Clinical features and biomarker research advances in immunoglobulin 4-related digestive system disorders

Table 1 Differential diagnosis and diagnostic pitfalls: Type 1 autoimmune pancreatitis vs pancreatic cancer

Feature	AIP-1	PC	Diagnostic pitfalls & uncertainty
Clinical presentation	Often painless obstructive jaundice; multi-organ involvement	Painless jaundice; weight loss; rapid progression	Overlap: Both can present with “painless jaundice” and weight loss in elderly patients
Serum IgG4	Significantly elevated (> 2 × ULN is highly suggestive)	Usually normal	Pitfall: Approximately 10% of PC patients show mild IgG4 elevation. Normal IgG4 does not rule out AIP (seronegative cases)
Imaging (CT/MRI)	“Sausage-like” enlargement; delayed enhancement; capsule-like rim	Focal mass; hypo-vascular (low-density) enhancement	Uncertainty: Atypical mass-forming AIP can perfectly mimic the focal appearance of PC
Ductal signs	Long or multiple strictures without upstream dilation	“Double duct sign” (abrupt cutoff with upstream dilation)	Trap: AIP can occasionally cause distal ductal dilation, simulating malignancy-induced obstruction
Histology (biopsy)	Dense lymphoplasmacytic infiltrate; storiform fibrosis; obliterative vasculitis	Atypical cells; disorganized glandular structure (adenocarcinoma)	Biopsy pitfall: EUS-FNA/FNB samples are small; “storiform fibrosis” is often missed. False positive: Peritumoral stroma in PC can show high IgG4+ cell counts
Treatment response	Rapid radiological resolution with steroids	No response to steroids (disease progresses)	Risk: A “steroid trial” should only be performed after rigorous exclusion of malignancy to avoid delaying surgery

AIP: Autoimmune pancreatitis; PC: Pancreatic cancer; IgG4: Immunoglobulin G4; ULN: Upper limit of normal; CT: Computed tomography; MRI: Magnetic resonance imaging; EUS-FNA/FNB: Endoscopic ultrasound-guided fine-needle aspiration/fine-needle biopsy.