Introduction: Primary deposition of amyloid can take several forms including amyloidoma organ restricted among which is brain. Brain amyloidoma can mimic several lesions and offers a diagnostic challenge to the physician. The present work reports an additional case and summarizes the salient characteristics of previously published cases. Case Report: A 61-year-old, woman experienced paroxystic auditory hallucinations followed at times by generalized tonico-clonic seizures. Examination revealed a mild left pyramidal weakness. Head CT scan and MRI revealed a lobular lesion of the right atrium with contrast enhancement. The diagnosis of amyloidoma Lambda light chain (λLC) type was performed by means of a stereotactic biopsy. The patient was treated by 3 cures of high dose methotrexate (15 mg/m 2). At 24 months follow up the patient remains stable clinically and biologically. The 2 years follow-up MRI showed the same findings. Conclusion: No guidelines can be suggested for brain amyloidoma treatment; the “wait and see” was the mind-set in the literature. However, a non-tumour like pattern of a cerebral mass developing near the ventricle with a fine, irregular radiating margin enhancement and lack of oedema, and mass effect are important MRI clues for brain amyloidoma diagnosis. The diagnosis is histological after biopsy or excision.
Cerebral amyloidoses are part of a complex group of chronic and progressive diseases caused by protein folding and metabolism abnormalities, bracketed under the denomination of “protein folding disorders” [
Primary deposition of amyloid in the brain can take several forms including senile plaques (Alzheimer disease), Spongiform encephalopathy’s, diffuse vascular deposit in meningo-cortical vessels (cerebral amyloid angiopathy—CAA), and focal mass like deposition (amyloidoma) [
Amyloidoma organ restricted is defined as primary solitary amyloidosis where no plasma-cell dyscrasia or abnormal serum proteins are detectable [
Amyloidoma can mimic several brain lesions [
The present work reports an additional case and summarizes the salient features of the previously published cases.
A 61-year-old, right-handed, Caucasian woman was admitted at local hospital on July 2010 with a recent history of paroxystic auditory hallucinations (music and bell sounds) at times followed by generalized tonico-clonic seizures. Initial cranial Computed Tomography (CT) scan [
On admission, examination revealed a mild left pyramidal weakness with symmetrical and normal myotatic reflexes. The mental status, speech, cranial nerves, gait, and sensory examination were normal. There were no clinical signs of increased intracranial pressure and the remaining physical examination was unremarkable as were patient’s and family’s history.
Laboratory assay including full blood count, erythrocyte sedimentation rate, serologic test for HIV, hepatic and renal functional tests were normal as were the electrocardiogram and the chest x-ray.
Magnetic resonance imaging (MRI); Fluid-Attenuated Inversion Recovery (Flair) sequences showed a right parietal infiltrating lesion [
lipid pick. [
The suggested diagnosis was brain lymphoma. Several specimens were retrieved, by means of stereotactic biopsy, from more than one site of the tumour. The post-operative course was uneventful.
Pathological findings: Several brain specimen measuring between 0.2 to 0.5 cm were embedded in paraffin and stained with haematoxylin and eosin (HE), periodic acid-Schiff (PAS), Prussian blue reagent (or Perl's reagent), May-Grünwald Giemsa (MGG), and Congo red stains.
Microscopy: On HE-stained sections [
Immunohistochemistry: Staining with Lambda (λ) amyloid antibody showed a strong labelling of the deposit [
The final pathologic diagnosis was cerebral amyloidoma Lambda light chain (λLC) type. The patient was initially treated with corticotherapy and Phenobarbital and referred to Internal Medicine Department, with an unchanged clinical examination.
On extensive staging evaluation, no evidence of clinical symptom or syndrome suggestive of systemic amyloidoses was found. Additional laboratory assay including C-reactive protein level, liver, and renal function tests were normal. Serum protein electrophoresis revealed a slight increase in the monoclonal Ig M Lambda (1.37 g/dl) whereas urinary electrophoresis was normal. CT scan of the chest, abdomen and pelvis were normal, as were trans-thoracic echocardiography with Doppler studies, and salivary gland biopsy. Bone marrow biopsy showed a normal maturation of the hematopoietic system cells and both the degree of plasmacytosis and the morphology of plasma cells were normal and no cell suggestive of malignancy was found. In the present case, no finding could support the diagnosis of systemic amyloidosis or multiple myeloma. The French Amyloidosis Centre confirmed the diagnosis of brain amyloidoma with MGUS. The patient was treated by 3 cures of high dose methotrexate (15 mg/m2). At 24 months follow up the patient remains stable clinically and biologically. The 2-years follow-up MRI showed the same findings [Figures 5(A)-(C)].
To identify relevant articles, MEDLINE and GOOGLE SCHOLAR search was performed using the following combinations of keywords: “amyloidoma” and “brain” or “intracranial” or “central nervous system”. No language restrictions were applied and no time limit. Articles were eligible for inclusion if they dealt with brain amyloidoma. Furthermore, references cited in the selected articles were reviewed for additional relevant reports. Data were independently extracted by three authors (AH, YD, and SD) and differences were resolved by consensus.
1) Inclusion criteria
Thirty-nine reports describing 47 patients harbouring brain amyloidoma with enough clinical, radiological and biological data were selected (
Number and sex of cases | Mean of Duration | Mean of Age | Surgery | Mean of Follow up | reference | |
---|---|---|---|---|---|---|
Seizure | 14(8F, 6M) | 3.9 y | 45.8 | Stereotaxic biopsy (7), open biopsy (1), excision (4), autopsy (1), NA(1) | 4.6y, NA(9) | [ |
Neuro Def | 21(13F, 8M) | 5.7y | 52.7 | Stereotaxic biopsy (10), open biopsy (7), excision (3), autopsy (1) | 3.4y, NA(13) | [ |
Co Def | 7(6F, 1M) | 1.9y | 60.3 | Stereotaxic biopsy (3), autopsy (4) | 1.3y, NA(4) | [ |
Seizure + CoD | 2(1F, 1M) | 4y | 56 | open biopsy (1), Stereotaxic biopsy (1) | 5y, NA(1) | [ |
Co+ Neuro Def | 1(M) | 0.5 | 59 | Stereotaxic biopsy | NA(1) | [ |
Loss of Cons | 1(M) | NA | 64 | Open biopsy | NA(1) | [ |
Autopsy | 1(M) | NA | 60 | Autopsy | NA(1) | [ |
NA | 1(M) | NA | 35 | Excision | NA(1) | [ |
Y = year, F = female; M = male; Neuro Def = neurological deficit, Co def = cognitive deficit; Loss consc = loss of consciousness; NA = not available.
2) Exclusion criteria
The cases of Tomiyasu et al. [
There were 48 patients (including the present one): 28 women and 20 men. The overall mean age at presentation was 52 years (range: 15 - 76). The mean age for men was 50 years (range: 15 - 76) and that of women 53 years (range: 26 - 73) (
The mean duration of symptoms before diagnosis was 54 months (range 1 - 444 months).
Protean progressive neurological signs revealed the disease in 22 cases although the most common presenting symptom is seizure (16 cases). Cognitive function deterioration was an inaugural feature in 10 cases. Like in our case, most cases seizure was linked to a normal neurological examination [
CT scan and MRI data were, respectively, more or less available in 24 and 31 reports (
On native CT scan, although amyloidoma shows more frequently a homogeneous or heterogeneous hyper-density, it may have an iso, or hypo-dense aspect. Following iodine infusion it enhances constantly revealing various aspects including nodular [
On MRI, the lesion discloses a hyper, iso, or hypo-intense signal on T1-WI
Features (Number) | Reference | ||
---|---|---|---|
CT | CT− | Hyper (18), hypo (3), iso (1), mixte (1), NA (25) | [ |
CT+ | Yes (17), NA (31) | ||
MRI | T1 | Hyper (6), hypo (13), iso (2), mixte (2), NA (25) | |
T2 | Hyper (6), hypo (4), mixte (11), NA (27) | [ | |
T1+ Gado | Yes (28), No (2), NA (18) | ||
Mass Effect | Yes (7), No (21), NA (20) | ||
Type of LC | 3/4 λLC; 1/4 κ LC(1) | [ | |
λLC (18) | [ | ||
1/2 λLC; 1/2 κ LC(1) | [ | ||
λLC; κLC; TTR(3) | [ | ||
λLC; κ LC(3) | [ | ||
λLC; SAP(3) | [ | ||
λLC; Anti cystatin(1) | [ | ||
NA(18) | [ |
NA = not available; CT− = native CT; CT+ = post contrast CT; hypo = hypo dense or intense; hyper = hyper dense or intense; Mixte = hypo-hyper-intense; gado = gadolinium; LC = light chain, λLC = Lambda light chain; κ LC = Kappa light chain; TTR = transthyretrin; SAP =; λLC -- = Lambda LC negative.
and it may show a hypo, hyper-signal or a combination of both on T2-WI. Following gadolinium infusion, whatever the signal type on T1 and T2-WI, the lesion almost enhances except in two cases [
Others radiological examinations, occasionally performed, included Flurodeoxyglucose positron emission tomography (FDG-PET) scan [
Most patients underwent a biopsy whether by stereotactic or free hand technique; 10 had had lesion excision and in 7 cases autopsy established [
Mostly all amyloidomas were diagnosed on the basis of the dichromism and apple green birefringence characteristic of amyloid under polarized light and in only 30 cases the type of protein was specified (see
The management of amyloidoma is still controversial. Most patients had no other treatment than the “wait and see” attitude. Radiotherapy was performed in 5 patients [
Although more than 25 different proteins are known to self-assemble and form fibrillar amyloid structures in Humans, only about one third of amyloid proteins, known to be linked to disease, produce fibrillar deposits including amyloidoma in the CNS [
The molecular mechanisms underlying brain amyloidoma formation and deposition are still unidentified, and the matter is whether the amyloid fibril protein is derived from components which leak from the vessels or the protein is synthesised at the site of deposition [
It has been suggested that in systemic amyloidosis the amyloid fibril protein is typically produced at distant sites and carried in the bloodstream with deposition at multiple sites, whereas in localized amyloidosis the protein is typically deposited at the site of production and not transported in the bloodstream [
At presentation, the mean age of patients harbouring a cerebral amyloidoma is 52 years, and men are slightly younger than women and there is a slight female predominance.
The natural history of this rare lesion is not fully understood, its clinical course seems benign as demonstrated by some reports in which a long-lasting clinical history is reported [
There are no specific clinical features for brain amyloidoma. The clinical presentation is similar to that of slowly growing neoplasm. Signs and symptoms vary according to the location and the severity of brain involvement. Although seizure was a frequent onset, often linked with a normal neurological examination, signs and symptoms of intracranial hypertension have rarely been mentioned [
Cerebral amyloidoma occurs mostly in supra-tentorial compartment (90%), without side predominance. It may occur, either as a single (58%) or multiple lesions (42%), the latter involving both hemispheres in 25%. Simultaneous supra and infra tentorial compartments involvement is rare; the pons being constantly involved in the latter.
On native CT scan the lesion most often appears as a homogeneous or heterogeneous hyper-density and it invariably enhances following iodine infusion. Calcification, mass effect, and oedema are lacking.
On T1-WI, amyloidoma has not specific feature it may show a hyper, iso, or hypo-intense signal. On T2-WI a mixed or patchy distribution with areas of high and low signal intensity is frequently observed. The exact reason for the different signals in the mass is unclear, but it is likely to represent an inhomogeneous amyloid deposition throughout the lesion and the areas with much denser amyloid deposits would show brighter signal [
On gadolinium-enhanced T1-WI, irregular faint or intense enhancement of the lesion with a more or less important irradiating edge of the tumour has been observed in several cases [
The ADC study may be normal [
The diagnosis of amyloidoma, poses a particular problem. Although the radiologic exams reveal the lesion, imaging findings are not consistent with brain tumour even if the majority of presenting cases were initially diagnosed as intra-cerebral neoplasm including gliomas [
Our review reveals that MRI characteristics of brain amyloidoma are: a para-ventricular location with radials enhancement of the tumour edge following gadolinium infusion, together with lack of neo angiogenesis, mass effect, and oedema. Thus these features should support the preoperative diagnosis and histological examination is only mandatory for the diagnosis of the type of protein deposit which determines the class of amyloidoma.
The amyloidoma consists of large confluent or isolated acellular masses of pale eosinophilic deposits, mostly found within the white matter and centred or not on blood vessels [
Immunohistochemistry: Only 30 cases have been investigated immunohistochemically: 18 showed an isolated λLC expression and in 10 cases λLC expression was associated with another protein expression mostly κLC and 2 cases were both λLC and κLC negative. Although bi-clonality of a monoclonal protein can exist in a patient, [
Because local amyloidosis can occur within meningiomas [
The brain parenchyma can be affected by other types of amyloid including LCDD [
After histological verification, the second step must be to exclude the presence of systemic amyloidoses and plasma cell dyscrasia. Thus biological, radiological and haematological screening and bone or fat biopsy are mandatory for evaluation of systemic diseases.
Currently, no firm level A, evidence-based data exist for managing brain amyloidoma. The management of brain amyloidomas varied including surgical excision, radiotherapy [
The ideal treatment is to inhibit aggregation or to render existing deposits soluble; such passive immunotherapy directed against the amyloid deposits has been explored in AL amyloidoses with promising results: when one such prototypic antibody was injected into an amyloidoma-bearing mouse, the antibody localized only in the tumour and led to the elimination of tumours [
From the neurosurgical point of view, a risk-adapted strategy involves suppression of the “tumour” whenever possible with no functional risks. Total or sub-total removal rarely seems necessary and feasible, owing to the most frequent deep seated para-ventricular location of amyloidoma. Such removal was initially performed mostly due to concerns of primary brain tumour, so most cases have been diagnosed by means of stereotactic or open biopsy. Therefore surgical resection could be performed for cortical locations and whenever feasible with no detrimental risks and stereotactic biopsy is a minimal kind of surgery to perform the diagnosis of the type of protein folding. Schroder et al suggested that for such biopsied cases, one can wait and control the local findings, especially when no malignant plasma cells are present in the biopsy specimen [
Because some amyloidomas have recurred after surgical resection [
From the limited reported follow-up data, the clinical course seems benign. Localized amyloidomas seem to have no documented risk for increased mortality. Unlike CAA, in which the risk of intracranial haemorrhage is known to be high [
A major limitation of this study is that, despite extensive research, only case reports were found that could be considered eligible for consideration. No level A, evidence-based, medical studies exist to support an official recommendation or guidelines for managing brain amyloidoma.
The most important MRI clues of amyloidoma brain restricted are the non-tumour like pattern of a cerebral mass developing near the ventricle with a fine, irregular, radiating margin enhancement with lack of oedema, and mass effect on surrounding anatomy. These important radiological features could possibly add specificity to this disease and should consistently raise diagnosis suspicion of brain amyloidoma.
For help with editing in English, and other valuable advice, we thank Dr Mabandine Djagri Temoukale.
The authors declare no conflicts of interest regarding the publication of this paper.
El Kader Moumouni, A., Memia Zolo, D., Kpelao, E., Compaore, P., Tamou Tabe, D.A., Lawson, L., Plante, P.R., Gueouguede, E.K., Souho, B. and Hamlat, A. (2020) Brain Amyloidoma: Case Report and Literature Review. Open Journal of Modern Neurosurgery, 10, 403-421. https://doi.org/10.4236/ojmn.2020.104043