Strategy to differentiate autoimmune pancreatitis from pancreas cancer

Table 1 Diagnosis of definitive and probable type 1 autoimmune pancreatitis using international consensus diagnostic criteria

Diagnosis	Primary basis for diagnosis	Imaging evidence	Collateral evidence
Definitive type 1 AIP	Histology	Typical/indeterminate	Histologically confirmed LPSP (level 1 H)
	Imaging	Typical	Any non-D level 1/level2
		indeterminate	Two or more from level 1 (+ level 2 D1)
	Response to steroid		Level 1 S/OOI + Rt or level 1 D + level 2 S/OOI/H + Rt
Probable type 1 AIP		Indeterminate	Level 2 S/OOI/H + Rt

AIP: Autoimmune pancreatitis; LPSP: Lymphoplasmacytic sclerosing pancreatitis; H: Histology of the pancreas; S: Serology; D: Ductal imaging; OOI: Other organ involvement.

¹Level 2 D is counted as level 1 in this setting.

Table 2 Level 1 and level 2 criteria for type 1 autoimmune pancreatitis

Criterion	Level 1	Level 2
Parenchymal imaging	Typical:	Indeterminate (including atypia2 ):
	Diffuse enlargement with delayed enhancement (sometimes associated with rim-like enhancement)	Segmental/focal enlargement with delayed enhancement
Ductal imaging (ERP)	Long (> 1/3 length of the main pancreatic duct or multiple strictures without marked up stream dilatation	Segmental/focal narrowing without marked upstream dilatation (duct size, < 5 mm )
Serology	IgG4, > 2x upper limit of normal value	IgG4, 1-2x upper limit of normal value
other organ involvement	a or b	a or b
	a: Histology of extrapancreatic organs	a: Histology of extrapancreatic organs including
	Any three of the following:	endoscopic biopsies of bile duct3:
	(1) Marked lymphoplasmacytic infiltration	Both of the following:
	with fibrosis and without granulocytic infiltration	(1) Marked lymphoplasmacytic infiltration
	(2) Storiform fibrosis	without granulocytic infiltration
	(3) Obliterative phlebitis	(2) Abundant (> 10 cells/HPF) IgG-positive cells
	(4) Abundant (> 10 cells/HPF) IgG4-positive cells
	b: Typical radiological evidence	b: Physical or radiological evidence
	At least one of the following:	At least one of the following:
	(1) Segmental/multiple proximal (hilar/intrahepatic)	(1) Symmetrically enlarged salivary/lachrymal glands
	or proximal and distal bile duct stricture	(2) Radiological evidence of renal involvement
	(2) Retroperitoneal fibrosis	described in association with AIP
Histology of the pancreas	LPSP (core biopsy/resection)	LPSP (core biopsy)
	At least 3 of the following:	Any 2 of the following:
	(1) Periductal lymphoplasmacytic infiltrate without	(1) Periductal lymphoplasmacytic infiltrate without
	grnulocytic infiltration	grnulocytic infiltration
	(2) Obliterative phlebitis	(2) Obliterative phlebitis
	(3) Storiform fibrosis	(3) Storiform fibrosis
	(4) Abundant (> 10 cells/HPF) IgG4-positive cells	(4) Abundant (> 10 cells/HPF) IgG4-positive cells
	Diagnostic steroid trial
Response to steroid (Rt)1	Rapid ( ≤ 2 wk) radiologicallydemonstrable resolution or marked improvement in pancreatic/extrapancreatic manifestations

AIP: Autoimmune pancreatitis; LPSP: Lymphoplasmacytic sclerosing pancreatitis; HPF: High power field; ERP: Endoscopic retrograde pancreatography.

¹Diagnostic steroid trial should be conducted carefully by pancreatologists with caveats (see text) only after negative workup for cancer including endoscopic ultrasound-guided fine needle aspiration;

²Atypical: Some AIP cases may show low-density mass pancreatic ductal dilatation, or distal atrophy. Such atypical imaging findings in patients with obstructive jaundice and/or pancreatic mass are highly suggestive of pancreatic cancer. Such patients should be managed as pancreatic cancer unless there is strong collateral evidence for AIP, and a thorough workup for cancer is negative (see algorithm);

³Endoscopic biopsy of duodenal papilla is a useful adjunctive method because ampulla often is involved pathologically in AIP.