Malignancies in Immunoglobulin G4-Related Ophthalmic Disease

Abstract Purpose: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the affected organs affected have different risks of malignancies. We attempt to determine the association of malignances with IgG4-related ophthalmic disease (IgG4-ROD). Design: Retrospective cohort study. Methods: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of patients fulfilling the “probable” or “definite” comprehensive diagnostic criteria of IgG4-RD from 2005-2019. Findings: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n=108), orbital mass (n=30), infiltrated orbital fat (n=10), conjunctiva (n=2) or extraocular muscles (n=3), 16 (13%) developed malignancies over 73±48months’ follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs=10.0, 95%CI=4.5-17.6) while that of extraorbital malignancy was similar. The SIR was highest within the first year (SIR=46.7, 95%CI=18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients when diagnosed of IgG4-ROD (64.9±7.1, 68.3±8.5 versus 55.2±15.0 years, p<0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%)were associated with OAL (all p<0.05). Pre-treatment serum IgG4 level or pattern of extraorbital involvement was similar among patients with or without malignancies. Conclusion: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

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Low-dose ‘boom-boom’ radiotherapy for ocular lymphoma arising from IgG4-related ophthalmic disease: Case report and literature review

European Journal of Ophthalmology ◽

10.1177/11206721211018372 ◽

2021 ◽

pp. 112067212110183

Author(s):

Katherine Meng ◽

Mei Chin Lim ◽

Michelle Li Mei Poon ◽

Gangadhara Sundar ◽

Balamurugan Vellayappan

Keyword(s):

Low Dose ◽

Elevated Serum ◽

Infraorbital Nerve ◽

Immunoglobulin Light Chain ◽

Immunoglobulin G4 ◽

Systemic Involvement ◽

Disease Case ◽

Serum Igg4 ◽

Ophthalmic Disease

Ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) and immunoglobulin G4-related ophthalmic disease (IgG4-ROD) may exist on a continuum. Presence of immunoglobulin light-chain restriction and clonal gene rearrangement suggests presence of lymphoma; whereas bilateral, infraorbital nerve and systemic involvement accompanied by elevated serum IgG4 levels may indicate synchronous IgG4-ROD. Although steroids have been the mainstay for the treatment of IgG4-ROD, radiotherapy (RT) has been used occasionally. The reported RT doses range between 24 and 30 Gy, which can result in acute and late toxicities. A low-dose regimen of four Gy has not been previously described. We describe a patient with bilateral OA-EMZL arising from IgG4-ROD successfully treated with low dose ‘boom-boom’ radiotherapy. In addition, we review the literature for the association between these two conditions and the role of RT in their management.

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Roles of CRTH2+ CD4+ T Cells in Immunoglobulin G4-Related Lacrimal Gland Enlargement

International Archives of Allergy and Immunology ◽

10.1159/000337761 ◽

2012 ◽

Vol 158 (s1) ◽

pp. 42-46 ◽

Cited By ~ 15

Author(s):

Yukari Saito ◽

Shin-ichiro Kagami ◽

Saki Kawashima ◽

Kentaro Takahashi ◽

Kei Ikeda ◽

...

Keyword(s):

T Cells ◽

Lacrimal Gland ◽

Cd4 T Cells ◽

Immunoglobulin G4 ◽

Gland Enlargement

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Immunoglobulin G4 related disease: an overview

IMC Journal of Medical Science ◽

10.3329/imcjms.v15i2.55878 ◽

2021 ◽

Vol 15 (2) ◽

pp. 44-51

Author(s):

Saika Farook ◽

Abdullah Ahmed Solaiman ◽

Md Shariful Alam Jilani

Keyword(s):

Retroperitoneal Fibrosis ◽

Tubulointerstitial Nephritis ◽

The Body ◽

Histopathological Analysis ◽

Immunoglobulin G4 ◽

Related Disease ◽

Serum Igg4 ◽

First Time ◽

Gland Enlargement

Immunoglobulin G4 related disease (IgG4-RD) is a recently perceived fibroinflammatory condition, identified as a systemic illness for the first time in the early 2000. It can involve virtually every organ of the body, commonly presenting as lymphadenopathy, retroperitoneal fibrosis, autoimmune pancreatitis, tubulointerstitial nephritis, parotid or lacrimal gland enlargement. The diagnosis is confirmed by histopathological analysis and is often, but not always accompanied by an increased level of serum IgG4 concentration. In fact, the name addressing this autoimmune fibroinflammatory condition may be considered a misnomer, as the role of the non-inflammatory immunoglobulin IgG4 in the immune mechanism of IgG4-RD remains to be elucidated. Ibrahim Med. Coll. J. 2021; 15(2): 44-51

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Salivary and lacrimal gland enlargement with serum immunoglobulin G4 elevation

Clinical and Experimental Pediatrics ◽

10.3345/cep.2020.01319 ◽

2020 ◽

Author(s):

Jinseok Lee ◽

Da-Eun Kim ◽

Jeong-Hwan Yang ◽

Misun Lim ◽

Hye Yung Yum ◽

...

Keyword(s):

Lacrimal Gland ◽

Serum Immunoglobulin ◽

Immunoglobulin G4 ◽

Gland Enlargement

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Evaluate the Differences in CT Features and Serum IgG4 Levels between Lymphoma and Immunoglobulin G4-Related Disease of the Orbit

Journal of Clinical Medicine ◽

10.3390/jcm9082425 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2425

Author(s):

Wei-Hsin Yuan ◽

Anna Fen-Yau Li ◽

Shu-Yi Yu ◽

Ying-Yuan Chen ◽

Chia-Hung Wu ◽

...

Keyword(s):

Elevated Serum ◽

Hounsfield Unit ◽

Immunoglobulin G4 ◽

Related Disease ◽

Serum Igg4 ◽

Orbital Lymphoma ◽

Serum Igg Levels ◽

Igg Level ◽

Ct Features ◽

Higher Sensitivity

Background: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)—characterized as tumors mimicking malignant orbital lymphoma (OL)—responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL. Methods: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios. Results: Significantly related to IgG4-ROD (all p < 0.05) were the presence of lesions with regular borders, presence of multiple lesions—involving both lacrimal glands on CT scans—higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674–1.000, p = 0.005] vs. 0.766 [95% CI: 0.615–0.917, p = 0.002]), higher sensitivity (0.889 [95% CI: 0.518–0.997] vs. 0.75 [95% CI: 0.509–0.913]), higher specificity (0.813 [95% CI: 0.544–0.960] vs. 0.778 [95% CI: 0.578–0.914]) and a higher cutoff value (≥132.5 mg/dL [milligrams per deciliter] vs. ≥89.5). Conclusions: IgG4-ROD showed distinct CT features and elevated serum IgG4 (≥132.5 mg/dL), which could help distinguish IgG4-ROD from OL.

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Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22084083 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4083

Author(s):

Asami Nishikori ◽

Yoshito Nishimura ◽

Rei Shibata ◽

Koh-ichi Ohshima ◽

Yuka Gion ◽

...

Keyword(s):

Marginal Zone ◽

Somatic Hypermutation ◽

Cytidine Deaminase ◽

Marginal Zone Lymphoma ◽

Immunoglobulin G4 ◽

Intensity Index ◽

Activation Induced Cytidine Deaminase ◽

Systemic Disorder ◽

Lymphoplasmacytic Infiltration ◽

Ophthalmic Disease

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.

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Immunoglobulin G4-related masses surrounding coronary arteries: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytab055 ◽

2021 ◽

Vol 5 (3) ◽

Author(s):

Takuya Nakamura ◽

Yutaka Goryo ◽

Takuya Isojima ◽

Hiroyuki Kawata

Keyword(s):

Coronary Artery ◽

Coronary Angiography ◽

Cardiovascular System ◽

Coronary Arteries ◽

Elevated Serum ◽

High Serum ◽

Immunoglobulin G4 ◽

Coronary Arteritis ◽

Serum Igg4 ◽

Mass Formation

Abstract Background Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with high serum IgG4 levels affecting various organs, such as the pancreas, lacrimal and salivary glands, thyroid, kidney, and lung. Typical cardiovascular manifestations of IgG4-RD include periaortitis, coronary arteritis, and pericarditis. However, reports of IgG4-RD associated with coronary arteritis are rare. Here, we report a case of IgG4-related masses surrounding the coronary arteries. Case summary A 59-year-old man was referred to our hospital because of mediastinal masses detected by computed tomography (CT). Coronary CT angiography revealed masses surrounding the right coronary artery and the left anterior descending coronary artery. An elevated serum level of IgG4 and histological findings led to the diagnosis of IgG4-related coronary arteritis with mass formation. Coronary angiography showed numerous feeding arteries to the masses, which were demonstrated as multiple microchannels in the intravascular ultrasound (IVUS) images. Discussion IgG4-RD involving the cardiovascular system has been reported. However, coronary artery disease associated with IgG4-RD is very rare, and the mechanism of mass formation in IgG4-related coronary arteritis is unclear. In our case, within the cardiovascular system, IgG4-RD was limited to the coronary arteries, suggesting that the affected coronary arteries may provide the necessary blood supply to the mass, thus, aiding its growth. These findings were supported by the images from coronary angiography and IVUS.

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