IgG4 plasma cells in inflammatory myofibroblastic tumor: inflammatory marker or pathogenic link?

Abstract

Inflammatory myofibroblastic tumor is a rare mesenchymal neoplasm that harbors an anaplastic lymphoma kinase (ALK) gene rearrangement in the majority of cases. It is composed of fibroblastic-myofibroblastic cells with a characteristic inflammatory infiltrate that consists predominantly of plasma cells. In contrast, IgG4-related sclerosing disease is a recently described multisystem disorder with a histological appearance similar to inflammatory myofibroblastic tumor. The plasma cell infiltrate is characteristic in IgG4-related sclerosing disease and has been studied as a tool to render this diagnosis. Histologically, the two disorders overlap, although there are significant clinical differences. This study analyzes the histological appearance of 36 inflammatory myofibroblastic tumors, compares them with IgG4-related sclerosing disease, and assesses the plasma cell profile using immunohistochemistry to determine the range and proportion of IgG4 plasma cells. The majority of patients were children and young adults, mainly with solitary masses and no clinical manifestations of IgG4-related sclerosing disease. ALK-1 positivity was present in 23 cases (64%). None showed obliterative phlebitis or prominent lymphoid aggregates. Of 36 inflammatory myofibroblastic tumors, 15 cases showed an IgG4/IgG ratio Z0.10, a cutoff described in the literature as supportive of IgG4-related sclerosing disease and up to 33 IgG4-positive plasma cells per high-power field indicating a mild-to-moderate increase as compared with IgG4-related sclerosing disease. Currently, the diagnostic recognition of inflammatory myofibroblastic tumor is based on clinicopathological features and diagnostic adjuncts, such as ALK-1 reactivity and genetic tests. Although inflammatory myofibroblastic tumor and IgG4-related sclerosing disease are distinct entities, a subset of inflammatory myofibroblastic tumors exhibit an IgG4/IgG ratio that is within the range for IgG4-related sclerosing disease. Therefore, the ratio alone cannot be used as a reliable discriminator between these two entities and other clinical and pathologic features must always be taken into account.

Histopathological findings in 29 lymph node biopsies with increased IgG4 plasma cells

“…Six cases (Cases 1, 5, 13, 14, 18 , 27; Table 2) were tested for human herpes virus 8 (HHV8) by immunohistochemical staining and were negative. S100 staining was done in four cases (2,3,9,18); one case was also tested for CD1a (Case 2) showing co-expression of S-100 protein and CD1a staining on increased scattered Langerhans cells. Features of Rosai-Dorfman disease were not seen.…”

“…Features of Rosai-Dorfman disease were not seen. Plasma cells were shown to be polyclonal in ten cases using in situ stains for kappa and lambda (Cases 1,5,8,9,11,13,14,18,25,27). Polyclonal kappa and lambda staining was demonstrated by immunohistochemistry in three cases (Case 24, 25, 27).…”

“…These patterns are: multicentric Castleman disease-like, follicular hyperplasia, interfollicular expansion, progressive transformation of germinal centers and nodal inflammatory pseudotumor-like. 5,[7][8][9] We selected cases with these histological findings and other features of benign adenopathy in adult patients, and evaluated for IgG and IgG4 by immunostaining.…”

Primary Inflammatory demyelinating pseudotumor in the left frontal lobe with meningeal involvement presenting as malignant neoplasms

“…IP primarily affecting the central nervous system is rare. In most cases, the etiology of IP often is uncertain although several subset lesions are inflammatory and associated with a variety of infectious agents and may be caused by autoimmune disorders [9,10]. In addition, demyelinating diseases presented with tumor-like lesions, such as multiple sclerosis, acute disseminated encephalomyelitis and myelinoclastic diffuse sclerosis had also been reported in the literature [11,12].…”

IgG4-Related Disease of the Gastrointestinal Tract: A 21st Century Chameleon

“…29 An inflammatory myofibroblastic tumor is another diagnostic consideration because some of those neoplasms show more IgG4 þ plasma cells. 40,41 Approximately one-half of those neoplasms are positive for ALK, a finding not observed in IgG4-related disease.…”