IgG4-related Inflammatory Pseudotumor with Imaging Findings Similar to Meningioma

Abstract

IgG4-related inflammatory pseudotumor is a feature of IgG4-related disease and develops in various organs. Intracranial IgG4-related inflammatory pseudotumor is rare, and data on the clinical course and response to treatment are insufficient in the literature. We herein report a patient with IgG4-related inflammatory pseudotumor who had magnetic resonance imaging findings similar to meningioma. Tumorectomy was discontinued because of the intraoperative rapid diagnosis, which revealed the infiltration of lymphocytes and plasma cells. She received oral prednisolone therapy for IgG4-related inflammatory pseudotumor, and the tumor size had significantly decreased after six months of treatment.

Introduction

IgG4-related disease (IgG4-RD) is an immune-mediated condition characterized by tumefaction, tissue infiltration by IgG4-positive plasma cells, fibrosis, and elevated serum IgG4 concentrations (1-3). These characteristics were first reported in 2001 in patients with autoimmune pancreatitis. IgG4-RD involves various organs, including the lacrimal and salivary glands, thyroid, lung, bile duct, and kidneys (1-3). In addition, when the nervous system is involved in IgG4-RD, the development of hypertrophic pachymeningitis, hypophysitis, orbital inflammation, and peripheral nerve disease has been described (4-7).

IgG4-related inflammatory pseudotumor has been recognized as a feature of IgG4-RD. Although IgG4-related inflammatory pseudotumors develop in various organs, including the nervous system (8), information on intracranial IgG4-related inflammatory pseudotumor, particualrly its natural clinical course and response to treatment, is insufficient at present.

We herein report the clinical features of a case of IgG4-related inflammatory pseudotumor that exhibited similar imaging findings to meningioma wherein the lesion was significantly decreased with oral prednisolone therapy.

Case Report

A 57-year-old woman experienced a transient feeling of floating. Although she had no neurological deficit, she underwent brain magnetic resonance imaging (MRI). The scan revealed an extra-axial, well-defined, and round-shaped tumor developing from the dura mater in the left frontal region. Furthermore, the tumor exhibited an isointense signal on T1- and T2-weighted imaging. This signal was uniformly enhanced on MRI with gadolinium enhancement, and the dural tail sign was observed (Fig. 1). Head computed tomography (CT) revealed that, compared with the brain, the tumor signal demonstrated slightly high density uniformly. In addition, tumor internal calcification and bone thickening were not observed. The patient was referred to the Department of Neurosurgery at our hospital. The CT and MRI findings indicated that the tumor was a meningioma, so follow-up MRI was performed at the outpatient department.

Figure 1.

Series of brain magnetic resonance imaging (MRI) findings in the clinical course. (A-C) MRI results on the first visit. (A, B) The IgG4-related inflammatory pseudotumor is shown as an isointense signal on T1- and T2-weighted axial images. (C) This tumor was uniformly enhanced with gadolinium. (D-G) Follow-up studies of brain MRI. After the initiation of oral prednisolone therapy, the tumor size decreased gradually over six months.

Follow-up MRI performed two years after the first visit revealed slow enlargement of the tumor. Although she still had no neurological deficit, tumorectomy with craniotomy was planned. During the surgery, however, the intraoperative rapid diagnosis of the tumor revealed infiltrations of lymphocytes and plasma cells, and this finding was not compatible with meningioma. Therefore, tumorectomy was discontinued after the tumor biopsy for a pathological examination. The final pathological diagnosis of the biopsy specimen was IgG4-RD. She was referred to the Department of Neurology at 59 years old.

The patient was alert and well oriented. Her height and body weight were 157 cm and 73 kg, respectively. Her cranial nerve functions as well as the muscle strength of the trunk and extremities were intact. The deep tendon reflexes were normal, and flexor plantar responses were observed bilaterally. No sensory disturbances were observed in the body or extremities, and she showed no neurological deficit.

Her blood cell and differential leukocyte counts were normal. The IgG, IgA, and IgM levels were also normal (IgG level 877 mg/dL, normal 870-1,700 mg/dL; IgA 117 mg/dL, normal 110-410 mg/dL; IgM level 195 mg/dL, normal 50-260 mg/dL; elevated IgE level 265 IU/mL, normal <170 IU/mL), and the serum IgG4 level was within the normal range (36 mg/dL, normal: 5-105 mg/dL). The serum autoantibody test was positive for antinuclear antibody (1:40, normal <1:40) but negative for anti-SS-A and anti-SS-B antibodies. The test was also negative for myeloperoxidase anti-neutrophil cytoplasmic autoantibody and proteinase 3 anti-neutrophil cytoplasmic autoantibody. A cerebrospinal fluid examination was not performed.

Thoracoabdominal CT revealed a tumor on the left adrenal gland, which was diagnosed as a non-functioning adrenal tumor after endocrine examinations. Brain MRI revealed an extra-axial tumor with an isointense signal on T1- and T2-weighted imaging. The tumor was enhanced on MRI with gadolinium and had developed over the past two years.

A tumor biopsy revealed fibrosis and infiltration of lymphocytes and plasma cells. Immunohistochemical assessments revealed a mixture of CD20-positive B lymphocytes and CD3-positive T lymphocytes in the specimen. Furthermore, IgG4-positive plasma cells were observed, and the ratio of IgG4-/IgG-positive cells was 50% (Fig. 2).

Figure 2.

Brain biopsy findings. (A, B) Fibrosis and infiltration of lymphocytes and plasma cells were observed [A, Hematoxylin and Eosin (H&E) staining, scale bar=200 μm; B, H&E staining, scale bar=50 μm]. (C, D) IgG- and IgG4-positive plasma cells were observed. IgG4-positive plasma cells were observed, and the ratio of IgG4-positive plasma cells/IgG-positive cells was 50% (C, IgG immunostain, scale bar=50 μm; D, IgG4 immunostain, scale bar=50 μm).

The patient was diagnosed with IgG4-RD and classified as probable IgG4-RD using the 2020 revised comprehensive diagnostic criteria for IgG4-RD (9). Although she had no neurological deficit, we opted for immunotherapy to avoid tumor progression and the appearance of neurological symptoms in the future. Accordingly, immunotherapy using oral prednisolone (45 mg/day) was initiated (Fig. 3). The dose of prednisolone was tapered gradually for 4 months, and low-dose oral prednisolone therapy (5 mg/day) was continued. MRI was performed at one, three, and six months after the initiation of prednisolone therapy, showing a decrease in the tumor size (Fig. 1). The serum IgG4 level was found to be 12 mg/dL following treatment for 6 months.

Figure 3.

Clinical course of our case. MRI was performed at the first visit and at one and two years during the observation period. MRI was also performed at one, three, and six months after the initiation of prednisolone therapy.

Discussion

Inflammatory pseudotumor has been described as a clinical feature of IgG4-RD from the initial period (1-3). However, while IgG4-related inflammatory pseudotumor has been reported to develop in various organs, its occurrence in the brain is rare (10).

In the present case, the pseudotumor was observed as a slowly developing intracranial tumor from the dura mater. The presenting lesions of the intracranial IgG4-related inflammatory pseudotumor were described as Sylvian fissure, skull base, and cavernous sinus in previous reports (11-16). Most pseudotumors develop from the dura mater; therefore, differentiation from dura-based tumors is important. The MRI findings of IgG4-related inflammatory pseudotumor include isointense signal on T1- and T2-weighted imaging and tumor enhancement with gadolinium; these findings are similar to those of meningioma (11,12,14-18). Furthermore, CT in the present case showed that the characteristics of the slightly high-density tumor were similar to those of a meningioma.

According to the “The 2020 revised comprehensive diagnostic criteria for IgG4-RD” in Japan, an elevated serum IgG4 level (>135 mg/dL) is one of the 3 criteria for the diagnosis of IgG4-RD (9). However, other reports have stated that IgG4 level elevation was observed in only around 50% of patients with pathologically proven IgG4-RD (19). In fact, the serum IgG4 levels of patients with intracranial IgG4-related inflammatory pseudotumor have ranged from normal to increased in previous reports, showing no consistency (12-14,16-18). In our case, an elevated serum IgG4 level was not observed. Therefore, making a definitive diagnosis without a histopathological specimen was difficult.

In patients with IgG4-RD, hypertrophic pachymeningitis has been identified as having nervous system involvement. The MRI findings of the dura mater in patients with IgG4-related hypertrophic pachymeningitis have shown a hypointense or isointense signal on T1- and T2-weighted imaging and homogeneous gadolinium enhancement (6,7,20). However, IgG4-related inflammatory pseudotumors have been defined as mass-forming lesions in various regions and organs of patients with IgG4-RD (10), and the MRI findings of intracranial IgG4-related inflammatory pseudotumors have demonstrated a hypointense or isointense signal on T1- and T2-weighted imaging and homogeneous gadolinium enhancement (11,12). Although MRI in the present case showed thickening of the dura mater with gadolinium enhancement near the tumor, the MRI findings revealed a slowly evolving tumor with typical MRI signals of an IgG4-related inflammatory pseudotumor. Therefore, we described this tumor as an IgG4-related inflammatory pseudotumor.

In our case, fortunately, there were no clinical symptoms throughout the clinical course. Previous reports found that patients with intracranial IgG4-related inflammatory pseudotumors presented with neurological symptoms. In addition, it is rare for a patient to be asymptomatic for several years. The clinical symptoms of intracranial IgG4-related inflammatory pseudotumor usually appear due to the compression of brain tissue and cranial nerve involvement because of tumor expansion. Therefore, surgical resection of the tumor for decompression is performed as treatment of intracranial IgG4-related inflammatory pseudotumor (11,14,15,18).

Glucocorticoids are recognized as the first-choice treatment for IgG4-related disease (1-3). Regarding IgG4-related inflammatory pseudotumor, the treatment responsiveness to glucocorticoids and immunosuppressive agents has been described as good for various body organs and intracranial lesions (10,11,13-16,18). In the present case, significant tumor reduction was also achieved by oral prednisolone therapy with minimal surgical invasion.

In conclusion, we presented the case of a patient with IgG4-related inflammatory pseudotumor showing imaging findings similar to meningioma. It was difficult to diagnose the present case based on MRI and serological findings alone, and a pathological examination was required for an accurate diagnosis. Most patients with IgG4-related inflammatory pseudotumor are treated with invasive tumor resection for the preoperative diagnosis of dural-based tumors, such as meningioma. In some patients with IgG4-related inflammatory pseudotumor, however, glucocorticoid therapy is extremely effective for tumor size reduction, and considerations of an intraoperative rapid diagnosis might be useful for ensuring minimal surgical invasion in the patients with dural-based tumor which had imaging findings similar to meningioma.

The authors state that they have no Conflict of Interest (COI).