Keiko Toyoda, MD

The concept of IgG4-related disease (IgG4-RD) was first proposed by Hamano¹ in 2001, and Japanese investigators have subsequently continued to play a leading role in defining its clinical spectrum and diagnostic criteria. In 2001 and 2002, Hamano et al^1,2 reported autoimmune pancreatitis (AIP) associated with increased serum IgG4 levels and characterized histologically by lesions with abundant IgG4-positive plasma cell infiltration, fibrosis, and obliterative phlebitis. Subsequently, many extrapancreatic lesions, including sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis, interstitial pneumonia, and mediastinal fibrosis, have been reported to show similar histopathologic features and an association with increased serum IgG4 levels. Such lesions may develop with or without AIP. In radiology numerous reports from Japan on the chest and abdomen have continued to appear. Initially, reports on the head and neck were few because the disease had only been newly recognized, and the condition originally referred to as Mikulicz disease was first reported to be part of the spectrum of IgG4-RD by Yamamoto and other Japanese physicians. In the head, neck, and brain, manifestations of IgG4-RD include enlargement of salivary and lacrimal glands, inflammatory pseudotumor, pituitary lesions, thickening of the dura mater/pachymeningitis, thyroid lesions, and others. We have undertaken multi-institutional case conference meetings with presentations of IgG4-RD images in the head and neck region. Even though the number of such cases at individual institutions has been small, based on this experience we have been able to summarize the imaging findings of IgG4-RD.

Based on our results, the diagnosis of IgG4-RD should be considered in patients presenting with T2-hypointense lacrimal gland, pituitary, or cranial nerve enlargement, or a T2-hypointense orbital mass, especially if multiple

sites in the head and neck are involved in the presence of elevated serum IgG4. In particular, cranial nerve involvement is shown. The infraorbital nerve, a branch of the V2, is involved with diffuse concentric thickening of the nerve.

With increasing dissemination of the disease concept of IgG4-RD, it can now be suspected from the imaging findings, allowing radiologists to suggest to clinicians that the serum IgG4 level be measured or biopsy of specific sites performed. Moreover, when thickening of the infraorbital nerve is noted, IgG4-RD should be most strongly suspected, although this may depend on the race of the patient. In Caucasians perineural spread of cutaneous malignant melanoma may also be considered in the differential diagnosis. This disease characteristically involves multiple sites in the head and neck region metachronously, including the lacrimal gland, major salivary gland, pituitary gland, dura mater, and perineural and perivascular sites. When neuroradiologists suspect IgG4-RD, identification of lesions in other organs (chest, abdomen) on CT or PET-CT can be of great value in confirming the diagnosis.

Of IgG4-RD perineural lesions, those of the infraorbital nerve, V2, V1, and trigeminal nerve are most common. Those of the facial nerve have also been encountered, while other brain perineural lesions are thought to be rare. It is not known why the trigeminal nerve is preferentially involved. Also, in IgG4-RD, perivascular masses may be formed and, so, neurovascular lesions are also of interest. In this disease, progression of fibrosis is associated with fluctuations of the clinical course, suggesting that follow-up of changes in the MRI findings on long-term follow-up observation may be important. In the future I intend to address these and other unresolved issues after accumulating additional cases.

Reference

1. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 2001;344:732–38, 10.1056/NEJM200103083441005
2. Hamano H, Kawa S, Ochi Y, et al. Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet 2002;359:1403–04, 10.1016/S0140-6736(02)08359-9

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