OPHTHALMIC PATHOLOGY SPECIALTY CONFERENCE
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1 DISCLOSURE STATEMENT OPHTHALMIC PATHOLOGY SPECIALTY CONFERENCE No financial disclosures No off-label usage Diva Regina Salomão, M.D. Professor of Laboratory Medicine and Pathology Mayo Clinic College of Medicine CLINICAL HISTORY 12 year-old female previously healthy Referral for evaluation of orbital mass inflammatory pseudotumor Symptoms started 3 years earlier Right side proptosis Visual changes Oct
2 RLEOM RPO Oct 2012 RLO RPO Orbital biopsies Oct
3 CD3 CD20 PATHOLOGY Battery of immunostains CD163, CD68 (macrophages) S100, CD34, CD1a and Alk-1 All negative Orbital fibroadipose tissue with marked chronic inflammation CLINICAL HISTORY Patient was treated with steroids Good clinical and radiographic response Vision declined tapering of steroids Infliximab following 4 months Jun 2013 (6 m) right 6 th nerve palsy Jan Right side hearing loss March
4 Nasopharynx and Parapharyngeal mass Biopsies Parapharyngeal mass biopsy PATHOLOGY Extensive battery of immunostains CD3, CD4, CD8, CD10, CD15, CD20, CD21, CD30, CD34, CD35, CD46, CD56, CD68, CD163, PAX-5, PGM1, ALK-1, calponin, cytokeratins (AE1/AE3 and 19), factor 13A, fascin, PGP9.5, Bcl-2, Kappa and Lambda, S100 Lymphoma was ruled out Descriptive diagnosis pseudotumor Parapharyngeal mass biopsy 4
5 CLINICAL HISTORY Brain MRI - FLAIR July radiation therapy 20 cgy Sept 2015 left arm and leg weakness + sensory changes Brain and Spine MRI new lesions October 2015 CLINICAL HISTORY Extensive systemic work-up Neg Infectious etiology Autoimmune disease Steroid therapy Improvement of symptoms Patient referred to Mayo for second opinion (Nov 2015) 5
6 CLINICAL HISTORY Proptosis Visual changes June 13 6 th nerve palsy Jan 15 Hearing loss April 15 Parapharyngeal mass Sep 15 Arm & leg weakness Nov 15 Referred Mayo CLINICAL HISTORY Proptosis Visual changes Steroids - Infliximab June 13 6 th nerve palsy Steroids Jan 15 Hearing loss Steroids April 15 Parapharyngeal mass Radiation Sep 15 Arm & leg weakness Steroids Nov 15 Referred Mayo Steroids DISCUSSION DISCUSSION Challenging case Patient of young age Unusual clinical course Extensive disease Diagnosis Management of disease 6
7 DISCUSSION Differential diagnosis 1. Inflammatory process Infectious etiology 2. Lymphoma 3. Neoplasm with exuberant inflammatory component 4. Inflammatory process Non infectious etiology ORBITAL CELLULITIS Differential Diagnosis Infection of soft tissues posterior to orbital septum Extension of sinuses infection More common in children than adults Males > females Median age (hospitalization) 7-12 yrs Bergin DJ et al. Br J Ophthalmol 1986; 70 (3):174-8 Garcia G et al. Ophthalmol 2000; 107(8): ORBITAL CELLULITIS Differential Diagnosis 90% aerobic bacteria Strept., Staph., Haemophillus Less common: Pseudomonas, Klebsiella Fungal etiology Ocular and intracranial complications Tissue biopsy obtained rare cases Case of orbital cellulitis McKinley SH et al. Am J Ophthalmol 2007; 144:
8 ORBITAL LYMPHOMA Differential Diagnosis Uncommon in children Large series* median age 69 yrs Burkitt lymphoma Extranodal marginal zone lymphoma Orbital involvement by leukemia Immunophenotyping is necessary *Demirci H et al. Ophthalmol 2008; 115 (9): Rasmussen PK et al. JAMA Ophthalmol 2014; 132:851-8 Clinical picture courtesy of Dr. James Garrity Immunophenotype by flowcytometry Case of orbital Burkitt Lymphoma NEOPLASMS WITH INFLAMMATION Differential Diagnosis Neoplasms associated with marked inflammatory infiltrate Rhabdomyosarcoma Retinoblastoma extending to the orbit 8
9 Desmin+ MyoD1+ Myogenin+ RHABDOMYOSARCOMA NON INFECTIOUS INFLAMMATORY ORBITAL LESIONS Lesions with specific features Sarcoidosis Granulomatosis with polyangiitis Rosai-Dorfman disease Orbital IgG4-related disease Lesion without specific features Idiopathic orbital inflammation Granulomatosis with Polyangiitis (Wegener s) Rosai-Dorfman Disease 21 years old woman Bilateral proptosis 15 years old woman Bilateral orbital masses Histiocytic disorder CD68+, S100+, CD1a- 9
10 IgG4- related disease IgG4- related disease 52 years old woman Right blurred vision and diplopia Enlarged right lacrimal gland 52 years old woman Right blurred vision and diplopia Enlarged right lacrimal gland Consensus conf. criteria 100 IgG4+ cells/hph IgG4/IgG ration >40% Consensus conf. criteria 100 IgG4+ cells/hph IgG4/IgG ration >40% Deshpande V et al. Mod Pathol 2012; 25: IgG4 Deshpande V et al. Mod Pathol 2012; 25: IgG4 NON INFECTIOUS INFLAMMATORY ORBITAL LESIONS Lesions with specific features Vasculitis Sarcoidosis Rosai-Dorfman disease Orbital IgG4-related disease Lesion without specific features Idiopathic orbital inflammation Idiopathic Orbital Inflammation Diagnosis of exclusion Cases with typical presentation Middle age patient, pain Steroid test No biopsy Unusual presentations Tissue biopsy 10
11 Idiopathic Orbital Inflammation Sclerosing type Idiopathic Orbital Inflammation Children Uncommon diagnosis in pediatric population 6-17% of all orbital lesions Largest series Mottow and Jakobiec 29 patients < 20 yrs Systemic symptoms 55% Bilateral involvement 45% Eosinophilia 28% Mottow LS et al. Arch Ophthalmol 1978; (96): Belanger C et al. Am J Ophthalmol 2010; 150: Idiopathic Orbital Inflammation Extra-orbital extension Uncommon < 50 cases reported Middle cranial fossa, cavernous sinus Extension outside the orbit Superior orbital fissure Optic canal Inferior orbital fissure Patients required additional therapy Mahr et al. Am J Ophthalmol 2004;138:396 Lee EJ et al. Korean J Radiol 2005;6:82 Zborowska et al. Eye 2006; 20:107 PRESENT CASE Last follow-up recent Improvement of disease in orbit Vision loss in right eye remains unchanged Improvement of spine and brain lesions 11
12 PRESENT CASE Steroid discontinued Scheduled to return in 2 months Brain MRI Flair February 2016? Inflammatory? Demyelinating? Radiation induced SUMMARY Case of idiopathic orbital inflammation Young patient (9 years at presentation) Extra-orbital extension Resistant to steroids Brain lesions of unknown etiology Acknowledgements Dr. John Chen Dr. James Garrity Dr. Karen Grogg Dr. Gesina Keating 12
13 QUESTIONS? 13
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