Intraductal Tubular Carcinoma of the Pancreas

Definition

• Cytologically atypical nodular pancreatic intraductal epithelial proliferation with a predominantly tubular architecture

Alternate/Historical Names

• Intraductal and cystic tubulopapillary adenocarcinoma
• Intraductal tubular carcinoma
• Intraductal tubular neoplasm with high grade dysplasia
• Intraductal tubular tumor
• Microcystic tubulopapillary carcinoma
• Intraductal tubulopapillary neoplasm (WHO 2010 preferred term)

Diagnostic Criteria

• Nodular intraductal growth
  • Duct dilated locally
    • May fill and obliterate duct lining
  • Upstream pancreas may be atrophic
• Tubular growth pattern predominates
  • Tightly packed tubules
  • Variable sized tubules
  • May be cribriform
  • May be focally to predominantly papillary
• Cuboidal to columnar cells resembling normal pancreatic duct cells
  • Scant to moderate amount of cytoplasm
    • Eosinophilic to amphophilic cytoplasm
    • Scant to absent cytoplasmic mucin
  • No evidence of mucin secretion
  • No distension of ducts by mucin
  • No goblet cells
• No acinar differentiation
• Moderate to marked cytologic atypia
  • Frequent mitotic figures
  • Frequent necrosis
• May be associated with invasive carcinoma
  • Metastases reported to local nodes, liver and peritoneum
  • Even in the presence of metastases, behavior of carcinoma appears better than for conventional pancreatic carcinoma, with few deaths
• Intraductal tubular adenoma does not appear to be related to intraductal tubular carcinoma

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : August 25, 2009

Supplemental studies

CK7	Pos
CK19	Pos
MUC1	Pos luminal border
MUC2	Neg
MUC5AC	Neg
MUC6	Pos
SMAD4	Pos
Trypsin	Neg
Fascin	Neg

• KRAS and BRAF wild type by PCR
• Mucin stains negative to faint/scant positive

Differential Diagnosis

• Intraductal tubular adenoma
• Mucinous cystic neoplasm (IPMN)
• Pancreatic intraepithelial neoplasia
• Intraductal papillary mucinous neoplasm (IPMN)
• Intraductal oncocytic papillary neoplasm (IOPN)
• Acinar cell carcinoma

Intraductal Tubular Adenoma	Intraductal Tubular Carcinoma
Composed of mucin positive pyloric type cells	Generally mucin poor or negative
Frequent goblet cells	No goblet cells
Low grade atypia	High grade atypia
Mitotic rate 1-5/50 hpf	Mitotic rate frequently >5/50 hpf
No necrosis	Frequent necrosis
Not associated with invasive carcinoma	May have associated invasive carcinoma

Intraductal tubular adenoma and carcinoma do not appear to be related

Intraductal Tubular Carcinoma	Mucinous Cystic Neoplasm of the Pancreas
Nodular intraductal growth	Mucin filled cyst or cysts
Males and females affected	Nearly all female
Involves segments of ducts	Does not communicate with ducts
Extensive tubule formation	No tubules
No ovarian type stroma	Ovarian type stroma

Intraductal Tubular Carcinoma	PanIN
Usually clinically detectable	Usually not clinically detectable
Grossly visible	Not grossly visible
Well formed tubules	No well formed tubules

Intraductal Tubular Carcinoma	Intraductal Papillary Mucinous Neoplasm
Nodular indtraductal growth dilates duct locally	Distended ducts filled with mucin
Tubular or tubulopapillary pattern	Papillary pattern
Cuboidal to columnar cells without cytoplasmic mucin	Columnar mucin filled cells (may lose mucin if high grade)
Uniform high grade atypia	Atypia may vary from low to high
Necrosis common	Necrosis rare
No goblet, neuroendocrine or paneth cells	May have scattered goblet, neuroendocrine or paneth cells
MUC2, MUC5AC, Fascin negative	MUC2, MUC5AC, Fascin positive
KRAS wild type	KRAS frequently mutated

Intraductal Tubular Carcinoma	Intraductal Oncocytic Papillary Neoplasm
Tubular or tubulopapillary pattern	Papillary and solid patterns
Lacks granular cytoplasm	Eosinophilic granular cytoplasm
No goblet cells	Goblet cells frequently present
PASd negative or weak	PASd positive
MUC2, MUC5AC negative	MUC2, MUC5AC positive

Intraductal Tubular Adenoma	Acinar Cell Carcinoma of the Pancreas (Intraductal Variant)
Trypsin negative	Trypsin positive
PASd negative to weak/focal	PASd positive

These may be indistinguishable by standard microscopy

Lists

Cystic Pancreatic Lesions

• Acinar cell cystadenocarcinoma
• Acinar cell cystadenoma
• Enterogenous duplication cyst
• Epidermoid cyst in intrapancreatic accessory spleen
• Intraductal oncocytic papillary neoplasm
• Intraductal papillary mucinous neoplasm
• Islet cell / well differentiated neuroendocrine tumor (occasionally cystic)
• Lymphangioma
• Lymphoepithelial cyst
• Mucinous cystic neoplasm
• Paraduodenal wall cyst
• Pseudocyst
• Serous cystadenocarcinoma
• Serous oligocystic adenoma
• Serous microcystic adenoma
• Solid and cystic hamartoma
• Solid pseudopapillary neoplasm
• Squamoid cyst of pancreatic ducts
• von Hippel Lindau associated cystic lesions

Bibliography

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