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CC BY-NC-ND 4.0 · Indian J Radiol Imaging
DOI: 10.1055/s-0045-1811211
Case Report

Perplexing Case of IgG4-Related Mastitis: Hitherto Undescribed Contrast-Enhanced Mammography Features

Veenu Singla
1   Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
,
Dollphy Garg   *
1   Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research, Chandigarh, India
,
Debajyoti Chatterjee
2   Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
,
Raghav Lal
3   Department of Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
,
Rajender Kumar Basher 
4   Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
,
Siddhant Khare
5   Department of General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
› Author Affiliations

Funding None.
› Further Information
Also available ateRefMedOne
 
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Abstract

Immunoglobulin G4-related mastitis (IgG4-RM) represents localized form of IgG4-related disease (IgG4-RD), an immune-driven condition marked by abnormal infiltration of plasma cells and raised IgG4 levels. Breast involvement is exceedingly rare and often misinterpreted as malignancy. We report a case of a 40-year-old woman presenting with right axillary lymphadenopathy and clinical suspicion of occult breast malignancy. Contrast-enhanced mammography (CEM) revealed multiple small, equal-density, microlobulated masses in both breasts, exhibiting moderate heterogeneous enhancement. The findings and pattern of involvement favored a secondary breast involvement rather than primary malignancy. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography demonstrated FDG-avid lesions in the breasts, liver, and spleen, pointing toward systemic immune-mediated pathology. Core biopsy from the breast confirmed IgG4-RM. The patient responded extremely well to oral corticosteroids. This case highlights the diagnostic challenges of IgG4-RM and underscores the critical role of radiologic-pathologic correlation. To the best of our knowledge, this case is the first report in the literature to illustrate the CEM features of IgG4-RM, offering novel imaging insights into this underrecognized entity.


 

Keywords

IgG4-related mastitis - IgG4-related disease - contrast-enhanced mammography - breast malignancy - pseudotumor - storiform fibrosis

Introduction

Immunoglobulin G4-related mastitis (IgG4-RM) is a rare manifestation of IgG4-related disease (IgG4-RD), a systemic, immune-mediated fibroinflammatory disorder characterized by mass-forming lesions, lymphoplasmacytic infiltration, and storiform fibrosis affecting multiple organs with raised serum IgG4 levels.[1] [2] [3] [4] [5] [6] [7] [8] [9] While IgG4-RD is well recognized in the pancreatic tissue, retroperitoneum, lacrimal, and salivary glands, involvement of the mammary glands is extremely uncommon and frequently underdiagnosed.[5] [6] [7] [8] [9] A very few cases of IgG4-RM have been reported globally,[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] with only two studies originating from India.[9] [12] Typically affecting middle-aged women, IgG4-RM can present as painless solitary or multiple breast masses or with clinical features suggestive of mastitis.[13] Its imaging features closely mimic breast malignancy, leading to a diagnostic dilemma and, in many instances, unwarranted surgical intervention.[3] [4] [5] [6] [7] [8] [9] [10]

We present a rare case of biopsy-confirmed IgG4-related mastitis (IgG4-RM), manifesting as unilateral axillary lymphadenopathy and multiple bilateral breast masses, an uncommon presentation described in only three prior case reports globally.[13] This case exemplifies the diagnostic challenges associated with IgG4-RM and emphasizes the importance of radiology-pathology correlation in accurate diagnosis and management. To the best of our knowledge, this is the first report to describe the contrast-enhanced mammography (CEM) features of IgG4-RM, thereby contributing novel imaging insights to the existing radiological literature on this underrecognized entity.


 

Case History

A 40-year-old woman presented with a gradually enlarging, painless swelling in the right axilla, first noticed 2 months earlier. She denied systemic symptoms such as fever, weight loss, or night sweats. She had a history of a laparoscopic cholecystectomy performed 3 months prior for symptomatic cholelithiasis, with histopathology revealing a biliary intraepithelial neoplasm. Family history was negative for breast cancer or any other malignancies.

On clinical evaluation, a single, firm, nontender, mobile lymph node was palpable in the right axilla. No palpable masses, skin tethering, or nipple changes were noted in either breast. In view of her oncologic history and isolated right axillary lymphadenopathy, a malignant etiology—either metastatic disease or an occult primary breast carcinoma—was clinically suspected.

The patient underwent CEM, followed by breast and axillary ultrasound ([Fig. 1]). Low-energy images from CEM demonstrated multiple bilateral irregular, equal-density masses with microlobulated and indistinct margins. No associated features, such as skin thickening, microcalcifications, or architectural distortion, were observed. A right axillary lymph node appeared irregular and enlarged, with loss of the lucent fatty hilum ([Fig. 1A, B]). On recombined images, the breast masses showed heterogeneous enhancement of moderate conspicuity ([Fig. 1C, D]). Subsequent ultrasound examination confirmed multiple irregular heterogeneously hypoechoic, microlobulated masses in bilateral breasts, measuring between 0.8 and 1.2 cm ([Fig. 1E, F]). Few of the masses resembled enlarged intramammary lymph nodes ([Fig. 1G]). The enlarged right axillary lymph node was irregular, hypoechoic, measured 3.6 × 2.8 cm, and showed cortical thickening with loss of fatty hilum ([Fig. 1H]). The left axilla appeared unremarkable. The multifocal nature and atypical morphology of the masses favored a systemic etiology over primary breast malignancy. These findings were categorized as per the American College of Radiology Breast Imaging Reporting and Data Systems (BI-RADS) into category 4B.

Zoom
Fig. 1 (A, B) Low-energy contrast-enhanced mammography (CEM) images in the mediolateral oblique (MLO) (A) and craniocaudal (CC) (B) views demonstrate multiple bilateral, irregular, equal-density masses (white arrows) with microlobulated as well as indistinct margins. An enlarged right axillary lymph node (arrowhead in A) is seen with loss of the lucent fatty hilum. (C, D) Corresponding recombined CEM images (MLO and CC views) reveal heterogeneous enhancement of the masses with moderate conspicuity (arrows). The enlarged right axillary node (arrowhead in C) also shows heterogeneous enhancement. No calcifications or architectural distortions are seen. (E–H) Ultrasound images illustrate the morphology of representative masses in bilateral breasts: (E, F) Heterogeneous, irregular hypoechoic masses with microlobulated margins. (G) An irregular, hypoechoic mass with a central echogenic area and internal vascularity on color Doppler, suggestive of an enlarged intramammary lymph node. (H) Enlarged hypoechoic necrotic right axillary node with loss of fatty hilum.

To evaluate for systemic involvement or a potential occult primary, a whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography was performed ([Fig. 2]). The scan revealed FDG-avid subcentimetric lymph nodes in the right axilla, with an enlarged necrotic level I node (maximum standardized uptake value (SUVmax) of 17.5). FDG-avid enhancing soft tissue lesions were also seen in bilateral breasts (highest SUVmax 14.8). Additionally, mildly FDG-avid nodes were also noted in the mediastinum (SUVmax of 3.1). The liver was enlarged and showed low-grade FDG uptake focally in segment VIII (SUVmax 6.6). Hypodense lesions with avidity were also seen in the spleen (SUVmax 7.5). No abnormal uptake was seen in the brain, adrenals, skeleton, or pancreas.

Zoom
Fig. 2 (A) Whole-body maximum intensity projection (MIP) image from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) shows multiple foci of increased tracer uptake involving the right axilla, bilateral breasts, mediastinum, liver, spleen, and lymph nodes at various levels. (B–D) Axial CT (top row) and fused PET-CT (bottom row) images at three levels: (B) FDG-avid right axillary level I necrotic lymph node (arrowhead), right breast soft tissue lesion (arrow), and anterior mediastinal lymph node (dashed arrow). (C) FDG-avid soft tissue lesion in the lower outer quadrant of the left breast (arrow). (D) Intense uptake in hypodense lesions in the spleen (arrow), consistent with splenic involvement.

An ultrasound-guided core needle biopsy using a 14-gauge needle was performed from a representative right breast mass and the enlarged right axillary node. Histopathology from the breast mass revealed dense lymphoplasmacytic infiltrates with storiform fibrosis. Immunohistochemistry demonstrated > 50 IgG4-positive plasma cells/high-power field (HPF), with an IgG4 to total IgG ratio of 62% ([Fig. 3]). The axillary node exhibited reactive lymphoid hyperplasia, without evidence of malignancy or granulomatous inflammation. Special stains and cultures for tuberculosis, fungal, and bacterial infections were negative. Serum IgG4 levels were elevated (148 mg/dL).

Zoom
Fig. 3 (A) Hematoxylin and eosin (H&E, ×100) stained section from right breast mass core biopsy shows infiltration by numerous plasma cells with storiform fibrosis in the background, consistent with features of immunoglobulin G4 (IgG4)-related sclerosing mastitis. (B) Immunohistochemistry (IHC, ×200) for IgG4 demonstrates numerous IgG4-positive plasma cells (brown nuclear staining), confirming IgG4-related disease.

The integrated radiological and histopathological findings established the diagnosis of IgG4-related sclerosing mastitis as part of systemic IgG4-related disease. She was initiated on oral corticosteroid therapy (prednisolone 1 mg/kg/day), which resulted in a rapid and sustained clinical as well as radiological response. At 6-month follow-up, she remained asymptomatic, with normalized IgG4 levels and complete resolution of breast masses on ultrasound.


 

Discussion

IgG4-related mastitis (IgG4-RM), also referred to as “sclerosing mastitis” or “inflammatory pseudotumor,” is a rare manifestation of IgG4-related disease (IgG4-RD), a chronic, immune-mediated fibroinflammatory disorder that may affect any organ system.[3] [9] [13] First recognized in the context of autoimmune pancreatitis, IgG4-RD is now known to show salivary, lacrimal, renal, retroperitoneal, and lymphatic involvement.[11] [12] [13] Breast involvement remains so uncommon that only a handful of cases have been documented worldwide.

The pathogenesis is hypothesized to involve a B-cell-driven immune response to an unknown antigen, modulated by follicular helper T cells, resulting in class switching that induces IgG4 production.[10] [11] [12] [13] Factors such as genetic susceptibility, environmental exposures, and estrogenic influence have been proposed to contribute, given the strong female predominance in IgG4-RM. An associated atopic diathesis is also noted, with elevated eosinophil counts and increased prevalence of allergic conditions such as rhinitis and asthma in affected individuals.[11] [12] [13]

Histopathology is the cornerstone of diagnosis, with the 2012 international consensus recommending the presence of any two out of the following three hallmark features: (1) dense lymphoplasmacytic infiltration, (2) storiform fibrosis, and (3) obliterative phlebitis.[5] In breast tissue, however, obliterative phlebitis and storiform fibrosis may be indistinct or completely absent, making the diagnosis more difficult.[5] A threshold of > 10 IgG4-positive plasma cells per HPF and an IgG4 to IgG ratio of more than 40% is generally regarded as diagnostic. It is imperative to note that raised levels of serum IgG4 > 135 mg/dL, although supportive, are not specific and may be seen in other conditions, including infections, autoimmune disorders, and malignancies.[5] [7] [9] [10] [11] [12] [13]

Radiological literature on IgG4-related mastitis (IgG4-RM) remains limited, and its imaging features may mimic breast carcinoma. On mammography, there may be a focal asymmetry or equal-density irregular masses, which can be solitary or multiple, unilateral, or bilateral. Ultrasound demonstrates irregular, hypoechoic masses with microlobulated margins, internal vascularity, and occasionally skin thickening.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] In rare instances, the presentation may mimic mastitis with a recurrent breast abscess.[12] Magnetic resonance imaging and CEM help in comprehensively evaluating the disease extent and may demonstrate mass or nonmass enhancement. The mass is usually irregular, microlobulated, with heterogeneous and early enhancement. Nonmass enhancement is nonspecific and heterogeneous with segmental or regional distribution.[14] Due to overlapping features with malignancy, the condition is often categorized as BI-RADS 4, prompting biopsy or even surgical excision. However, with adequate tissue sampling and comprehensive clinico-radiologic-pathologic correlation, a definitive diagnosis can often be achieved, potentially avoiding unnecessary surgery. Although both IgG4-RM and plasma cell mastitis demonstrate dense plasma cell infiltration on histopathology, IgG4-RM is distinguished by the presence of storiform fibrosis, a markedly increased number of IgG4-positive plasma cells (> 10 per HPF), and an elevated IgG4 to total IgG ratio exceeding 40%. Additionally, obliterative phlebitis and evidence of systemic organ involvement—hallmarks of IgG4-related disease—are commonly observed in IgG4-RM but are absent in plasma cell mastitis. Radiologically, plasma cell mastitis often reveals characteristic rod-like calcification, ductal ectasia with inspissated secretions, a feature not typically seen in IgG4-RM.[9] [15]

IgG4-RM responds well to systemic corticosteroids, which remain the first-line treatment. Recommended dosing is typically 0.6 to 1 mg/kg/day of prednisolone, tapered gradually over months.[11] [12] Clinical and radiologic remission is usually rapid and sustained, as seen in the majority of reported cases.[13] Other immunosuppressive agents, including azathioprine, methotrexate, and cyclosporine, have also been used as adjuncts to reduce steroid dependence.[2] For patients with recurrent disease or contraindications to steroids, rituximab has shown promise as a steroid-sparing agent.[2] [11] [12] [13]


 

Conclusion

IgG4-related sclerosing mastitis is an uncommon but important differential diagnosis in patients presenting with breast masses and atypical axillary lymphadenopathy, particularly when imaging features are not characteristic of malignancy. Diagnosis hinges on histopathological findings of lymphoplasmacytic dense infiltration in the background of storiform fibrosis and obliterative phlebitis, supported by immunohistochemical confirmation of IgG4-positive plasma cell infiltration. Increasing awareness of this condition is prudent to assist accurate diagnosis and effective treatment.


 

 

Conflict of Interest

None declared.

* Contributed equally with the first author and shares first authorship.



Address for correspondence

Veenu Singla, MD
Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research
Sector 12, Chandigarh 160012
India   

Publication History

Article published online:
14 August 2025

© 2025. Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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Zoom
Fig. 1 (A, B) Low-energy contrast-enhanced mammography (CEM) images in the mediolateral oblique (MLO) (A) and craniocaudal (CC) (B) views demonstrate multiple bilateral, irregular, equal-density masses (white arrows) with microlobulated as well as indistinct margins. An enlarged right axillary lymph node (arrowhead in A) is seen with loss of the lucent fatty hilum. (C, D) Corresponding recombined CEM images (MLO and CC views) reveal heterogeneous enhancement of the masses with moderate conspicuity (arrows). The enlarged right axillary node (arrowhead in C) also shows heterogeneous enhancement. No calcifications or architectural distortions are seen. (E–H) Ultrasound images illustrate the morphology of representative masses in bilateral breasts: (E, F) Heterogeneous, irregular hypoechoic masses with microlobulated margins. (G) An irregular, hypoechoic mass with a central echogenic area and internal vascularity on color Doppler, suggestive of an enlarged intramammary lymph node. (H) Enlarged hypoechoic necrotic right axillary node with loss of fatty hilum.
Zoom
Fig. 2 (A) Whole-body maximum intensity projection (MIP) image from 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) shows multiple foci of increased tracer uptake involving the right axilla, bilateral breasts, mediastinum, liver, spleen, and lymph nodes at various levels. (B–D) Axial CT (top row) and fused PET-CT (bottom row) images at three levels: (B) FDG-avid right axillary level I necrotic lymph node (arrowhead), right breast soft tissue lesion (arrow), and anterior mediastinal lymph node (dashed arrow). (C) FDG-avid soft tissue lesion in the lower outer quadrant of the left breast (arrow). (D) Intense uptake in hypodense lesions in the spleen (arrow), consistent with splenic involvement.
Zoom
Fig. 3 (A) Hematoxylin and eosin (H&E, ×100) stained section from right breast mass core biopsy shows infiltration by numerous plasma cells with storiform fibrosis in the background, consistent with features of immunoglobulin G4 (IgG4)-related sclerosing mastitis. (B) Immunohistochemistry (IHC, ×200) for IgG4 demonstrates numerous IgG4-positive plasma cells (brown nuclear staining), confirming IgG4-related disease.