Dural Based Extranodal Rosai Dorfman Disease
First described in 1969 (1), sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease (RDD) is a rare disease of unknown cause characterized by a proliferation of non-malignant histiocytes which characteristically exhibit the phenomenon of emperipolesis of intact lymphocytes and plasma cells (2). Although initially thought to be a nodal based entity, subsequent reports of extra-nodal disease have surfaced, the extra-nodal involvement being up to 43% in a study (1). In the absence of nodal disease (which is the scenario in our patient), involvement of the central nervous system only is relatively uncommon with around 180 cases reported in the medical literature (2). Most cases present as dural-based mass resembling meningioma on imaging as most of the current MRI sequences are unable to discriminate the two entities (3).
On pathological examination, RDD shows the characteristic feature of a proliferation of histiocytes with abundant clear to pink cytoplasm (3,4). The histiocytes exhibit the phenomenon of emperipolesis which is a non-destructive form of 'phagocytosis' of lymphocytes, plasma cells and neutrophils (Fig. 1b and Fig. 1e). Significantly, it is easier to demonstrate the presence of emperipolesis as well as nuclear details of the histiocytes on crush smears (5) than on frozen section tissue during intra-operative consultation as in our case. A prominent infiltrate of background plasma cells and lymphocytes is often present. Fibrosis may be a prominent feature and can mask the histiocytes and emperipolesis (3). The histiocytes express S-100 protein, a helpful feature in separating RDD from other inflammatory histiocytic proliferations as well as in highlighting the phenomenon of emperipolesis in problematic situations. Besides S-100 protein expression, the histiocytes express histiocyte-associated markers such as CD68 and CD163. They are however negative for CD1a.
In terms of differential diagnoses, the rare lymphoplasmacyte-rich variant of meningioma may appear similar as RDD due to the presence of a prominent chronic inflammatory cell infiltrate (3, 4). However, an EMA stain will help detect the neoplastic meningothelial cells. In cases of plasma cell granuloma of the dura, an S-100 stain is needed to rule-out RDD as emperipolesis may be masked by fibrosis and/or heavy inflammatory background (1). Idiopathic hypertrophic pachymeningitis may present as a meningioma-like mass on imaging and resemble RDD in terms of the presence of a chronic inflammatory cell infiltrate (4). However, granulomas are often present in idiopathic hypertrophic pachymeningitis and this entity lacks S-100 protein positive histiocytes.
Langerhans cell histiocytosis is a histiocyte-rich disease which can be confused with RDD as the Langerhans cells are S-100 protein positive as well (3, 4). However, twisted nuclei and nuclear grooves as seen in Langerhans cells are not features of RDD histiocytes. Besides, CD1a expression in Langerhans cells is not present in histiocytes of RDD.
Infectious and inflammatory processes may also enter the list of differential diagnoses, especially those with a prominent histiocytic component (4). Examples include mycobacterial infections and certain fungal infections such as Cryptococcus and in such instances, stains for micro-organisms may be useful in identifying the etiology.
Unlike in other sites, it appears that spontaneous resolution does not occur in RDD patients with central nervous system disease (2). There is generally no consensus on the treatment of central nervous system RDD. Nonetheless, some authors opine that patients with limited disease should undergo surgical resection which may be followed by radiotherapy. In cases with widespread central nervous system disease resistant to radiotherapy, steroids with or without methotrexate-based chemotherapy may be considered as an alternate therapy.
Contributed by Shaun Kian Hong Cheng, MB ChB, Yee Lin Tang, MBBS, Rao Jai Prashanth, MBBS, FRCSEd, Khoon Leong Chuah, MBBS, FRCPA