Pancreatic Intraepithelial Neoplasia (PanIN)

(Hyperplasia / Atypical Hyperplasia / Dysplasia)

Epidemiology:

Common sites:

Gross features:

• not seen grossly
• not mass forming

Histologic features:

• non-dilated ducts involved (by definition) (see IPMN if dilated) 
• PanIN-1A:
• simple, columnar, mucin-filled, perfectly polarized cells
• small nuclei
• PanIN-1B:
• Papillary mucinous epithelium without dysplasia
• PanIN-2:
• Mild to moderate dysplasia
• Mild to moderate cytologic atypia / nuclear irregularity / hyperchromasia
• Pseudostratification of nuclei
• Nuclear enlargement
• PanIN-3 (carcinoma in situ):
• Severe dysplasia
• Loss of polarity
• Irregular stratification
• Marked cytologic atypia / nuclear irregularity / hyperchromasia
• Cribriforming often
• Intraluminal blebbing often
• Budding off of noncohesive cells
• Necrosis maybe
• Mitoses
• Acidic sialomucin type mucin usually

Immunophenotype:

Marker:	Sensitivity:	Specificity:
MUC1		Not expressed in intestinal-type IPMN
MUC2 (neg)		Expressed in intestinal-type IPMN

Molecular features:

• progressive mutations from PanIN-1A to PanIN-3:
• telomere shortening
• mutations in K-RAS oncogene (36% 1A / 44% 1B / 87% 2&3)
• CDKN2A (p16 tumour suppressor gene) mutations (PanIN-2)
• inactivation of p53, SMAD4, and MRCA2 tumour suppressor genes (PanIN-3 most often

Other features:

•  presumed precursor of ductal carcinoma
• PanIN-1 is a common incidental finding in normal pancreata
• PanIN-3 is very common in pancreata with invasive ductal carcinoma, and exceedingly uncommon otherwise

References:

• Robbins 2005
• Essentials of Anatomic Pathology 2006