Billing and Coding: Genetic Testing for Oncology

This Billing and Coding Article provides billing and coding guidance for Local
Coverage Determination (LCD) L39367 Genetic Testing for Oncology. Please refer
to the LCD for reasonable and necessary requirements.  
  
All instructions provided within the American Medical Association (AMA)
Current Procedural Terminology (CPT) Codebook with rules and guidelines from
the AMA's CPT Editorial Panel and the Medicare NCCI Policy Manual should be
followed when utilizing CPT codes for billing. Proper coding involves
interpreting code descriptions provided by these sources as well as any
associated parentheticals. The instructions below do not represent the full
breadth or depth of instructions found in the CPT Codebook and the Medicare
NCCI Policy Manual. Providers that bill Medicare are expected to follow all
instructions found in these sources.  
  
Molecular code descriptions in the CPT Codebook generally have some or all of
the following components:

  1. Medical condition under investigation
  2. Genetic content to be tested
  3. Technology/methodology used for testing
  4. Specimen type evaluated

Providers must ensure that their use of molecular CPT codes represent the
highest level of specificity in what testing was performed. The following
reviews each of these components with general tips for each:  
  
 **1\. Medical Condition  
  
** When a code designates coverage of a specific medical condition (e.g., CPT
code 81432 - "Hereditary breast cancer- related disorders"), all genes billed
under this code must fall under the description of the medical condition. Even
if all the genes described by a CPT code are tested in a claim, the CPT code
can only be used if the described medical condition matches the documented
disease.  
  
 **2\. Genetic Content  
  
** Commonly, molecular CPT codes have a gene(s) listed within their coding
description. Special attention must be paid to what elements of a gene are
analyzed since not all codes describe the analysis of an entire gene. A gene
could be tested for a single well-known variant (e.g., CPT code 81210 - V600
variants in the _BRAF_ gene) or the gene could be fully sequenced (e.g., CPT
code 81406 - full sequence of the _BRAF_ gene). In fact, several codes in the
Tier 1 molecular section cover the same gene but differ in what element of
that gene they cover.

  * For instance, the CPT codes 81201, 81202, and 81203 all describe tests for the same gene, _APC_ , but cover different elements of the gene such as full gene sequence, known familial variants or duplication/deletion variants.
  * As stated in the Medicare NCCI Policy Manual Chapter 10, these codes in general should not be billed together. An exception could be in **uncommon** **scenarios** such as billing a code for "full gene sequence" with another code for "duplication/deletion variants" when the disease variants cannot be identified by performing full gene sequencing. "Procedures reported together must be both medically reasonable and necessary (e.g., sequencing of procedures) and ordered by the physician who is treating the beneficiary and using the results in the management of the beneficiary's specific medical problem."

Less commonly, molecular CPT codes are defined by only a test methodology, as
is seen in codes for Fluorescence _In Situ_ Hybridization (FISH) found in the
Surgical Pathology section of the CPT Codebook. In brief, FISH is a technique
where a probe (a short, single-stranded nucleic acid sequence) targets a
specific genetic sequence and is labeled/tagged with a fluorescent dye. If the
target is found, the fluorescent dye becomes attached to that target and can
be seen under microscopy or other related imaging. In oncology, FISH probes
are used to evaluate many different genes for many different cancers; however,
many FISH CPT codes do not specify which genes or which cancers are being
evaluated. As a result, special attention must be paid to what unit of service
(UOS) is found in the code description.  
  
A UOS for FISH testing could be defined in numerous ways, including number of
slides evaluated, number of single source specimens evaluated, number of FISH
probes used, number of FISH procedures performed, or number of cells counted.
For Medicare, both the CPT Codebook and the Medicare NCCI Policy Manual
specify which of these UOS applies, and billing for more UOS than were
actually performed is not permitted.  
  
The NCCI manual states that regardless of how many blocks or slides are
created from a surgical, cytologic, or hematologic specimen, testing multiple
blocks or slides from the same specimen source (e.g., tube of blood) still is
considered as 1 UOS per source specimen.

For example:

  * The UOS described for CPT code 88373 is both "per specimen" and "each additional single probe stain procedure." Depending on the testing scenario, the code may or may not be used, and should only be used in relation to additional probes NOT additional specimens.
    * If one single probe procedure is used for a specimen from one source (e.g., right iliac crest bone marrow aspiration), only 1 UOS may be claimed, even if multiple _slides_ from the specimen are tested with the same probe:
    * 1 UOS with the parent CPT code 88367,
    * 0 UOS should be reported with CPT code 88373 since only one single probe procedure was used, regardless of how many slides are made with the single source specimen.
  * If two different single probe procedures are used to evaluate several slides from one source specimen, only 2 UOS may be claimed:
    * 1 UOS with the parent CPT code 88367, AND
    * 1 UOS with the additional CPT code 88373
  * If one single probe procedure is used on two source specimens (e.g., one bone marrow aspiration specimen from the right iliac crest and another specimen from the left iliac crest), only 2 UOS may be claimed: 
    * 2 UOS with the parent CPT code 88367,
    * 0 UOS should be reported with CPT code 88373 since only one single probe procedure was used.
  * The same logic for single probe stain procedures is also true of using multiplex probe stain procedures (CPT code 88374); the UOS is based on the overall multiplex probe stain _procedure_ NOT the number of _probes_ within the multiplex stain.

CPT codes that describe a genomic sequencing panel (GSP) often include
instructions that define the number of genes covered, for instance using a
range (5-50 genes) or using a minimum number required (e.g., "at least" 10
genes).  
  
For instance:

  * CPT code 81436 covers at least five genes and must include the genes MLH1, MSH2, EPCAM, SMAD4, and STK11.
  * This means any test matching the CPT code description for 81436, regardless of whether the test analyzed five genes or 20 genes, would be billed under the CPT code 81436 code with only 1 UOS.
  * Additionally, this means that any test without all five mandatory genes (MLH1, MSH2, EPCAM, SMAD4, and STK11) would NOT be billed with this code.
  * When a CPT code for a panel is used in this context, _no other CPT codes may be used to describe the panel, regardless of presence or absence of modifiers_.

**3\. Technology/Methodology  
  
** When a CPT code description specifies a particular technology and/or
testing methodology, only that technology and/or methodology may be used when
billing that code. Therefore, special attention must be paid to the full code
description, especially if the type of content tested has technology that
typically varies from CPT code to CPT code. For example, CPT codes describing
a gene expression profiling (GEP) test often include the specific methodology
used for that test, such as RT-PCR (e.g., 81518), microarray (e.g., 81521),
and next-generation sequencing (e.g., 81523).  
  
Conversely, if a technology and/or methodology is NOT specified in a code
description, there is no need to match the technology and/or methodology to
that code (e.g., a full sequence analysis of three different genes can be
performed by Sanger Sequencing or NGS). For example, CPT code 81279 describes
targeted sequence analysis for the gene JAK2 without specifying a sequencing
technology. JAK2 is often part of a sequence of reflexive tests evaluating for
a myeloproliferative neoplasm, and commonly each step is performed using real
time/quantitative (RT/q) PCR. However, each step of that testing sequence
could also be performed with Sanger sequencing technology. Additionally, JAK2
could be part of a small NGS panel test with other genes, which, if less than
five genes, could be billed as CPT code 81279 and three additional CPT codes
representing three other genes. Finally, as technology advances, whole
exome/genome sequencing is being utilized more and more as a backbone to
customized testing, wherein all unanalyzed data is masked (only certain
genetic content is made visible while the rest of the data is hidden from the
interpreter) and only a smaller set of genes is analyzed and billed. The
benefit to this newer method is the collected data can be reanalyzed as
additional customized panels by unmasking additional genetic content without
having to rerun the whole exome/genome sequencing. Again, if the custom panel
is small, CPT code 81279 would be billed in tandem with up to three other gene
codes.  
  
Per the Medicare NCCI Policy Manual Chapter 10, "A Tier 1 or Tier 2 molecular
pathology procedure CPT code **should not** , in general, be reported with a
genomic sequencing procedure, molecular multianalyte assay, multianalyte assay
with algorithmic analysis, or proprietary laboratory analysis CPT code where
the CPT code descriptor includes testing for the analyte described by the Tier
1 or Tier 2 molecular pathology code. Procedures reported together must be
both medically reasonable and necessary (e.g., sequencing of procedures) and
ordered by the physician who is treating the beneficiary and using the results
in the management of the beneficiary's specific medical problem."  
  
 **4\. Specimen Type  
  
** Some CPT codes (particularly PLA codes) define what type of specimens or
specimen sources are covered by the code description. For instance, some
multianalyte assays with algorithmic analyses evaluate gene expression in
tumor tissue. Sometimes these tests are restricted to fresh tissue whereas
other tests have been optimized to use formalin-fixed, paraffin-embedded
tissue. These definitions are often clearly stated within the CPT code
description and must be followed when present.  
  
 **Definitions  
  
** Providers should be familiar with all terminology found within the CPT code
descriptions before billing Medicare for these codes. Many of the molecular
terms utilized in the CPT Codebook describe specific parameters that limit a
code's scope of coverage. Definitions are frequently provided at the beginning
of sections and subsections within the CPT Codebook. The following are
selected definitions of terminology and phrases commonly seen in the code
descriptions:

  * **" always including"/"must include"**: Targets that are required in testing described by a CPT code.
  * **" at least"/"or greater"**: Minimum number of genes required to bill for a specific CPT code.

  *     * For instance, if a CPT code description for a panel requires "at least" 10 genes, this means the panel size must, at minimum, analyze 10 genes. However, if the panel analyzes 11, 20, 50, or 100 genes and this code is used, _no other codes may be used to describe the panel, regardless of presence or absence of modifiers_.

  * **Common variants/Common deletions/etc.** : Genetic variants most predominantly associated with a disease, as defined by professional society guidelines. Billing CPT codes with "common" variants in the code description should not include testing for uncommon and/or rare variants. If a variant is felt to be "common," _this designation must be supported by a professional society 's guidelines_.
  * **Deletion/duplication analysis** : Testing that evaluates for loss (deletion) or gain (duplication) of stretches of genetic sequence (dosage of a particular genomic region).
  * **" e.g.,"**: Examples of ... Depending on the context, listed examples following an "e.g.," may or may not be required in the testing described by a code.
  * **Full gene sequence/full sequence analysis** : Testing that evaluates, at a minimum, all exons of a gene. Depending on the testing methodology used, a full sequence analysis may also include additional non-coding sequence (e.g., promotor region, introns) and/or may NOT include data on certain types of variants, such as duplication/deletion variants.
  * **Qualitative** : Results of a test provided as descriptive terms (e.g., positive, negative, inconclusive).
  * **Quantitative** : Results of a test provided as numeric measurements/values (e.g., International Units per milliliter [IU/mL]).
  * **Targeted genomic sequence analysis/targeted sequence analysis** : Typically defined as testing that focuses on (targets) a specific part(s) of a gene. This term is also used to describe selective review of larger regions of the genome when the term is used in the context of more comprehensive sequencing, such as whole genome/exome sequencing.

**Coding Guidance  
  
** **Notice:** It is not appropriate to bill Medicare for services that are
not covered (as described by the entire LCD) as if they are covered. When
billing for non-covered services, use the appropriate modifier.  
  
Per the Medicare NCCI Policy Manual Chapter 10, "CPT codes 81445, 81450, and
81455 describe targeted genomic sequence, DNA analysis or combined DNA and RNA
analysis. CPT code 81445 applies to solid organ neoplasm type (5-50 genes) and
CPT code 81450 applies to hematolymphoid neoplasm type (5-50 genes), while CPT
code 81455 applies to the number of genes analyzed for either a solid or
hematolymphoid neoplasm (51 or greater genes). Providers/suppliers may not
report CPT code 81455 with either CPT code 81445 or 81450. CPT codes 81449,
81451, and 81456 describe targeted genomic sequence RNA analysis using a
separate method."  
  
"All genomic sequencing procedures and molecular multianalyte assays (e.g.,
CPT codes 81410-81471), many multianalyte assays with algorithmic analyses
(e.g., CPT codes 81490-81599, 0004M-XXXXM), and many Proprietary Laboratory
Analyses (PLA) (e.g., CPT codes 0001U-XXXXU) are DNA or RNA analytic methods
that simultaneously assay multiple genes or genetic regions. A
provider/supplier shall not separately report testing for the same gene or
genetic region by a different methodology (e.g., CPT codes 81105-81408, 81479,
88364-88377). CMS payment policy does not allow separate payment for multiple
methods to test for the same analyte."  
  
"If one laboratory procedure evaluates multiple genes using a next generation
sequencing procedure, the laboratory shall report only one unit of service of
one genomic sequencing procedure, molecular multianalyte assay, multianalyte
assay with algorithmic analysis, or proprietary laboratory analysis CPT code.
If no CPT code accurately describes the procedure performed, the laboratory
may report CPT code 81479 (Unlisted molecular pathology procedure) with one
unit of service or may report multiple individual CPT codes describing the
component test results when medically reasonable and necessary. Procedures
reported together must be both medically reasonable and necessary (e.g.,
sequencing of procedures) and ordered by the physician who is treating the
beneficiary and using the results in the management of the beneficiary's
specific medical problem."  
  
For tests that are genomic sequencing procedures that simultaneously assay
multiple genes or genetic regions, coverage would be dependent on the genetic
content examined and whether the content is covered for the patient's specific
medical condition by the LCD.

  * A targeted genomic sequence analysis panel that tests 5 to 50 genes and contains genes that meets LCD coverage criteria for the management of the patient's specific medical condition to improve the patient's outcome may be billed with CPT codes 81445, 81449, 81450, or 81451.
  * A targeted genomic sequence analysis panel that tests for 51 or greater genes and contains genes that meets LCD coverage criteria for the management of the patient's specific medical condition to improve the patient's outcome may be billed with the CPT codes 81455 or 81456.
  * A targeted genomic sequence analysis panel that tests five or greater genes and contains NO genetic content covered by the LCD criteria is billed with CPT codes 81445, 81449, 81450, 81451, 81455, or 81456 and the appropriate modifier to indicate a non-covered service.

It would not be expected that providers would perform, for an oncologic
condition, a genomic sequencing procedure (e.g., next generation sequencing)
that simultaneously assays multiple genes or genetic regions which would not
be accurately described by CPT codes 81445, 81449, 81450, 81451, 81455 or
81456. Frequent utilization of CPT code 81479 and/or multiple individual CPT
codes describing the component test results will be subject to review.

**Note** : For coverage information regarding CPT codes 0022U, 0037U, 0111U,
0172U, 0239U, and 0242U, please refer to NCD 90.2 Next Generation Sequencing
(NGS).

**Note:** For all DNA-only NGS testing for non-hematologic malignancies, the
NCD 90.2 section B or section D criteria must be met.

The NCD 90.2 is only applicable to DNA sequencing diagnostic laboratory tests
using NGS for non-hematologic, somatic (acquired) and germline (inherited)
cancers.

  * For non-hematologic DNA sequencing NGS tests that meet CMS FDA approval or clearance in NCD 90.2 **section B.1.b. or section B.2.b.,** follow NCD requirements in section B.1.a. or section B.2.a.
  * For non-hematologic DNA sequencing NGS tests that do not meet CMS NCD 90.2 section B requirements that are performed in CLIA-certified laboratories, refer to NCD 90.2 **section D** **AND** the LCD for coverage criteria.
  * For NGS tests with combined DNA and RNA analysis of somatic and germline cancers, RNA analysis of somatic and germline cancers, and NGS tests for hematologic cancers, refer to the LCD for coverage criteria.

**Note:** For coverage information regarding CPT codes 88230 through 88291,
please refer to NCD 190.3 Cytogenetics Studies.  
  
 **Note** : For coverage information regarding CPT code 81327 and 81528,
please refer to NCD 210.3 Colorectal Cancer Screening Tests.  
  
 **Note:** Unlisted CPT codes 81479, 81599, and 88299 will be reviewed on a
claim-by-claim basis to determine if coverage criteria in an NCD and/or an LCD
are met. Include the gene(s) or specific laboratory test name on the claim and
submit documentation with the claim to support the service was performed and
meets LCD coverage criteria.  
  
For coding guidance on Tier 1 and Tier 2 codes, CPT code 81479 (Unlisted
Molecular Pathology), testing for multiple genes, -59 Modifier, Next
Generation Sequencing (NGS), Genomic Sequencing Profiles (GSP), Multianalyte
Assays with Algorithmic Analyses (MAAAs) and Proprietary Laboratory Analyses
(PLAs), please refer to the billing and coding article A58918 Molecular
Pathology and Genetic Testing.  
  
Table 1. Tier 2 codes' genes meeting LCD coverage criteria



**Gene/Test**

|

**CPT Code**

|

**Covered Indications per review of NCCN, OncoKB and/or ClinGen**  
  
---|---|---  
  
ABL1 (ABL proto oncogene 1, non-receptor tyrosine kinase) (e.g., acquired
imatinib resistance), T315I variant

|

81401

|

Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, B-Lymphoblastic
Lymphoma

  
  
CBFB/MYH11 (inv(16)) (e.g., acute myeloid leukemia), qualitative, and
quantitative, if performed

|

81401

|

Acute Myeloid Leukemia  
  
DEK/NUP214 (t(6;9))(e.g., acute myeloid leukemia), translocation analysis,
qualitative, and quantitative, if performed

|

81401

|

Acute Myeloid Leukemia  
  
E2A/PBX1 (t(1;19)) (e.g., acute lymphocytic leukemia), translocation analysis,
qualitative, and quantitative, if performed

|

81401

|

Acute Lymphoblastic Leukemia, B-Lymphoblastic Lymphoma

  
  
EML4/ALK (inv(2)) (e.g., non-small cell lung cancer), translocation or
inversion analysis

|

81401

|

Non-Small Cell Lung Cancer

  
  
ETV6/RUNX1 (t(12;21)) (e.g., acute lymphocytic leukemia), translocation
analysis, qualitative and quantitative, if performed

|

81401

|

Acute Lymphoblastic Leukemia, B-Lymphoblastic Lymphoma  
  
EWSR1/ATF1 (t(12;22)) (e.g., clear cell sarcoma), translocation analysis,
qualitative, and quantitative, if performed

|

81401

|

Soft Tissue Sarcoma-Angiomatoid Fibrous Histiocytoma, Soft Tissue Sarcoma-
Clear Cell Sarcoma  
  
EWSR1/ERG (t(21;22)) (e.g., Ewing sarcoma/peripheral neuroectodermal tumor),
translocation analysis, qualitative and quantitative, if performed

|

81401

|

Bone Cancer - Ewing Sarcoma, Soft Tissue Sarcoma - Ewing Sarcoma/Peripheral
Neuroectodermal Tumor  
  
EWSR1/FLI1 (t(11;22)) (e.g., Ewing sarcoma/peripheral neuroectodermal tumor),
translocation analysis, qualitative and quantitative, if performed

|

81401

|

Bone Cancer - Ewing Sarcoma, Soft Tissue Sarcoma - Ewing Sarcoma/Peripheral
Neuroectodermal Tumor  
  
EWSR1/WT1 (t(11;22)) (e.g., desmoplastic small round cell tumor),
translocation analysis, qualitative and quantitative, if performed

|

81401

|

Soft Tissue Sarcoma - Desmoplastic Small Round Cell Tumor, Acute Myeloid
Leukemia  
  
FGFR3 (fibroblast growth factor receptor 3) (e.g., achondroplasia,
hypochondroplasia), common variants (eg, 1138G>A, 1138G>C, 1620C>A, 1620C>G)

|

81401

|

Bladder Cancer  
  
FIP1L1/PDGFRA (del[4q12]) (e.g., imatinib-sensitive chronic eosinophilic
leukemia), qualitative and quantitative, if performed

|

81401

|

Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Fusion Genes,
Systemic Mastocytosis, Chronic Eosinophilic Leukemia,
Myelodysplastic/Myeloproliferative Neoplasms, Gastrointestinal Stromal Tumor  
  
FOXO1/PAX3 (t(2;13)) (e.g., alveolar rhabdomyosarcoma), translocation
analysis, qualitative and quantitative, if performed

|

81401

|

Soft Tissue Sarcoma - Alveolar Rhabdomyosarcoma  
  
FOXO1/PAX7 (t(1;13)) (e.g., alveolar rhabdomyosarcoma), translocation
analysis, qualitative and quantitative, if performed

|

81401

|

Soft Tissue Sarcoma - Alveolar Rhabdomyosarcoma  
  
FUS/DDIT3 (t(12;16)) (e.g., myxoid liposarcoma), translocation analysis,
qualitative, and quantitative, if performed

|

81401

|

Soft Tissue Sarcoma - Myxoid/Round Cell Liposarcoma  
  
IGH@/BCL2 (t(14;18)) (e.g., follicular lymphoma), translocation and analysis;
single breakpoint (e.g.) major breakpoint region [MBR] or minor cluster region
[mcr]), qualitative or quantitative

|

81401

|

Follicular Lymphoma, High Grade B-Cell Lymphoma  
  
MLL/MLLT3 (t(9;11)) (e.g., acute myeloid leukemia) translocation analysis,
qualitative and quantitative, if performed

|

81401

|

Acute Myeloid Leukemia  
  
MUTYH (mutY homolog [E.coli]) (e.g., MYH-associated polyposis), common
variants (e.g., Y165C, G382D)

|

81401

|

Colorectal Carcinoma  
  
NPM1/ALK (t(2;5)) (e.g., anaplastic large cell lymphoma), translocation
analysis

|

81401

|

Non-Small Cell Lung Cancer

  
  
PRAME (preferentially expressed antigen in melanoma)(e.g., melanoma),
expression analysis

|

81401

|

Uveal Melanoma  
  
RUNX1/RUNX1T1 (t(8;21)) (e.g., acute myeloid leukemia) translocation analysis,
qualitative and quantitative, if performed

|

81401

|

Acute Myeloid Leukemia  
  
SS18/SSX1 (t(X;18)) (e.g., synovial sarcoma), translocation analysis,
qualitative and quantitative, if performed

|

81401

|

Soft Tissue Sarcoma - Synovial Sarcoma  
  
SS18/SSX2 (t(X;18)) (e.g., synovial sarcoma), translocation analysis,
qualitative and quantitative, if performed

|

81401

|

Soft Tissue Sarcoma - Synovial Sarcoma  
  
Chromosome 1p-/19q- (e.g., glial tumors), deletion analysis

|

81402

|

Adult Glioma: Oligodendroglioma  
  
COL1A1/PDGFB (t(17;22)) (e.g., dermatofibrosarcoma protuberans), translocation
analysis, multiple breakpoints, qualitative, and quantitative, if performed

|

81402

|

Soft Tissue Sarcoma - Dermatofibrosarcoma Protuberans  
  
TRD@ (T cell antigen receptor, delta) (e.g., leukemia and lymphoma), gene
rearrangement analysis, evaluation to detect abnormal clonal population

|

81402

|

Myelodysplastic Syndromes, Myeloid/Lymphoid Neoplasms with Eosinophilia and TK
Fusion Genes  
  
CTNNB1 (catenin [cadherin-associated protein], beta 1, 88kDa) (e.g., desmoid
tumors), targeted sequence analysis (e.g., exon 3)

|

81403

|

Adult Medulloblastoma, Soft Tissue Sarcoma - Desmoid Fibromatosis

  
  
DNMT3A (DNA [cytosine-5-]-methyltransferase 3 alpha) (e.g., acute myeloid
leukemia), targeted sequence analysis (e.g., exon 23)

|

81403

|

Chronic Myeloid Leukemia, Myelodysplastic Syndromes  
  
EPCAM (epithelial cell adhesion molecule) (e.g., Lynch syndrome),
duplication/deletion analysis

|

81403

|

Myelodysplastic Syndromes, Hereditary Cancer Testing Criteria: Breast Cancer,
Ovarian Cancer, Pancreatic Cancer, and Lynch syndrome  
  
FGFR3 (fibroblast growth factor receptor 3) (e.g., isolated craniosynostosis),
targeted sequence analysis (e.g., exon 7)

(For targeted sequence analysis of multiple FGFR3 exons, use 81404)

|

81403

|

Bladder Cancer  
  
UBA1 (ubiquitin-like modifier activating enzyme 1) (e.g., spinal muscular
atrophy, X-linked), targeted sequence analysis (e.g., exon 15)

|

81403

|

Myelodysplastic Syndromes  
  
VHL (von Hippel-Lindau tumor suppressor) (e.g., von Hippel-Lindau familial
cancer syndrome), deletion/duplication analysis

|

81403

|

Central Nervous System Cancers - Primary Spinal Cord Tumors, Malignant
Peritoneal Mesothelioma, Malignant Pleural Mesothelioma, Neuroendocrine Tumors
of the Pancreas (Well-Differentiated Grade 1/2), Neuroendocrine and Adrenal
Tumors -Pheochromocytoma/Paraganglioma, Neuroendocrine and Adrenal Tumors -
Well-Differentiated Grade 3 Neuroendocrine Tumors, Von Hippel-Lindau Syndrome,
Hereditary Renal Cell Carcinoma  
  
CDKN2A (cyclin-dependent kinase inhibitor 2A) (e.g., CDKN2A-related cutaneous
malignant melanoma, familial atypical mole-malignant melanoma syndrome), full
gene sequence

|

81404

|

Ampullary Adenocarcinoma, Malignant Peritoneal Mesothelioma, Malignant Pleural
Mesothelioma, Cutaneous Melanoma, Neuroendocrine and Adrenal Tumors - Well-
Differentiated Grade 3 Neuroendocrine Tumors, Pancreatic Adenocarcinoma, Soft
Tissue Sarcoma - Malignant Peripheral Nerve Sheath Tumor, Acute Myeloid
Leukemia with BCR-ABL1, B-Lymphoblastic Leukemia/Lymphoma, T-Lymphoblastic
Leukemia/Lymphoma, Hereditary Cancer Testing Criteria: Breast Cancer and
Ovarian Cancer  
  
FGFR2 (fibroblast growth factor receptor 2) (e.g., craniosynostosis, Apert
syndrome, Crouzon syndrome), targeted sequence analysis (e.g., exons 8, 10)

|

81404

|

Bladder Cancer  
  
FGFR3 (fibroblast growth factor receptor 3) (e.g., achondroplasia,
hypochondroplasia), targeted sequence analysis (e.g., exons 8, 11, 12, 13)

|

81404

|

Bladder Cancer  
  
HRAS (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) (e.g., Costello
syndrome), full gene sequence

|

81404

|

Salivary Gland Tumors  
  
MEN1 (multiple endocrine neoplasia I) (e.g., multiple endocrine neoplasia type
1, Wermer syndrome), duplication/deletion analysis

|

81404

|

Adrenal Gland Tumors, Multiple Endocrine Neoplasia, Type 1, Neuroendocrine
Tumors of the Gastrointestinal Tract (Well-Differentiated Grade 1/2),
Neuroendocrine and Adrenal Tumors -Lung and Thymus, Neuroendocrine Tumors of
the Pancreas (Well-Differentiated Grade 1/2), Neuroendocrine and Adrenal
Tumors - Well-Differentiated Grade 3 Neuroendocrine Tumors  
  
RAF1 (v-raf-1 murine leukemia viral oncogene homolog 1) (e.g., LEOPARD
syndrome), targeted sequence analysis (e.g,, exons 7, 12, 14, 17)

|

81404

|

Erdheim-Chester Disease,

Langerhans Cell Histiocytosis,

Rosai-Dorfman Disease  
  
RET (ret proto-oncogene) (e.g., multiple endocrine neoplasia, type 2B and
familial medullary thyroid carcinoma), common variants (e.g., M918T,
2647_2648delinsTT, A883F)

|

81404

|

Ampullary Adenocarcinoma, Extrahepatic Cholangiocarcinoma, Intrahepatic
Cholangiocarcinoma, Gallbladder Cancer, Erdheim-Chester Disease, Langerhans
Cell Histiocytosis, Rosai-Dorfman Disease, Multiple Endocrine Neoplasia, Type
2B, Neuroendocrine and Adrenal Tumors -Pheochromocytoma/Paraganglioma,
Pancreatic Adenocarcinoma, Medullary Thyroid Cancer  
  
SDHC (succinate dehydrogenase complex, subunit C, integral membrane protein,
15kDa) (e.g., hereditary paraganglioma-pheochromocytoma syndrome),
duplication/deletion analysis

|

81404

|

Neuroendocrine and Adrenal Tumors -Pheochromocytoma/Paraganglioma, Soft Tissue
Sarcoma - Carney-Stratakis Syndrome (Gastric Gastrointestinal Stromal Tumor
and Paraganglioma), Hereditary Renal Cell Carcinoma  
  
SDHD (succinate dehydrogenase complex, subunit D, integral membrane protein)
(e.g., hereditary paraganglioma), full gene sequence

|

81404

|

Neuroendocrine and Adrenal Tumors - Pheochromocytoma/Paraganglioma, Soft
Tissue Sarcoma - Carney-Stratakis syndrome (Gastric Gastrointestinal Stromal
Tumor and Paraganglioma), Hereditary Renal Cell Carcinoma  
  
STK11 (serine/threonine kinase 11) (e.g., Peutz-Jeghers syndrome),
duplication/deletion analysis

|

81404

|

Ampullary Adenocarcinoma, Pancreatic Adenocarcinoma, Hereditary Cancer Testing
Criteria: Breast Cancer, Ovarian Cancer, Pancreatic Cancer, and Peutz-Jeghers
Syndrome  
  
VHL (von Hippel-Lindau tumor suppressor) (e.g., von Hippel-Lindau familial
cancer syndrome), full gene sequence

|

81404

|

Central Nervous System Cancers - Primary Spinal Cord Tumors, Malignant
Peritoneal Mesothelioma, Malignant Pleural Mesothelioma, Neuroendocrine Tumors
of the Pancreas (Well-Differentiated Grade 1/2), Neuroendocrine and Adrenal
Tumors -Pheochromocytoma/Paraganglioma, Neuroendocrine and Adrenal Tumors -
Well-Differentiated Grade 3 Neuroendocrine Tumors, Von Hippel-Lindau Syndrome,
Hereditary Renal Cell Carcinoma  
  
ZEB2 (zinc finger E-box binding homeobox 2) (e.g., Mowat-Wilson syndrome),
duplication/deletion analysis

|

81404

|

Acute Myeloid Leukemia - Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)  
  
FH (fumarate hydratase) (e.g., fumarate hydratase deficiency, hereditary
leiomyomatosis with renal cell cancer), full gene sequence

|

81405

|

Hereditary Renal Cell Carcinoma  
  
KRAS (Kirsten rat sarcoma viral oncogene homolog) (e.g., Noonan syndrome),
full gene sequence

|

81405

|

Ampullary Adenocarcinoma, Chronic Myeloid Leukemia, Colon Cancer, Rectal
Cancer, Erdheim-Chester Disease, Langerhans Cell Histiocytosis, Rosai-Dorfman
Disease, Myelodysplastic Syndromes, Myeloproliferative Neoplasms, Non-Small
Cell Lung Cancer, Pancreatic Adenocarcinoma, Soft Tissue Sarcoma - Embryonal
Rhabdomyosarcoma, Juvenile Myelomonocytic Leukemia  
  
MEN1 (multiple endocrine neoplasia I) (e.g., multiple endocrine neoplasia type
1, Wermer syndrome), full gene sequence

|

81405

|

Adrenal Gland Tumors, Multiple Endocrine Neoplasia, Type 1, Neuroendocrine
Tumors of the Gastrointestinal Tract (Well-Differentiated Grade 1/2),
Neuroendocrine and Adrenal Tumors -Lung and Thymus, Neuroendocrine Tumors of
the Pancreas (Well-Differentiated Grade 1/2), Neuroendocrine and Adrenal
Tumors - Well-Differentiated Grade 3 Neuroendocrine Tumors  
  
NF2 (neurofibromin 2 [merlin]) (e.g., neurofibromatosis, type 2),
duplication/deletion analysis

|

81405

|

Malignant Peritoneal Mesothelioma, Malignant Pleural Mesothelioma  
  
RET (ret proto-oncogene) (e.g., multiple endocrine neoplasia, type 2A and
familial medullary thyroid carcinoma), targeted sequence analysis (e.g., exons
10, 11, 13-16)

|

81405

|

Ampullary Adenocarcinoma, Extrahepatic Cholangiocarcinoma, Intrahepatic
Cholangiocarcinoma, Gallbladder Cancer, Erdheim-Chester Disease, Langerhans
Cell Histiocytosis, Rosai-Dorfman Disease, Multiple Endocrine Neoplasia, Type
2A, Neuroendocrine and Adrenal Tumors -Pheochromocytoma/Paraganglioma,
Pancreatic Adenocarcinoma, Medullary Thyroid Cancer  
  
RPS19 (ribosomal protein S19) (e.g., Diamond-Blackfan anemia), full gene
sequence

|

81405

|

Myelodysplastic Syndromes  
  
SDHB (succinate dehydrogenase complex, subunit B, iron sulfur) (e.g.,
hereditary paraganglioma), full gene sequence

|

81405

|

Gastrointestinal Stromal Tumors (GIST),

Neuroendocrine and Adrenal Tumors - Pheochromocytoma/Paraganglioma, Soft
Tissue Sarcoma - Carney-Stratakis syndrome (Gastric GIST and Paraganglioma),
Hereditary Renal Cell Carcinoma  
  
SDHC (succinate dehydrogenase complex, subunit C, integral membrane protein,
15kDa) (e.g., hereditary paraganglioma-pheochromocytoma syndrome), full gene
sequence

|

81405

|

Neuroendocrine and Adrenal Tumors - Pheochromocytoma/Paraganglioma, Soft
Tissue Sarcoma - Carney-Stratakis Syndrome (Gastric Gastrointestinal Stromal
Tumor and Paraganglioma), Hereditary Renal Cell Carcinoma  
  
SMAD4 (SMAD family member 4) (e.g., hemorrhagic telangiectasia syndrome,
juvenile polyposis), duplication/deletion analysis

|

81405

|

Hereditary Cancer Testing Criteria: Juvenile Polyposis Syndrome  
  
STAT3 (signal transducer and activator of transcription 3 [acute-phase
response factor]) (e.g., autosomal dominant hyper-IgE syndrome), targeted
sequence analysis (e.g., exons 12, 13, 14, 16, 17, 20, 21)

|

81405

|

Myelodysplastic Syndromes, T-Cell Lymphomas - Hepatosplenic T-Cell Lymphoma,
T-Cell Lymphomas - T-Cell Large Granular Lymphocytic Leukemia  
  
STK11 (serine/threonine kinase 11) (e.g., Peutz-Jeghers syndrome), full gene
sequence

|

81405

|

Ampullary Adenocarcinoma, Pancreatic Adenocarcinoma, Hereditary Cancer Testing
Criteria: Breast Cancer, Ovarian Cancer, Pancreatic Cancer, and Peutz-Jeghers
Syndrome  
  
TSC1 (tuberous sclerosis 1) (e.g., tuberous sclerosis), duplication/deletion
analysis

|

81405

|

Neuroendocrine Tumors of the Pancreas (Well-Differentiated Grade 1/2),
Neuroendocrine and Adrenal Tumors - Well-Differentiated Grade 3 Neuroendocrine
Tumors, Uterine Sarcoma, Encapsulated Glioma, Hereditary Renal Cell Carcinoma  
  
WT1 (Wilms tumor 1) (e.g., Denys-Drash syndrome, familial Wilms tumor), full
gene sequence

|

81405

|

Chronic Myeloid Leukemia, Malignant Peritoneal Mesothelioma, Malignant Pleural
Mesothelioma, Myelodysplastic Syndromes, Wilms Tumor (Nephroblastoma), Acute
Myeloid Leukemia  
  
ZEB2 (zinc finger E-box binding homeobox 2) (e.g., Mowat-Wilson syndrome),
full gene sequence

|

81405

|

Acute Myeloid Leukemia - Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)  
  
BRAF (B-Raf proto-oncogene, serine/threonine kinase) (e.g., Noonan syndrome),
full gene sequence

|

81406

|

Ampullary Adenocarcinoma,

B-Cell Lymphomas - Splenic Marginal Zone Lymphoma, Adult Gliomas, Chronic
Myeloid Leukemia, Gastrointestinal Stromal Tumors (GIST), Extrahepatic
Cholangiocarcinoma, Intrahepatic Cholangiocarcinoma, Gallbladder Cancer,
Erdheim-Chester Disease, Langerhans Cell Histiocytosis, Rosai-Dorfman Disease,
Pancreatic Adenocarcinoma  
  
BTK (Bruton agammaglobulinemia tyrosine kinase) (e.g., X-linked
agammaglobulinemia), full gene sequence

|

81406

|

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma  
  
CDH1 (cadherin 1, type 1, E-cadherin [epithelial]) (e.g., hereditary diffuse
gastric cancer), full gene sequence

|

81406

|

Gastric Cancer, Hereditary Cancer Testing Criteria: Breast Cancer and Ovarian
Cancer  
  
MAP2K1 (mitogen-activated protein kinase 1) (e.g., cardiofaciocutaneous
syndrome), full gene sequence

|

81406

|

Erdheim-Chester Disease, Langerhans Cell Histiocytosis, Rosai-Dorfman Disease  
  
MAP2K2 (mitogen-activated protein kinase 2) (e.g., cardiofaciocutaneous
syndrome), full gene sequence

|

81406

|

Erdheim-Chester Disease, Langerhans Cell Histiocytosis, Rosai-Dorfman Disease  
  
MUTYH (mutY homolog [E. coli]) (e.g., MYH-associated polyposis), full gene
sequence

|

81406

|

Colorectal Carcinoma  
  
NF2 (neurofibromin 2 [merlin]) (e.g., neurofibromatosis, type 2), full gene
sequence

|

81406

|

Malignant Peritoneal Mesothelioma, Malignant Pleural Mesothelioma  
  
PTPN11 (protein tyrosine phosphatase, non-receptor type 11) (e.g., Noonan
syndrome, LEOPARD syndrome), full gene sequence

|

81406

|

Chronic Myeloid Leukemia, Myelodysplastic Syndromes,

Juvenile Myelomonocytic Leukemia  
  
RAF1 (v-raf-1 murine leukemia viral oncogene homolog 1) (e.g., LEOPARD
syndrome), full gene sequence

|

81406

|

Erdheim-Chester Disease, Langerhans Cell Histiocytosis, Rosai-Dorfman Disease  
  
RET (ret proto-oncogene) (e.g., Hirschsprung disease), full gene sequence

|

81406

|

Ampullary Adenocarcinoma, Extrahepatic Cholangiocarcinoma, Intrahepatic
Cholangiocarcinoma, Gallbladder Cancer, Erdheim-Chester Disease, Langerhans
Cell Histiocytosis, Rosai-Dorfman Disease, Multiple Endocrine Neoplasia, Type
2A and B, Neuroendocrine and Adrenal Tumors - Pheochromocytoma/Paraganglioma,
Pancreatic Adenocarcinoma, Medullary Thyroid Cancer  
  
SDHA (succinate dehydrogenase complex, subunit A, flavoprotein [Fp]) (e.g.,
Leigh syndrome, mitochondrial complex II deficiency), full gene sequence

|

81406

|

Neuroendocrine and Adrenal Tumors - Pheochromocytoma/Paraganglioma, Hereditary
Renal Cell Carcinoma  
  
SMAD4 (SMAD family member 4) (e.g., hemorrhagic telangiectasia syndrome,
juvenile polyposis), full gene sequence

|

81406

|

Hereditary Cancer Testing Criteria: Juvenile Polyposis Syndrome  
  
TSC1 (tuberous sclerosis 1) (e.g., tuberous sclerosis), full gene sequence

|

81406

|

Neuroendocrine Tumors of the Pancreas (Well-Differentiated Grade 1/2),
Neuroendocrine and Adrenal Tumors - Well-Differentiated Grade 3 Neuroendocrine
Tumors, Uterine Sarcoma, Encapsulated Glioma, Hereditary Renal Cell Carcinoma  
  
TSC2 (tuberous sclerosis 2) (e.g., tuberous sclerosis), duplication/deletion
analysis

|

81406

|

Neuroendocrine Tumors of the Pancreas (Well-Differentiated Grade 1/2),
Neuroendocrine and Adrenal Tumors - Well-Differentiated Grade 3 Neuroendocrine
Tumors, Uterine Sarcoma, Encapsulated Glioma, Hereditary Renal Cell Carcinoma  
  
NOTCH1 (notch 1) (e.g., aortic valve disease), full gene sequence

|

81407

|

T-Lymphoblastic Leukemia/Lymphoma  
  
TSC2 (tuberous sclerosis 2) (e.g., tuberous sclerosis), full gene sequence

|

81407

|

Neuroendocrine Tumors of the Pancreas (Well-Differentiated Grade 1/2),
Neuroendocrine and Adrenal Tumors - Well-Differentiated Grade 3 Neuroendocrine
Tumors, Uterine Sarcoma, Encapsulated Glioma, Hereditary Renal Cell Carcinoma  
  
ATM (ataxia telangiectasia mutated) (e.g., ataxia telangiectasia), full gene
sequence

|

81408

|

Ampullary Adenocarcinoma, Pancreatic Adenocarcinoma, Prostate Cancer,
Hereditary Cancer Testing Criteria: Breast Cancer, Ovarian Cancer, and
Pancreatic Cancer  
  
NF1 (neurofibromin 1) (e.g, neurofibromatosis, type 1), full gene sequence

|

81408

|

Gastrointestinal Stromal Tumors (GIST), Myelodysplastic Syndromes,
Neuroendocrine Tumors of the Pancreas (Well-Differentiated Grade 1/2),
Neuroendocrine and Adrenal Tumors - Pheochromocytoma/Paraganglioma,
Neuroendocrine and Adrenal Tumors - Well-Differentiated Grade 3 Neuroendocrine
Tumors, Soft Tissue Sarcoma - Embryonal rhabdomyosarcoma, Soft Tissue Sarcoma
- Malignant peripheral nerve sheath tumor, Neurofibroma, Chronic
Myelomonocytic Leukemia, Juvenile Myelomonocytic Leukemia, Hereditary Cancer
Testing Criteria: Breast Cancer and Ovarian Cancer  
  
**  
Utilization Parameters  
  
** Genetic testing for hereditary cancer syndromes is considered germline
testing, and therefore only permitted once per beneficiary's lifecycle.  
  
The following tests are germline tests:

  * 81202
  * 81215
  * 81217
  * 81293
  * 81296
  * 81299
  * 81308
  * 81318
  * 81322
  * 81353
  * 81432
  * 81433
  * 81435
  * 81436
  * 81437
  * 81438
  * 0101U
  * 0102U
  * 0103U
  * 0129U
  * 0130U
  * 0131U
  * 0132U
  * 0133U
  * 0134U
  * 0135U
  * 0162U
  * 0238U

**Documentation Requirements**

****

  1. All documentation must be maintained in the patient's medical record and made available to the contractor upon request.
  2. Every page of the record must be legible and include appropriate patient identification information (e.g., complete name, dates of service[s]). The documentation must include the legible signature of the physician or non-physician practitioner responsible for and providing the care to the patient.
  3. The submitted medical record must support the use of the selected ICD-10-CM code(s). The submitted CPT/HCPCS code(s) must describe the service performed.
  4. The medical record must demonstrate that the treating clinician who is responsible for the management of the patient's cancer or substantiated suspicion of cancer is the same person as the ordering clinician.
  5. The medical record must include documentation to support an established diagnosis of cancer or a substantiated suspicion of cancer.
  6. The medical record must include documentation of how the test results will directly impact the management of the patient's specific medical problem.
  7. The medical record must clearly document the communication and discussion of pre-test and post-test counseling and the risk associated with genetic testing.
  8. The medical record from the ordering clinician must clearly indicate all tests that are to be performed.