Immunoglobulin G4-related disease requiring clinical attention: A case report and review of literature

Table 1 Differential diagnosis between immunoglobulin G4-related cholecystitis and gallbladder cancer

Key points for differentiation		IgG4-related cholecystitis	Gallbladder carcinoma
Clinical features	Demographics	Middle-aged and elderly (> 50 years), with sex ratio variations across regions	Middle-aged to elderly, slightly more females, associated with gallstones
	Symptoms	Mild abdominal pain, jaundice, possible multi-organ involvement	Persistent right upper quadrant pain, weight loss, progressive jaundice, cachexia
	Associated conditions	Often associated with autoimmune pancreatitis, sclerosing cholangitis, retroperitoneal fibrosis	Frequently associated with gallstones/polyps; may metastasize in advanced stages
Laboratory findings	Serum IgG4 Levels	Markedly elevated, > 135 mg/dL, about 70% sensitivity	Usually normal or mildly elevated, nonspecific
	Tumor marker CA19-9	Mildly elevated or normal	Markedly elevated, > 100 U/mL suggests malignancy
	Inflammatory biomarkers (CRP, WBC, etc.)	Mildly elevated in active inflammation	May be elevated, especially with infection
	Liver function tests	Elevated bilirubin and ALP if bile duct involvement	Markedly elevated bilirubin and ALP in obstructive jaundice
Imaging findings	Gallbladder wall changes	Diffuse uniform thickening (> 3 mm) with homogeneous enhancement	Irregular or asymmetric thickening, focal mass or nodule
	Bile duct involvement	Segmental stenosis (long-segment, smooth)	Focal stenosis (rigid, cut-off-like)
	Lymphadenopathy	Common findings (without necrosis or fusion)	May exhibit necrosis, fusion, or capsular invasion
	Other characteristics	May be accompanied by pancreatic enlargement (“sausage-like” appearance)	Liver infiltration and distant metastasis (advanced stage)
Pathological features comparison	Histological features	Dense lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis	Atypical glandular structures, mitotic figures, stromal invasion
	IgG4-positive plasma cell count	> 10/HPF, IgG4/IgG > 40%	Non-specific (occasionally reactive increase)
Treatment response		Glucocorticoid responsiveness (symptomatic/imaging improvement within 2 weeks)	Refractory (requiring surgical resection or chemoradiotherapy)
Prognosis comparison		Favorable (may recur, requires long-term follow-up)	Poor prognosis (5-year survival < 20%, stage-dependent)

IgG4: Immunoglobulin G4; WBC: White blood cell; CRP: C-reactive protein; CA19-9: Carbohydrate antigen 19-9; HPF: High-power field; ALP: Alpha-fetoprotein.

Table 2 Diagnostic pathway and key decision points for immunoglobulin G4-related cholecystitis

Diagnosis phase	Critical examination	Key decision point	Next steps in treatment
Initial suspicion	Medical history, physical examination, serum IgG4	Are there any red-flag signs of IgG4-RD?	If yes: Proceed to next step; if no: Consider alternative diagnoses
Imaging evaluation	Contrast-enhanced CT or contrast-enhanced MRI, ultrasound	Are the imaging findings consistent with IgG4-related cholecystitis?	If consistent: Obtain tissue (for histopathology); if inconsistent but high suspicion remains: MDT discussion
Pathological confirmation	Biopsy specimen or resection specimen	Are the pathological diagnostic criteria for IgG4-RD fulfilled?	If criteria are met: Confirm diagnosis (definitive diagnosis of IgG4-RD); if pathological criteria are fulfilled: Establish definitive diagnosis of IgG4-RD
Treatment monitoring	Symptoms; serum IgG4, IL-6, sIL-2R, ELR; imaging	Is there a response to the administered therapy?	Response to treatment: Supports diagnosis; no response: Re-evaluate

IgG4: Immunoglobulin G4; CT: Computed tomography; MRI: Magnetic resonance imaging; IL: Interleukin; sIL-2R: Soluble interleukin-2 receptor; ELR: Eosinophil-to-lymphocyte ratio; IgG4-RD: Immunoglobulin G4-related disease; MDT: Multidisciplinary team.