Orbital Pseudotumor Research Articles

Ocular Phenotypes in Patients With Hemophagocytic Lymphohistiocytosis: A Retrospective Analysis in a Single Center Over 7 Years

To investigate the presence and type of ocular abnormalities in patients with hemophagocytic lymphohistiocytosis (HLH). A retrospective cross-sectional study. Observational report of ocular findings and their associations with age, sex, underlying disease, and hematologic parameters. HLH was defined according to the 2004 criteria, and the patients were enrolled from March 2013 to December 2021. Analysis began in July 2022 and ended in January 2023. The main outcome measures were ocular abnormalities associated with HLH and their potential risk factors. Of 1525 HLH patients, 341 had ocular examinations, and 133 (133 of 341, 39.00%) had ocular abnormalities. Mean age at presentation was 30.21 ± 14.42 years. The multivariate analysis indicated that old age, autoimmune disorders, decreasing red blood cell count, decreasing platelet count, and increasing fibrinogen level were independent risk factors of ocular involvement in HLH patients. The most common presenting ocular findings were posterior segment abnormalities (66 patients, 49.62%), including retinal and vitreous hemorrhage, serous retinal detachment, cytomegalovirus retinitis, and optic disc swelling. Other HLH-associated ocular abnormalities included ocular surface infection (conjunctivitis, 34 patients, 25.56%; keratitis, 16 patients, 12.03%), subconjunctival hemorrhage (11 patients, 8.27%), chemosis (5 patients, 3.76%), anterior uveitis (11 patients, 8.27%), glucocorticoid-induced glaucoma (5 patients, 3.76%), radiation cataract (1 patient, 0.75%), dacryoadenitis (2 patients, 1.50%), dacryocystitis (1 patients, 0.75%), orbital cellulitis (2 patients, 1.50%), orbital pseudotumor (2 patients, 1.50%), and strabismus (2 patients, 1.50%). Eye involvement is not uncommon in HLH. Better awareness among both ophthalmologists and hematologists is necessary for prompt diagnosis and institution of appropriate management strategies with potential to save sight and life.

IgG4 related disease: a novel association with hypertrophic osteoarthropathy

IgG4 related disease (IgG4-RD) is a recently recognized disease that has several associated clinical phenotypes including autoimmune pancreatitis, sclerosing cholangitis, major salivary gland enlargement (Mikulicz disease), orbital pseudotumor, retroperitoneal fibrosis, and inflammatory vascular disease manifesting as aortitis or coronary artery calcification. Histopathology of affected organs shows lymphoplasmacytic infiltrations with a predominance of IgG4-positive plasma cells in the affected tissue and an increased number of eosinophils. Serum IgG4 levels are elevated in two-thirds of patients, and IgE is also often elevated. We report here the first known associated case of presumed IgG4-RD with hypertrophic osteoarthropathy. Hypertrophic osteoarthropathy (HOA) is frequently a paraneoplastic disease of bone, but HOA can be associated with chronic infection, chronic pulmonary disease, cardiac shunts, and cirrhosis. HOA is a clinical diagnosis consisting of arthralgia, digital clubbing, and periostosis of tubular bones seen on imaging with or without synovial effusion. Our 35 yo male LatinX patient presented with typical clinical symptoms of HOA that were confirmed on imaging. During the negative work up for malignancy, disproportionate-for-age coronary artery calcification was identified, which prompted an evaluation for IgG4-RD. The patient also had lung disease (peribronchial thickening), atopic dermatitis, subtle clubbing, elevated IgE, elevated IgG4 (9× normal), and eosinophilia. The patient's symptoms and inflammatory markers improved on prednisone and methotrexate, but a decision to treat with rituximab was made after having to discontinue methotrexate for transaminitis. Rituximab has been used in patients with IgG4-RD with some success, and our patient continues to improve in his skin, respiratory, and bone symptoms with reduction in IgG4, inflammatory markers, and bone turnover markers (alkaline phosphatase).

Wegener’s Granulomatosis Revealed by Bilateral Orbital Inflammatory Pseudotumor: a Case Report and Literature Review

Purpose: To describe the chronology and the extent of orbital involvement in a case of granulomatosis with polyangiitis (GPA). Methods: Descriptive case report and literature review. Results: A thirty-two years old male consulted with the following complaints: A retro-orbital discomfort in both eyes, a bilateral fast progressive proptosis and a decrease in visual acuity in the left eye. Eye examination revealed a proptosis, ptosis, epiphora and a motility restriction and peripheral corneal ulcer infiltrates with nodular scleritis in the left eye. A palpable orbital mass was located in the sub temporal orbit in both eyes. Orbit magnetic resonance imaging (MRI) unveiled a diffuse and elongated enlargement of both lacrimal glands with enhancing mass in the superior lateral aspect of both eyes globe. The diagnosis of an orbital pseudotumor was suspected. The biological work-up revealed a high blood levels of inflammation markers and antineutrophil cytoplasmic antibodies (c-ANCA). The diagnostic of active systemic granulomatosis with polyangiitis was then made. Conclusion: As seen in this case, clinicians should consider a differential diagnosis of granulomatosis with polyangiitis in patients with an orbital pseudotumor mimic aspect.

A162 RARE PRESENTATION OF EXTRANODAL NK/T-CELL LYMPHOMA INVOLVING STOMACH AND EYE: CASE REPORT AND LITERATURE REVIEW

Abstract Background Extranodal NK/T-cell lymphoma (ENKTL) is a rare and aggressive form of non-Hodgkin lymphoma. ENKTL are predominantly localized to nasal and upper aerodigestive sites, but extranasal involvement including gastrointestinal tract are rarely seen. Small and large intestines are primary sites of gastrointestinal ENKTL. Gastric involvements are exceedingly rare accounting for less than 5% of all gastrointestinal ENKTL. Purpose We present a literature review on gastrointestinal ENKTL and a case report of gastrointestinal bleed secondary to ENKTL involving stomach and left orbit. Method Case report and literature review. Result(s) 33-year-old female was admitted to a tertiary hospital with 3-week history of epigastric pain and left periorbital swelling. Abdominal CT showed edema and thickening of gastric folds. Head CT showed grossly enlarged left lateral rectus muscle and periorbital soft tissue swelling suggestive of left orbital pseudotumor. Esophagogastroduodenoscopy revealed multifocal Forrest classification II-C ulcerations throughout her stomach and duodenum. Biopsies from stomach showed gastric mucosa with extensive infiltration by an atypical lymphoid cell population. Immunohistochemistry demonstrated high grade lymphoid cells with uniform expression of CD2, CD3, CD30, CD56, TIA1, perforin and granzyme B. EBV-encoded small RNA in-situ hybridization (EBER ISH) was strongly positive. Findings were consistent with gastric ENKTL. Left orbital biopsy revealed similar morphology and phenotypic features consistent with concurrent ENKTL involvement of her orbit. Patient was initiated on intravenous corticosteroids, but unfortunately developed hemorrhagic shock secondary to gastrointestinal bleeding from gastric ulcer and passed away. Gastrointestinal ENKTL is a rare presentation of a rare disease. Gastric involvement is especially rare and described only in few case reports. Gastrointestinal ENKTL are often initially asymptomatic but can progress to abdominal pain, bleeding and even bowel perforation. Due its nonspecific clinical features and rarity, diagnosis can be difficult and requires careful examination by an experienced pathologist. This aggressive lymphoma is characterized by positive CD2, CD3, CD30, CD56, TIA, granzyme B, perforin and EBER ISH. Optimal treatment approach remains unclear due to lack of prospective clinical studies. Currently, treatment modalities used for other lymphomas including radiotherapy and non-anthracycline-based chemotherapy are used. Despite treatment, prognosis is grim with median overall survival period of 7-8 months. Image Conclusion(s) We present a case of gastric and orbital ENKTL with gastric ulcer bleeding. Gastric ENKTL disease is a rare presentation of a rare disease. Due to non-specific clinical features, diagnosis is often difficult and relies on careful pathology examination by experienced pathologist. Prognosis is poor without optimal treatment approach due to rarity of disease and lack of validated data. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared INFLAMMATORY BOWEL DISEASES MECHANISMS AND TREATMENTS

Role of imaging classification in the diagnosis and management of orbital inflammatory pseudotumor

Orbital inflammatory pseudotumor (OIP) is a kind of orbital idiopathic benign space-occupying lesion with no clear etiology and mainly characterized by inflammatory response. The clinical diagnosis of OIP should be based on exclusion of other diseases or surgical biopsy. Medication and surgical excision are both diagnostic and therapeutic methods. The choice of which is a problem that baffles clinicians. This article discusses a new strategy basing on the imaging features and classifications of OIP. It is expected to be further discussed and promoted in clinical practice to improve the diagnosis and treatment of OIP.

A Case of Adenoid Cystic Carcinoma Mimicking Orbital Pseudotumor

Introduction: Clinical approach to the case of dacryoadenitis. Case Report: A 41-year-old male patient was admitted to our clinic with complaints of decreased vision in the left eye, periorbital and headache for 2 days. On examination, his visual acuity was full on the right and counting fingers at 2 meters on the left. There was a slight swelling and dimness in the margins of the optic disc on the left, other eye examination findings were normal. The patient was treated with intravenous methylprednisolone at a dose of 1gr/day for three days with the prediagnosis of orbital pseudotumor. However, it was observed that the patient's complaints recurred after methylprednisolone was discontinued. In repeated orbital MRI, at the level of the orbital apex on the left, infiltrating the dural structures, indenting the cavernous sinus, affecting the soft tissue structures adjacent to the nasopharyngeal lumen on the left, are seen. The left optic nerve was found to be slightly thicker than normal, especially at the apex level. For histopathological diagnosis, endoscopic biopsy was performed from the tumor and surrounding tissue from the left maxillary sinus. The biopsy result was reported as adenoid cystic carcinoma. Discussion: The diagnosis of orbital pseudotumor is made in accordance with clinical, radiological and pathological data. Orbital pseudotumor is histopathologically characterized by polymorphous inflammatory cell infiltration accompanied by varying degrees of fibrosis. It is difficult to distinguish an orbital pseudotumor from a true neoplasm. Lymphomas constitute 20% of orbital mass lesions. Our case was initially treated with a preliminary diagnosis of orbital pseudotumor localized in the posterior orbit and responded to steroids. However, lack of complete recovery and recurrence after steroid discontinuation brought to mind other underlying pathologies and directed to further examination and biopsy. As a matter of fact, the patient, who was diagnosed with adenoid cystic carcinoma as a result of biopsy, was included in the oncological follow-up and treatment program. It is necessary to be vigilant in terms of malignancy in orbital pseudotumors and not to avoid biopsies in suspected cases.

Not all orbital inflammations in the COVID-19 era are due to mucormycosis – A case of orbital pseudotumour leading to vision loss

A 57-year-old male patient with type 2 diabetes mellitus who had survived severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) presented with loss of vision in the right eye (RE) of 20-day duration. The patient had been diagnosed elsewhere with orbital mucormycosis and had been treated for it. The patient developed vision loss in RE 1 week after the initiation of treatment. At the time of presentation in our institute, vision in RE had reduced to no perception of light. Examination showed a relative afferent pupillary defect and pale optic disc in RE. Gadolinium-enhanced contrast magnetic resonance imaging of the brain, orbit and paranasal sinuses suggested perineuritic type of idiopathic orbital inflammation. In the present COVID-19 scenario, diagnosis other than mucormycosis should be kept in mind when dealing with cases of orbital inflammation.

Non specific orbital inflammatory disease – A review article

Non Specific Orbital Inflammatory Disease (NSOID) is a benign, noninfective inflammatory condition of the orbit which does not have any identifiable local or systemic causes. Orbital pseudotumor was first described in 1903 by Gleason. The clinical diagnosis is one of exclusion with evaluation directed to exclude neoplasms, infections and systemic disorders. IOI is diagnosed by clinical history and evaluation to rule out other causes of orbital disease. Orbital pseudotumor is the third most common orbital disease following Graves ophthalmopathy and lymphoproliferative disease.

Value of diffusion-weighted magnetic resonance imaging (DWI) in differentiating orbital lymphoma from idiopathic orbital inflammatory pseudotumor

BackgroundDiffusion-weighted MR imaging can provide physiological information complementing morphological findings from conventional MRI. It detects early tissue changes associated with changes in water content, such as changes in the permeability of cell membranes, cell swelling or cell lysis. Areas of diseased tissue are highlighted with increased signal intensity on diffusion-weighted MR imaging. A decrease in the ADC is expected with increased intracellular tissue caused by either cell swelling or increased cellular density. DWI can be performed without the need for the administration of exogenous contrast medium, so it may of use when contrast administration is contraindicated. It yields quantitative and qualitative information that reflects changes at the cellular level and indicates the integrity of cell membranes. The purpose of this study was mainly to assess the diagnostic value of DWI for the discrimination of orbital lymphoma from idiopathic orbital inflammatory pseudotumor.ResultsOf our 53 cases presented with proptosis or visual disturbances, 32 cases (60.4%) had found to be present with idiopathic orbital inflammatory pseudotumor and 21 cases (39.6%) had orbital lymphoma. On conventional MR imaging, ill-defined tumor margin and orbital preseptal space involvement had a significant association with orbital lymphoma, whereas intense post-contrast enhancement of lesion and radiologic evidence of sinusitis were associated with orbital inflammatory pseudotumor. The mean ADC value of orbital lymphoma was significantly lower than those of benign inflammatory pseudotumor, yielding 100% sensitivity, 99% specificity, and 90.5% accuracy for differentiating both entities.ConclusionsDiffusion-weighted MR imaging (DWI) is valuable in discriminating orbital inflammatory pseudotumor from malignant orbital lymphoma that help patients to initial management.

UNUSUAL CAUSE OF PERIORBITAL ANGIOEDEMA.

<h3>Introduction</h3> We present a case of eyelid edema initially thought to be due to allergic conjunctivitis, angioedema and periorbital cellulitis that was eventually discovered to be due to Immunoglobulin G4-related disease (IgG4-RD). <h3>Case Description</h3> Our patient was a 57 year-old female with asthma and allergic rhinosinusitis, who presented to clinic with right eyelid edema, injected conjunctiva, and pruritus. She had a history of left eyelid swelling attributed to meibomian gland dysfunction. Initially we treated her for allergic conjunctivitis. A year later, she was treated with clindamycin for periorbital cellulitis, and the year after that, treated for angioedema by the emergency department. Soon after, she developed left eyelid swelling and thick eye discharge. Neuro-ophthalmology evaluation was concerning for polyclonal lymphoid proliferation and sclerosing orbital pseudotumor. Serum IgG4 was elevated and a lacrimal gland biopsy revealed reactive lymphoid hyperplasia compatible with IgG4-RD. She was treated with prednisone for several weeks with good response. <h3>Discussion</h3> IgG4-RD is an uncommon medical condition that can present similarly to more common diseases and can be challenging to diagnose.

Antineutrophil Cytoplasmic Antibody–Associated Orbital Inflammatory Syndrome Without Extraocular Manifestations

The differential diagnosis of acute visual loss includes many ischemic, infiltrative, and rheumatologic etiologies. We present a case of antineutrophil cytoplasmic antibody (ANCA)-associated orbital inflammatory syndrome without extraocular manifestations. Initial complaints were vision loss and pain during mastication. Giant cell arteritis was suspected, but biopsy was negative. On withdrawal of steroids, symptoms returned and a head computed tomography scan showed an orbital pseudotumor. Testing showed strongly positive c-ANCA, and symptoms resolved after pulsed steroids. The patient was discharged with a probable diagnosis of ANCA-associated orbital inflammatory syndrome, prednisone, and methotrexate. This case highlights the importance of an extensive work-up in the evaluation of acute visual loss.

AN UNUSUAL PRESENTATION OF ORBITAL PSEUDOTUMOR

The term orbital pseudotumor refers to a broad category of non-specic idiopathic inammations of the orbit, which may affect any orbital structure. A 28-year-old female presented with swelling in the right upper eyelid for 1 month associated with pain and mild redness of the eye. She was previously been seen by other ophthalmologists and diagnosed as Hordeolum Internum prescribed oral antibiotics and advised incision and drainage. She visited our OPD for secondary opinion and surgical treatment. Best Corrected Visual Acuity- R/E- 6/9, LE -6/6P. No Proptosis. No Limitation of Extra Ocular Movements. Considering the clinical presentation of the patient Computed Tomography orbit was advised, revealed abnormal soft tissue density in lateral aspect of right orbit within extraconal compartment suggestive of Orbital Pseudotumor. The patient was started on oral steroids and had a favourable outcome with no recurrence till date.

Orbital Inflammatory Pseudotumor following mRNA COVID-19 Vaccination

ABSTRACT The authors present a case of orbital pseudotumor after mRNA COVID-19 vaccination. A 40-year-old otherwise healthy woman was referred to our oculoplastics unit because of left blepharoptosis of 2 months duration starting 1 week after she received her first Pfizer-BioNTech mRNA vaccination. On presentation, her best-corrected visual acuity was 20/20 in each eye. The external examination revealed left blepharoptosis and mild upper eyelid swelling. Orbital magnetic resonance imaging revealed left lacrimal gland enlargement with homogeneous contrast enhancement and diffuse mild enlargement of the left lateral and superior rectus muscles. The results of the extended workup for autoimmune and infectious etiologies and the systemic examination findings were normal. Systemic corticosteroids were started for the orbital pseudotumor. The presented case of orbital pseudotumor development after the mRNA vaccine may be considered to be an immunological process targeting the orbital tissue following immunization, although the cause–effect relationship remains uncertain.

Preseptal Cellulitis Versus Orbital Cellulitis: A Pediatric Case.

Eye infection with or without swelling is a common complaint in pediatric patients. It commonly affects the eyelid, which can be confused with an insect bite, orbital pseudotumor, or panophthalmitis. The article highlights the differences between preseptal and orbital cellulitis. Preseptal and orbital cellulitis originate from other infections because of the thin bone barrier that separates the eye from other facial structures. The clinical manifestations of preseptal and orbital cellulitis may be perplexing, and emergency nurse practitioners must distinguish between the two infections. The incorrect diagnosis may lead to complications. The complications associated with orbital cellulitis are vision loss, brain abscess, vision loss, cavernous sinus thrombophlebitis, orbital cellulitis, subperiosteal abscess, and death. Thus, early diagnosis and treatment will prevent these complications.

A rare case of rapid evolution of choroidal osteoma

We present a case of a 19-year-old male with a history of right-sided orbital pseudotumor with suspected Burkitt's lymphoma. His best-corrected visual acuity (BCVA) was 6/36 in the right eye (RE) and 6/6 in the left eye (LE). On fundus examination, the patient had a large choroidal osteoma at the posterior pole with macular scarring, along with two additional satellite osteomas inferior and superonasal to the disc in OD, while OS was unremarkable. After conservative management with oral corticosteroids, the patient demonstrated an additional choroidal osteoma lesion nasal to the disc in the OD which had evolved over a period of merely 3 months. To the best of our knowledge, this is the first reported case to document such a rapid development of choroidal osteoma. This case highlights the need for frequent follow-up of these patients for early detection and monitoring of these lesions.

A single-institution review of lacrimal gland biopsies between 1962 and 2017

ABSTRACT Purpose To examine the clinical and histopathologic characteristics of lacrimal gland biopsies at a tertiary academic center. Methods A retrospective chart review of patients undergoing lacrimal gland biopsy or excision between 1962 and 2017 was performed via the ocular pathology specimen log. All cases were reviewed for demographics, clinical presentation, and histopathologic diagnoses. Results Four hundred and two eyes in 356 patients were included in the analysis. Median age was 49 (range 5–91) with a female predominance (255, 72%, p < .001). Most had unilateral involvement (308, 86.5%) and visual acuity of 20/50 or better (332 eyes, 83%). Limitation in extraocular motility was present in 71 eyes (18%), relative afferent pupillary defect in 10 eyes (2.5%), and intraocular pressure 20 mmHg or above in 80 eyes (20%). The pre-operative radiology report commented on the enlargement of the lacrimal gland in 236 eyes (58.7%), and lack thereof in 73 eyes (18.2%). The most common histopathologic diagnoses were nonspecific inflammation or orbital pseudotumor (170, 42%), lymphoma (65, 16%), pleomorphic adenoma (22, 5.5%), adenoid cystic carcinoma (19, 4.7%), granulomatous inflammation (19, 4.7%), and normal lacrimal gland (16, 4%). Three hundred and seven cases were benign (76%) and 95 malignant (24%). The biopsy specimen was diagnostic in 343 (85%), and non-diagnostic in 59 (15%). Conclusions This is a comprehensive review of one of the largest ocular pathology databases of lacrimal gland lesions. This study confirms the wide range of inflammatory and neoplastic conditions affecting the lacrimal gland and highlights the nuances of histopathologic diagnoses and diagnostic yield of biopsies in clinical practice.

Correlation Between IVIM-DWI Parameters and Pathological Classification of Idiopathic Orbital Inflammatory Pseudotumors: A Preliminary Study.

ObjectiveTo investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and the pathological classification of idiopathic orbital inflammatory pseudotumors (IOIPs).MethodsNineteen patients who were diagnosed with IOIPs (a total of 24 affected eyes) between November 2018 and December 2020 were included in the study. All the patients underwent magnetic resonance imaging orbital plain scans and IVIM-DWI multiparameter scans before an operation. The true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were obtained. Based on histopathology, the lesions were divided into three types: lymphocytic infiltration, fibrosclerotic, and mixed. The correlation between IVIM-DWI parameters and pathological classification was tested with the histopathological results as the gold standard. The data were analyzed using SPSS version 17.0, with P < 0.05 defined as significant.ResultsAmong the 19 patients (24 eyes) affected by IOIP, there were no significant differences between IOIP pathological classification and gender or age (P > 0.05). There were statistically significant differences between the D and f values for different pathological types of IOIP and IVIM parameters (P < 0.05), and there was no significant difference in D* value between the different pathological types (P > 0.05).ConclusionThe D and f values showed correlation with different types of IOIP, and the sensitivity of the D value was higher than that of the f value. The D* value showed no significant distinction between pathological types of IOIP.

Orbital inflammatory disease.

Orbital inflammatory disease (OID), commonly known as orbital pseudotumour, is an inflammatory disease of unknown cause. It has different forms of presentation and different degrees of severity. Its variable nature is the main cause for this disease to be misdiagnosed and misclassified. The prognosis of OID depends on the tissues affected and the histology. OID usually responds favourably to systemic steroid treatment. However, empiric steroids may mask other underlying diseases that respond well to this treatment as well, namely, IgG4-related disease or lymphoproliferative disorders. This fact has led to controversy among various authors as some recommend performing a biopsy in most of the cases, whereas others defend that this procedure should only be performed if the patient has not responded to empiric steroid treatment. Although steroids have been the mainstream treatment of OID, the side effects, relapse rates and lack of response in some cases have resulted in them being replaced by immunosuppressive and immunomodulator therapies that currently stand as a key steroid-sparing treatment option, in addition to radiotherapy and surgery. The aim of this review is to update the evidence on the diagnosis and treatment of OID.

Comparative study between Corticosteroid and Methotrexate treatment for patients with orbital pseudo tumor

Comparative study between Corticosteroid and Methotrexate treatment for patients with orbital pseudo tumor

O29 Keeping a watchful eye: IgG4-positive lymphoma masquerading as IgG4-related ocular disease

Case report - IntroductionIgG4-related disease (IgG4-RD) is increasingly recognised in rheumatology practice. We describe a case of orbital swelling initially diagnosed as IgG4-RD. It was exquisitely steroid responsive and she was treated with 6 years of immunosuppression but her symptoms later deteriorated. She developed worsening left eye swelling that required debulking surgery; histopathology demonstrated IgG4-positive lymphoma. She had an excellent response to localised radiotherapy and remains in remission. Although her initial presentation was typical of IgG4-RD, her subsequent lack of response to steroids prompted reconsideration of the initial diagnosis and re-examination of her previous biopsy specimen, confirming IgG4-positive Iymphoma at both timepoints.Case report - Case descriptionA 25-year-old lady presented in 2008 with a swollen left eye. She had a history of childhood eczema, asthma and sinusitis. Diagnostic excision was undertaken; histology was considered to show chronic inflammation, scattered eosinophils, dense fibrosis and no granulomas. She was diagnosed with a ‘granulomatosis with polyangiitis-like’ orbital pseudotumour. It was exquisitely steroid responsive; mycophenolate mofetil was added from an early stage of treatment.The patient was referred to rheumatology 3 years after diagnosis as she was unable to reduce her prednisolone below 5mg daily. Her immunology screen was negative. Although her plasma IgG4 levels were normal at 0.14g/L, the original histology was reviewed and immunostained for IgG4. This demonstrated more than 80% of plasma cells to be IgG4 positive, with the previously noted dense fibrosis and chronic inflammatory infiltrate. Her diagnosis was revised to orbital IgG4-RD. She commenced azathioprine as she was planning a pregnancy.Following an uncomplicated pregnancy in 2014, her symptoms significantly deteriorated, with worsening pain, discharge and swelling in her left eye. A repeat MRI scan showed a new cuff of abnormal tissue within the lateral aspect of the left orbit. She was referred to ophthalmology and underwent left anterior orbitotomy with debulking. Histopathology at this time was consistent with extranodal marginal zone lymphoma (EMZL) of MALT (mucosa-associated lymphoid tissue) type, IgG4 positive. An extraordinary feature was an abundance of crystal-storing histiocytes, presumed to contain ingested IgG4.To investigate whether she had an IgG4-secreting lymphoma from the beginning or whether there had been malignant transformation of her orbital IgG4-RD, the histology from 2009 was reviewed. This was considered to indicate a MALT-type EMZL.The patient was referred to haematology and she was treated with localised radiotherapy with an excellent response. She remains in remission following this and she has subsequently been discharged from haematology follow-up.Case report - DiscussionIgG4-RD is a condition involving fibroinflammatory lesions that can affect any organ in the body. As a newly recognised condition, the role of IgG4 in IgG4-RD is still not fully understood. Questions that remain unanswered include whether or not IgG4 is directly pathogenic and whether there is an increased risk of malignancy in patients with IgG4-RD.Our patient’s case demonstrates how IgG4-positive lymphoma can mimic IgG4-RD. It is important to keep a broad differential diagnosis in complex cases, and to support the eventual diagnosis with blood results, imaging studies and histology. It is essential to involve colleagues in radiology and histopathology so that a multidisciplinary decision can be made with regards to management. IgG4-RD is a steroid-responsive condition. When there is poor response to conventional treatment, this should raise doubts regarding the diagnosis, and it would be prudent to consider a repeat biopsy as well as obtaining previous pathology specimens so that they can be re-reviewed.Ocular adnexal lymphomas form 1—2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. Over recent decades the incidence has increased, partly reflecting better diagnostic techniques. The most common subtype of ocular adnexal lymphomas are EMZL of MALT type, as in our patient.There are several case reports of lymphoma arising in patients with established IgG4-RD, raising the question of potential lymphomagenesis in IgG4-RD. The earliest reports come from Asia and most have been reported in patients with ocular IgG4-RD. However, the link between malignancy and IgG4-RD is still being investigated. It is important to consider a potential malignancy when managing patients with IgG4-RD, especially if there is a lack of response to steroids.Case report - Key learning pointsThere is no single diagnostic test for IgG4-RD. Diagnosis should be based on the overall clinical picture, supported by blood results, imaging and histopathology.IgG4-RD is a steroid-responsive disease. If there is a poor response to treatment, the diagnosis should be re-considered.Re-examination of previous biopsy specimens can be invaluable, especially in patients refractory to standard treatment.The link between IgG4-RD and malignancy has not been established and it is important to remain vigilant. As ocular adnexal lymphomas are not uncommon, it is important to keep this differential diagnosis in mind when reviewing patients with eye swelling thought to be secondary to IgG4-related ocular disease.