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Year : 2017  |  Volume : 60  |  Issue : 3  |  Page : 443-444
Immunoglobulin G4-related orbital disease: An important differential diagnosis for orbital swellings with lymphoplasmacytic infiltration

Department of Pathology, Anand Diagnostic Laboratory, Bowring Hospital Road, Shivajinagar, Bengaluru, Karnataka, India

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Date of Web Publication22-Sep-2017

How to cite this article:
Bordoloi S, Iyengar J. Immunoglobulin G4-related orbital disease: An important differential diagnosis for orbital swellings with lymphoplasmacytic infiltration. Indian J Pathol Microbiol 2017;60:443-4

How to cite this URL:
Bordoloi S, Iyengar J. Immunoglobulin G4-related orbital disease: An important differential diagnosis for orbital swellings with lymphoplasmacytic infiltration. Indian J Pathol Microbiol [serial online] 2017 [cited 2021 Jul 23];60:443-4. Available from: https://www.ijpmonline.org/text.asp?2017/60/3/443/215385


Immunoglobulin IgG4-related diseases (IgG4-RDs) are systemic syndromes characterized by elevated serum levels of IgG4 and IgG4-positive lymphoplasmacytic infiltrative lesions in the body. Orbital tissues are affected by IgG4-related conditions. It was first observed that Mikulicz's disease correlated with IgG4-RD and later determined that IgG4-RD can occur in any ocular adnexal tissues.[1]

Diagnostic criteria for IgG4-RD: (1) Serum IgG4 concentration >135 mg/dl and (2) >10 IgG4+ plasma cells/hpf of biopsy sample and the ratio of IgG4+/IgG+ plasma cells being: >40% of IgG+ plasma cells.[2]

A 48-year-old male presented to the outpatient department of a private medical institute with an unilateral proptosis. Initial investigations revealed a lacrimal gland growth. A clinical differential diagnosis of a lymphoproliferative state or chronic dacryoadenitis was considered.

A biopsy was done. Grossly, the tissue bit was 1 cm × 0.5 cm × 0.4 cm. Histopathology section showed fragments of tissue completely effaced by a lymphoplasmacytic infiltration along with prominent stromal fibrosis in the form of thick fibrous septa running through the tissue [Figure 1]. There were focal areas showing aggregates of plasma cells. At the periphery of tissue, native lacrimal gland acini were identified in between the lymphoplasmacytic infiltration. A light microscopy diagnosis of chronic sclerosing dacryoadenitis was provided with the advice for further investigations to rule out the possibility of IgG4-related orbital disease (ROD). Patient's serum IgG4 level was analyzed, and it was 259 mg/dl (adults: 2.4–121 mg/dl). Immunohistochemistry study was done, and IgG4+ plasma cells were 110/hpf [Figure 2]. The IgG4+/IgG+ plasma cells ratio was 61%. Immunohistochemistry (IHC) findings and serum IgG4 levels confirmed the diagnosis of IgG4 orbital disease.
Figure 1: Dense lymphoplasmacytic infiltration with fibrosis (×40)

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Figure 2: Immunoglobulin G4 positive plasma cells (110/hpf)

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The patient was treated with glucocorticoids and the swelling reduced in size. The patient continued the treatment for 1 month. After 1 month the patient stopped the treatment due to financial restrains and the swelling increased in size within a month of stopping treatment. At present, the patient has been restarted on glucocorticoids, and the swelling has subsided.

(IgG4-RD) is a recently recognized syndrome with many unexplained aspects, but with specific serological, clinical, and histological features. It generally presents with a unique organ infiltration and is frequently misdiagnosed as malignancy.[3] Many reports of inflammatory pseudotumor in different sites may be examples of undiagnosed IgG4-RD.[4],[5]

Histopathological and IHC diagnosis of IgG4-RD is defined when the ratio of IgG4+/IgG+ plasma cells is higher than 40% and IgG4+ plasma cells >10/hpf. In case of storiform fibrosis and obliterative phlebitis, the specificity goes up to 100% but decreases the sensitivity to <50% of cases, which supports the need of more data to define diagnostic criteria.[6]

Lacrimal and orbital involvements are rare and are called IgG4-related orbital disease, frequently presenting as chronic dacryoadenitis, orbital myositis, perineuritis of the optic and trigeminal nerves, orbital inflammation, or scleritis.[5]

Glucocorticoids are the first-line therapy to IgG4-RD, regardless of the organ involvement.[3],[5] The expected response to therapy is symptomatic relief, which depends on organ volume decrease and, generally, is followed by reduction in serum IgG4 levels.[2] Distinctively, reactivation of the disease may be accompanied by the elevations of serum IgG, and the response to glucocorticoid can be monitored by decreases in the dosage.[4]

The relevance in reporting IgG4-RD cases, especially in unusual scenarios, such as the orbital pseudotumor, remains an important contribution to the many possible disease presentations, as this is still an underdiagnosed condition, in which the treatment may lead to remission and prevent significant morbidity and mortality. Future studies should focus on identifying biomarkers to assist with noninvasive methods of diagnosis and testing novel treatments that might supplant glucocorticoids as first-line agents of treatment, providing better responses or, at least, requiring minimal doses of steroids.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Kubota T, Moritani S. Orbital IgG4-related disease: Clinical features and diagnosis. ISRN Rheumatol 2012;2012:412896.  Back to cited text no. 1
Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 2012;22:21-30.  Back to cited text no. 2
Brito-Zerón P, Ramos-Casals M, Bosch X, Stone JH. The clinical spectrum of IgG4-related disease. Autoimmun Rev 2014;13:1203-10.  Back to cited text no. 3
Neild GH, Rodriguez-Justo M, Wall C, Connolly JO. Hyper-IgG4 disease: Report and characterisation of a new disease. BMC Med 2006;4:23.  Back to cited text no. 4
Origuchi T, Yano H, Nakamura H, Hirano A, Kawakami A. Three cases of IgG4-related orbital inflammation presented as unilateral pseudotumor and review of the literature. Rheumatol Int 2013;33:2931-6.  Back to cited text no. 5
Pieringer H, Parzer I, Wöhrer A, Reis P, Oppl B, Zwerina J. IgG4- related disease: An orphan disease with many faces. Orphanet J Rare Dis 2014;9:110.  Back to cited text no. 6

Correspondence Address:
Samrat Bordoloi
Anand Diagnostic Laboratory, No 54, Bowring Tower, Bowring Hospital Road, Shivajinagar, Bengaluru - 560 001, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_476_16

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