1. Matthew Maeder MD Jane Lee MD Dana Shani MD Bidyut Pramanik MD
Diagnostic Challenge in a Case of Bing Neel Syndrome with Orbital Involvement Imaging Findings Before and After Treatment
Matthew Maeder MD
Jane Lee MD
Dana Shani MD
Bidyut Pramanik MD

2. The authors have nothing to disclose

3. Case presentation 65-year-old Caucasian female
History of hypertension, Non Hodgkins Lymphoma (NHL) treated 10 years ago, and Waldenström Macroglobulinemia (WM)
Presented with acute onset of expressive aphasia for 6 hours
Chronic headaches and chronic blurry vision in right eye
Unsteady gait, “veering to the left”

4. Initial CT Head No significant findings

5. FLAIR: Minimum nonspecific white matter disease
Initial MRI Brain
FLAIR: Minimum nonspecific white matter disease

6. Diffusion-weighted imaging: No acute ischemia
Initial MRI Brain
Diffusion-weighted imaging: No acute ischemia
DWI ADC map

7. Pre-contrast T1 Post-contrast T1
Initial MRI Brain
Post contrast T1: Minimum linear and nodular enhancement in bilateral internal auditory canals
initial mri
min WM disease
no acute ischemia
post contrast images demo minimum linear and nodular enha in b IACs
Pre-contrast T Post-contrast T1

8. Initial MRI Brain
Summary: Minimum nonspecific white matter disease, no acute ischemia, abnormal enhancement in the IACs
Impression: No acute ischemia. Abnormal enhancement in the IACs suspicious for leptomeningeal disease.

9. Lumbar Puncture
Cytopathology Results: Consistent with CNS involvement by a CD10 positive low-grade B cell lymphoma
Cytopathology Addendum Report
Addendum
INTERPRETATION
FLOW CYTOMETRY ANALYSIS FOR LYMPHOPROLIFERATIVE DISORDERS
COMMENT
Involvement by CD10+ B-cell lymphoma.
subset of large B-cell lymphoma and Burkitt's lymphoma.
Phenotypically, the possibilities include follicular lymphoma, a
physiochemical analysis and other clinical parameters suggested.
lymphoma diagnosis?), image study of the brain, cytology,
Correlation with patient's past medical history (any confirmed
GROSS DESCRIPTION
prepared for Flow Cytometry. A cytocentrifuge preparation is
Received colorless fluid measuring 3 cc. in volume. The fluid is
iMS
stained with Wright-Giemsa.
7AAD: 96%
Percentage of Abnormal Cells: 27% Cell Size: Small Viability
IMMUNOPHENOTYPIC ANALYSIS
A monoclonal kappa, CD10 positive B-cell population is present.
B-Cell Associated Activation
Antibody Description Result Antibody Description Result
RESULTS
B, myeloid Positive,
CD19 Pan B-cell antigen Positive, Moderate CD Activated T,
CD10 Follicle center B-cells, CALLA, Positive, Moderate Anchor
B-cell subset Moderate
CD20 Pan B-cell antigen Positive, Moderate cells,
CD Leukocyte common Positive,
myeloid subset
antigen Moderate
cell leukemia
CD11c Monocytes, myeloid subset, hairy Negative
FMC-7 B-Cell associated antigen in B- Negative
 CD23 Mature B-cells, CLL Negative
Cell subset
plasma cells
Kappa Kappa Ig light chain, B-cells, Positive, Moderate
Lambda Lambda Ig light chain, B-cells, Negative
CD2 Thymic and peripheral T-cells, NK Negative
T-Cell Associated
Antibody Description Result
cells
subunit
CD3 Pan T-cell antigen, TCR-epsilon Negative
CD4 Helper T-cells, thymocyte subset, Negative
monocytes
(B1a cells)
CD5 Pan T-cells, mature B-cell subset Negative
CD7 Thymic and peripheral T-cells, NK Negative
CD8 Suppressor T-cells, NK cells, Negative
thymocyte subset
CD57 T-cell subset, NK cells Negative
CD56 T-cell subset, NK cells Negative
a specialized BioReference Laboratory. Testing has been performed
Lymphoproliferative Disorders, reported on 07/10/2014 by GenPath,
This addendum reports the results of Flow Cytometry Analysis for
Hospital specimen 75-NG , with GenPath ID:
Elmwood Park, NJ 07470, phone: , on Lenox Hill
at BioReference Laboratories, Inc., 481 Edward H. Ross Drive,
Please refer to the official GenPath report, which is on file in
 the Pathology Department.
Ryan DesJean, M.D.
Reported on: 07/11/14
(Electronic Signature)
Cytopathology Report
CEREBROSPINAL FLUID
Specimen(s) Submitted
Clinical History
Waldenstroms macroglobulinemia
Gross Description
2 cytospins
3 cc. clear fluid
Satisfactory for interpretation.
Statement of Adequacy
CEREBROSPINAL FLUID:
Final Diagnosis
SIGNIFICANT FINDINGS.
specimen is sent for flow cytometry which reveals a CD10 positive
some showing a plasmacytoid morphology. A portion of the
Examination of this specimen reveals abundant small lymphocytes,
cytometry is consistent with CNS involvement by a CD10 positive
morphology of this lymphoid infiltrate combined with the flow
B cell lymphoma (see addendum for further details). The
Bonomo and Dr. Shani on 7/11/2014.
low-grade B cell lymphoma. These results are discussed withDr.
Ami Fujii Yeh, CT(ASCP)
________________________________________________________________

10. Diagnosis: Bing Neel Syndrome
WM is a lymphoplasmacytic lymphoma
When it involves the CNS it is called Bing Neel Syndrome
Few reported cases of CNS or orbital involvement
Our case is unusual because it involves both CNS & orbital structures
The reported imaging findings of BNS is nonspecific. Our case demonstrates the diagnostic dilemma, with multifocal areas of FLAIR signal abnl and enhancement

11. Diagnosis: Bing Neel Syndrome
The white matter lesions and pattern of enhancement are nonspecific; MRI findings shown are typical and demonstrate the diagnostic difficulty
There are no established treatment guidelines for this disease
The reported imaging findings of BNS is nonspecific. Our case demonstrates the diagnostic dilemma, with multifocal areas of FLAIR signal abnl and enhancement

12. Treatment
The patient began chemotherapy week 1, soon after presentation
Systemic chemotherapy was given every 4 weeks
Rituximab 375 mg/m2
Bendamustine 90 mg/m2
Intrathecal chemotherapy was given via Ommaya reservoir
Methotrexate 15 mg twice weekly for 3 months
Started on 9/2 ~week 8?
Until 10/30
Started after second MR….

13. Clinical Picture
CSF cytology and flow cytometry at week 10 no longer identified a monoclonal B-cell population of cells
Aphasia had resolved but there was persistent blurry right eye vision and new onset right eye lateral gaze deviation
*Was there any hearing or vision symptoms?

14. Follow Up MRI (Week 8)
Now demonstrates confluent FLAIR signal abnormalities in the midbrain, pons, optic chiasm and tracts, periventricular white matter and the corpus callosum
What happened for 7 weeks? E.g. patient was followed closely observed symptoms for 6 wks
All
Subsequent MRI demo improvaeent enh in IAC, however interval dev of subependymal enhancement lining vents esp front horns, diffuse infilt of the retrobulb fat with enh,
IMP: Extensive prog of signal abnl and enhancement
FLAIR conflu signal abn along the head of caudate (ax 20), bilateral perifrontal ependymal (1201:14), splenium. FLAIR midb/pons optic chiasm and tracts (ax 16), ax 14.
Intrapeduncular cistern (post C 16) (8), orbits (ax 7) and (cor 11), STIR (cor 11) preT1 (cor 9).
Post 19,
Summary slide of images

15. Follow Up MRI (Week 8)
Development of new multifocal areas of nodular and subependymal enhancement
All
Subsequent MRI demo improvaeent enh in IAC, however interval dev of subependymal enhancement lining vents esp front horns, diffuse infilt of the retrobulb fat with enh,
IMP: Extensive prog of signal abnl and enhancement
FLAIR conflu signal abn along the head of caudate (ax 20), bilateral perifrontal ependymal (1201:14), splenium. FLAIR midb/pons optic chiasm and tracts (ax 16), ax 14.
Intrapeduncular cistern (post C 16) (8), orbits (ax 7) and (cor 11), STIR (cor 11) preT1 (cor 9).
Post 19,
Summary slide of images
Post-contrast T1

16. However, there was improvement in enhancement in bilateral IACs
Follow Up MRI (Week 8)
However, there was improvement in enhancement in bilateral IACs
All
Subsequent MRI demo improvaeent enh in IAC, however interval dev of subependymal enhancement lining vents esp front horns, diffuse infilt of the retrobulb fat with enh,
IMP: Extensive prog of signal abnl and enhancement
FLAIR conflu signal abn along the head of caudate (ax 20), bilateral perifrontal ependymal (1201:14), splenium. FLAIR midb/pons optic chiasm and tracts (ax 16), ax 14.
Intrapeduncular cistern (post C 16) (8), orbits (ax 7) and (cor 11), STIR (cor 11) preT1 (cor 9).
Post 19,
Summary slide of images
Post-contrast T1

17. MRI (Week 8)
Dedicated orbital imaging: Diffuse infiltration of the retrobulbar fat with enhancing soft tissue
All
Subsequent MRI demo improvaeent enh in IAC, however interval dev of subependymal enhancement lining vents esp front horns, diffuse infilt of the retrobulb fat with enh,
IMP: Extensive prog of signal abnl and enhancement
FLAIR conflu signal abn along the head of caudate (ax 20), bilateral perifrontal ependymal (1201:14), splenium. FLAIR midb/pons optic chiasm and tracts (ax 16), ax 14.
Intrapeduncular cistern (post C 16) (8), orbits (ax 7) and (cor 11), STIR (cor 11) preT1 (cor 9).
Post 19,
Summary slide of images
Post-contrast T1
fat-suppressed
STIR
Pre-contrast T1

18. MRI (Week 8)
Summary of corresponding brain images: Extensive progression of FLAIR signal abnormalities and enhancement
Week 1
Week 8
All
Subsequent MRI demo improvaeent enh in IAC, however interval dev of subependymal enhancement lining vents esp front horns, diffuse infilt of the retrobulb fat with enh,
IMP: Extensive prog of signal abnl and enhancement
FLAIR conflu signal abn along the head of caudate (ax 20), bilateral perifrontal ependymal (1201:14), splenium. FLAIR midb/pons optic chiasm and tracts (ax 16), ax 14.
Intrapeduncular cistern (post C 16) (8), orbits (ax 7) and (cor 11), STIR (cor 11) preT1 (cor 9).
Post 19,
Summary slide of images

19. Clinical Picture
The patient continued chemotherapy and continued to gradually improve
An MRI was ordered to evaluate new right eye ptosis
*Was there any hearing or vision symptoms?

20. MRI 13 weeks after start of chemotherapy (Week 14)
Improved subependymal enhancement
All findings obtained X weeks / months after treatment.
Orbits 10/7: 1101:12 decreased enh interpedunclar cistern
Cor 1001:9
10/5: 11:16
FLAIR
“The brain involvement has dramatically improved
The response in the orbits was some, still significant disease
Summary slide of images
Week 8
Week 14

21. MRI 13 weeks after start of chemotherapy (Week 14)
Improved enhancement in interpeduncular cistern
All findings obtained X weeks / months after treatment.
Orbits 10/7: 1101:12 decreased enh interpedunclar cistern
Cor 1001:9
10/5: 11:16
FLAIR
“The brain involvement has dramatically improved
The response in the orbits was some, still significant disease
Summary slide of images
Week 8
Week 14

22. MRI 13 weeks after start of chemotherapy (Week 14)
Mild improvement in infiltration of the retrobulbar fat and enhancing orbital soft tissues
Week 8
Week 14
All findings obtained X weeks / months after treatment.
Orbits 10/7: 1101:12 decreased enh interpedunclar cistern
Cor 1001:9
10/5: 11:16
FLAIR
“The brain involvement has dramatically improved
The response in the orbits was some, still significant disease
Summary slide of images

23. MRI (Week 14)
Summary: The brain involvement responded to therapy. However, significant disease still remained in the orbits.
All findings obtained X weeks / months after treatment.
Orbits 10/7: 1101:12 decreased enh interpedunclar cistern
Cor 1001:9
10/5: 11:16
FLAIR
“The brain involvement has dramatically improved
The response in the orbits was some, still significant disease
Summary slide of images

24. What exactly can happen in the CNS?
Commonly, WM causes CNS symptoms due to hyperviscosity of blood
More rarely, there is direct invasion by the malignant cells in WM
Lymphocytes, plasma cells
Appearance of invasion is divided into diffuse or tumoral forms 2,5

25. MRI Features of Bing Neel in the CNS
T2 and FLAIR: Hyperintensity is typical
Typical locations are pons, medulla, periventricular white matter, leptomeninges 2,3,5
Contrast enhancement: Some cases have associated foci of enhancement within the T2/FLAIR hyperintense regions 2,3
DWI: Few case reports describe scattered foci of diffusion restriction in different arterial territories 4

26. MRI Features of Bing Neel in the Orbit
Few reports of orbital involvement describe infiltration of the optic nerve, retrobulbar fat, and extraocular muscles 5
Infiltration consists of fat-suppressed T2 hyperintensity, enhancement, or both
Infiltration of retrobulbar fat may lead to proptosis

27. Conclusion
Bing Neel Syndrome is rare, and should be considered when given a history of Waldenström Macroglobulinemia
MRI Brain may show T2/FLAIR hyperintensity, sometimes with associated foci of enhancement
Imaging findings may worsen during treatment
Evaluate the orbits for retrobulbar fat infiltration and proptosis

28. References
Cuenca HR, Guzman DVLJ, Roa ME, et al. Bing-Neel syndrome as an initial sign of Waldenström macroglobulinaemia associated with orbital infiltration. Neurologia (Barcelona, Spain) (2013)
Kim HJ, Suh SI, Kim JH, et al. Brain magnetic resolution imaging to diagnose bing-neel syndrome. Journal of Korean Neurosurgical Society 46.6 (2009):
Van Cauwenberge MG, Depreter B, Dumoulin EN, et al. Bing–Neel syndrome: Two unexpected cases and a review of the literature. Journal of the neurological sciences (2015): 19-26
Arias M, Pereiro Zabala I, Requena Caballero I, et al. [Rapidly progressing dementia as the presenting symptom of Waldenström’s macroglobulinemia : findings from magnetic resonance imaging of the brain in Bing Neel syndrome.] Rev Neurol 38 : , 2004
Stacy RC, Jakobiec FA, Hochberg FH, et al. Orbital involvement in bing-neel syndrome. Journal of Neuro-Ophthalmology 30.3 (2010):