Eastern Ophthalmic Pathology Society September 13-15, 2018 Idiopathic Orbital Inflammation (Inflammatory Orbital Pseudotumor) with Bone Erosion and Extension into the Paranasal Sinuses Alan D. Proia, M.D., Ph.D. Eastern Ophthalmic Pathology Society September 13-15, 2018 Proia/DUMC

Clinical History Woman in middle 30s with four month history of gradually worsening: Tearing, crusty discharge, itching, and photophobia in her right eye Difficulty focusing and eye strain after closing and then reopening her eyes Diplopia Pain in right eye during up, down, left, and right gaze Protrusion of right eye One month history of nausea when looking at objects close to her face Proia/DUMC

Examination Proptosis O.D. Exophthalmometry: 23 mm O.D. and 20 mm O.S. Intraocular pressure 23 mmHg O.D. and 19 mmHg O.S. Full extraocular movements but pain in right eye during left, right, up, and down movement Proia/DUMC

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Computed Tomography 2.8 x 1.9 x 3.2 cm mass involving the intraconal and extraconal nasal right orbit and extending to the orbital apex Anterior displacement of the globe Mass abutting the globe with loss of fat margin; effacement of the medial rectus muscle, portions of the fat plane, and the superior oblique muscle Erosion of the mass through the orbital floor into the superior maxillary sinus and into the ethmoid sinus through the lamina papyracea Proia/DUMC

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Surgery and Follow-up Anterior orbitotomy with biopsy 1.0 x 0.9 x 0.3 cm aggregate of tissue Dense fibrous connective tissue with numerous lymphocytes and macrophages; rare cells expressing cytokeratins One month later – anterior orbitotomy with biopsy of orbit and right ethmoid and maxillary sinuses Diagnosis: Idiopathic orbital inflammation/idiopathic inflammatory pseudotumor Proia/DUMC

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CD3 CD20 CD138 Kappa Lambda Proia/DUMC

IgG IgG4 Proia/DUMC

Idiopathic Orbital Inflammation Enlarged structure or mass in the orbit that is of unknown cause and is manifest histologically by nonspecific inflammation with varying degrees of fibrosis Other names: orbital pseudotumor, idiopathic orbital pseudotumor, inflammatory orbital pseudotumor, idiopathic orbital inflammatory syndrome, non-specific orbital inflammation Proia/DUMC

Idiopathic Orbital Inflammation Incidence 11% of lesions at Wills Eye Hospital Philadelphia, PA 8.5% at Erasmus University Medical Center, Rotterdam, Netherlands 5.2% at The University of Texas M.D. Anderson Cancer Center, Houston, TX Classified by anatomic distribution Mombaerts: dacryoadenitis, myositis, diffuse (several structures involved), or perineuritis Proia/DUMC

Idiopathic Orbital Inflammation All age groups Slight predominance in male gender Most common symptoms and signs Pain, diplopia, decreased vision, periorbital swelling, proptosis, restricted ocular motility Histology Nonspecific chronic inflammatory infiltrate of lymphocytes, plasma cells, histiocytes, eosinophils with degranulation, sometimes neutrophils Proia/DUMC

Idiopathic Orbital Inflammation Histology, continued Eosinophils may be prominent in children Lymphoid follicles with germinal centers may be present, most common in chronic stage of disease Degree of fibrosis is variable T-lymphocytes predominate over B-lymphocytes Polyclonal Variants: Granulomatous IOI and idiopathic sclerosing orbital inflammation Proia/DUMC

Idiopathic Orbital Inflammation Extraorbital extension Bone erosion: 16 prior reports Predominantly in diffuse IOI Dacryoadenitis and myositis more common in patients without bone erosion Through fissures and foramina without eroding through bone: 32 reported cases Clifton and coworkers found extraorbital extension in CT scans of 8/90 (9%) of patients with biopsy confirmed IOI Proia/DUMC

Extraorbital Extension Conclusion from review of the literature Not possible to predict a priori which patient with diffuse IOI will exhibit bone erosion Treatment similar to IOI without extension Corticosteroids Radiotherapy, immunosuppressive drugs, and/or surgical debulking in non-responsive IOI Proia/DUMC

Inflammatory Osteolysis From: G Mbalaviele, et al., Inflammatory osteolysis: a conspiracy against bone, J Clin Invest 127:2030-2039, 2017 Green = pro-osteoclast factors and red = anti-osteoclast factors Proia/DUMC