Molecular analysis of pancreatic cyst fluid: a comparative analysis with current practice of diagnosis

Cancer. 2009 Jun 25;117(3):217-27. doi: 10.1002/cncy.20027.

Abstract

Background: The management of patients with pancreatic cysts is based on the preoperative distinction of nonmucinous and mucinous cysts in general and of benign and malignant cysts in particular. An accurate diagnosis is challenging, because endoscopic ultrasound (EUS) and cyst fluid analysis for carcinoembryonic antigen (CEA) and cytology have low sensitivity and specificity. Currently, molecular analysis is a commercially available test that promises an accurate diagnosis. The objective of the current study was to correlate a commercially provided molecular diagnosis (MDx) with a clinical consensus diagnosis (CCD) in the general categories of malignant, benign mucinous, and benign nonmucinous pancreatic cysts.

Methods: Pancreatic cysts that had aspirated fluid submitted for a commercially available molecular test (PathFinderTG) were reviewed. The CCD, defined by histology, malignant cytology, or 2 concordant tests (such as EUS, cytology, or CEA >/=192 ng/mL for mucinous cysts), was categorized as malignant, benign mucinous, or benign nonmucinous cyst in 35 patients. Their MDx, based on the PathFinderTG report, including analysis of k-ras mutation, loss of heterozygosity, and quantity/quality of DNA, also was classified as malignant, benign mucinous, or benign nonmucinous cyst. These 2 diagnoses were compared and correlated.

Results: The concordance between CCD and MDx was 5 of 6 (83%), 13 of 15 (87%), and 13 of 14 (93%), respectively, for malignant, benign mucinous, and benign nonmucinous cysts, with an overall Cohen kappa statistic of 0.816. The sensitivity, specificity, and positive predictive value of the MDx were 83%, 100%, and 100%, respectively, for a malignant cyst and 86%, 93%, and 95%, respectively for a benign mucinous cyst.

Conclusions: Molecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis with high sensitivity, specificity, and positive predictive value for the diagnosis of malignant and benign mucinous pancreatic cysts.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Cyst Fluid / metabolism
  • DNA, Neoplasm / genetics
  • Diagnosis, Differential
  • Female
  • Genes, ras / genetics
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques / methods
  • Mucins / metabolism
  • Pancreas / metabolism
  • Pancreas / pathology*
  • Pancreatic Cyst / diagnosis*
  • Pancreatic Cyst / genetics
  • Pancreatic Cyst / metabolism
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Point Mutation
  • Sensitivity and Specificity

Substances

  • DNA, Neoplasm
  • Mucins