Familial Hypercholesterolemia Presenting as Intracranial Xanthoma

Case Report
Familial Hypercholesterolemia Presenting as
Intracranial Xanthoma
Anita Basavaraj**, S Jadhav*, J Dhadwad*
Abstract
A 22 years female who was diagnosed as having cholestseatoma of right ear was referred to us for medical
fitness. On examination she incidentally had evidence of tuberous and tendon xanthomas. She was found to
have hypercholesterolemia. On mastoid exploration a yellowish groomous mass was seen which was
surrounded by foamy macrophages, suggestive of ‘mastoid xanthoma’. The purpose of this case presentation
is to report occurrence of such rare case and importance of early detection that will warrant treatment with
proper diet and medical management. This will stabilize lesions and delay complications. ©
INTRODUCTION
Intracranial xanthomas are rare entity. They occur
among patients with hyperlipidemia which consists
of several entities such as polygenic
hypercholesterolemia, combined familial
hyperlipoproteinemia and familial hypercholesterolemia.
Pharmacologic agents along with dietary
measurement are the basis of treatment. Medical
treatment includes bile resins, niacin and statins that
work indirectly to increase low-density receptors and
reduce serum low- density lipoprotein levels. 2,3 These
measures stabilize lesions and sometimes may cause
regression.
We present a case of intracranial xanthoma associated
with type 2 familial hypercholesterolemia.
CASE REPORT
A 20 years female was admitted with complaints of
reduced hearing in the right ear with mucopurulent
discharge since 3 months associated with occipital
headache there; was no history of fever, giddiness,
convulsions or vomiting. She was diagnosed as having
a cholesteatoma and was posted for modified radical
mastoidectomy. She was referred to us for medical fitness,
when we incidentally noted cutaneous xanthomas,
which were distributed symmetrically over both elbows
(Fig. 1), knees, popliteal and antecubital fosse. Her eyes
showed evidence of arcus juveniles (Fig. 2). Right ear
showed sagging of postero-superior tympanic membrane
**Associate Professor, *Resident, Department of Medicine, BJ
Medical College, Pune.
Received : 22.12.2004; Revised : 5.1.2006; Accepted : 10.3.2006
Fig. 1 : Tendon xanthoma on elbow
Fig. 2 : Arcus juvenilis
and ear canal with scanty mucopurulent discharge. Her
routine lab investigations were normal except for a high
cholesterol level (687mg%). Table 1 shows the lipid
profile of the patient. An X-ray of right mastoid
(Schuller’s view) showed evidence of sclerosis of
mastoid air cells. CT scan brain (Fig. 3) showed a soft
tissue density enhancing on contrast (C.T. Value 28 to
36.3 HU on plain, 41 HU on contrast) involving the
mastoid air cells, middle ear cavity and external auditory
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Table 1 : Lipid profile of patient
On admission
8 months later
Total chol 687 311
HDL 73 62
LDL 551 139
VLDL 13 47
Triglycerides 164 214
Chylomicrons — 42
Table 2 : Lipid profile of patient’s family
Patient Father Mother Sister Brother
Total chol 687 281 233 491 237
HDL 73 38 39 42 44
LDL 551 196 150 417 155
VLDL 13 23 15.60 32 13.60
Triglycerides 164 147 78 159 68
the right sided facial palsy which had developed postoperatively
has recovered.
DISCUSSION
Fig. 3 : Intracranial xanthoma
canal on the right side with erosion of the mastoid,
temporal bone, anterior wall and sinus plate; this was
thought to be a cholesteatoma, Periossicular soft tissue
density was noted, however the ossicular chain was
preserved. A possibility of mastoid xanthoma (ectopic
occurrence of fat) was also kept in mind.
During her tympanomastoid exploration it was noted
that, there was erosion of the lateral wall of the mastoid
antrum, posterior wall of the external auditory canal.
The surgeons tried to remove the disease from middle
ear by limited excision. Postoperatively, patient had a
right lower motor neuron facial palsy.
Histopathologic examination of the tissue removed
during surgery revealed a yellowish groomous material.
On microscopy it shows multiple cholesterol crystals
surrounded by foamy macrophages, inflammation and
calcification suggestive of mastoid- xanthoma. Other
family members were also investigated for lipid profile
(Table 2).
Thus we had a patient of familial homozygous hypercholesterolemia
(Type-II a) with rare presentation of
intracranial xanthoma. She was treated with Tab.
Atorvastatin 20 mg HS which was increased to 30 mg/
day for better control. The patient soon developed statin
induced proximal myopathy, hence the dose of
atorvastatin was reduced to 20 mg/day and Tab.
Ezetimibe 10mg was added.
Her current lipid profile 8 months later is given in
Table 1, the cutaneous xanthomas have flattened and
The heritable hyperlipidemia is of six types, I, IIa, IIb,
III, IV and V. Subcutaneous xanthomas typically occur
in patient with heritable hyperlipidemia. Types II and
III hyperlipidemia are caused due to excess circulating
lipoproteins and moderately elevated serum cholesterol
levels. Accelerated atherosclerosis frequently occurs,
resulting in premature coronary artery disease and
stroke.
Abnormal lipid storage in the setting of normal serum
lipids may occur in conditions such as histiocytosis X,
leading to xanthoma formation 4 and needs to be
distinguished from xanthomas due to hyperlipidemia.
Xanthomas develop because of lipid leakage from the
vascular into the surrounding tissue, where
macrophages subsequently phagocytose these lipids.
Because cholesterol is not degraded, it accumulates
within these cells, creating “foamy” macrophages. The
extracellular cholesterol crystallizes into clefts and
induces an inflammatory reaction with giant cells and
resultant fibrosis. 1 Systemic xanthomas most commonly
occur along the Achilles, patellar, and extensor tendons
of the hands, buttocks, elbows, eyelids, and hand
creases. 3
Intracranial xanthomas have been reported rarely
among patients with hyperlipidemia, most commonly
type II. Familial hypercholesterolemia has a dominant
inheritance pattern. Combined familial
hyperlipoproteinemia occurs in 1% to 2% of the
population and presents in the 3 rd to 4 th decade of life. It
is usually not associated with xanthomas. It arises from
a reduced number of hepatic low-density lipoprotein
receptors, leading to reduced low density lipoprotein
clearance from the blood.
Intracranial and extracranial xanthomas can occur
© JAPI • VOL. 54 • APRIL 2006 www.japi.org 331

in the temporal bone, 3 the skull base (clivus), 1 and over
the cerebral convexities. Most occur in middle- aged and
elderly patients, although they have been reported in
young patients. 6 Because of their slow progression, they
tend to present late in life. 3,4,6 Clinical presentation
depends on lesion location and extent. Symptoms may
include severe headache, 1 otorrhea, 6 cranial nerve
palsies, tinnitus, 1-6 and otitis media.
Although the diagnosis of an intracranial xanthoma
may be suggested by its imaging appearance, the
diagnosis is usually not considered because of its rarity.
These are circumscribed, extraaxial masses that are
hypodense to brain on unenhanced CT scans. 1 Osseous
abnormalities include bony destruction and
remodeling. 1,3,6 The MR imaging appearance of
xanthomas is in part due to their high lipid content. On
Unenhanced T1- weighted images, most are
hyperintense, with corresponding heterogeneous low
signal intensity on T-2 weighted images. After the IV
administration of contrast material, these lesions do not
show significant enhancement.
Pharmacological agents (bile resins, niacin, statins)
used alone or in combination with dietary measures are
the basis of treatment of the hyperlipidemia. These may
stabilize and sometimes, regress the lesions. So early
medical intervention is important.
REFERENCES
1. Friedman O, Hockstein N, Willcox TO Jr, Keane WM.
Xanthoma of the temporal bone: a unique case of this rare
condition. Ear Nose Throat J 2000;79:433-6.
2. Fukushima M, Marubayashi T, Matsukado. A case of familial
type IIa hyperlipoproteinemia with intracranial xanthoma.
No To Shinkei 1984;36:375-81.
3. Yamaha H, Kurata H, Nomura K. Adult Xantho
granulomatous intracranial lesion involving familial
hypercholesterolemia. Jpn J Med 1989;28:757-61.
4. Jackler RK, Brackmann DE. Xanthoma of the temporal bone
and skull base. Am J Otol 1987;8:111-5.
5. Carr D, Thornes HM, Rutter AC, Finney RD, Turner PR.
Sheehan's syndrome presenting with type III
hyperlipoproteinaemia. Postgrad Med J 1987;63:1099-100.
6. Bonhomme GR, Loevner LA, Yen DM, et al. Extensive
Intracranial Xanthoma Associated with Type II
Hyperlipidemia. Am J Neuroradiol 2000;21:353-5.
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