DIAGNOSTIC SLIDE SESSION CASE 8

Michelle Madden Felicella, MDJuan Bilbao, MDArie 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

IgG4IgG

SPECIAL STAINS• CD3, CD5: numerous reactive T-cells• CD20, CD21, CD23, CD10, BCL6: small lymphocytes in

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 pachymeningitisIgG4-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

• Differential diagnosis: • Lymphoplasmacyte rich meningioma• Idiopathic hypertrophic pachymeningitis• Lymphoproliferative disorder• IgG4-related hypertrophic pachymeningitisIgG4-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

• 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

DIAGNOSTIC POINTS

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.