Presentation number: eEdE-114

Orbital Lymphoproliferative Disorders: The great Mimicker.

Purpose Present the varying imaging appearances of orbital lymphoproliferative disorders from the common to the uncommon and discuss the patterns of orbital involvement that it may assume Reinforce several CT/MRI findings that may provide specificity in the proper inclusion of lymphoproliferative disorders of the orbit in the radiologists’ differential diagnosis

Approach Why How Where

Approach Why: – Most common primary orbital tumor in adults 10% of all orbital masses. 55% of malignant orbital tumors. Non-Hodgkin B-cell type lymphoma, specifically the mucosa-associated lymphoid tissue (MALT) subtype, is the most common primary orbital lymphoma – Wide spectrum from benign (lymphoid hyperplasia, IgG4-related ophthalmic disease, etc.) to malignant lesions – The Great Mimicker: Challenging diagnosis due to broad clinical and radiological presentation

Approach How: – CECT with coronal and sagittal reformations  Common 1st study for orbital symptoms – MR should be modality of choice for evaluating location and extent of disease Pre- and post-gadolinium enhancement unless contraindication  Axial and coronal images: T1, T2, and post contrast with fat suppression

Approach Where: – Extraconal lesion*  Lacrimal gland – Intraconal lesion – Extraocular muscle enlargement – Optic Nerve/Sheath complex lesion – Ocular mass  Conjunctival * Most frequent

Approach Where: – Extraconal lesion*  Lacrimal gland – Intraconal lesion – Extraocular muscle enlargement – Optic Nerve/Sheath complex lesion – Ocular mass  Conjunctival * Most frequent Often is a Diffuse process May appear as a Trans-spatial lesion

Findings Common pattern: – Older patients, indolent, painless mass with proptosis – Anterior extraconal region – Unilateral, smooth, circumscribed mass that molds to and encases orbital structures – Isointense to muscle on T1-weighted sequences and mildly hyperintense on T2-weighted sequences and lower ADC (DWI) values than other orbital masses (due to its high cellularity) – Uniform enhancement It can be located anywhere in the orbit and be found in various forms: Uncommon patterns

Findings Common pattern: – Older patients, indolent, painless mass with proptosis. – Anterior extraconal region. – Unilateral, smooth, circumscribed mass that molds to and encases orbital structures. – Isointense to muscle in T1-weighted sequences. Mildly hyperintense in T2-weighted sequences and lower ADCs (DWI) values than other orbital masses (due to its high cellularity).* – Uniform enhancement. It can be located anywhere in the orbit and be found in various forms: Uncommon patterns

Findings - Lymphoma 1.Extraconal lesion ‒ Homogeneous pliable enhancing mass CECT of typical imaging features of follicular lymphoma in the extraconal compartment, presenting as an homogenous enhancing infiltrative mass in the right lateral extraconal orbit that extends to the temporal fossa

Findings 1. Extraconal lesion – DDX: Infection/hematoma – DDX: Cavernous venous malformation – DDX: Dermoid and epidermoid Frontozygomatic suture is classic location for orbital dermoid/epidermoid, diffusion-restricted, fat-containing (dermoid) – NO ENHANCEMENT

1. Extraconal lesion: Lacrimal Gland – Involved in nearly 40% of cases. – Lymphoproliferative disorders constitute up to 50% of nonepithelial lacrimal lesions – Older patient age, presence of lymphadenopathy elsewhere, and lack of osseous remodeling are all characteristics suggestive of lymphoma – Lower ADC values may also be indicative of lymphoma, as opposed to other lacrimal gland diseases Findings - Lymphoma

1. Extraconal lesion: Lacrimal Gland

Findings 1. Extraconal lesion: Lacrimal Gland – DDX: Sarcoidosis Diffuse enlargement and homogenous enhancement of lacrimal glands +/- muscles bilaterally. Granulomatous diseases often have other ocular manifestations such as uveitis, keratitis, and conjunctivitis)

1. Extraconal lesion: Lacrimal Gland – DDX: Epithelial lesions - Pleomorphic adenoma (Most common benign neoplasm of lacrimal gland. Attempts should be made to distinguish lacrimal lymphoma from pleomorphic adenoma, as biopsy of the latter is generally avoided because of potential risk of tumor seeding) Findings Imaging: May remodel bone, T2 hyperintense, more heterogeneous with homogenous enhancement

Findings 1. Extraconal lesion: Lacrimal Gland – DDX: Dacryoadenitis (Involvement of orbital septum and soft tissue thickening and enhancement, local periosteal reaction)

Findings 2. Intraconal lesion – DDX: Cavernous hemangioma (venous malformation) (Most common intraconal mass in adults) Well-defined, ovoid, may remodel bone, T2 hyperintense, patchy enhancement that fills in over time)

Findings 2. Intraconal lesion – DDX: Lymphatic malformation (Hamartomatous malformation) Lobulated and multicystic, fluid-fluid levels, minimal rim enhancement

Findings - Lymphoma 3.Extraocular muscle enlargement – Diffuse, homogenous enhancement – Hypointense T2 signal (increased nuclear/cytoplasmic ratio)

Findings 3. Extraocular muscle enlargement – DDX: Idiopathic orbital inflammatory pseudotumor (Acute onset, pain, unilateral, tubular configuration of affected muscle, tendinous insertion involvement, adjacent fat stranding)

Findings 3. Extraocular muscle enlargement – DDX: Thyroid orbitopathy Bilateral, sparing of tendinous insertions, expanded retrobulbar fat ( star), low density within EOM bellies in late disease (arrow)

Findings - Lymphoma 4. Optic Nerve/Sheath complex lesion ‒ Pliable tumor that conforms to normal structures

Findings 4. Optic Nerve/Sheath complex lesion - DDX: Meningioma Homogenous enhancing mass surrounding and distinct from optic nerve (normal appearance of nerve and surrounding CSF, arrow). Calcifications (30-50%), "Tram-track" appearance, perioptic cyst behind optic nerve head

Findings 4. Optic Nerve/Sheath complex lesion – DDX: Glioma Children, NF1, kinking/buckling common (arrow), may involve nerve, chiasm, tract, or central pathways, variable enhancement

Findings - Lymphoma 5. Ocular mass: Conjunctival – Conjunctiva-associated lymphoid tissue (CALT) – Usually with reddish decoloration of the conjunctiva (“salmon patch”), due to its vascularization. Indolent course Conjunctival lymphoma situated in the lower-medial quadrant of the right eye – DDX: Benign ocular surface tumors, malignant tumors (squamous cell carcinoma and amelanotic melanoma), epi/scleritis, ectopic lacrimal gland, foreign body...

6. Diffuse and ill-defined lesion - Nearly half of lymphoproliferative lesions are diffuse and ill defined at imaging Findings - Lymphoma Example: IgG4- related disease

Findings 6. Diffuse and ill-defined lesion – DDX: Pseudotumor Pain, 75% retrobulbar, infiltration or thickening of EOMs, isointense to orbital fat in T2-WI Diffuse involvement and enhancement of involved structures

Findings 6. Diffuse and ill-defined lesion – DDX: Cellulitis Pain, peri/intraorbital soft tissue infiltration with mass effect and enhancement (arrow), sinus as most frequent source of infection, peds>adults, +/- dehiscence of lamina papyracea

Findings - Lymphoma 7. Trans-spatial mass – Infiltrative appearance and bone destruction associated with unfavorable histology of lymphoproliferative condition Trans-spatial multiple myeloma

Findings - Lymphoma 7. Trans-spatial mass Post-lung transplant EBV+ diffuse large B-cell lymphoma

Findings 7. Trans-spatial mass – DDX: Orbital metastases Not rare! Breast most common, melanoma often metastasizes to orbit. Carcinoid tumor may involve EOMs Prostate cancer metastasis to left orbit

Findings 7. Trans-spatial mass – DDX: Rhabdomyosarcoma Rare in adults, variable contrast enhancement, +/- bone remodelation/destruction.

Conclusion Orbital lymphoproliferative disease can assume many appearances and be everywhere in the orbit Makes almost all differential diagnosis lists of orbital disease Some imaging findings can be helpful in the differential diagnosis – Uniformity of MR appearance, hypointense T2, restricted diffusion

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