IgG4-Related Perineural Disease

Abstract

Aims. To elucidate characteristics of IgG4-related disease involving the peripheral nervous system. Methods. Retrospective review of 106 patients with IgG4-related disease identified 21 peripheral nerve lesions in 7 patients. Clinicopathological and radiological features were examined. Results. Peripheral nerve lesions were commonly identified in orbital or paravertebral area, involving orbital (n = 9), optic (n = 4), spinal (n = 7), and great auricular nerves (n = 1). The predominant radiological feature was a distinct perineural soft tissue mass, ranging 8 to 30 mm in diameter. Histologically, the epineurium was preferentially involved by massive lymphoplasmacytic infiltration rich in IgG4(+) plasma cells. All lesions were neurologically asymptomatic and steroid-responsive at the first presentation, but one recurrent lesion around the optic nerve caused failing vision. Conclusion. IgG4-related disease of the peripheral nervous system is characterized by orbital or paravertebral localization, perineural mass formation, and rare neurologic symptoms. The term "IgG4-related perineural disease" seems appropriate to describe this entity.

Figure 1

CT (a) and MRI ((b and d): T2-weighted images; (c, e, and f): T1-weighted images) of orbital space in 55-year-old man (case 1). CT image reveals soft tissue around the bilateral infra orbital nerve (a; arrows). MRI shows soft tissue around the left orbital nerve (b–d; small arrows), bilateral infraorbital nerve (c–f; arrows) and right supraorbital nerve (c and d; arrowheads). Left orbital nerve can be detected in the lesion (b and d).

Figure 2

CT (a) and MRI (b: T2-weighted image; (c and d): contrast-enhanced T1-weighted images) of orbital space in 44-year-old man (case 4). Soft tissue mass is detected in the right orbital space (a; arrow). This lesion extends along the right optic nerve in MRI (b–d; arrows). The right optic nerve penetrating the lesion is detectable in MRI (b and d; small arrows). Soft tissue mass along the right infraorbital nerve is also noted (a–c; arrowheads).

Figure 3

MRI ((a and d): T2-weighted images; b: T1-weighted image; c: contrast-enhanced T1-weighted image) of orbital space in 61-year-old man (case 3). MRI shows the soft tissue around the left supraorbital nerve (a–c; arrows) and optic nerve (c and d; arrowheads). The left optic nerve can be detected in the lesion.

Figure 4

CT (a, c, and e) and FDG-PET (b, d, and f: fusion images; g: coronal MIP image) of whole body in 58-year-old man (case 5). CT shows soft tissue density around the left C6 (a; arrow), right L5 (c; arrows), and S1 nerves (e; arrow). High FDG uptakes are identified as perineural masses (b, d, f, and g; arrows).

Figure 5

Histological features of resected IgG4-related perineural disease in 61-year-old man (case 7). (a) The epineurium is involved in a massive inflammatory process, where nerve fascicles (*) are embedded. (b) The endoneurium is unremarkable without inflammatory cell infiltration. (c) Inflammatory cells consist predominantly of lymphocytes and plasma cells. (d) Immunostaining for IgG4 reveals a large number of IgG4+ plasma cells.