A 61‐YEAR‐OLD MAN WITH INSTABILITY OF GAIT AND RIGHT HAND CLUMSINESS

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 gadolinium enhancement (Figure 1).

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 immunoelectrophoresis 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 scintigraphy. 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 isolated 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 sections from three specimens revealed amorphous eosinophilic material, either extra‐vascular or thickening vessel walls (Figure 2a). In close proximity to the deposited material, the cerebellar parenchyma 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‐κ light chain (Figure 2e), while anti‐λ antibodies failed to label them. The deposits were also immunonegative for transthyretin amyloid, Aβ amyloid and AA amyloid. Under UV light, the deposits were slightly fluorescent after thioflavine staining, strongly immunofluorescent for κ light chain (figure 2f) and negative for λ light chain. Electron microscopy revealed the non‐fibrillar ultrastructure of the deposits which presented as finely granular aggregates (Figure 3).

Figure 2.

Figure 3.

What is the diagnosis?

DIAGNOSIS

Tumor‐like deposits of κ 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 proximity to the deposits (7). The cell infiltrate observed in the present case was composed of monotypic κ producing plasma cells showing no cytologic atypia, associated with a few mature T lymphocytes 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 presenting 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 characterized by a relatively indolent course 2, 5. Intracerebral light chain amyloidomas are almost invariably of λ type, as for the two previously reported cases of LCD 3, 7. We report the first case of intracerebral κ LCD presumably derived from local synthesis by mature plasma cells and mimicking CNS neoplasm on MRI.

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 electrophoresis was unremarkable. CT scans of the abdomen, chest and pelvis were normal as were cervical echography and bone scintigraphy. 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 κ light chain deposits and κ‐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 amyloidogenic 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 κ light chain deposits which presumably derived from local synthesis by mature plasma cells.