer quadrant of unspecified female breast

C50.521 Malignant neoplasm of lower-outer quadrant of right male breast

C50.522 Malignant neoplasm of lower-outer quadrant of left male breast

C50.529 Malignant neoplasm of lower-outer quadrant of unspecified male breast

C50.611 Malignant neoplasm of axillary tail of right female breast

C50.612 Malignant neoplasm of axillary tail of left female breast

C50.619 Malignant neoplasm of axillary tail of unspecified female breast

C50.621 Malignant neoplasm of axillary tail of right male breast

C50.622 Malignant neoplasm of axillary tail of left male breast

C50.629 Malignant neoplasm of axillary tail of unspecified male breast

C50.811 Malignant neoplasm of overlapping sites of right female breast

C50.812 Malignant neoplasm of overlapping sites of left female breast

C50.819 Malignant neoplasm of overlapping sites of unspecified female breast

C50.821 Malignant neoplasm of overlapping sites of right male breast

C50.822 Malignant neoplasm of overlapping sites of left male breast

C50.829 Malignant neoplasm of overlapping sites of unspecified male breast

C50.911 Malignant neoplasm of unspecified site of right female breast

C50.912 Malignant neoplasm of unspecified site of left female breast

C50.919 Malignant neoplasm of unspecified site of unspecified female breast

C50.921 Malignant neoplasm of unspecified site of right male breast

C50.922 Malignant neoplasm of unspecified site of left male breast

C50.929 Malignant neoplasm of unspecified site of unspecified male breast

C56.1 Malignant neoplasm of right ovary

C56.2 Malignant neoplasm of left ovary

C56.9 Malignant neoplasm of unspecified ovary

C57.00 Malignant neoplasm of unspecified fallopian tube

C57.01 Malignant neoplasm of right fallopian tube

C57.02 Malignant neoplasm of left fallopian tube

C61 Malignant neoplasm of prostate

D05.00 Lobular carcinoma in situ of unspecified breast

D05.01 Lobular carcinoma in situ of right breast

D05.02 Lobular carcinoma in situ of left breast

D05.10 Intraductal carcinoma in situ of unspecified breast

D05.11 Intraductal carcinoma in situ of right breast

D05.12 Intraductal carcinoma in situ of left breast

D05.80 - D05.82 - Opens in a new window Other specified type of carcinoma in situ of unspecified breast - Other specified
type of carcinoma in situ of left breast

D05.90 - D05.92 - Opens in a new window Unspecified type of carcinoma in situ of unspecified breast - Unspecified type of
carcinoma in situ of left breast

Z85.07 Personal history of malignant neoplasm of pancreas

Z85.43 Personal history of malignant neoplasm of ovary

Z85.46 Personal history of malignant neoplasm of prostate