A Comparative Study of Inflammatory Myofibroblastic Tumors and Tumefactive IgG4-related Inflammatory Lesions: the Relevance of IgG4 Plasma Cells

Abstract

IgG4-related disease is a recently recognized systemic condition characterized by tumefactive lesions at various sites. Inflammatory pseudotumor (IPT), a tumefactive mass lesion with an unknown etiology, belongs to the spectrum of IgG4-related disease. Inflammatory myofibroblastic tumor (IMT), previously considered under the umbrella of IPT, is now classified as a clonal neoplasm. Previously, both the terms were used interchangeably, because of overlapping morphologic features. This study was carried out to compare the morphologic and the immunohistochemical features of these entities and to study the role of IgG4 in their pathogenesis. Thirty-nine cases comprising of IMT (n=18) and IPT (n=21) were retrieved, and their clinical, morphologic, and immunohistochemical features were studied. IMT was more common in children as compared with IPT. IMT cases showed the proliferation of myofibroblastic cells accompanied by a variable inflammatory infiltrate, whereas IPT cases showed predominantly stromal fibrosis and a lymphoplasmacytic infiltrate with a subset of cases showing a storiform fibrosis and obliterative phlebitis. Anaplastic lymphoma kinase-1 (ALK-1) was positive in 12 of the 18 (66.7%) IMT cases, whereas none of the IPT cases showed ALK-1 immunoreactivity. IPT cases showed significantly increased IgG4+ plasma cells (mean, 127.8/high-power fields vs. 17.8/high-power fields) and a higher IgG4/IgG ratio (mean, 48.2% vs. 10.7%) as compared with IMT. Fluorescence in situ hybridization analysis was positive for ALK rearrangement in 6 of the 9 IMT cases tested. In conclusion, most of the IPT cases can be considered as IgG4 related on the basis of their histopathologic features and immunohistochemistry criteria. However, IMT represents a myofibroblastic neoplasm with ALK-1 overexpression and is clearly not IgG4 related.

Inflammatory Myofibroblastic Tumour of the Submandibular Gland

“…Immunoprofiling helps to establish the diagnosis of IMT, with the identification of myofibroblasts, and with 50% of IMTs being ALKpositive [3]. Recently the relationship between IgG4 related disease (multi-organ system disease) and IMT has gained attention, with the possibility of overlap of the two conditions, as highlighted in this case [9]. Diagnosing IgG4 related disease is however challenging and even though biopsy is the gold standard investigation, samples are often inconclusive which creates the need for multiples procedures.…”

Inflammatory Myofibroblastic Tumor of the Lung

“…In one patient with lung IMT, concurrent B-cell lymphoma was seen [9]. IgG4 syndrome [45,46] has been reported with IPTs; these tumors have been seen to form a subset of this syndrome. Pulmonary and extra-pulmonary IMTs have also been reported following hematopoietic stem cell [47][48][49], graft versus host disease [50] and solid-organ transplant [51][52][53][54].…”

“…ALK expression may be negative by IHC; rearrangement for ALK locus by fluorescence in situ hybridization (FISH) may be required [39] or newer IHC methods may have to be adopted [70]. Another difference between IPTs and IMTs is that on the basis of IHC and FISH characteriwww.journals.viamedica.pl stics, IMTs have not been found to always be IgG4 related [46]. As seen later, this fact may explain the response to steroids.…”

Clinical characteristics and outcomes of 17 cases of inflammatory myofibroblastic tumor at a University Hospital in China

“…Generally, the proliferation and nuclear atypia of spindle cells in IMT are more marked, and ALK-1 staining is positive in some patients (13). Lymphoplasmacytic infiltrate, storiform-fibrosis and obliterative phlebitis (14) are more prominent in IgG4-related IPT, whereas ALK expression is negative (12,13). Next generation sequencing-based RNA fusion assays have been suggested to be a primary method, which may be used to provide a more accurate diagnosis than immunohistochemical platforms and FISH-based assays of ALK (14).…”

“…At present, some clinicians still use the terms ITP and IMT interchangeably. IPT is an inflammatory reactive mass, which is currently considered to be an IgG4-related disease (12). Although they exhibit certain similarities with regards to morphology, IMT and IPT are different diseases.…”