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Tests that integrate microscopic analysis with molecular tissue analysis are generally called topographic genotyping. Interpace Diagnostics offers two such tests that use the PathFinderTG platform (eg, PancraGEN, BarreGEN). These molecular tests are intended to be used adjunctively when a definitive pathologic diagnosis cannot be made because of inadequate specimen or equivocal histologic or cytologic findings, to inform appropriate surveillance or surgical strategies.
Topographic genotyping, also called molecular anatomic pathology, integrates microscopic analysis (anatomic pathology) with molecular tissue analysis. Under microscopic examination of tissue and other specimens, areas of interest may be identified and microdissected to increase tumor cell yield for subsequent molecular analysis. Topographic genotyping may permit pathologic diagnosis when first-line analyses are inconclusive.
RedPath Integrated Pathology (now Interpace Diagnostics) has patented a proprietary platform called PathFinderTG; it provides mutational analyses of patient specimens. The patented technology permits analysis of tissue specimens of any size, “including minute needle biopsy specimens,” and any age, “including those stored in paraffin for over 30 years.” Interpace currently describes in detail one PathFinderTG test called PancraGEN on its website and describes another PathFinder test called BarreGEN™ as "in the pipeline" (listed and briefly described in Table 1). As stated on the company website, PancraGEN integrates molecular analyses with first-line results (when these are inconclusive) and pathologist interpretation. The manufacturer calls this technique integrated molecular pathology. Test performance information is not provided on the website.
Table 1. PathFinderTG Tests
Test Description Specimen Types
ERCP: endoscopic retrograde cholangiopancreatography.
Management of Mucinous Neoplasms of the Pancreas
True pancreatic cysts are fluid-filled, cell-lined structures, which are most commonly mucinous cysts (intraductal papillary mucinous neoplasm [IPMN] and mucinous cystic neoplasm [MCN]), which are associated with future development of pancreatic cancers. Although mucinous neoplasms associated with cysts may cause symptoms (eg, pain, pancreatitis), an important reason that such cysts are followed is the risk of malignancy, which is estimated to range from 0.01% at the time of diagnosis to 15% in resected lesions.
There is no single standardized approach to evaluating and managing pancreatic cysts. Given the rare occurrence but poor prognosis of pancreatic cancer, there is a need to balance potential early detection of malignancies while avoiding unnecessary surgical resection of cysts. Several guidelines address the management of pancreatic cysts, but high-quality evidence to support these guidelines is not generally available. Although recommendations vary, first-line evaluation usually includes examination of cyst cytopathologic or radiographic findings and cyst fluid carcinoembryonic antigen (CEA). In 2012, an international consensus panel published statements for the management of IPMN and MCN of the pancreas. These statements are referred to as the Fukouka Consensus Guidelines and were based on a symposium held in Japan in 2010 and updated a 2006 publication (Sendai Consensus Guidelines) by this same group. The panel recommended surgical resection for all surgically fit patients with main duct IPMN or MCN. For branch duct IPMN, surgically fit patients with cytology suspicious or positive for malignancy are recommended for surgical resection, but patients without “high-risk stigmata” or “worrisome features” may be observed with surveillance. “High-risk stigmata” are: obstructive jaundice in proximal lesions (head of the pancreas); presence of an enhancing solid component within the cyst; or 10 mm or greater dilation of the main pancreatic duct. “Worrisome features” are: pancreatitis; lymphadenopathy; cyst size 3 cm or greater; thickened or enhancing cyst walls on imaging; 5 to 10 mm dilation of the main pancreatic duct; or abrupt change in pancreatic duct caliber with distal atrophy of the pancreas.
In 2015, the American Gastroenterological Association published a guideline on the evaluation and management of pancreatic cysts; it recommends patients undergo further evaluation with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) only if the cyst has two or more worrisome features (size ≥3 cm, a solid component, a dilated main pancreatic duct). The guideline recommends that patients with a solid component, dilated pancreatic duct and/or “concerning features” on EUS-FNA should undergo surgery.
Management of Barrett Esophagus
Barrett esophagus refers to the replacement of normal esophageal epithelial layer with metaplastic columnar cells in response to chronic acid exposure from gastroesophageal reflux disease (GERD). The metaplastic columnar epithelium is a precursor to esophageal adenocarcinoma (EAC). These tumors frequently spread before symptoms are present so detection at an early stage might be beneficial. Surveillance for EAC is recommended for those diagnosed with Barrett esophagus. However, there are few data to guide recommendations about management and surveillance, and many issues are controversial. In 2015 guidelines from the American College of Gastroenterology (ACG) and a consensus statement from an international group of experts (Benign Barrett’s and CAncer Taskforce [BOB CAT]) regarding management of Barrett esophagus were published. ACG recommendations for surveillance are stratified by presence of dysplasia. When no dysplasia is detected, ACG reports the estimated risk of progression to cancer for patients ranges from 0.2% to 0.5% per year and ACG recommends endoscopic surveillance every 3 to 5 years. For low-grade dysplasia, the estimated risk of progression is about 0.7% per year and ACG recommends endoscopic therapy or surveillance every 12 months. For high-grade dysplasia, the estimated risk of progression is about 7% per year and ACG recommends endoscopic therapy. The BOB CAT consensus group did not endorse routine surveillance for people with no dysplasia and was unable to agree on surveillance intervals for low-grade dysplasia.
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Patented diagnostic tests (eg, PancraGEN™) are available only through Interpace Diagnostics (Pittsburgh, PA and New Haven, CT; formerly RedPath Integrated Pathology) under the auspices of CLIA. Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.
POLICYMolecular testing using the PathFinderTG® system is considered investigational for all indications including the evaluation of pancreatic cyst fluid and Barrett esophagus.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Genetic counseling is primarily aimed at patients who are at risk for inherited disorders, and experts recommend formal genetic counseling in most cases when genetic testing for an inherited condition is considered. The interpretation of the results of genetic tests and the understanding of risk factors can be very difficult and complex. Therefore, genetic counseling will assist individuals in understanding the possible benefits and harms of genetic testing, including the possible impact of the information on the individual’s family. Genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
POLICY HISTORY4/29/2008: Policy added
7/17/2008: Reviewed and approved by the Medical Policy Advisory Committee (MPAC)
4/27/2009: Policy reviewed, no changes
07/09/2010: Policy description revised to define PCR as "polymerase chain reaction." Policy statement unchanged.
08/02/2011: Policy reviewed; no changes.
07/17/2012: Policy reviewed; no changes.
08/14/2013: Policy reviewed; no changes.
07/31/2014: Policy reviewed; description revised. Policy statement revised to add "and Barrett esophagus." It previously stated: Molecular testing using the PathFinderTG® system is considered investigational for all indications including the evaluation of pancreatic cyst fluid and of suspected or known gliomas.
08/03/2015: Code Reference section updated for ICD-10.
09/22/2015: Policy reviewed; policy statement unchanged. Investigative definition updated in Policy Guidelines section.
06/06/2016: Policy number added.
08/19/2016: Policy description updated to remove tests that are no longer commercially available and to add information regarding management of mucinous neoplasms of the pancreas and Barrett Esophagus. Removed "suspected or known gliomas" from the investigational policy statement. Policy Guidelines updated to add genetic counseling information.
SOURCE(S)Blue Cross & Blue Shield Association Policy # 2.04.52
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.