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C O M S E P T 2 0 0 9 C A S E 2

A 61-YEAR-OLD MAN WITH INSTABILITY OF GAIT AND RIGHT

HAND CLUMSINESSbpa_349 273..274Anne Vital, MD, PhD1; Emmanuel Ellie, MD2; Hugues Loiseau, MD3

1 CNRS UMR 5227, Victor Segalen-Bordeaux 2 University, Bordeaux, France2 Neurology Department, Cte Basque General Hospital, Bayonne, France3 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 serumprotein 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 patients recovery was good and two months later an iso-

lated mild clumsiness of the right hand was noted. However the

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 (CD138 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-klight chain (Figure 2e), while anti-lantibodies failed to label them.The deposits were also immunonegative for transthyretin amyloid,

Ab amyloid and AA amyloid. Under UV light, the deposits wereslightly fluorescent after thioflavine staining, strongly immuno-

fluorescent for k light chain (figure 2f) and negative for l lightchain. Electron microscopy revealed the non-fibrillar ultrastructure

of the deposits which presented as finely granular aggregates(Figure 3).

What is the diagnosis?

Figure 1.

Figure 3. Figure 2.

doi:10.1111/j.1750-3639.2009.00349.x

273Brain Pathology 20 (2010) 273274

2010 The Authors; Journal Compilation 2010 International Society of Neuropathology

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DIAGNOSIS

Tumor-like deposits ofk light chain surrounded by mature kappachain-expressing plasma cells.

DISCUSSION

Light chains are well known for their amyloidogenic properties, butin 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 cellsshowing 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 inthis 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 ofltype, as for the twopreviously reported cases of LCD (3, 7). We report the first case of

intracerebral kLCD presumably derived from local synthesis bymature plasma cells and mimicking CNS neoplasm on MRI.

REFERENCES

1. Daicker BC, Mihatsch MJ, Strm EH, Fogazzi GB (1995). Ocularpathology in light chain deposition disease. Eur J Ophtalmol5:7581.

2. Fischer B, Palkovic S, Rickert C, Weckesser M, Wassmann H (2007)

Cerebral AL l-amyloidoma: clinical and pathomorphological

characteristics. Review of the literature and of a patient. Amyloid

14:1119.

3. Fischer L, Korfel A, Stoltenburg-Didinger G, Ransco C, Thiel E

(2006) A 19-year-old male with generalized seizures,

unconsciousness and a deviation of gaze. Brain Pathol16:185186.

4. Grassi MP, Clerici F, Perin C, Borella M, Gendarini A, Quattrini A,

Nemni R, Mangoni A (1998) Light chain deposition disease

neuropathy resembling amyloid neuropathy in a multiple myeloma

patient. Ital J Neurol Sci 19:229233.

5. Laeng RH, Altermatt HJ, Scheithauer BW, Zimmermann DR (1998)

Amyloidomas of the nervous system. A monoclonal B-cell disorderwith monotypic amyloid light chain lamyloid production. Cancer

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6. McMillion L, Melton DM, Erickson JC (2008) Teaching neuroimage:

Primary cerebral amyloidoma mimicking CNS neoplasm. Neurology

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7. Popovic M, Tavcar R, Glavac D, Volavsek M, Pirtosek Z, Vizjack A

(2007) Light chain deposition disease restricted to the brain: the first

case report. Hum Pathol38:179184.

8. Ragel BT, Blumenthal DT, Browd SR, Salzman KL, Jensen RL

(2006) Intracerebral amyloidoma can mimic high-grade glioma on

magnetic resonance imaging and spectroscopy. Arch Neurol

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(1976) Manifestations of systemic light chain deposition. Am J Med

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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

patients recovery was good, with normal total body PET scan and

bone marrow biopsy.

Pathological study evidenced k light chain deposits andk-immunopositive mature plasma-cells in the vicinity. The depositsfailed 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 rareand the tumor-like MRI presentation is reminiscent of primary

intracerebral amyloidoma presenting as a mass lesion. This is the

first report of intracerebral klight chain deposits which presumablyderived from local synthesis by mature plasma cells.

Correspondence

274 Brain Pathology 20 (2010) 273274

2010 The Authors; Journal Compilation 2010 International Society of Neuropathology