DIAGNOSTIC SLIDE SESSION
CASE 8
Michelle Madden Felicella, MD
Juan Bilbao, MD
Arie Perry, MD
Clinical history, follow-up and MR images
kindly provided by Dr. Todd Mainprize
CLINICAL HISTORY
• 42-yo woman with headache and left transverse sinus
occlusion
• Treated with warfarin and followed by neurology
• MRI: prominent dural thickening and nodularity of cerebral
hemispheres including the falx and tentorium
• Repeat MRI a few months later: worsened thickening
• Referred to neurosurgery for biopsy of the left temporal
lobe
DIAGNOSIS???
EMA
EMA
CD3
CD20
Kappa
Lambda
IgG
IgG4
SPECIAL STAINS
• CD3, CD5: numerous reactive T-cells
• CD20, CD21, CD23, CD10, BCL6: small lymphocytes in
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germinal centers
BCL2: positive in scattered interstitial small lymphocytes
Cyclin D1: negative
EMA: positive in meningothelial cells (limited to surface)
and numerous plasma cells
ISH for kappa and lambda: polyclonal
Ki-67: moderate LI
IgG4: 80 plasma cells/HPF
IgG4/IgG: 15%
DIAGNOSIS
• Chronic pachymeningitis with meningothelial
proliferation and increased IgG4-positive plasma
cells
• Most likely represent IgG4 sclerosing disease and
meningothelial hyperplasia
DIAGNOSTIC POINTS
• Differential diagnosis:
• Lymphoplasmacyte rich meningioma
• Idiopathic hypertrophic pachymeningitis
• Lymphoproliferative disorder
• IgG4-related hypertrophic pachymeningitis
• Key Histologic features:
• Dense lymphoplasmacytic infiltrate with many plasma cells
• Storiform Fibrosis
• Phlebitis
• Scattered eosinophils
• Average count of 5 HPF in the area of greatest concentration:
• Our case: 80 IgG4 + cells/HPF and 518 IgG + cells/HPF
• IgG4:IgG ratio of 15%.
• Normal ratio in serum is <5%
• Average IgG4 PCs in other inflammatory conditions <10 HPF
DIAGNOSTIC POINTS
• Although cut-offs well established in other organ systems,
they are not well established for meningeal disease
• Can form a mass or a more diffuse plaque-like growth
pattern. More commonly is mass forming in other organs.
• Highly steroid responsive
• Serum IgG4 levels may be helpful in some cases and
should be done
• Hyper-eosinophilia also common
FOLLOW-UP
• Rx after bx: high dose steroids for about 2 months
• CT scans of neck, chest, abdomen negative for systemic
evidence of a lymphoproliferative disorder.
• MRI at 2 months showed significant improvement. She
was tapered from steroids subsequently due to side
effects. Follow-up MRI scans show continued
improvement.
• She is much improved clinically although she still has
transverse sinus occlusion and is on warfarin.
PRE-RX
POST-RX
REFERENCES
• Smyrk TC. Pathological features of IgG4-related
sclerosing disease. Curr Opin Rheumatol 2011;23(1):74-9.
• Cheuk W, Chan JK. IgG4-related sclerosing disease: a
critical appraisal of an evolving clinicopathologic entity.
Adv Anat Pathol 2010;17(5):303-32.
• Lindstrom KM, Cousar JB, Lopes MB. IgG4-related
meningeal disease: clinico-pathological features and
proposal for diagnostic criteria. Acta Neuropathol
2010;120(6):765-76.
• Stone JH, Zen Y, Deshpande V. IgG4 related disease. N
Engl J Med 2012;366:539-51.