Disseminated intracranial xanthoma disseminatum: a rare case report and review of literature

XD, also named as Montgomery syndrome, was first described by Von Graefe in 1867, and then reviewed and credited by Virchow in 1871 [6]. It is reported that XD affected populations aged from 5 months to 70 years old with most before 25 years old. It is more prevalent in males with a male-to-female ratio of 2:1 [7]. No typical inheritance pattern is confirmed. XD is a histiocytic disorder of non-Langerhans cell origin morphologically characterized by xanthomatous deposits in the absence of lipid metabolism disorder and hyperlipidemia [8].

Although it is widely acknowledged that XD is a systematic disease, involvement of CNS is quite rare [9]. Clinical manifestations of patients with CNS XD varied greatly according to the involving positions, including headache, nausea, vomiting, dizziness, seizures, ataxia, or visual field defects. Hammond and Mackenzie reviewed the literatures and summarized that less than 100 cases of CNS XD had been reported [6]. XD always affects the dura mater, which is actually extra-axial [10]. The first axial case located in the pontine was reported by Chiari [6]. Most cases involving the parenchymal CNS are located in the pituitary or hypothalamus, whereas the number of the outside is less than 5 % [11]. It is believed that besides the pituitary and hypothalamus, the brainstem and cerebellum were always involved because of the local environment such as the blood–brain barrier and short distance from the ventricle or meninges [6].

The exact diagnosis of XD is relied on pathological examination, and other neoplasms of histiocytic origin such as LCH and Rosai-Dorfman disease (RDD) are under differential diagnosis. Typical histopathological manifestations of XD are large pleomorphic cells with cytoplasmic bubbles, which can merge and form multinucleated Toutan giant cells. Inflammation is not striking, and varying number of mature T lymphocytes is mixed in the lesion. By immunohistochemistry, the tumor cells are positive for histiocytic markers including CD68, CD163, CD11c and so on, whereas negative for S-100 protein and CDla. Eosinophils are one of components in LCH, and nuclear grooves are the prominent feature of the tumor cells. In addition, immunohistochemical S-100 and CDla are positive, and Birbeck bodies are detected under electron microscopic examination, which can be identified from XD. Inflammatory background is striking in RDD, and the tumor cells are remarkably huge with intracytoplasmic small lymphocytes swallowed and immunohistochemically S-100 positive. Sometimes, intraparenchymal XD is also supposed to be distinguished from Pleomorphic xanthoma astrocytoma (PXA), and immunohistochemical staining of GFAP is crucial [12].

Since XD is always one systemic disease, cutaneous or mucous biopsy is supposed to perform before diagnosis. Serum lipid examination is also necessary. However, our case is quite distinct, which multiple locations of CNS were involved and no other differences were founded, including skin or mucous papules, masses of the other organs besides serum lipid.

According to natural course and outcome, XD was divided into three clinical types by Caputo [13]. The most common is persistent form, followed by progressive form with systemic involvement, and the rare is regression form. Thus, XD seems to have self-healing tendency. Besides, as far as XD with intracranial involvement is concerned, prognosis is also closely related with the involving location. Hammond and Mackenzie reported that fatality rate of XD patients with the pituitary/the hypothalamus was 63 %, and yet that of the posterior fossa was 100 % [11]. For cases with intracranial XD, symptoms progress is supposed to be observed and mass change should be reviewed by MR imaging to determine the clinical types and following therapies. The present case was identified of persistent form in the follow-up, thus operation seemed unnecessary, and yet no accurate diagnosis was established until operation.

Treatments for intracranial XD remain determined because of limited cases and paradoxical results [11, 14]. Steroids or combined with chemotherapy drugs were usually adopted for cases with intracranial wide-spread or large mass. It is generally believed that the radiotherapy had no satisfactory effect for intracranial XD, but multi-mode radiation may have some effect. Surgery was always the choice for localized XD. So, it is easy to see different strategies for different cases, but dynamic observation is the premise. In principle, clinical treatments such as surgery or chemotherapy were performed for the cases with progress or large volume, dynamic observation was taken for the cases ofself-limited tendency or slow progress without obvious symptoms.