IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria

Abstract

IgG4-related disease has evolved from originally being recognized as a form of pancreatitis to encompass diseases of numerous organs including the hypophysis and one reported case of dural involvement. A search of the University of Virginia, Division of Neuropathology files for 10 years identified ten cases of unexplained lymphoplasmacytic meningeal inflammation that we then evaluated using immunohistochemical stains for IgG4 and IgG. Ten control cases including sarcoidosis (4), tuberculosis (1), bacterial abscess (2), Langerhans cell histiocytosis (2), and foreign body reaction (1) were also examined. The number of IgG4-positive plasma cells was counted in five high power fields (HPFs) and an average per HPF was calculated. Cases that contained greater than ten IgG4-positive cells/HPF were considered to be IgG4-related. Five of the study cases met these criteria, including one case of leptomeningeal inflammation. All cases exhibited the typical histological features of IgG4-related disease including lymphoplasmacytic inflammation, fibrosis, and phlebitis. The dural-based lesions appear to represent a subset of the cases historically diagnosed as idiopathic hypertrophic pachymeningitis. While the leptomeningeal process most closely resembles non-vasculitic autoimmune inflammatory meningoencephalitis. Given these findings, IgG4-related meningitis should be considered in the differential diagnosis of meningeal inflammatory lesions after stringent clinical and histologic criteria are used to rule out other possible diagnoses.

IgG4-related Disease Manifesting as Pachymeningitis and Aortitis

“…Histologically, a dense lymphoplasmacytic infiltrate in a storiform pattern is characteristic, yet not entirely specific. The abundant macrophages seen in this case are unusual for IgG4-RD in many tissues, but have been reported in meningeal disease 4 . For diagnosis, immunostaining must demonstrate an elevated absolute number of IgG4-positive plasma cells per HPF, and an elevated ratio of IgG4 to IgG-positive plasma cells may aid in confirmation.…”

“…In contrast, IgG4-RD of the central nervous system is rare, with a few cases of pituitary and meningeal involvement described 6 . Recently, cases of both intracranial and spinal pachymeningitis due to IgG4-RD have been reported; these would previously have been classified as idiopathic hypertrophic pachymeningitis 4,6,7 . Consensus criteria for meningeal IgG4-RD would classify this case as "probable histological features of IgG4-RD" based on histological features and > 10 IgG4-positive cells per HPF 8 .…”

Consensus statement on the pathology of IgG4-related disease

“…6,8,10,12,[15][16][17]27,28,30,32,34,35,49,51,52,[55][56][57][58][59][60][61][62][63] Consensus statement on the pathology of IgG4-related disease V Deshpande et al which is designed to bind to the Fc portion of IgG4 molecules. 7,10,11,31,40,41 Polyclonal antibodies have been also used by some groups.…”

Multifocal Fibrosclerosis with Hypertrophic Pachymeningitis and a Soft Tissue Mass around the Thoracic Vertebral Bodies: A Case Report with Review of the Literature

“…IgG4-related disease includes a wide variety of diseases, such as Mikulicz's disease, Riedel's thyroiditis, interstitial pneumonia, autoimmune pancreatitis, interstitial nephritis, and retroperitoneal fibrosis (9)(10)(11). Recently, there have been several reports of IgG4-related disease with hypertrophic pachymeningitis (12)(13)(14)(15). In some cases, multifocal fibrosclerosis and IgG4-related disease are considered as probably the same entity because they have a similar distribution of multiple organ involvement (9,16,17).…”