A 54-year-old man with a 4-month history of recurrent sinusitis, 100-lb unintentional weight loss, gait instability, and generalized weakness presented with headache and painless, bilateral visual loss. Bilateral temporal artery biopsies were performed and showed no arteritis. Magnetic resonance imaging (MRI) of the brain revealed mild meningeal enhancement and a chronic subdural hematoma causing mild midline shift. Following surgical drainage, visual acuity remained unchanged, and his headaches worsened. Pertinent clinical findings were no light perception in both eyes, amaurotic pupils, and bilateral mild, temporal optic disc pallor. Ocular coherence tomography (OCT) of both optic nerves demonstrated normal nerve fiber layer thickness. Laboratory tests failed to suggest an etiology of his vision loss. Lumbar puncture showed lymphocytic pleocytosis but cytology and flow cytometry were negative for lymphoma. Repeat brain MRI was performed and demonstrated diffuse pachymeningeal enhancement (Fig. a) with possible involvement of the optic nerve sheath (Fig. b); a dural biopsy was performed.\nHistopathology demonstrated a dense infiltrate of lymphocytes and plasma cells, with no definite vasculitis or granulomatous inflammation (Fig. c, d). The possibility of marginal zone lymphoma was considered but was ruled out by immunohistochemistry, with T cells (CD3-positive) outnumbering B cells (CD20-positive), and with in situ hybridization revealing a kappa:lambda ratio of <4:1 among the plasma cells (not shown). In situ hybridization for Epstein-Barr virus was negative (not shown). Additionally, molecular genetic studies did not show any evidence of a clonal IgH gene rearrangement by polymerase chain reaction (PCR). However, IgG4 immunostain was markedly positive, with 40 IgG4-positive cells per high-power field (HPF), comprising over 40 % of the total plasma cell population (Fig. e, f). (The total plasma cell population was assessed with CD138 immunostain, and IgG immunostain was also obtained, showing that all IgG-positive cells were also IgG4-positive, i.e., IgG4:IgG ratio of 1, not shown). Subsequent bone marrow biopsy also showed no evidence of lymphoma (small CD19-positive B-cell population with normal kappa:lambda light chain ratio), and fine-needle aspiration biopsy of a left supraclavicular lymph node showed similar findings negative for lymphoma.\nOn his systemic work-up, p-ANCA was borderline positive, and serum IgG showed elevated IgG4 subclasses (148.0; normal range 2.4–121.0). Accordingly, the diagnosis of IgG4-related meningeal disease was made. The patient was started on aggressive immunosuppression with high-dose corticosteroids to be followed by either cyclophosphamide or rituximab. However, due to insurance issues, he was able to receive only methotrexate. There was near-total resolution of meningeal enhancement on repeat MRI, but his visual acuity improved to only bare light perception in both eyes. He remains stable on methotrexate almost 1 year from his diagnosis.
A 23-year-old Indian female presented to a tertiary institute of Northeast India with the chief complaints of dimness of vision, pain and redness in the right eye (OD) for 3 months. The patient was previously treated elsewhere with two posterior sub-Tenon injections of triamcinolone acetonide given 6 weeks apart. She was also on topical steroids and cycloplegic. She did not report any benefit from the previous treatment. There was no history of trauma to the eye or elsewhere. Other medical, surgical, and family histories were unremarkable.\nOn examination, ocular alignment was normal with a visual acuity of counting finger at 3 m in the OD. There was minimal sclerouveitis noted in the inferior-temporal quadrant of OD. On slit-lamp examination, OD showed 360° posterior synechiae with anterior chamber flare and cells (+++) with 1 mm hypopyon []. There was a suspected mass in the inferior-temporal quadrant behind the iris, pushing it anteriorly. The left eye examination was unremarkable.\nB-scan ultrasound (B-scan USG) of OD was suggestive of ciliary body mass with adjoining exudative retinal detachment (ERD). USG bio-microscopy findings were consistent with the findings of B-scan USG. The patient was advised with complete blood count with peripheral blood smear which was within normal limit. Syphilis screening (venereal disease research laboratory) was nonreactive with normal thyroid function test and negative Mantoux test (5TU) reading. Based on the clinical examination and baseline investigations, we came to the differential diagnosis of ciliary body melanoma or similar tumors. Magnetic resonance imaging suggested the possibility of ciliary body melanoma in OD [Fig. and ]. After obtaining informed consent, enucleation was carried out in OD, and eyeball specimen was sent to ocular pathology laboratory for histopathological analysis. In grossing, there was a grayish-white-colored tumor seen in the inferior-temporal part of the ciliary body measuring (10.99 × 7.98) mm. Adjoining the grayish-white ciliary body mass, there was an ERD noted [].\nMicroscopic description of enucleated eyeball showed peripheral corneal vascularization. Few inflammatory cells were seen in the anterior chamber []. Part of the iris tissue showed inflammation. An eosinophilic mass was seen in the ciliary body with diffuse plasmacytoid cells, with reactive lymphoid follicle and other inflammatory cells []. Episcleral and scleral tissue were inflamed and infiltrated by various inflammatory cells [Fig. and ]. Occasional vascularization of the sclera was noted []. Cut end of the optic nerve did not show any tumor involvement. Immunohistochemistry (IHC) was advised to explore the possibility of various inflammatory lesions. The steps for IHC were carried by kit methods available commercially.\nIHC for both Kappa and Lambda was positive. Cluster differentiation (CD20, CD3, and CD45) was focal-positive. CD138 was positive in the specimen and HMB45 was negative. IHC for IgG4 was positive in occasional cells which also expressed CD138 (plasma cells). All positive controls showed appropriate positive immunostaining. Negative control slide did not show immunostaining. IgG4-positive plasma cells were seen in high-power field in the documented slides. Nearly, 30% of all the CD138 positive plasma cells were found to be IgG4-positive [].\nProtein chemistry revealed hypergammaglobulinemia with higher levels of total protein and gamma fraction. No myeloma band or Bence Jones protein was detected []. Serum IgG4 levels were also elevated. A hematologist was consulted, and bone marrow examination revealed mild anemia, for which she was given supportive treatment. In the postoperative period, the patient was given a course of oral steroids. On follow-up at 6 weeks, she was given prosthesis in OD, and the patient was doing well till her last review.