[109] IgG4 Plasma Cells in Inflammatory Myofibroblastic Tumor: Inflammatory Marker or Pathogenic Link?

ST Saab, JL Hornick, CD Fletcher, S Olson, CM Coffin. Vanderbilt University, Nashville, TN; Brigham and Women's Hospital, Harvard University, Boston, MA

Background: Inflammatory myofibroblastic tumor (IMT) harbors a plasma cell rich inflammatory infiltrate. In contrast, IgG4 related sclerosing disease (IgG4SD) encompasses a syndrome with multisystem involvement by a fibroinflammatory proliferation with abundant lymphoid aggregates (LA) and obliterative phlebitis (OP). Cellular IgG4SD overlaps histologically with IMT. We investigated clinicopathologic and immunohistochemical features with IgG4 plasma cells in 36 IMTs.
Design: IMTs were retrieved from consultation and institutional files. Pathology materials and medical records were reviewed. Diagnosis was based on WHO criteria. Immunohistochemical stains on formalin-fixed paraffin-embedded tissue included ALK, smooth muscle actin, IgG, IgG4, CD35, CD21, and CD23. IgG and IgG4 positive plasma cells were counted in 6 40x HPF, with calculation of the IgG4/IgG ratio.
Results: 36 IMTs (ages 1-41 years, 92% in first 3 decades; 19 females, 17 males), originated in the mesentery (47%), lung (19%), urinary bladder (11%), pelvis/peritoneum (14%), or elsewhere (8%).Diameter ranged from 2-41 cm. None had OP or abundant LA. 64% were reactive for ALK. Mean IgG4 plasma cells per HPF ranged from 0-33. 16 IMTs (44%) had an IgG4/ IgG ratio>0.10 with no significant difference between ALK positive and negative cases. The IgG4/IgG ratio ranged from 0.1 to 3.24. 63%were ALK positive, 47% were CD35 positive (all negative for CD21 and CD23), 37% had the inflammatory clinical and laboratory syndrome associated with IMT, and 17% had recurrence.
Conclusions: IMTs have distinctive histology, lack OP and prominent LA of IgG4SD, and have fewer IgG4 plasma cells than IgG4SD. Although the number of IgG4 positive plasma cells in IMT is lower than published ranges for IgG4SD (33 vs. 60-100 per HPF), the IgG4/IgG ratio in 44% of IMTs in this series overlapped with the published cutoff of > 0.10 for IgG4SD. There was no significant difference in IgG4 expression between ALK positive and ALK negative IMTs. CD35 reactivity may reflect complement involvement in the inflammatory process. We conclude that IgG4 plasma cell counts and IgG4/IgG ratios are not reliable diagnostic discriminators. Clinical and histologic features, presence or absence of obliterative phlebitis and use of diagnostic adjuncts as ALK immunohistochemistry allow recognition of IMT, which has clinical and therapeutic significance. The findings in this study do not support the hypothesis that IMT is a variant of IgG4SD.
Category: Bone & Soft Tissue

Monday, March 22, 2010 1:00 PM

Poster Session II # 8, Monday Afternoon


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