IgG4-related lymphadenopathy is the lymphatic involvement of IgG4-related disease (IgG4-RD), with lymphadenopathy accompanying up to 80% of all IgG4-RD patients. IgG4-RD is a systemic fibro-inflammatory disease characterized by chronic inflammation, IgG4-positive plasma cell infiltration, storiform fibrosis, and obliterative phlebitis. Lymph node involvement may be isolated or coexist with organ involvements such as autoimmune pancreatitis, retroperitoneal fibrosis, salivary/lacrimal gland involvement, and sclerosing cholangitis. Serum IgG4 levels are generally elevated (>135 mg/dL). Typically seen in men aged 50-70 (M:F=3:1). On imaging, nonspecific enlarged lymph nodes are observed; the presence of multiorgan involvement is a diagnostic clue. Shows dramatic response to steroids.
Age Range
40-80
Peak Age
60
Gender
Male predominant
Prevalence
Rare
The pathogenesis of IgG4-related lymphadenopathy is based on complex interactions between CD4+ T cells, B cells, and plasma cells. The initiating event is likely a T-cell response to autoantigens or environmental antigens. Activated CD4+ T cells (especially Th2 and T follicular helper cells) trigger B-cell differentiation and IgG4 class switching. IgG4-positive plasma cells accumulate in lymph node parenchyma and expand interfollicular areas. Simultaneously, fibroblasts activate to form storiform (whorled, cartwheel-like) fibrosis — this fibrotic process changes tissue contrast on imaging and causes signal loss at fibrosis foci on T2. Obliterative phlebitis (complete occlusion of vein wall by fibrosis) is a characteristic histological finding. Homogeneous enhancement on imaging reflects the rich vascular stroma of plasma cell infiltration. Multiorgan involvement results from systemic immune dysregulation triggering the fibro-inflammatory process simultaneously in all tissues containing IgG4-positive plasma cells.
The combination of multiple organ involvements (pancreas/'sausage pancreas', retroperitoneal fibrosis, salivary gland enlargement), concurrent lymphadenopathy, and elevated serum IgG4 is pathognomonic for IgG4-related disease.
On B-mode ultrasonography, mildly to moderately enlarged, homogeneously hypoechoic lymph nodes are seen. Hilum is preserved in most cases or mildly thinned. Nodes generally maintain oval shape. Internal echo structure is homogeneous — necrosis or calcification is not expected. Concurrent salivary gland enlargement (submandibular, parotid) or lacrimal gland enlargement may provide a clue.
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On US, mildly to moderately enlarged, homogeneously hypoechoic lymph nodes with preserved hilum are noted; IgG4-related disease should be considered in the presence of concurrent salivary gland enlargement.
On contrast-enhanced CT, mildly to moderately enlarged, homogeneously enhancing lymph nodes are seen — generally short axis 10-25 mm range. No necrosis or calcification. Concurrent organ involvements are diagnostic clues: pancreas (diffuse enlargement + peripancreatic halo = 'sausage pancreas'), retroperitoneal soft tissue (retroperitoneal fibrosis), salivary/lacrimal glands (bilateral symmetric enlargement), kidneys (multifocal lesions), lungs (GGO, consolidation). This multiorgan involvement + LAP combination is highly characteristic of IgG4-RD.
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Contrast-enhanced CT demonstrates enlarged, homogeneously enhancing lymph nodes at multiple stations along with pancreatic diffuse enlargement/retroperitoneal fibrosis/salivary gland enlargement; findings are consistent with IgG4-related disease.
On color Doppler, hilar vascular pattern is generally preserved in enlarged lymph nodes. Vascularity may be normal or mildly increased. Peripheral vascularity is generally not seen. These findings similar to benign reactive pattern reflect the non-destructive nature of IgG4-RD.
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Doppler ultrasonography demonstrates preserved hilar vascular pattern in enlarged lymph nodes without peripheral vascularity.
On DWI, enlarged lymph nodes may show mild to moderate diffusion restriction. ADC values are generally in the range of 1.0-1.4 × 10⁻³ mm²/s — higher than lymphoma. ADC values may decrease as fibrosis proportion increases (fibrotic tissue mechanically restricts water diffusion).
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On DWI, mild diffusion restriction is noted in enlarged lymph nodes with ADC values (___×10⁻³ mm²/s) higher than lymphoma; findings consistent with IgG4-related lymphadenopathy.
On FDG PET-CT, enlarged lymph nodes demonstrate mild to moderate FDG uptake (SUVmax generally 3-7). Concurrently involved organs (pancreas, salivary glands, retroperitoneum) may also be FDG-avid. PET-CT is used for assessing disease extent and treatment response. Intense uptake (SUVmax >10) may suggest lymphoma transformation.
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FDG PET-CT demonstrates mild to moderate FDG uptake (SUVmax: ___) in enlarged lymph nodes and concurrent organ involvements; findings are consistent with IgG4-related disease.
On T2-weighted images, enlarged lymph nodes show mildly hyperintense signal. In advanced stages, as storiform fibrosis proportion increases, T2 signal decrease (hypointensity foci) may be observed — this is a finding specific to fibrosis. Homogeneous enhancement is seen on contrast-enhanced T1.
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On MRI T2, enlarged lymph nodes demonstrate mildly hyperintense signal with focal hypointense areas due to advanced fibrosis; consistent with the inflammation-fibrosis coexistence expected in IgG4-related disease.
Criteria
Prominent follicular hyperplasia, hyper-vascular germinal centers. May mimic Castleman disease.
Distinct Features
More prominent enhancement on imaging (vascular germinal centers). IgG4/IgG ratio >40% and >10 IgG4+ plasma cells/HPF meets diagnostic criteria.
Criteria
Florid follicular hyperplasia, expanded germinal centers, interfollicular IgG4+ plasma cell infiltration.
Distinct Features
Most common pattern. Imaging findings similar to nonspecific reactive LAP — diagnosis made histopathologically.
Criteria
Prominent expansion of interfollicular areas by IgG4+ plasma cell infiltration and storiform fibrosis. Follicular structures compressed.
Distinct Features
T2 hypointensity due to fibrosis more prominent. Response to steroids may be more limited due to advanced fibrosis.
Distinguishing Feature
In sarcoidosis bilateral hilar LAP predominates with pulmonary involvement (perilymphatic nodules, bilateral hilar LAP); in IgG4-RD peripheral LAP predominates with pancreas/salivary gland involvement. Serum IgG4 not elevated in sarcoidosis.
Distinguishing Feature
FDG uptake more intense in NHL (SUVmax >10) and steroid response not expected; in IgG4-RD uptake is lower and dramatic steroid response is diagnostic.
Distinguishing Feature
In Castleman (hyaline vascular) single dominant hypervascular node is common; in IgG4-RD generalized mildly-moderately enlarged nodes predominate. In multicentric Castleman IL-6 elevation and systemic symptoms dominate; in IgG4-RD serum IgG4 is elevated and organ involvements are specific.
Distinguishing Feature
In reactive LAP multiorgan involvement (pancreas, retroperitoneum, salivary glands) does not accompany and serum IgG4 is normal; characteristic organ involvements in IgG4-RD are distinguishing.
Urgency
routineManagement
medicalBiopsy
NeededFollow-up
6-monthIgG4-RD lymphadenopathy should be evaluated as part of systemic disease. Diagnosis must be histopathologically confirmed — IgG4+ plasma cells >10/HPF and IgG4/IgG ratio >40% meets diagnostic criteria. First-line treatment is prednisolone 0.6 mg/kg/day with dose taper after 3-4 weeks. Dramatic steroid response (nodal regression within 2-4 weeks) supports diagnosis. Relapse is common (30-50%) and steroid dependency may develop; rituximab is effective as second-line therapy. Long-term follow-up should be vigilant for lymphoma transformation (MALT lymphoma, DLBCL).
IgG4-related disease responds dramatically to corticosteroids, and this therapeutic response supports the diagnosis. However, untreated disease may lead to progressive fibrosis and organ damage. Steroid-sparing agents (rituximab, azathioprine) are used in relapsed cases. Malignancy risk may be increased, requiring surveillance. Histopathological confirmation (storiform fibrosis, obliterative phlebitis, dense IgG4+ plasma cell infiltration) is the gold standard for diagnosis.