Brain Pathology Case of the Month - October 2017


Rosai-Dorfman meningeal disease with IgG4-related disease histological features.


Rosai-Dorfman (RD) disease, also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare condition of unknown etiology caused by a non-clonal proliferation of S100-positive histiocytes (1). It can present in nodal or extranodal sites, the latter including meninges and orbit. Emperipolesis is a histological hallmark.

IgG4-related disease is a chronic inflammatory condition characterized by tissue infiltration by IgG4-positive plasma cells and lymphocytes leading to tissue sclerosis. Possible disease sites are very broad, also including orbit and meninges. A consensus statement including diagnostic criteria has been published: diagnosis is based on morphological findings, the presence of IgG4-positive plasma cells and a IgG4+/IgG+ ratio > 40% (2). The three major morphological features are: a dense lymphoplasmocytic infiltrate, fibrosis, arranged at least focally in a storiform pattern, and obliterative phlebitis. In case of meningeal disease, > 10 IgG4-positive plasma cells/HPF together with the presence of at least 1 morphological feature has been proposed as sufficient for a diagnosis of "Probable histological features of IgG4-related disease". No criteria for a diagnosis of "Histologically highly suggestive of IgG4-related disease" have been defined for the meningeal site because of the limited data available. IgG4 serum levels have been investigated as a possible diagnostic aid, but their use is limited by their unsatisfactory sensitivity and specificity.

In our meningeal RD disease case, criteria for a diagnosis of probable histological features of IgG4-related disease were also met. Increased IgG4-positive plasma cells in RD disease have been extensively reported in literature, but the question wherever a true association between these entities exists or if it is a mere non-specific coincidental finding remains open (4). This can be especially true in meningeal disease, since, as previously described, diagnostic criteria for meningeal IgG4-related disease are less defined and this could lead to over-diagnosis of this condition.

RD disease treatment approach is mainly based on general clinical conditions, sites involved and disease progression. After diagnosis and disease staging, a close follow up can be suggested for patients without symptoms or critical organs involvement. If active treatment is indicated, steroids are the first-line option and are sufficient to achieve disease control in most of the cases. Surgery, radiotherapy and chemotherapy can be taken into consideration in specific situations (1). Steroids are the mainstay treatment for IgG4-related disease too and improvement is usually rapid: however, early diagnosis and prompt treatment are important because sclerosis and organ damage can be irreversible (3).

As a concluding remark, the different histological findings between the material submitted for intraoperative examination and the additional tissue samples highlight the limits of intraoperative diagnoses and the importance of adequate sampling.


  1. Dalia S, Sagatys E, Sokol L, Kubal T (2014) Rosai-Dorfman disease: tumor biology, clinical features, pathology, and treatment. Cancer Control 21:322-327.
  2. Deshpande V, Zen Y, Chan JKC et al. (2012) Consensus statement on the pathology of IgG4-related disease. Modern Pathology 25:1181-1192.
  3. Kamisawa T, Zen Y, Pillai S, Stone JH (2015) IgG4-related disease. Lancet 385:1460-1471.
  4. Menon MP, Evbuomwan MO, Rosai J, Jaffe ES, Pittaluga S (2014) A subset of Rosai-Dorfman disease cases exhibit increased IgG4 positive plasma cells: another red herring or a true association with IgG4 related disease? Histopathology 64:455-459.

Contributed by Luca Bertero, Francesco Zenga, Francesca Maletta, Rebecca Senetta, Paola Cassoni

International Society of Neuropathology