Disseminated intracranial xanthoma disseminatum: a rare case report and review of literature
Yang et al. Diagnostic Pathology
Disseminated intracranial xanthoma disseminatum: a rare case report and review of literature
Guang-Zhi Yang 0
Jing Li 0
Lu-Ping Wang 0
0 Department of Pathology, the General Hospital of Beijing Military Command of PLA, Nan Men Cang , No. 5, Dong Si, Dongcheng District, Beijing 100700 , People's Republic of China
Background: Xanthoma disseminatum (XD) is a rare benign histiocytic proliferating disease of non-Langerhans cell origin, which is clinically mainly characterized by cutaneous or mucous lesions. Although XD is acknowledged of one systematic disease, involvement of the central nervous system is quite rare. Case presentation: We presented one 34-year-old Chinese female with disseminated intracranial XD without cutaneous or oral mucosal papules and masses of the other organs. MR imaging displayed multiple heterogeneous masses with intense enhancement in the right frontal lobe, temporal lobe, corpus callosum, left cuneus, suprasellar region, and right cerebellum. Pathological examination showed a neoplastic lesion composed of plentiful epitheloid or spindle cells. The cell had pink cytoplasm of vacuolation and foam with deviated nucleus absent of atypia and mitosis. The histiocytic markers including CD163, CD11c, Mac387 and CD68 were positive, whereas S-100, CD1a, GFAP, CD21, CD23 and so on were negative immunohistochemically. Conclusions: Intracranial XD without systemic involvement was extremely rare, which was supposed to be considered in differential diagnosis with other neoplasms of histiocytic origin or gliomas.
Xanthoma disseminatum; Disseminated; Histiocytic neoplasm; MR; Immunohistochemistry
Xanthoma disseminatum (XD) is a rare benign histiocytic
proliferating disease of non-Langerhans cell origin [
is clinically mainly characterized by a number of
symmetrically distributed cutaneous yellow-brown papules, often
affecting faces, trunk and limbs. XD may also involve the
mucous membranes of conjunctivae, lips, tongue, cheeks,
gingiva, palate, and so on. Respiratory tract, including the
pharynx, larynx, trachea and bronchi, is sometimes
involved. In addition, involvement of the viscera has been
occasionally reported [
]. Although XD is always a
systemic disease , involvement of the central nervous
system (CNS) is quite rare, and until now less than 100
cases in the literature written in English have been reported.
In our medical practice, we experienced with one rare case
of intracranial XD without involvement of other organs.
Herein, we presented the case and discussed with review of
One 34-year-old Chinese female presented with 1-month
history of dizziness, nausea, and vomiting, and followed by
difficulty in swallowing and walking instability. Physical
examinations revealed no significant abnormality. Laboratory
tests showed that results of complete blood count and
biochemical profiles were roughly normal. Brain magnetic
resonance (MR) imaging displayed multiple heterogeneous
masses with intense enhancement in the right frontal lobe,
temporal lobe, corpus callosum, left cuneus, suprasellar
region, and right cerebellum (Figs. 1 and 2). Diagnosis of
lymphoma was preferred and biopsy was performed in the
right cerebellum then.
The samples obtained at surgery were fixed in 10 %
buffered formalin and embedded in paraffin for
pathological study. Sections were stained by
HematoxylinEosin for routine histopathological investigation.
Immunohistochemical analysis was performed by steam
heatinduced epitope retrieval and the Dako Envision
Pathological examination showed a neoplastic lesion
composed of plentiful epitheloid or spindle cells instead
of the normal cerebellum (Fig. 3). The cells had
numerous pink cytoplasm of vacuolation and foam with
deviated nucleus. Atypia and mitotic figures were nearly
absent. There were also a few mature lymphocytes
infiltrating, especially around focal vessels.
Immunohistochemical studies displayed that CD163,
CD11c, Mac387 and CD68 (both KP1 and PGM clones)
were diffusely positive, which verified that the neoplasm
cells were of histiocytic origin (Fig. 4a). CD3 was
scattered positive for the small T lymphocytes (Fig. 4b).
Other markers, including S-100, CD1a, glial fibrillary
acidic protein (GFAP), oligo-2, CD21, CD23, CD35,
CD30, CD20, Melan-A and HMB45, were all negative,
which excluded Langerhans cell histocytisis (LCH),
glioma, lymphoma, and follicular dendritic cell sarcoma,
and so on. The pathological diagnosis was disseminated
In the comprehensive examinations during the
preoperative preparation, no mass in the internal organs,
including the liver, gallbladder, kidneys, pancreas,
bladder, uterus, and ovary examined by B ultrasound
and lungs scanned by computed tomography (CT), was
found. No cutaneous or oral mucosal papules were
found after careful consultation from the dermatologist
since XD was diagnosed morphologically. So diagnosis
of intra-axial brain XD without systemic involvement
The patient hadn’t received any treatments after
surgery. Follow-up for 1 year showed that the lesions
had still kept stable.
XD, also named as Montgomery syndrome, was first
described by Von Graefe in 1867, and then reviewed and
credited by Virchow in 1871 [
]. 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 [
]. 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 [
Although it is widely acknowledged that XD is a
systematic disease, involvement of CNS is quite rare [
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 [
]. XD always
affects the dura mater, which is actually extra-axial [
The first axial case located in the pontine was reported by
]. Most cases involving the parenchymal CNS are
located in the pituitary or hypothalamus, whereas the
number of the outside is less than 5 % [
]. 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 [
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 [
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 [
]. 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 % [
]. 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 [
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.
Here, we presented the case of intracranial XD without
systemic involvement. MR imaging displayed multiple
heterogeneous masses with intense enhancement.
Pathological examination showed a neoplasm composed of
plentiful epitheloid or spindle cells with vacuolated and
foamy pink cytoplasm. The tumor cells were absent of
atypia and positive for histiocytic markers
immunohistochemically. Such case was extremely rare, which was
supposed to be considered in differentiation with other
neoplasms of histiocytic origin or gliomas.
CNS, central nervous system; CT, computed tomography; GFAP, glial fibrillary
acidic protein; LCH, langerhans cell histocytisis; MR, magnetic resonance;
PXA, pleomorphic xanthoma astrocytoma; RDD, rosai-dorfman disease; XD,
There was no funding for this article.
Availability of data and material
Data and materials of this work are available on request by the corresponding
GY performed the pathological observation and immunohistochemistry and
collected the clinical information. JL made the pathological diagnosis and
made up the manuscript. LW participated in manuscript revision. All authors
read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of
this Case Report and any accompanying images. A copy of the written
consent is available for review by the Editor-in-Chief of this journal.
Ethics approval and consent to participate
A statement of ethics approval for this case report by the General Hospital of
Beijing Military Command is available on request.
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