Loss-of-Heterozygosity Based Topographic Genotyping with PathfinderTG ^®

This LCD supplements but does not replace, modify or supersede existing Medicare applicable National Coverage Determinations (NCDs) or payment policy rules and regulations for Loss-of-Heterozygosity Based Topographic Genotyping with PathfinderTG^® services. Federal statute and subsequent Medicare regulations regarding provision and payment for medical services are lengthy. They are not repeated in this LCD. Neither Medicare payment policy rules nor this LCD replace, modify or supersede applicable state statutes regarding medical practice or other health practice professions acts, definitions and/or scopes of practice. All providers who report services for Medicare payment must fully understand and follow all existing laws, regulations and rules for Medicare payment for Loss-of-Heterozygosity Based Topographic Genotyping with PathfinderTG^® services and must properly submit only valid claims for them. Please review and understand them and apply the medical necessity provisions in the policy within the context of the manual rules. Relevant CMS manual instructions and policies may be found in the following Internet-Only Manuals (IOMs) published on the CMS Web site.

IOM Citations:

• CMS IOM Publication 100-08, Medicare Program Integrity Manual, Chapter 13, Section 13.5.4 Reasonable and Necessary Provision in an LCD

Social Security Act (Title XVIII) Standard References:

• Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states that no Medicare payment shall be made for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury.
• Title XVIII of the Social Security Act, Section 1862(a)(7). This section excludes routine physical examinations.
• Title XVIII of the Social Security Act, Section 1833(e) states that no payment shall be made to any provider for any claim that lacks the necessary information to process the claim.

Notice: It is not appropriate to bill Medicare for services that are not covered (as described by this entire LCD) as if they are covered. When billing for non-covered services, use the appropriate modifier.

Compliance with the provisions in this policy may be monitored and addressed through post payment data analysis and subsequent medical review audits.

History/Background and/or General Information

Evaluating tissue samples pathologically is crucial to the diagnosis and treatment of patients with malignancy. At times, standard pathologic analyses provide inconclusive information. Combining pathologic study with molecular analyses of microdissected tissue, is claimed to enhance the ability to provide more specific diagnostic information, to help guide treatment decisions. These testing combinations are generally known as "topographic genotyping."

Covered Indications

1. PathfinderTG^® will be considered medically reasonable and necessary when selectively used as an occasional second-line diagnostic supplement:
   
   
   • only where there remains clinical uncertainty as to either the current malignancy or the possible malignant potential of the pancreatic cyst based upon a comprehensive first-line evaluation; AND
   • a decision regarding treatment (e.g. surgery) has NOT already been made based on existing information.

Criteria for Coverage

The specific requirements for medical necessity involve:

1. Highly-concise affirmation, documented in the medical record, that a decision regarding treatment has not already been made and that the results of the molecular evaluation will assist in determining if more aggressive treatment than what is being considered is necessary.
   
   
2. Previous first-line diagnostics, such as, but not restricted to, the following have demonstrated:
   • A pancreatic cyst fluid carcinoembryonic antigen (CEA), which is greater than or equal to 200 ng/ml, suggesting a mucinous cyst, but is not diagnostic.
   • Cyst cytopathologic or radiographic findings, which raise the index of malignancy suspicion, but where second-line molecular diagnostics is expected to be more compelling in the context of a surgical vs. non-surgical care plan.

Limitations

All PathfinderTG^® indications other than pancreatic cyst fluid evaluation are considered investigational and are therefore not considered medically reasonable and necessary due to insufficient data on both analytical and clinical validity.

Specific criteria of Non-coverage to include either:

1. Image guided needle aspiration of the pancreatic cyst or cystic component of a mass lesion or dilated duct demonstrate definitive diagnosis of malignancy by cytology; OR
   
   
2. Cytology not showing malignancy but meets AGA guidelines to reach a definitive diagnosis of benign disease. Lesions must be:
   • Under 1 cm;
   • Lack a solid component;
   • Lack concerning cytology features;
   • Lack main pancreatic duct dilatation of > 1cm in diameter with absence of abrupt change in duct diameter;
   • Have fluid CEA level not exceeding 5 ng/ml

Notice: Services performed for any given diagnosis must meet all of the indications and limitations stated in this policy, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules. Refer to Billing and Coding: Loss-of-Heterozygosity Based Topographic Genotyping with PathfinderTG^®, (A56897), for applicable CPT codes and diagnosis codes.

N/A

N/A

Refer to the Local Coverage Article: Billing and Coding: Loss-of-Heterozygosity Based Topographic Genotyping with Pathfinder TG^®, A56897, for all coding information.

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 medical record documentation must support the medical necessity of the services as stated in this policy.
4. The medical record must clearly indicate the purpose of the Pathfinder TG^® test.
5. The medical record should clearly support why and how the first-line diagnostic work-up was insufficient to adequately monitor or manage the pancreatic cyst(s) under evaluation, such that this very specialized second-line PathfinderTG^® testing has become necessary.

Utilization Guideines

In accordance with CMS Ruling 95-1 (V), utilization of these services should be consistent with locally acceptable standards of practice. It is not expected that repeat PathfinderTG^® is warranted for pancreatic cyst evaluation.

Contractor is not responsible for the continued viability of websites listed.

Other Contractor(s)' Policies

Contractor Medical Directors

ICD-9 LCD L31144, Loss-of-Heterozygosity Based Topographic Genotyping with PathfinderTG ^®

1. Al-Haddad M, Kowalski T, Siddiqui A, et al. Integrated Molecular Pathology Accurately Determines the Malignant Potential of Pancreatic Cysts. Endoscopy. 2015; 47:136-142 (reprint).
2. Cai G, Siddiqui U, Aslanian H, et al. Molecular Analysis of Pancreatic Cyst Fluid: Correlation with Cytologic Diagnosis and Surgical Follow-Up. CT USCAP. March 23, 2010.
3. Das A, Callenberg KM, Styn MA, et al. Endoscopic ablation is a cost-effective cancer preventative therapy in patients with Barrett’s esophagus who have elevated genomic instability. Endoscopy International Open. 2016;4(5):E549-559.
4. Ellsworth E, Jackson SA, Thakkar SJ, et al. Correlation of the presence and extent of loss of heterozygosity mutations with histological classifications of Barrett’s esophagus. BMC Gastroenterology. 2012;12:181.
5. Eluri S, Brugge WR, Daglilar ES, et al. The Presence of Genetic Mutations at Key Loci Predicts Progression to Esophageal Adenocarcinoma in Barrett’s Esophagus. Am. J. Gastroenterol. 2015; 110(6):828-834. doi: 10.1038/ajg.2015.152.
6. Khalid A, Pal R, Sasatomi E, et al. Use of Microsatellite Marker Loss of Heterozygosity in Accurate Diagnosis of Pancreatobiliary Malignancy from Brush Cytology Samples. Gut. 2004; 53: 1860-5.
7. Khalid A, Nodit L, Zalid M, et al. Endoscopic Ultrasound Fine Needle Aspirate DNA Analysis to Differentiate Malignant and Benign Pancreatic Masses [see comment]. American Journal of Gastroenterology. 2006; 101: 2493-500.
8. Khara H, Jackson SA, Nair S, et al. Assessment of Mutational Load in Biopsy Tissue Provides Additional Information about Genomic Instability to Histological Classifications of Barrett’s Esophagus. J Gastrointest Cancer. 2014;45(2):137-145.
9. Kung JS, Lopez OA, McCoy EM, et al. Fluid Genetic Analysis Predict the Biological Behavior of Pancreatic Cysts: Three-year Experience. J Pancreas. Sep 2014;15, (5):, 427-432.
10. Lin X, Finkelstein SD, Zhu B, et al. Loss of Heterozygosities in Barrett Esophagus, Dysplasia, and Adenocarcinoma Detected by Esophageal Brushing Cytology and Gastroesophageal Biopsy. American Cancer Society, Cancer Cytopathology. 2009;2:57-66.
11. Pitman MB, Lewandrowski K, Shen J, et al. Pancreatic Cysts: Preoperative Diagnosis and Clinical Management. Cancer Cytopathol. 2010 Feb 25; 118(1): 1-13.
12. Raja S, Finkelstein SD, Baksh FK, et al. Correlation Between Dysplasia and Mutations of Six Tumor Suppressor Genes in Barrett’s Esophagus. Ann Thorac Surg. 2001;72:1130-5
13. Shen J, Brugge WR, Dimaio CJ, et al. Molecular Analysis of Pancreatic Cyst Fluid: A Comparative Analysis with Current Practice of Diagnosis. Cancer Cytopathol. 2009; 117(3): 217-27.
14. Tanaka M, Fernández-del C, Adsay V, et al. International Consensus Guidelines 2012 for the Management of IPMN and MCN of the Pancreas. Pancreatology 2012; 12(3):183-197.
15. Trikalinos TA, Terasawa T, Raman G, Ip S, Lau J. A Systematic Review of Loss-of-Heterozygosity Based Topographic Genotyping with PathfinderTG^®: Technology Assessment Report. Rockville, MD: Agency for Healthcare Research and Quality, US Dept of Health and Human Services; 2010.
16. www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretative/89509