Pulmonary inflammatory myofibroblastic tumor versus IgG4-related inflammatory pseudotumor: differential diagnosis based on a case series

Background: Pulmonary inflammatory myofibroblastic tumor (IMT) has been considered as a synonym for inflammatory pseudotumor (IPT) for a long time. Recent studies have indicated that IMT and I(g)G4-related IPT are distinct diseases. However, no consensus criteria have been recommended. Here we propose a set of criteria for the differential diagnosis. Methods: Twenty-six archived IMT and I(g)G4-related IPT samples were examined for histological characteristics and the expression of I(g)G, I(g)G4, SMA and ALK-1. Based on our proposed criteria, we reclassified the cases into either IMT or IgG4-related IPT group and compared the clinicopathological features, laboratory findings, overall survivals (OS) and disease-free survivals between groups to validate the effectiveness and dependability of the diagnostic criteria. Results: The average age of IgG4-related IPT group was higher than IMTs (48.82 vs. 39.22 years, P= 0.031). In IMT group, tumors were characterized by bigger tumor sizes (3.47 vs. 2.22 cm, P= 0.007), diffuse and total destroyed alveoli (88.89% vs. 17.65%, P= 0.002), fewer lymphoid follicles (1.6/ HPF vs. 3.0/ HPF, P= 0.045) and lower expression of IgG (74.7/ HPF vs. 149.1/ HPF; P < 0.001). As an exclusion criterion of IgG4-related IPT, ALK-positivity was correlated with the higher cytological atypia (mean 3.7/ HPF, P < 0.001) and lesser lymphoid follicles (mean 1.2/ HPF, P= 0.021). And it's the first study to show the liner positive correlation between the lymphocytes + plasma cells count and IgG4-positive plasma cells count in these lesions (r= 0.914, P < 0.001). The negative correlation between the IgG4-positive plasma cells count and the expression of ALK-1 are reported for the first time as well (rs=-0.632, P= 0.001). However, despite two patients with recurrence or metastasis were divided into IMT group, only borderline values were detected in the survival analysis (OS 88.89% vs. 100%, P= 0.197, DFS 77.78% vs. 100.00%; P= 0.056). Conclusions: The significant differences of clinicopathological characteristics between the IMTs and I(g)G4-related IPTs indicated that a combination of lymphocytes + plasma cells count, cytological atypia, IgG4 and ALK-1 staining will be helpful in differential diagnosis.