Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Pancreatic cyst.
Treatment: Topographic Genotyping (cpt 81479).
The insurer denied the Topographic Genotyping (cpt 81479).
The denial is overturned.

The patient is a female. With a two-week history of left upper quadrant pain, she underwent CT (computed tomography) scan of the abdomen, which revealed a 2.2 cm (centimeter) cyst in the body of the pancreas (indeterminate), with an upstream pancreatic duct dilation. Her CBP (complete blood picture) and CMP (comprehensive metabolic panel) were unremarkable. She had no history of pancreatitis.

The patient underwent Endoscopic ultrasound, and FNA (fine needle aspiration) of the pancreatic cyst was done. The multicystic lesion was identified in the tail of the pancreas, and it communicated with the main pancreatic duct. The cyst measured 33mm (millimeters) x 16 mm (millimeters) in size. The cyst was suggestive of branched intraductal mucinous cystic neoplasm. The cystic fluid analysis resulted as follows: The amylase levels were 34 IU/L (international units/liter), and CEA (carcinoembryonic antigen) 407 ng/ml (nanograms per milliliter). The fluid was sent for GNAS (guanine nucleotide binding protein, alpha stimulating) fluid analysis.

Yes, the health plan should cover the molecular analysis of the pancreatic fluid for the evaluation of the pancreatic cyst.
Currently, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with pancreatic cyst fluid (PCF) analysis is the standard of care for the preoperative diagnosis of pancreatic cysts. There are many different types of cysts in the pancreas, but the most common differential diagnosis of cysts that provide PCF (pancreatic cyst fluid) includes non-neoplastic pseudocysts, benign neoplastic serous cysts, premalignant mucinous cysts, malignant mucinous cysts (such as those with invasive carcinoma), and secondarily cystic solid malignancies, such as cystic pancreatic neuroendocrine tumors.

The Papanicolaou Society for Cytopathology (PSC) System for Reporting Pancreaticobiliary Cytology [1], published in 2015, promotes using a multimodal approach for the diagnosis of pancreatic cysts, whereby all the clinical, radiologic, cytologic, biochemical, and molecular information available are incorporated to provide the optimal preoperative risk assessment. PCF (pancreatic cyst fluid) combines cytology and biochemical analysis for carcinoembryonic antigen (CEA) and amylase to distinguish mucinous from non-mucinous cysts and to assess for high-risk features [2,3].  Cytologic evaluation provides high specificity, but lower sensitivity, for the detection of a mucinous cyst.

The interpretation of CEA (carcinoembryonic antigen) levels are also not without limitations: in one study, using a cutoff of 192 ng/mL (nanograms per milliliter) resulted in the misdiagnosis of 39% of cystic mucinous neoplasms risk for malignancy.  With the addition of routine molecular analysis, where KRAS/GNAS (Kirsten rat sarcoma viral oncogene homolog/ guanine nucleotide binding protein, alpha stimulating) mutations are highly specific for a mucinous etiology, the detection of mucinous cysts by PCF (pancreatic cyst fluid) has been shown to have a sensitivity of 90% and specificity >90% [5-7]. The use of molecular analysis provides clinicians with very important information in decision making to risk-stratify the patient and decide as to which pancreatic cysts are at high risks for malignant transformation and require surgical resection or ablation.

Therefore, given the above, the health plan should cover the Topographic Genotyping.

Yes, the requested molecular analysis of the pancreatic fluid is more beneficial than biochemical analysis to risk stratify the patient for management of the patient long-term.