Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Pancreatic cyst.
Treatment: Pathfinder TG genetic testing.
The insurer denied the Pathfinder TG genetic testing.
The denial is upheld. 

The patient is a female.  Computed tomography (CT) scan raised concern for an incidental cystic pancreatic collection of "clustered cysts in the head together measuring 3.5cm, largest individual cyst measures 2.5cm. No ductal dilation." Follow-up magnetic resonance cholangiopancreatography (MRCP) showed a "3.6cm cystic lesion in the head. This consists of a few larger unilocular cysts up to 2.4cm and innumerable tiny clustered cysts. A few thin mildly enhancing septa are present. No solid nodular enhancing component is seen. No inflammatory changes. No main pancreatic ductal dilation."

Pertinent to this review, the patient's provider interpreted the magnetic resonance image (MRI) findings as a "complex lesion in the head of the pancreas consistent with cystic neoplasm, favor serous cystadenoma." The patient's physician performed an endoscopic ultrasound (EUS) with fine need aspiration (FNA) of a 38 millimeter (mm) anechoic cystic collection, and four cubic centimeters (cc) of thin yellow fluid was aspirated. Additional endoscopic findings included: LA grade B esophagitis, Hill grade II valve, normal stomach, normal duodenum, normal major papilla, gallbladder sludge, fatty pancreas, and normal liver.

Pancreatic cyst cytology was reported (within 48-hours of specimen collection). Results proved "negative for malignant cells, no thick mucin or high-grade dysplasia is identified."

At issue, the patient's provider also submitted pancreatic cyst fluid to Interpace Diagnostics for Pathfinder TG analysis with reflex testing to PancraGen. No results were provided.

No, the proposed Pathfinder TG genetic testing was not medically necessary.

It should be noted that PancraGen/Pathfinder TG is propriety and not subject to FDA oversight.  Although commercially available, the role of the service in question in clinical decision making, including selecting treatment options, has not been adequately defined to qualify the study as standard-of-care for the patient's circumstance.

Per the American College of Gastroenterology (ACG) guidelines (11), pancreatic cysts are often detected as in patient's case incidentally on abdominal imaging performed for non-pancreatic indications. Their prevalence in an asymptomatic population is reported from 2.4 to 13.5% with increasing incidence with age. A review of abdominal MRI imaging performed for non-pancreatic indications in patients over the age of 70 showed a 40% incidence of incidental pancreatic cysts. High-risk or invasive interventions are not warranted for small cysts like that of the patient that have no high-risk features. The risk of cancer in a patient like this patient with a small stable cyst that lacks high-risk features is likely less than one percent.

Relative specifically to the PancraGen assay, Sreenarasimhaiah et al report a series of 27 patients "with cysts had samples submitted for DNA analysis which included 15 men and 12 women (mean age 62.8 and 61.3 years, respectively). Consistency in histology, CEA levels, and K-ras-2 and loss of heterozygosity mutations was seen in only 35% of cases, all of which were benign cysts. In the detection of malignant cysts, elevated CEA levels were more predictive of histology in comparison to K-ras-2 or loss of heterozygosity mutations. Additionally, false positivity of loss of heterozygosity mutations was noted to be considerably higher than K-ras-2 mutations or even fluid CEA levels. These findings suggest that DNA mutation analysis should not be used routinely but rather selectively in the evaluation of pancreatic cysts."  

That "cytology adds value to the radiologic assessment of predicting malignancy in mucinous cysts" (Genevay, 2011) is well-recognized as the gold standard. The patient's cyst cytologic examination was unequivocally negative for malignancy. The PathFinder assay was ordered supplemental to her negative cytology.  As such, available records do not support the medical necessity of the Pancragen (PathFinder TG) and GNAS assays under review when conventional management strategies as in the patient's case were definitive.