A Rare Image. Dean M. Cestari, MD Fred Jakobiec, MD Fred Hochberg, MD Joseph F. Rizzo III, MD Rebecca C. Stacy, MD PhD

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1 A Rare Image Dean M. Cestari, MD Fred Jakobiec, MD Fred Hochberg, MD Joseph F. Rizzo III, MD Rebecca C. Stacy, MD PhD Harvard Neuro-ophthalmology Service Boston, Massachusetts

2 51 year-old male financial consultant urgently referred to us for eye movement abnormalities by his neurologist at Massachusetts General Hospital

3 History of Present Illness 3 years prior to MEEI 1 year prior to MEEI Gradual and progressive decrease in reading vision Sensation of pressure behind both eyes

4 Medical History Ocular History Medical History Medications Social History Family History Perforated retinas (30 years earlier) Waldenström macroglobulinemia (diagnosed 3 years earlier) Rx RCVP chemo. Declared cancer free in 2007 by bone marrow biopsy; chronic low back pain Oxycodone PRN; Financial consultant; never smoked; occassional alcohol use Mother with epilepsy; father died of brain tumor

5 Examination Right Eye Left Eye Visual acuity 16/13 16/13 Near visual acuity J1 J1 (+1.25) Amsler grid Normal Normal Pupils Normal Normal Color (Ishihara) Normal Normal IOP 10 mm Hg 10 mm Hg Anterior segment Normal Normal

6 Humphrey visual fields (reliable OU)

7 Right optic disc Left optic disc

8 Examination Right Eye Left Eye Extra-ocular motility Slightly decreased adduction OU Orbital retropulsion Definite resistance OU Exophthalmometry 16 mm 17 mm

9

10 MRI T1 T2

11 14% 1. Normal OU 3% 5% 78% 2. Abnormal OD 3. Abnormal OS 4. Abnormal OU MRI? T1 T2

12 T1 T2 Normal Our Patient

13 Imaging T1 Pre-Gadolinium T1 Post-Gadolinium Fat Suppression

14 Imaging T1 Pre-Gadolinium T1 Post-Gadolinium Fat Suppression

15 Imaging T1 Post-Gadolinium Fat Suppression

16 Next step? 1. Treat with steroids 2. Treat with antibiotics/antifungals 3. Lumbar puncture 4. Biopsy 5. Refer to Neil Miller 32% 57% 4% 0% 6%

17 Orbital fat biopsy

18 Lymphoplasmacytoid cells: Nucleus of lymphocyte Cytoplasm of plasma cell

19 CD 20+ (B cell) BCL2 + (NHL)

20 + IgM heavy chain + Kappa light chain CD 10 negative: not acute lymphoma CD 23 negative: not a follicular lymphoma

21 Electron Microscopy Lymphoplasmacytoid Cell

22 Pathology Infiltration of orbital fat with CD20+ CD10- CD 23- B cells with IgM and monotypic kappa light chain expression: Waldenström Macroglobulinemia

23 Tumor infiltration into CSF Lumbar puncture: 16 WBC (0-5) 71 Lymph High protein levels 255 mg/dl (normal <55) Glucose 60 mg/dl CD19+ CD20+ CD23- CD5- CD10- B cells, with monotypic kappa light chain expression T1 Post-Gadolinium Fat Suppression

24 Final Diagnosis Waldenström macroglobulinemia + Central nervous system infiltration = Bing-Neel Syndrome

25 Jan Gosta Waldenström (1944) definition Chronic malignant proliferative disorder of lymphoid cells that infiltrates bone marrow Produces an IgM monoclonal protein in the serum (paraproteinemia) Signs and Symptoms: Fatigue Oronasal bleeding Lymphadenopathy Elevated ESR Hepatosplenomegaly Hyperviscosity: Retinopathy Vertigo Headache

26 What did Bing-Neel describe? Bing, J; Neel, A. Two Cases of Hyperglobulinaemia with Affection of the Central Nervous System on a Toxi-Infectious Basis (Myelitis, Polyradiculitis, Spinal Fluid Changes) Acta Medica Scandinavica 88:fascicle V-V1, , 1936 Jens Bing and Axel Neel (1936*) Association of hyperglobulinemia, CNS symptoms and brain infiltration (plasma cells and lymphocytes) in 2 patients They believed there was antibody-mediated damage causing a universal toxic effect and not a local effect

27 Bing-Neel Syndrome Hyperviscosity? Antibody mediated? IgM IgM bound to peripheral nerve

28 Bing-Neel Syndrome Mechanisms of CNS involvement: Direct infiltration of neoplastic cells into the CNS Diffuse Mass

29 25 Cases: Bing-Neel Literature All above 50 years Cognitive changes (14) Cord: myelopathy (8) Stroke-like episodes (5) 2 each: headaches, seizures Orbit: 1 case described with a unilateral mass involving the orbit without diffuse fat infiltration Our case is the first report of a patient with Bing-Neel Syndrome presenting with bilateral and symmetrical orbital infiltration

30 Management of This Patient Patient admitted for 2 grams IV solumedrol Received orbital radiation therapy 20 Gy over 2 weeks Began high-dose IV methotrexate

31 Humphrey visual fields after treatment

32 Take Home Points 1. Waldenström macroglobulinemia with central nervous system infiltration is the Bing-Neel Syndrome 2. Rarely Bing-Neel Syndrome can involve the orbit 3. This is the first report of Bing-Neel Syndrome presenting with bilateral and diffuse orbital fat infiltration

33 Thank you for your attention!

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