Definition/General
Introduction:
Pancreatic mucinous cystadenoma (MCA) or mucinous cystic neoplasm (MCN) is a cystic neoplasm with malignant potential composed of mucin-producing epithelium
It represents 10-45% of pancreatic cystic neoplasms depending on diagnostic criteria
FNAC shows characteristic thick mucoid cyst fluid with high CEA levels and mucinous epithelium
The presence of ovarian-type stroma is pathognomonic but rarely seen in FNAC specimens.
Origin:
MCN arises from pancreatic ductal epithelium with characteristic ovarian-type stroma
The stromal component contains estrogen and progesterone receptors explaining female predominance
Epithelium ranges from benign to high-grade dysplasia to invasive adenocarcinoma
Location predominantly in pancreatic body and tail (90%)
No communication with main pancreatic duct distinguishes from IPMN
Growth pattern typically slow with potential for malignant transformation.
Classification:
WHO classification recognizes mucinous cystic neoplasm with ovarian-type stroma
Dysplasia graded as low-grade or high-grade similar to PanIN
Invasive carcinoma may develop (15-20% of cases)
Non-invasive MCN has excellent prognosis after complete resection
High-grade dysplasia requires surgical resection due to malignant potential
Male MCN extremely rare and controversial entity.
Epidemiology:
Strong female predominance (95% of cases) in 4th-5th decades
Peak incidence between 40-50 years of age
Rare in males and when present, usually elderly patients
Size ranges from 2-25 cm with average 8-10 cm
Location: body/tail (90%), head (10%)
Indian population shows similar demographics
Hormone exposure may influence development.
Clinical Features
Presentation:
Abdominal pain most common symptom (80-90% of cases)
Mass effect symptoms with large tumors
Early satiety and weight loss in advanced cases
Some patients asymptomatic with incidental detection
Acute pancreatitis rarely associated (unlike IPMN)
Jaundice uncommon unless invasive carcinoma with metastases.
Symptoms:
Epigastric or left upper quadrant abdominal pain
Pain may radiate to back in large tumors
Nausea and vomiting with gastric compression
Early satiety and weight loss
Back pain suggests retroperitoneal extension
Diabetes mellitus may develop with extensive pancreatic replacement
Constitutional symptoms in malignant cases.
Risk Factors:
Female gender strongly associated (95% of cases)
Age 40-60 years typical range
Hormonal factors may play role (estrogen/progesterone exposure)
No clear genetic predisposition identified
Family history rarely contributory
No association with smoking or alcohol
Pregnancy may accelerate growth due to hormonal stimulation.
Screening:
No routine screening recommended for general population
Imaging with MRI/MRCP for characterization
High CEA in cyst fluid (>192 ng/mL) supports diagnosis
EUS-guided FNAC for definitive tissue diagnosis
Absence of duct communication distinguishes from IPMN
Surgical consultation required for all MCNs due to malignant potential.
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Gross Description
Appearance:
FNAC yields thick, viscous, mucoid fluid
Fluid appears turbid to opaque with high viscosity
Volume variable but typically substantial (5-50 mL)
Color ranges from clear to brown depending on blood content
Thick consistency makes aspiration challenging
Epithelial cells embedded in mucoid background.
Characteristics:
High viscosity fluid that may clog aspiration needles
Thick mucoid consistency unlike thin serous fluid
Protein content high (>3 g/dL)
CEA levels markedly elevated (typically >192 ng/mL)
Amylase levels variable but often low
Cytological yield moderate due to mucoid dilution effect.
Size Location:
Size ranges from 2-25 cm with most being 5-15 cm
Pancreatic body and tail location in 90% of cases
Pancreatic head involvement rare (10%)
Multilocular cystic architecture on imaging
No communication with main pancreatic duct
Central location within pancreatic parenchyma typical.
Multifocality:
Usually solitary lesions (>95% of cases)
Multiple MCNs extremely rare
Synchronous other pancreatic neoplasms possible
Different areas within same lesion may show varying grades of dysplasia
Solid components suggest high-grade dysplasia or invasion
Calcifications may be present in chronic cases.
Microscopic Description
Histological Features:
Mucin-producing columnar epithelium with variable degrees of dysplasia
Epithelial cells show abundant cytoplasmic mucin
Nuclei demonstrate varying degrees of atypia from bland to high-grade
Thick mucoid background predominates in FNAC specimens
Inflammatory cells may be present
Ovarian-type stroma rarely identified in FNAC.
Cellular Characteristics:
Tall columnar cells with abundant mucin-filled cytoplasm
Nuclei basally located in benign areas
Nuclear enlargement and stratification in dysplastic areas
Chromatin ranges from fine to coarse depending on grade
Prominent nucleoli in high-grade dysplasia
Goblet cell morphology common.
Architectural Patterns:
Epithelial cells in cohesive sheets and clusters
Papillary formations suggest higher grade dysplasia
Complex architectural patterns in high-grade areas
Single cells scattered in mucoid background
Three-dimensional clusters with overlapping nuclei
Cribriform patterns in advanced dysplasia.
Grading Criteria:
Low-grade dysplasia: uniform nuclei, minimal atypia, intact polarity
High-grade dysplasia: nuclear enlargement, pleomorphism, loss of polarity
Invasive carcinoma: single cells, marked atypia, necrosis
Most FNAC cases show low to moderate-grade features
High-grade features suggest need for urgent surgical evaluation.
Immunohistochemistry
Positive Markers:
MUC5AC strongly positive in mucinous epithelium
CK7 and CK19 positive in epithelial cells
CEA positive with increasing intensity in high-grade dysplasia
MUC1 positive in high-grade areas
CDX2 may be positive in intestinal-type areas
CA 19-9 often elevated in serum and cyst fluid.
Negative Markers:
MUC2 typically negative (distinguishes from IPMN)
Trypsin and chymotrypsin negative (excludes acinar origin)
Chromogranin and synaptophysin negative
TTF-1 negative
Inhibin negative (distinguishes from serous lesions)
p16 variable depending on dysplasia grade.
Diagnostic Utility:
MUC5AC essential for confirming mucinous differentiation
High CEA in cyst fluid (>192 ng/mL) strongly suggestive
Hormone receptors (ER/PR) positive in ovarian-type stroma when present
p53 overexpression correlates with high-grade dysplasia
Ki-67 increases with dysplasia grade
SMAD4 loss suggests malignant transformation.
Molecular Subtypes:
Gastric-type epithelium most common (MUC5AC+, MUC2-)
Intestinal-type less common (CDX2+, MUC2+)
Pancreatobiliary-type rare but described
High-grade dysplasia shows increased MUC1 expression
Invasive areas may lose mucinous markers
Ovarian stroma positive for inhibin and hormone receptors.
Molecular/Genetic
Genetic Mutations:
KRAS mutations in 50-75% of MCNs (more common in high-grade)
TP53 mutations in high-grade dysplasia and invasive carcinoma
PIK3CA mutations in subset of cases
GNAS mutations rare (distinguishes from IPMN)
CDKN2A alterations in advanced lesions
SMAD4 mutations in invasive carcinomas.
Molecular Markers:
KRAS mutations early event in mucinous transformation
p53 overexpression correlates with TP53 mutations
Loss of p16 expression with CDKN2A alterations
SMAD4 loss indicates poor prognosis
Microsatellite instability rare
Chromosomal instability pattern in advanced cases.
Prognostic Significance:
Non-invasive MCN has excellent prognosis after complete resection (>95% 5-year survival)
High-grade dysplasia carries 15-20% risk of malignant transformation
Invasive carcinoma has poor prognosis similar to ductal adenocarcinoma
Size >10 cm associated with higher malignant potential
Age >50 years correlates with advanced histology.
Therapeutic Targets:
Complete surgical resection curative for non-invasive MCN
KRAS mutations potential target in advanced cases
p53 pathway alterations suggest chemosensitivity patterns
Hormone receptor positivity in stroma not therapeutically relevant
Surveillance unnecessary after complete resection of benign MCN.
Differential Diagnosis
Similar Entities:
Intraductal papillary mucinous neoplasm (IPMN) shows duct communication
Serous cystadenoma has thin fluid and low CEA
Pancreatic pseudocyst lacks epithelial lining and has inflammatory history
Cystic degeneration of solid tumors shows primary tumor morphology
Lymphoepithelial cyst has lymphoid component
Simple pancreatic cyst acellular.
Distinguishing Features:
MCN shows thick mucoid fluid and high CEA (>192 ng/mL)
IPMN communicates with main pancreatic duct and affects elderly males
Serous lesions have thin watery fluid and low CEA (<192 ng/mL)
Pseudocysts lack epithelial cells and have inflammatory background
MCN predominantly affects middle-aged women
Ovarian-type stroma pathognomonic when present.
Diagnostic Challenges:
Distinguishing low-grade MCN from reactive mucinous metaplasia
Ovarian-type stroma rarely identified in FNAC specimens
High-grade dysplasia may be focal and missed
Concurrent chronic pancreatitis complicates morphology
Scant cellularity in some cases limits assessment
Clinical correlation with imaging essential.
Rare Variants:
Male MCN controversial entity requiring strict criteria
MCN with high-grade dysplasia shows complex architecture
Invasive carcinoma arising in MCN has ductal morphology
Mixed serous-mucinous lesions extremely rare
MCN with neuroendocrine differentiation reported
Calcifying MCN shows dystrophic calcification.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
EUS-guided aspiration of pancreatic cystic lesion, [volume] mL thick mucoid fluid obtained
Fluid Characteristics
Thick, viscous, mucoid fluid with high protein content, volume [X] mL
Cytomorphological Description
Mucin-producing columnar epithelium with [low-grade/high-grade] dysplasia. Abundant cytoplasmic mucin. Nuclei show [mild/moderate/marked] atypia. Thick mucoid background
Chemical Analysis
CEA: [X] ng/mL (reference >192 ng/mL suggestive of mucinous lesion), Amylase: [X] U/L
Cytological Diagnosis
Mucinous cystic neoplasm with [low-grade/high-grade] dysplasia (Category IV - Neoplastic or Category V - Suspicious)
Clinical Correlation
Findings correlate with imaging showing cystic lesion without duct communication in pancreatic [body/tail]
Recommendations
Surgical consultation recommended due to malignant potential. Complete resection curative for non-invasive lesions
Final Diagnosis
Pancreatic mucinous cystadenoma - Premalignant cystic neoplasm requiring surgical evaluation