IGG4-Related Disease in the Skull Base and Calvarium: A Systematic Review and Presentation of Two Cases

Purpose: IgG4-related disease (IgG4-RD) is an inflammatory condition that can affect nearly all locations of the body, but the nature of its skull base and calvarial manifestations are poorly understood in neurosurgical literature.

Methods: A systematic review discovered 113 publications which described IgG4-RD in the skull base and calvarium. Data were collected from these sources and two cases at the authors' institution were retrospectively analyzed.

Results: A total of 113 publications were described, 182 cases of IgG4-RD in the skull and skull base. IgG4-RD in the skull base and calvarium was equally prevalent among females and males, comprising 48.4%, and 51.6% of cases, respectively. The most common presenting symptoms included headache (57), visual impairment (57), cranial nerve dysfunction, (31), hearing loss (28), and seizures (17). Treatment most commonly consisted of corticosteroids (119) and immunosuppressive agents such as rituximab (51), azathioprine (14), and cyclophosphamide (8). Multidrug regimens were utilized in 73 cases. The most commonly affected locations were the meninges (60) and cavernous sinus (39). Surgical resection was used in 34 cases, and radiation therapy was used in 5 cases. Serum levels of IgG4 were elevated in 61% of cases and ranged from 8 to 3,410 mg/dL. Delayed diagnosis was common. Thirty-two cases reported a time to diagnosis greater than 1 year, and multiple biopsies were reported in 23 cases.

Case 1: A 53-year-old female developed a mandibular infection diagnosed as osteomyelitis in 2009. In 2017, she developed blurred vision, and two endonasal biopsies at another institution were inconclusive, and again a diagnosis of clival osteomyelitis was rendered. Oral antibiotics were given and continued until she presented at the authors' institution with worsening vision and suspected recurrence of her osteomyelitis in early 2020. An endonasal transsphenoidal biopsy of the clival region was performed. Additional surgical debridement of the clival mass was conducted along with reconstruction with a vascularized nasoseptal flap. Histopathological analysis revealed storiform fibrosis, IgG4+ lymphocytic infiltrate, and obliterative phlebitis which lead to a diagnosis of IgG4-RD. Postsurgery, a tapering course of prednisone and rituximab lead to resolution of symptoms which have remained stable.

Case 2: A 52-year-old female with worsening ear and facial pain and an abducens palsy. Imaging revealed a mass in the Meckel cave region. After two inconclusive endonasal biopsies, an extradural middle fossa approach for biopsy of tissue in Meckel's cave rendered a diagnosis of IgG4-RD; however, the lesion lacked the storiform fibrosis and obliterative phlebitis classically associated with IgG4-RD. Treatment with prednisone and rituximab lead to rapid improvement

Conclusion: IgG4-RD in the skull base and calvarium is an uncommon condition with a wide variety of presenting symptoms. Corticosteroid treatment combined with immunosuppressive agents yields a robust response. Surgical resection is needed in a number of cases, and more invasive biopsy methods may be required as delayed diagnosis is common.

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
12 February 2021