A 38-year-old Asian man with a history of sinusitis status presented at the Ophthalmology outpatient department following a surgical intervention at another hospital 3 months previously, with complaints of gradual painless blurred vision and proptosis for 6 months. There was no periocular sensory change or recent trauma. His family history was unremarkable.\nOn ophthalmic examination, best-corrected visual acuity (BCVA) was 20/30 on the right eye (OD) and 20/40 on the left eye (OS). Slit-lamp and funduscopic examination results were normal. The pupil reacted sluggishly without a relative afferent pupillary defect. Color vision was normal. Ocular motility was intact without diplopia, but exophthalmometry measurements were 21.5 mm with base 112 mm using one accurately calibrated Inami exophthalmometer (Hertel K-0161; Inami & Co., Ltd., Bunkyo-ku, Tokyo, Japan) on both eyes (OU). There was neither periocular sensory change nor palpated mass in the lower eyelid.\nThyroid function tests revealed normal free thyroxine and thyroid-stimulating hormone levels, but serological studies showed extremely high serum concentrations of IgG4 (2650 mg/dL; normal range < 135 mg/dL); elevated serum concentrations of IgG (2630 md/dL; normal range 751.0–1560.0 mg/dL); abnormal erythrocyte sedimentation rate (31 mm/h; normal range < 15 mm/1 h); and high levels of total IgE (1903.00 IU/dL; normal range < 87.00 IU/mL). The calculated serum IgG4/IgG ratio was 100% (normal range < 6%). No eosinophilia was found in the blood.\nPostcontrast T1-weighted fat-saturated magnetic resonance imaging (MRI) images showed a “doughnut” sign encircling the right optic nerve, and inferior sheath enhancement surrounding the left optic nerve was visible on the coronal MRI images (Fig. a). Bilateral “tram-track” signs were evident on the axial images (Fig. b). Bilateral enhancing lesions at the pterygoid plate, pterygomaxillary fissure, and sella region, with involvement of both maxillary nerves, were visualized using gadolinium-enhanced T1-weighted MRI (Fig. c, d). Bilateral infraorbital nerve involvement was also evident on the MR images (Fig. d, e). Enlargement of extraocular muscles, especially severe at the bilateral inferior rectus, right medial rectus, bilateral superior rectus, and bilateral lateral rectus muscles, was noted on coronal MRI images (Fig. e). Mucosal thickening in the ethmoid, maxillary, sphenoid, and frontal sinuses was also visible.\nWe referred this patient to the Department of Otolaryngology in our hospital for surgical biopsy. Biopsy with functional endoscopic sinus surgery was performed, and a tissue specimen measuring 0.5 × 0.3 × 0.2 cm was sent to the Department of Pathology for further testing. The result revealed chronic sinusitis with dense infiltrate of lymphocytes and plasma cells. Chronic inflamed granulation tissue, aggregates of foamy histiocytes, and fibrosis of sinonasal tissue were also noted (Fig. a–c). Organisms were not identified in the Periodic Acid-Schiff stain and the Acid-fact stain tests. Immunhistochemistry revealed CD138 accentuated plasma cells (Fig. d) and highlighted numerous IgG4-positive plasma cells (> 50 IgG4-positive plasma cells per high-power field), of which over 40% were IgG-positive plasma cells (Fig. e, f).\nThe patient underwent a treatment regimen comprising oral systemic corticosteroids (prednisolone 1 mg per kg body weight daily) for 2 weeks followed by slow tapering. Visual acuity improved to 20/25 (OU) 1 month after initiating treatment. Four months after the initial treatment, the vision got worse again, with the BCVA dropping to 20/30 (OD) and 20/50 (OS), respectively. Visual field test showed parafoveal scotoma (OD) and an enlarged blind spot (OS). Visual evoked potentials indicated bilateral delayed P100 latency (Fig. f). No active lesions were found after systemic screening. Based on the combined clinical, radiographic, and histopathologic findings, the final diagnosis was IgG4-RD with bilateral optic perineuritis, branches of trigeminal nerves involvement, and pansinusitis.\nThe patient underwent another course of oral prednisolone daily for 2 weeks with gradually tapering of dosage. This was followed by treatment with the immunosuppressive agent azathioprine (50 mg, twice daily). The final BCVA was 20/20 (OD) and 20/25 (OS) during the follow-up period of 2 years.
A 76-year old man with a history of bilateral lacrimal gland masses and an otherwise unremarkable ocular examination underwent left orbital biopsy at another institution. Clinical suspicion was high for possible lymphoma due to the additional presence of cervical and axillary lymphadenopathy. The histologic diagnosis at that time was reactive lymphoid hyperplasia with fibrosis. Immunohistochemistry, kappa/lambda in situ hybridization, and flow cytometry were negative for lymphoma. The patient was lost to follow-up without any further work-up. He presented a year later due to recurrence of orbital inflammation, at which point the surgeon requested histologic work-up for IgG4-related disease. The slides from the prior orbital biopsy were requested and reviewed, showing lymphoid follicles with intervening bands of fibrosis and mixed chronic inflammatory cells. The tissue block was also received, and additional sections were cut for CD138 and IgG4 immunostaining. There were at least 150–180 IgG4-positive plasma cells per high-power field, comprising over 40 % of the total plasma cell population (as assessed by CD138). (Serum IgG4 was not obtained.) This was considered consistent with IgG4-associated orbital inflammatory pseudotumor with sclerosing features. The patient was initially treated with prednisone and then transitioned to intravenous rituximab as first-line therapy and had an excellent response with no recurrence at 2 years following therapy.