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

Abstract

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 IgG4-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 IgG4-related IPT samples were examined for histological characteristics and the expression of IgG, IgG4, 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 IgG4-related IPTs indicated that a combination of lymphocytes + plasma cells count, cytological atypia, IgG4 and ALK-1 staining will be helpful in differential diagnosis.

Keywords: Inflammatory myofibroblastic tumor (IMT); differential diagnosis; inflammatory pseudotumor (IPT).

Figure 1

Computed tomography (CT) and macroscopic imaging data of the patient with intracranial metastasis (Case 2) (A,B). CT examinations of the patient before the resection. A solid tumor (Marked by the white arrows) in the right lower lobe of the lung with deep lobulated sign, pleural indentation and markedly inhomogeneous enhancement showed on CT imaging; (C) 5 months after surgery, magnetic resonance imaging (MRI) showed a few of subcortical nodules with obvious peripheral edema (Marked by the green arrows) which were considered as intracranial metastasis; (D) a macroscopic image of the lobectomy specimen showed that the tumor was circumscribed, and whitish-yellow in color on the cut-surface.

Figure 2

Hematoxylin and eosin staining in IMT and IgG4-related IPT. (A) Original alveolar structures were totally destroyed by intersecting fascicles of spindle tumor cells in IMTs; (B) tumor cells were admixed with numerous lymphocytes, plasma cells and lymphoid follicles (red arrows) in IgG4-related IPTs; (C) a large number of inflammatory cells were infiltrative and involves the small bronchi (green arrow) in IPTs; (D) inflammatory infiltration of vessel walls or obstructive phlebitis (yellow arrow) were only observed in the tumors diagnosed as IgG4-related IPT.

Figure 3

Immunohistochemical (IHC) staining of IMT and IgG4-related IPT. (A) Smooth muscle actin (SMA) was focally positive in spindle-shaped cells in inflammatory myofibroblastic tumors (IMT); (B) in IgG4-related IPTs, IgG expressions were patchy and cytoplasmic, arrows, IgG-positive plasma cells; (C) IgG4 immunostain showed numerous IgG4-positive plasma cells which marked by red arrows in the lesions of IgG4-related IPTs; (D) spindle-shaped tumor cells presented diffuse and strong reactivity for ALK-1 immunostain in the IMT, red arrows, ALK-1-positive spindle cells.

Figure 4

The results of statistical analysis based on the clinicopathological and immunohistochemical (IHC) findings. (A) Overall survival (OS) between the IMT and IgG4-related IPT group were found no statistically significant difference (P=0.197); (B) a borderline value was found in disease-free survival (DFS) between the two group (P=0.056); (C) Pearson correlation analysis showed that the lymphocytes + plasmocytes level had a possible linear positive correlation with the number of IgG4-positive plasma cells (r=0.914, P<0.001); (D) the significant differences were found in the average number of L + P between the ALK-negative and weakly or strongly positive lesions respectively (P=0.027 and P=0.002). And a negative correlation was found between the ALK-1 expression and L + P count as well (rs=−0.663, P<0.001); (E) similar results were also found between the ALK-1 expression and the number of IgG4-positive plasmocyte (P=0.018, P=0.001, rs=−0.632 and P=0.001). ALK-1 weakly focally positive reaction was represented by ALK-1 + in the graph.