IgG4-Related Inflammatory Pseudotumor of the Trigeminal Nerve: Another Component of IgG4-Related Sclerosing Disease?

Discussion

The etiology of IPT is still unclear but is thought to be infectious or autoimmune in nature. IPT is histologically characterized by a proliferation of spindle cells such as fibroblasts and myofibroblasts, admixed with inflammatory components consisting of lymphocytes, plasma cells, eosinophils, and histiocytes. However, the cell population can vary from one tumor to another or even from one microscopic field to another within the individual tumor.

Historically, IPT has been designated under various synonyms, such as plasma cell granuloma, xanthogranuloma, histiocytoma, and IMT. IMT is now considered as a “distinctive neoplastic proliferation” composed predominantly of myofibroblasts.³ Recent studies have revealed ALK gene rearrangements in IMT, suggesting a neoplastic cause, though, not all IMTs are positive for ALK by immunohistochemistry. Our case showed predominant lymphocyte proliferation with reactive fibrosis. Myofibroblastic spindle cells did not show cytologic atypia, and immunostaining for ALK was negative.

Recently, some populations of IPTs of the liver⁴ and lung⁵ have been reported to show pathologic characteristics similar to those of IgG4-related sclerosing disease as they involved lymphoplasmacytic infiltration and high IgG4+ plasma cell infiltrates. IgG4-related IPTs are occasionally complicated with IgG4-related pancreatitis and sialadenitis, suggesting that these types of IPTs may form part of the spectrum of systemic IgG4-related sclerosing disease.

There is currently no consensus on the number of IgG4+ plasma cells required for the diagnosis of IgG4-related IPT; however, several reports recommend that the ratio of IgG4+/IgG+ cells is also important for the diagnosis.^4,5 According to the literature, IgG4+ cells >60–100/HPF and the ratio of IgG4+/IgG+ cells >40%-50% seem to be highly suggestive of IgG4-related disease. Yamamoto et al⁶ recently reported that both of these values are significantly lower in IMTs than in IgG4-related lesions. In our case, the number of IgG4+ plasma cells per HPF was 128, and the ratio of IgG4+/IgG+ cells was 71%.

In the head and neck region, IgG4-related IPTs of the salivary glands, lacrimal glands, and pituitary glands are well known; however, nasal/paranasal,⁷ dura mater,⁸ and parapharyngeal space⁹ lesions have also been reported. Our report describes a case of IgG4-related IPT of the trigeminal nerve without involvement of any of the preferential organs. Seol et al¹⁰ described another case of skull base IPT, which showed perineural spread along the trigeminal nerve, very similar to our case. However, no attempt was made to investigate the possible linkage with IgG4-related systemic disease or to characterize the plasma cell immunophenotype.

Imaging findings of IPT, including IgG4-related IPT, frequently reveal a homogeneously enhancing soft-tissue mass. On T2-weighted images, the mass is usually iso- to hypointense relative to brain. This can possibly be explained by the combination of fibrosis and attenuated cellularity of IPTs, which may also explain why IPTs tend to appear hyperintense on DWI. Attempts to differentiate IPTs from cancer¹¹ and lymphoma¹² on DWI have been made. However, the various degrees of cellularity, fibrosis, and perfusion in IPTs account for differences in diffusion restriction and often make the diagnosis difficult. IPTs with bone involvement and internal carotid artery encasement have also been reported in the past,^13,14 including pathologically proved IgG4-related IPTs.⁷ In addition to these imaging features, our patient also had extensive perineural spread along the trigeminal nerve, highly suggestive of a neoplastic process.

IgG4-related IPT generally has a benign clinical course. These lesions usually respond to corticosteroids; however, relapse rates range from 30% to 40%.¹⁵ For unresponsive IPTs, surgical resection may be considered. Our patient did not seek further treatment. Her symptoms and follow-up MR images have not shown significant changes. However, a recent report suggests that there is a frequency of lymphomatous transformation in 10% of cases,¹⁶ adding yet another reason for close long-term surveillance.