CPT code 81479, 81403, 81292, 81211

Procedure Codes and Description

Group 1 Codes:

81206 BCR/ABL1 (T(9;22)) (EG, CHRONIC MYELOGENOUS LEUKEMIA) TRANSLOCATION ANALYSIS; MAJOR BREAKPOINT, QUALITATIVE OR QUANTITATIVE

81207 BCR/ABL1 (T(9;22)) (EG, CHRONIC MYELOGENOUS LEUKEMIA) TRANSLOCATION ANALYSIS; MINOR BREAKPOINT, QUALITATIVE OR QUANTITATIVE

81208 BCR/ABL1 (T(9;22)) (EG, CHRONIC MYELOGENOUS LEUKEMIA) TRANSLOCATION ANALYSIS; OTHER BREAKPOINT, QUALITATIVE OR QUANTITATIVE

81219 CALR (CALRETICULIN) (EG, MYELOPROLIFERATIVE DISORDERS), GENE ANALYSIS, COMMON VARIANTS IN EXON 9

81270 JAK2 (JANUS KINASE 2) (EG, MYELOPROLIFERATIVE DISORDER) GENE ANALYSIS, P.VAL617PHE (V617F) VARIANT

81402 MOLECULAR PATHOLOGY PROCEDURE, LEVEL 3 (EG, >10 SNPS, 2-10 METHYLATED VARIANTS, OR 2-10 SOMATIC VARIANTS [TYPICALLY USING NON-SEQUENCING TARGET VARIANT ANALYSIS], IMMUNOGLOBULIN AND T-CELL RECEPTOR GENE REARRANGMENTS, DUPLICATION/DELETION VARIANTS OF 1 EXON, LOSS OF HETEROZYGOSITY [LOH], UNIPARENTAL DISOMY [UPD])

81403 MOLECULAR PATHOLOGY PROCEDURE, LEVEL 4 (EG, ANALYSIS OF SINGLE EXON BY DNA SEQUENCE ANALYSIS, ANALYSIS OF >10 AMPLICONS USING MULTIPLEX PCR IN 2 OR MORE INDEPENDENT REACTIONS, MUTATION SCANNING OR DUPLICATION/DELETION VARIANTS OF 2-5 EXONS)

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

81450 TARGETED GENOMIC SEQUENCE ANALYSIS PANEL, HEMATOLYMPHOID NEOPLASM OR DISORDER, DNA ANALYSIS, AND RNA ANALYSIS WHEN PERFORMED, 5-50 GENES (EG, BRAF, CEBPA, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KRAS, KIT, MLL, NRAS, NPM1, NOTCH1), INTERROGATION FOR SEQUENCE VARIANTS, AND COPY NUMBER VARIANTS OR REARRANGEMENTS, OR ISOFORM EXPRESSION OR MRNA EXPRESSION LEVELS, IF PERFORMED

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

Coverage Indications, Limitations, and/or Medical Necessity


Usage and Billing Guide for CPT 81479

At times, Tier 1 or Tier 2 codes may not suitably describe biomarkers or analytes, or may not adequately represent the particular assay or testing performed; therefore code 81479 - Unlisted Molecular Pathology Procedure (Not Otherwise Classified “NOC” / miscellaneous ) was established for utilization and billing purposes. When considering appropriate codes to bill, laboratories should keep in mind that coding must reflect the analyte, methodology, and technology utilized in the particular assay or test.

Because unlisted and unspecified procedure codes do not describe a specific procedure or service, it is necessary to submit supporting documentation when filing a claim. Pertinent information should include:

• A clear description of the nature, extent, and need for the procedure or service.

• Whether the procedure was performed independent from other services provided, or if it was performed at the same surgical site or through the same surgical opening.

• Any extenuating circumstances which may have complicated the service or procedure.

• Time, effort, and equipment necessary to provide the service.

• The number of times the service was provided. When submitting supporting documentation, designate the portion of the report that identifies the test or procedure
associated with the unlisted procedure code. Required information must be legible and clearly marked. (Refer to the guideline below for documentation requirements.)


Procedure Code Category Example Documentation Requirements

Laboratory and pathology procedures:

all unlisted codes within the range of 80047–89398

• CPT 84999 — unlisted chemistry procedure
• CPT 89240 — unlisted miscellaneous pathology test
• CPT 81479 — unlisted molecular pathology procedure

Laboratory or pathology report


MyPRS™ Test for Multiple Myeloma Gene Expression Profile (CPT code 81479)

*Medicare does not have a National Coverage Determination (NCD) for MyPRS™ Test for Multiple Myeloma Gene Expression Profile.

* Local Coverage Determinations (LCDs) exist and compliance with these LCDs is required where applicable.

PancraGEN® (powered by Pathfinder TG) (CPT code 81479)

* Medicare does not have a National Coverage Determination (NCD) for PancraGEN®.

* Only one contractor has Local Coverage Determinations (LCDs) which address),

i.e., Novitas Solutions, Inc., for the following states: AR, CO, DC, DE, LA, MD, MS, NJ, NM, OK, PA, and TX. Compliance with these LCDs is required where applicable. See the LCD for Loss-of-Heterozygosity Based Topographic Genotyping with PathfinderTG® (L34864). This test is provided to Medicare beneficiaries throughout the United States by Interpace Diagnostics in Pittsburg, PA

Indications and Limitations of Coverage

This policy provides coverage for multi-gene non-NGS panel testing and NGS testing for the diagnostic workup for myeloproliferative disease (MPD), and limited coverage for single-gene testing of patients with BCR-ABL negative MPD. MPD includes polycythemia vera (PV), essential thrombocytopenia (ET), and primary myelofibrosis (PMF).

For laboratories performing single gene technologies, a sequential genetic testing approach is expected. Once a positive result is obtained and the appropriate diagnosis is established, further testing should stop. Reflex testing to the next gene will be considered reasonable and necessary if the following sequence of genetic tests produce a negative result:

BCR-ABL negative test results, progress to #2

JAK 2, cv negative test results, progress to #3 or #4

JAK, exon 12 (JAK2 exon 12 is only done when PV is suspected)

CALR/MPD (CALR/MPD is only done when either ET or PMF is suspected; testing for CALR/MPD does NOT require a negative JAK2 exon 12, just a negative JAK2 V617F result)


Genetic testing of the JAK2 V617F mutation (81270) is medically necessary when the following criteria are met:
Genetic testing impacts medical management; and

Patient would meet World Health Organization’s diagnostic criteria for myeloproliferative disease (i.e. polycythemia vera, essential thrombocytopenia, primary myelofibrosis) if JAK2 V617F were identified.


Genetic testing of JAK2 exon 12 (81403), performed to identify PV, is medically necessary when the following criteria are met:
Genetic testing impacts medical management; and

Patient would meet World Health Organization’s diagnostic criteria for PV, if JAK2 exon 12 testing were positive; and

JAK2 V617F mutation analysis was previously completed and was negative.


Genetic testing of the CALR gene (81479) (only found in ET and PMF) is medically necessary when the following criteria are met:
Genetic testing impacts medical management; and

JAK2 V617F mutation analysis was previously completed and negative; and

Patient would meet World Health Organization’s diagnostic criteria for MPD (i.e. ET, PMF) if a clonal marker were identified.


Genetic testing of the MPD gene (81402) is medically necessary when the following criteria are met:
Genetic testing impacts medical management; and

JAK2 V617F mutation analysis was previously completed and negative; and

Patient would meet World Health Organization’s diagnostic criteria for MPD (i.e. ET, MPF) if a clonal marker were identified.


Note: In a single-gene sequential approach (not mandated by this policy), CALR would be a higher priority single gene test than MPD because:
CALR mutations is more prevalent than MPD mutations in ET/PMF patients; and

CALF mutations are reported to predict a more indolent disease course than patients with JAK2 mutations.


For laboratories performing next generation sequencing (NGS or “hotspot”) testing platforms: Molecular testing for BCR-ABL, JAK 2, JAK, exon 12, and CALR/MPD genes by NGS is covered as medically necessary for the identification of myeloproliferative disorders.



Background

Myeloproliferative Disorders

Myeloproliferative disorders are a group of conditions that cause abnormal growth of blood cells in the bone marrow. They include polycythemia vera (PV), essential thrombocytosis (ET), primary myelofibrosis (PMF), and chronic myelogenous leukemia (CML). The World Health Organization (WHO) further classifies PV, ET, and PMF as Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). The diagnosis of an MPN is suspected based upon clinical, laboratory, and pathological findings (i.e. bone marrow morphology). MPNs are related, but distinct from, myelodysplastic syndromes (MDS). In general, MDS are characterized by ineffective or dysfunctional blood cells, while MPN are characterized by an increase in the number of blood cells.

Polycythemia Vera

Polycythemia vera is a chronic myeloproliferative disease characterized by increased hemoglobin, hematocrit, and red blood cell mass. There is an associated increased risk for thrombosis and transformation to acute myelogenous leukemia or primary myelofibrosis; however, patients are often asymptomatic. Criteria for a diagnosis of PV are based upon CBC and clinical features. The JAK2 V617F mutation is present in the vast majority of PV, accounting for approximately 90% of cases. Functionally similar mutations in JAK2 exon 12 account for most remaining cases of JAK2 V617F mutation-negative PV. Together, they are identified in 98% of PV cases and lead to high diagnostic certainty.

Among the proposed revised World Health Organization (WHO) criteria for diagnosis is presence of the somatic JAK2 V617F mutation or functionally similar exon 12 mutation. Absence of a JAK2 mutation, combined with normal or increased serum erythropoietin level, greatly decreases the likelihood of a PV diagnosis. WHO proposed revision criteria for PV do not address additional molecular markers, including CALR mutation status.

Essential Thrombocythemia

Essential thrombocythemia is a disorder of sustained increased platelet count. The majority of ET patients (60%) carry a somatic JAK2 V617F mutation, while a smaller percentage (5-10%) have activating MPD mutations. Revision to the WHO criteria for diagnosis of ET has been proposed and includes exclusion of PV, PMF, CML, myelodysplastic syndrome, or other myeloid neoplasm. Also included in the proposed major criteria for diagnosis is demonstration of somatic JAK2 V617F mutation or MPD exon 10 mutation 12. Proposed criteria additionally state that 70% of patients without a JAK2 or MPD mutation carry a somatic mutation of the calreticulin (CALR) gene. Among confirmed ET cases, mutations in CALR are more common than MPD. Positive CALR mutation status is suggested as indicating a more indolent course 5.

Primary Myelofibrosis

Primary myelofibrosis (PMF) is a rare disorder in which the bone marrow is replaced with fibrous tissue, leading to bone marrow failure. Clinical features are similar to ET. The approximate incidence is 1 in 100,000 individuals. Persons can be asymptomatic in the early stages of the disease. For such patients, treatment may not initially be necessary. Progression of the disease can include transformation to acute myeloid leukemia. Treatment is generally symptomatic and aimed at preventing complications.

Demonstration of a clonal marker is important for diagnosis. Somatic molecular markers in PMF patients are similar to those in patients with ET, and include JAK2 V617F, MPD, and CALR. Somatic mutations in JAK2 are identified in 50-60% of PMF cases, and MPD mutations in 10%. Mutations in CALR are less common than JAK2, but more common than MPD.

Molecular Genetic Testing 

One JAK2 gene mutation, V617K, is most commonly reported, occurring in over 90% of all polycythemia vera (PV) cases and about 50% of ET cases. Testing for JAK2 V617K gene mutations can be useful in diagnosis and is incorporated into the WHO’s diagnostic criteria for these conditions.

The thrombopoietin receptor MPD is one of several JAK2 cognate receptors and is considered essential for myelopoiesis. The mutation frequency of MPD mutations associated with myeloproliferative disorders is substantially less Calreticulin (CALR) mutations have been identified in patients with myeloproliferative neoplasms and recent studies have investigated the utility of CALR mutation testing for the diagnosis and classification of myeloproliferative neoplasms. The mutations themselves are variable; however, generally focused in the exon 9 region.

Studies have shown that a significant proportion of patients with myeloproliferative neoplasms and normal JAK2 617F mutation testing have a CALR gene mutation. CALR mutations account for a large proportion of JAK2/MPD-negative ET and PMF cases. Approximately 60% of JAK2/MPD-negative ET patients are CALR-positive and 30% of JAK2/MPD-negative PMF patients are CALR-positive. Overall, CALR mutations are identified in approximately 21% of ET cases and 16% of PMF cases. CALR mutations have not been reported in PV case series 2.

For this reason, CALR gene testing may be indicated for individuals who would meet World Health Organization’s diagnostic criteria for myeloproliferative disease if a clonal marker were identified. Proponents have argued for revised WHO criteria that includes CALR mutation status in the classification system for ET and PMF 12. Current NCCN guidelines do not make recommendations for CALR genetic testing; however, these guidelines are specific to MDS and do not broadly address myeloproliferative neoplasms, such as ET or PMF. Somatic mutations in non-MDS genes, such as CALR, are listed as being associated with conditions that can mimic other myelodysplastic syndromes.

Aside from diagnostic utility, some research suggests distinct clinical outcomes associated with CALR mutation status; however, the findings have not been confirmed in other studies. It is suggested that ET patients with CALR mutations have lower polycythemic transformation rates, but not lower myelofibrotic transformation rate, compared with ET patients harboring a JAK2 mutation. Others reported a higher platelet count, younger age of diagnosis, lower leukocyte count, and decreased risk for thrombosis, compared with a JAK2 positive ET population 1. CALR-mutated ET has also been associated with better thrombosis-free survival and lower leukocyte counts; overall survival has been reported as not different among CALR mutated and non-mutated ET 2,15.

Although they are useful for establishing a diagnosis, the presence of specific clonal markers does not dictate treatment. Controversy exists generally regarding the treatment of asymptomatic individuals with ET. Some argue against treatment if there are no associated complications. In general, the main goal of treatment with PV and ET is to identify persons at high risk for thrombosis and prevent complications. Persons with PV and ET are determined to be at high-risk due to age >60 years and past history of thrombotic event(s). CALR mutational status is not currently used for risk stratification 11.

In summary, multiple studies have demonstrated the diagnostic value of CALR mutation status in a population of JAK2 and MPD negative patients with suspected ET and PMF. The presence of a somatic CALR mutation can prove useful in obtaining an accurate diagnosis. Emerging evidence suggests possible differences in clinical phenotype among the associated clonal markers, including CALR-positive ET cases. However, CALR mutation status is currently not incorporated into clinical risk stratification and more research is needed in this area.


ICD-10 Codes that Support Medical Necessity

ICD-10 CODE DESCRIPTION

C88.8 Other malignant immunoproliferative diseases
C92.10 Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission
C92.20 Atypical chronic myeloid leukemia, BCR/ABL-negative, not having achieved remission
C92.21 Atypical chronic myeloid leukemia, BCR/ABL-negative, in remission
C92.22 Atypical chronic myeloid leukemia, BCR/ABL-negative, in relapse
C93.10 Chronic myelomonocytic leukemia not having achieved remission
C94.40 Acute panmyelosis with myelofibrosis not having achieved remission
C94.41 Acute panmyelosis with myelofibrosis, in remission
C94.42 Acute panmyelosis with myelofibrosis, in relapse
C94.6 Myelodysplastic disease, not classified
D45 Polycythemia vera
D46.0 Refractory anemia without ring sideroblasts, so stated
D46.1 Refractory anemia with ring sideroblasts
D46.20 Refractory anemia with excess of blasts, unspecified
D46.21 Refractory anemia with excess of blasts 1
D46.22 Refractory anemia with excess of blasts 2
D46.A Refractory cytopenia with multilineage dysplasia
D46.B Refractory cytopenia with multilineage dysplasia and ring sideroblasts
D46.C Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality
D46.4 Refractory anemia, unspecified
D46.Z Other myelodysplastic syndromes
D46.9 Myelodysplastic syndrome, unspecified
D47.1 Chronic myeloproliferative disease
D47.3 Essential (hemorrhagic) thrombocythemia
D47.4 Osteomyelofibrosis
D47.Z9 Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue
D47.9 Neoplasm of uncertain behavior of lymphoid, hematopoietic and related tissue, unspecified
D72.821 Monocytosis (symptomatic)
D72.829 Elevated white blood cell count, unspecified
D75.1 Secondary polycythemia
D75.81 Myelofibrosis
D75.89 Other specified diseases of blood and blood-forming organs
D75.9 Disease of blood and blood-forming organs, unspecified
Coverage Guidance

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:
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

MolDX Program - Next Generation Sequencing Coding and Billing Guidelines (M00127, V3)
* Next Generation Sequencing (NGS) NGS allows identification of somatic and/or germline alterations in multiple genes simultaneously. This guideline focuses on Targeted and Comprehensive Genomic Profile testing for somatic variant detection using tumor tissue onlybased panels. Panels involving germline variants, matched tumor-normal, or “liquid biopsies” (including circulating tumor cells (CTCs) or DNA (ctDNA), or cell-free DNA (cfDNA)) will be addressed separately, but should be billed using CPT 81479.

Next Generation Sequencing Coding and Billing Guidelines (M00127, V3)

* Effective July 1, 2017, laboratories with 1 to 4 gene(s) on their targeted NGS panel should use CPT 81479 and one (1) UOS along with their test identifier (DEX Z-code) to represent this service on their claims. (Similarly, CPT 81479 should be used to bill for somatic variant detection performed by a targeted NGS panel on a “fluid” sample (e.g., KRAS in pancreatic cyst fluid). Reimbursement is based on the number of reported genes in these small NGS panels. Tier 1 and/or Tier 2 individual biomarker CPT codes should not be used for a single gene or any combination of genes when testing is performed as part of a NGS or other multiplexing technology panel.

* Comprehensive Genomic Profile (CGP) Testing CGP refers to NGS-based testing that has been optimized to identify all types of molecular alterations (i.e., SNVs, small and large indels, CNAs, and SVs) in cancer-related genes in a single test using complex and often proprietary bioinformatics. CGP may also include testing for MSI (microsatellite instability) and TMB (tumor mutational burden).

* Because CGP includes SNVs, small (=40 bp) and large (> 40 bp) indels, CNAs, and SVs, CPT codes 81445, 81450, and 81455 do NOT describe a CGP service. Therefore, to report a CGP service, test providers should use CPT code 81479.

Biomarkers for Oncology LCD Article – Novitas Solutions

* When multiple biomarkers are performed on one specimen and ordered in the context of a set panel of tests then this scenario should be billed as the specific panel if it has its own CPT code or as 81479 if it does not have a specific CPT code. Billing each code separately is incorrect billing and may result in the denial of the claim.



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