Table 2:

Common Mimickers of IgG4-Related Disease in the Chest

Disease	Differentiating factors
Sjogren’s Syndrome	• Parotid gland involvement more common    • Positive Anti-SSA (Ro) and/or -SSB (La) exclude IgG4-RD
Sarcoidosis	• Cutaneous disease more common    • ACE may be elevated, not expected in IgG4-RD    • Splenomegaly can be seen but would be atypical in IgG4-RD    • Granulomas exclude IgG4-RD
ANCA-associated vasculitis (AAV, e.g. granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (EGPA))	• Fever and very high CRP may be present and atypical for IgG4-RD    • A positive MPO- or PR3-ANCA generally excludes IgG4-RD; only present in ~50% of EGPA cases    • High-grade eosinophilia >3,000/mm3, as seen in EGPA, generally excludes IgG4-RD    • Necrotizing vasculitis and/or granulomas exclude IgG4-RD
Giant Cell Arteritis	• Fever and very high CRP may be present and atypical in IgG4-RD    • Cranial symptoms (headache, scalp tenderness, jaw claudication, vision change) not typical in IgG4-RD
Lymphoma	• Fever may be present    • Malignant pathology excludes IgG4-RD    • Rapid progression across tissue planes not seen in IgG4-RD
Infection	• Fevers and very high CRP common, atypical in IgG4-RD    • Rapid progression across tissue planes not seen in IgG4-RD
Multicentric Castleman’s Disease (MCD)	• Fever and very high CRP often present and atypical in IgG4-RD    • MCD pathology is distinct from IgG4-RD though both may have IgG4+ plasma cells infiltrating tissue
Erdheim-Chester Disease	• Classic long-bone abnormalities (e.g., sclerosis)    • Distinct pathology which includes foamy histiocytes excludes IgG4-RD    • May have a BRAF mutation detectable in tissue and/or circulating blood
Inflammatory Myofibroblastic Tumor	• Much more common in pediatric patients than adult patients    • Distinct pathology reveals spindle cells    • ALK (anaplastic lymphoma kinase), ROS-1, and other gene rearrangements detectable in ~50% of cases