Pancreas
Cystic and intraductal lesions
Pancreatic cystic fluid analysis
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PubMed Search: Pancreatic cystic fluid analysis
Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Diagrams / tables | Laboratory | Gross description | Gross images | Cytology description | Cytology images | Molecular / cytogenetics description | Practice question #1 | Practice answer #1 | Practice question #2 | Practice answer #2Cite this page: Ravish NA, Chen W. Pancreatic cystic fluid analysis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreascysticfluidanalysis.html. Accessed September 25th, 2025.
Definition / general
- Pancreatic cysts are fluid filled sacs or growths that develop in the pancreas
- Cyst fluid analysis plays an important role in distinguishing various pancreatic cystic lesions
Essential features
- Endoscopic ultrasonography guided cyst fluid aspiration for cytologic (see Pancreas - cytology), biochemical and molecular analysis may help in the classification and risk stratification of pancreatic cystic lesions
- Most important goal is to identify high risk cystic lesions through a multidisciplinary, algorithmic evaluation
Terminology
- Abbreviations used in this topic include
- Intraductal oncocytic papillary neoplasm (IOPN)
- Intraductal papillary mucinous neoplasm (IPMN)
- Intraductal tubulopapillary neoplasm (ITPN)
- Mucinous cystic neoplasm (MCN)
- Serous cystadenoma (SCA)
Epidemiology
- Incidence of pancreatic cysts is rising, a trend that persists even when accounting for increased imaging use
- Prevalence increases with age (Pancreas 2021;50:1287)
- There is no independent association of pancreatic cyst lesion prevalence with geographic location (Europe, North America or Asia) (Clin Gastroenterol Hepatol 2024;22:1798)
- Serous cystadenomas predominantly occur in women (60% of cases) (N Engl J Med 2024;391:832)
- Mucinous cystic neoplasms and solid pseudopapillary neoplasms occur almost exclusively in women (90% of cases) (N Engl J Med 2024;391:832)
- IPMN affects both sexes equally, usually in the fifth to seventh decades of life and patients are usually asymptomatic (N Engl J Med 2024;391:832)
- ITPN and IOPN each account for < 1% of pancreatic exocrine neoplasms and represent ~3% and 4.5% of intraductal neoplasms, respectively (Am J Surg Pathol 2009;33:1164, J Nippon Med Sch 2013;80:224)
Sites
- Pancreas
Diagrams / tables
Table 1: Cyst fluid characteristics and genes altered in common types of pancreatic cysts (adapted from N Engl J Med 2024;391:832 and Diagnostics (Basel) 2022;12:2573)
| Cyst type | Cytologic features | CEA levels | Glucose levels | Amylase levels | Altered genes | Malignant potential | |
| Most common for cyst type | Enriched in advanced neoplasia | ||||||
| Pseudocyst | Macrophages, lymphocytes and debris | Variable | High | High | 0% | ||
| Serous cystadenoma | Proteinaceous debris and blood, glycogen rich cuboidal epithelial cells | Very low | High | Low | VHL | TP53, TERT promoter mutations | Near 0% |
| IPMN | Thick mucinous fluid, mucinous epithelial cells, papillary structures | High | Low | High | KRAS, GNAS, KLF4, RNF43 | TP53, SMAD4, CDKN2A, PTEN, PIK3CA, AKT1 | 1 - 85% |
| MCN | Thick mucinous fluid, mucinous epithelial cells, ovarian type stroma | High | Low | Low | KRAS, RNF43 | TP53, SMAD4, CDKN2A, PTEN, PIK3CA, AKT1 | 10 - 34% |
| Solid pseudopapillary neoplasm | Hemorrhagic debris; monomorphic, discohesive small cells; hyaline globules and grooved nuclei | Variable | Variable | Low | CTNNB1 | 10 - 15% | |
| Cystic neuroendocrine tumor | Uniform cells in loosely cohesive clusters, coarse, granular, chromatin containing nuclei | Variable | Variable | Low | MEN1, VHL | Loss of ATRX / DAXX; alternative lengthening of telomeres; loss of heterozygosity ≥ 3 genes | 5 - 10% |
Images hosted on other servers:
Key molecular alternations in pancreatic cystic lesions
Laboratory
- Biochemical analysis of pancreatic cyst fluid
- Carcinoembryonic antigen (CEA)
- High CEA (≥ 192 ng/mL) is a widely used marker for distinguishing mucinous from nonmucinous cyst
- 77% specificity and 61% sensitivity (Sci Rep 2017;7:45589)
- Glucose
- Emerging alternative to CEA for differentiating mucinous versus nonmucinous cysts
- More accessible and cost effective than CEA
- Low glucose (≤ 50 mg/dL) suggests mucinous cysts
- High glucose (> 50 mg/dL) suggests nonmucinous cysts
- 92% sensitivity, 87% specificity and 90% accuracy (Surgery 2018;163:600)
- Amylase
- Amylase > 250 U/L suggests pancreatic duct communication (e.g., pseudocysts, IPMNs)
- Mean amylase levels are higher in benign lesions than malignant cysts, with the highest levels seen in pseudocyst
- Not useful for distinguishing mucinous versus nonmucinous cysts
- 62.5% sensitivity and 69.4% specificity for diagnosis of premalignant / malignant lesions (Oncol Lett 2013;5:613)
- CA 19-9 (serum marker; not currently used for cyst fluid analysis)
- Elevated in malignant pancreatic tumors, when using 37 U/mL as cutoff value, 81.3% sensitive and 69.4% specific (Oncol Lett 2013;5:613)
- Can be elevated in benign conditions (e.g., pancreatitis, cholestasis)
- Less useful for distinguishing benign from premalignant cysts
- Important for surveillance and the detection of recurrent disease
- Other emerging cyst fluid markers
- Cyst fluid metabolites by mass spectrometry (Neoplasia 2021;23:1078)
- Cyst fluid methylation profile (World J Gastrointest Oncol 2020;12:1056)
- MicroRNAs expression in cyst fluid (J Clin Med 2021;10:2249, Sci Rep 2020;10:8723)
- Carcinoembryonic antigen (CEA)
Gross description
- Pseudocysts
- Single or multiple unilocular cysts that may contain debris and dark colored fluid (N Engl J Med 2024;391:832)
- Cyst wall formed by fibrous and granulation tissue without true epithelium (Ann Gastroenterol 2016;29:155)
- Serous cystadenomas
- Microcystic subtype: well demarcated, solitary pancreatic tumors (mean: 6.0 cm) composed of numerous small (< 2 mm) thin walled cysts filled with clear, straw colored fluid; a central calcified stellate scar is typical on imaging (Diagn Histopathol (Oxf) 2008;14:260)
- Macrocystic (oligocystic) subtypes tend to be poorly demarcated; a central scar is usually absent
- Mucinous cystic neoplasms
- Location: tail > head of the pancreas
- Solitary and well demarcated, thick walled (1 - 3 mm)
- 1 - 3 cm cysts usually contain tenacious mucin but some can contain degraded blood (Diagn Histopathol (Oxf) 2008;14:260)
- IPMNs
- Location: head > tail of the pancreas
- Often multifocal and communicate with dilated pancreatic ducts (main versus branch pancreatic duct), filled with thick mucin (Diagn Histopathol (Oxf) 2008;14:260)
- Mucin oozing from the ampulla of Vater is almost diagnostic on endoscopy (Int J Surg 2009;7:7)
- Solid pseudopapillary neoplasms
- Location: typically tail of the pancreas in females
- Solid, cystic or both, containing friable necrotic material and hemorrhage
Gross images
Images hosted on other servers:
Positive string sign
Cytology description
Cytology images
Molecular / cytogenetics description
- Molecular analysis of pancreatic cyst fluids
- Next generation sequencing (NGS) of pancreatic cystic fluid is a clinically proven diagnostic tool, although not widely available
- Helpful for the classification and risk stratification of pancreatic cystic lesions (Gut 2018;67:2131, Mod Pathol 2021;34:438, Surg Pathol Clin 2022;15:455)
- Mucinous cysts: mutations in KRAS or GNAS; 79% sensitivity and 98% specificity (Surg Pathol Clin 2016;9:441, Pancreatology 2023;23:868)
- IPMNs with advanced neoplasia (high grade dysplasia and invasion): alterations in TP53, p16 / CDKN2A, SMAD4 and TGFBR2; mutations of mTOR pathway genes (PTEN, PIK3CA and AKT1) (Cancers (Basel) 2024;16:1183, Surg Pathol Clin 2022;15:455, Cancer Cytopathol 2017;125:41)
- MCN: activating KRAS mutations are seen in 50 - 66% of MCNs as well as a loss of function in RNF43; GNAS mutations are rare (Surg Pathol Clin 2022;15:455, Surg Pathol Clin 2016;9:441)
- IOPN: recurrent ATP1B1::PRKACB, DNAJB1::PRKACA or ATP1B1::PRKACA fusion genes (Gastroenterology 2020;158:573)
- Some IOPNs harbor mutations of ARHGAP26, ASXL1, EPHA8 and ERBB4 (Mod Pathol 2016;29:1058)
- ITPN: alterations in chromatin remodeling genes (MLL1 / 2 / 3, BAP1, PBRM1, EED and ATRX) and PI3K pathway genes (PIK3CA, PIK3CB, INPP4A and PTEN) (Cancers (Basel) 2024;16:1183)
- Subset of ITPNs harbor FGFR2 fusion and STRN::ALK fusion (Mod Pathol 2017;30:1760)
- Serous cystadenoma: germline or somatic alterations of the tumor suppressor gene VHL (Proc Natl Acad Sci U S A 2011;108:21188, Surg Pathol Clin 2016;9:441)
- Solid pseudopapillary neoplasm: a somatic activating mutation in CTNNB1 (encoding beta catenin) (Proc Natl Acad Sci U S A 2011;108:21188, Am J Pathol 2002;160:1361, Cancer Res 2001;61:8401)
- See Diagrams / tables
Practice question #1
A 65 year old man presents with a pancreatic cyst discovered incidentally on imaging. Fine needle aspiration (FNA) of the cyst reveals highly viscous fluid that forms a stringy connection when drawn out between gloved fingers (positive string sign). Which of the following pancreatic cystic lesions is most strongly associated with this finding?
- Cystic neuroendocrine tumor
- Intraductal papillary mucinous neoplasm (IPMN)
- Serous cystadenoma
- Solid pseudopapillary neoplasm
Practice answer #1
B. Intraductal papillary mucinous neoplasm (IPMN) is characterized by the production of thick, mucinous fluid, which exhibits high viscosity and can form a stringy connection when drawn out between gloved fingers, known as the string sign. This feature is not observed in other pancreatic cystic lesions and is a useful diagnostic clue. Answer C is incorrect because serous cystadenomas produce thin, nonmucinous, serous fluid. Answer A is incorrect because cystic neuroendocrine tumors contain fluid that is typically hemorrhagic or proteinaceous but not mucinous or highly viscous. Answer D is incorrect because these cystic lesions contain necrotic, hemorrhagic and proteinaceous debris rather than mucinous fluid.
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Reference: Pancreatic cystic fluid analysis
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Reference: Pancreatic cystic fluid analysis
Practice question #2
A 58 year old woman underwent endoscopic ultrasound guided aspiration of a pancreatic tail cyst. The fluid analysis revealed the following biochemical markers.
Based on these findings, which pancreatic cystic lesion is most likely?
| Carcinoembryonic antigen (CEA) | 1,200 ng/mL |
| Glucose | < 10 mg/dL |
| CA 19-9 | Elevated |
| Amylase | Normal |
Based on these findings, which pancreatic cystic lesion is most likely?
- Cystic neuroendocrine tumor
- Mucinous cystic neoplasm (MCN)
- Pseudocyst
- Serous cystadenoma
Practice answer #2
B. Mucinous cystic neoplasms (MCN) are characterized by high CEA levels, often exceeding 200 ng/mL, along with low glucose levels due to mucinous epithelium consumption of glucose. CA 19-9 may be elevated. Amylase levels are typically low to normal as MCNs are not connected with the pancreatic duct. Answer D is incorrect because serous cystadenomas typically have low CEA and CA 19-9 levels and their cyst fluid contains glucose in normal ranges. Answer A is incorrect because cystic neuroendocrine tumors do not typically produce high CEA levels and their cyst fluid characteristics are more variable. Answer C is incorrect because pseudocysts typically show markedly elevated amylase due to pancreatic enzyme leakage and their CEA and CA 19-9 levels are usually undetectable or very low.
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Reference: Pancreatic cystic fluid analysis
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Reference: Pancreatic cystic fluid analysis
