doi:10.1111/j.1750-3639.2009.00349.
x
COM SEPT 2009 CASE 2
A 61-YEAR-OLD MAN WITH INSTABILITY OF GAIT AND RIGHT
HAND CLUMSINESS bpa_349 273..274
Anne Vital, MD, PhD ; Emmanuel Ellie, MD2; Hugues Loiseau, MD3
1
1
CNRS UMR 5227, Victor Segalen-Bordeaux 2 University, Bordeaux, France
2
Neurology Department, Côte Basque General Hospital, Bayonne, France
3
Neurosurgery Department, Bordeaux University Hospital, Bordeaux, France
CLINICAL HISTORY
A 60 year-old man, without relevant medical history, noted a slight
and progressive instability of gait for one month, and right hand
clumsiness two weeks before admission.
Initial examination showed wide-based gait, mild dysarthria and
right arm dysmetria. Strength and sensation were normal as was
body temperature. Brain MRI showed a unique cerebellar lesion,
posterior to the middle cerebellar peduncle, near the right dentate
nucleus. The lesion was heterogeneous and hyperintense on FLAIR
sequences, isointense on T1-weighted images, and showed gado-
linium enhancement (Figure 1).
Full blood count, erythrocyte sedimentation rate, C-reactive
protein level, liver function tests, serum electrolytes, and serum
protein electrophoresis were normal. Plasma and urine immuno-
electrophoresis showed no abnormality. Serologic tests for HIV,
Listeria, Legionella, and Lyme disease were negative. CT scans of
the abdomen, chest and pelvis were normal as was bone scintigra-
phy. Cervical echography was unremarkable and thyroid was
normal. CSF analysis showed slightly elevated protein content
(0.72 mg/dl), 5 white cells/mm3, and no oligoclonal banding on
CSF protein electrophoresis.
At surgery, a yellowish and firm lesion associated with abnormal
vessels was resected.
The patient’s recovery was good and two months later an iso-
lated mild clumsiness of the right hand was noted. However the
Figure 1.
Figure 3.
Brain Pathology 20 (2010) 273–274
© 2010 The Authors; Journal Compilation © 2010 International Society of Neuropathology
patient was able to resume his daily hobby of golfing. Total body
PET scan using fluorodeoxyglucose was normal, as were motor
and sensory nerve conduction studies and echocardiography.
Serum beta2 microglobulin was within normal limits and bone
marrow biopsy showed no abnormality. No change in the patient
condition was noted over a follow-up period of more than one year.
MICROSCOPIC PATHOLOGY
Microscopic examination on haematoxylin and eosin stained sec-
tions from three specimens revealed amorphous eosinophilic mate-
rial, either extra-vascular or thickening vessel walls (Figure 2a). In
close proximity to the deposited material, the cerebellar paren-
chyma was infiltrated by predominant mature plasma-cells (CD
138 immunopositive; Figure 2b) associated with a few mature T
lymphocytes (CD3 immunopositive; Figure 2c) and macrophages
of the foreign body type (CD68 immunopositive; Figure 2d). The
weak congophilia of the deposits failed to show any birefringence
in polarized light microscopy. There was a strong immunostaining
of the deposited material as well as the plasma-cells with anti-k
light chain (Figure 2e), while anti-l antibodies failed to label them.
The deposits were also immunonegative for transthyretin amyloid,
Ab amyloid and AA amyloid. Under UV light, the deposits were
slightly fluorescent after thioflavine staining, strongly immuno-
fluorescent for k light chain (figure 2f) and negative for l light
chain. Electron microscopy revealed the non-fibrillar ultrastructure
of the deposits which presented as finely granular aggregates
(Figure 3).
What is the diagnosis?
Figure 2.
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Correspondence
DIAGNOSIS
Tumor-like deposits of k light chain surrounded by mature kappa
chain-expressing plasma cells.
DISCUSSION
Light chains are well known for their amyloidogenic properties, but
in a few cases, they are non amyloidogenic and may cause tissue
deposits histologically similar to amyloid but Congo red-negative
and non fibrillary at ultrastructural examination. Non amyloid light
chain deposits have been reported as a complication of plasma cell
dyscrasia and particularly of multiple myeloma and the condition
has been designated light chain deposition (LCD) disease (9). The
kidney is usually the first and most severely affected organ but
others may be involved, including the peripheral nervous system
(4) and ocular globes (1). However, the blood-brain barrier likely
prevents entrance of protein macromolecules into the central
nervous system and the brain is not usually affected by systemic
light chain disorders, excepted in sites missing a tight blood-brain
barrier such as the choroids plexus and the periventricular areas
where they have no effect on the brain (10).
Occurrence of light chain deposits in the brain is rare, with only
two cases previously reported in the literature (3, 7). In one of these
cases, it was suggested that the light chain deposition originated
from a low-grade cerebral lymphoma diagnosed 3 months earlier
(3), while in the other case a monoclonal B-cell proliferation of
“neoplastic or other undefined nature” was found in close proxim-
ity to the deposits (7). The cell infiltrate observed in the present
case was composed of monotypic k producing plasma cells
showing no cytologic atypia, associated with a few mature T lym-
phocytes and macrophages of the foreign body type. There was
no evidence of an aggressive or systemic lymphoplasmacytic
neoplasm.
The tumor-like MRI presentation of the light chain disease in
this case is reminiscent of primary intracerebral amyloidoma pre-
senting as a mass lesion (6, 8) and likely produced by B-cell clone.
Nevertheless, most of such cases lack clinical evidence of an
aggressive or systemic lymphoplasmacytic neoplasm and are char-
acterized by a relatively indolent course (2, 5). Intracerebral light
chain amyloidomas are almost invariably of l type, as for the two
previously reported cases of LCD (3, 7). We report the first case of
intracerebral k LCD presumably derived from local synthesis by
mature plasma cells and mimicking CNS neoplasm on MRI.
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ABSTRACT
A 60 year-old man, without relevant medical history, noted a slight
and progressive instability of gait for one month and right hand
clumsiness. Brain MRI showed a cerebellar lesion, posterior to the
middle cerebellar peduncle. This lesion was heterogeneous and
hyperintense on FLAIR sequences, isointense on T1-weighted
images, and showed gadolinium enhancement. Hematological and
biological serum analyses were normal as were plasma and urine
immunoelectrophoresis. CSF analysis including protein electro-
phoresis was unremarkable. CT scans of the abdomen, chest and
pelvis were normal as were cervical echography and bone scintig-
raphy. A yellowish and firm lesion was surgically resected. The
patient’s recovery was good, with normal total body PET scan and
bone marrow biopsy.
Pathological study evidenced k light chain deposits and
k-immunopositive mature plasma-cells in the vicinity. The deposits
failed to show any birefringence in polarized light microscopy
after Congo red staining, and electron microscopy revealed their
granular ultrastructure. Light chains are well known for their
amyloidogenic properties, but in a few cases, they are non amy-
loidogenic and may cause tissue deposits histologically similar to
amyloid but Congo red-negative and non fibrillary at ultrastructural
examination. Occurrence of light chain deposits in the brain is rare
and the tumor-like MRI presentation is reminiscent of primary
intracerebral amyloidoma presenting as a mass lesion. This is the
first report of intracerebral k light chain deposits which presumably
derived from local synthesis by mature plasma cells.
Brain Pathology 20 (2010) 273–274