—  SPECIALTY CONFERENCE  —

Neuropathology

Case 3 - Primary Cerebral Amyloidoma

Suzanne Z. Powell
The Methodist Hospital
Houston, TX


Click on each slide thumbnail image for an enlarged view
Clinical Summary
A 57-year-old woman presented with complaints of impaired vision. Physical examination revealed a right homonomous hemianopsia. Preoperative CT and MRI scans showed a large left parieto-occipital intra-axial cerebral mass. Craniotomy and resection of the mass were performed.


Case 3 - Figure 1 - Pre-operative axial T2-weighted MRI without contrast. The lesion is not well demarcated or demonstrated.
Case 3 - Figure 2 - Pre-operative axial T2-weighted MRI with contrast. A parieto-occipital mass is seen.
Case 3 - Figure 3 - Pre-operative axial T2-weighted MRI with contrast. Parieto-occipital mass.



Case 3 - Figure 4 - Hyalinized, amorphous amyloid material forming the mass lesion. Focal perivascular chronic inflammatory cell infiltrates are also present (H&E; 2X)
Case 3 - Figure 5 - "Fluffy" plaque-like amyloid deposition (H&E, 40X)
Case 3 - Figure 6 - Vascular and plaque-like amyloid deposition (H&E, 40X)



Case 3 - Figure 7 - Higher power photomicrograph of "plaque-like" amyloid deposits (H&E, 100X)
Case 3 - Figure 8 - Amyloid deposits (H&E, 200X)
Case 3 - Figure 9 - Amyloid deposits (H&E, 200X)



Case 3 - Figure 10 - H&E stain showing "fluffy" amyloid deposits surrounding involved hyalinized vessels (200X)
Case 3 - Figure 11 - Unpolarized Congo red stain (40X)
Case 3 - Figure 12 - Unpolarized Congo red stain (40X)



Case 3 - Figure 13 - Polarized Congo red stain demonstrating "apple green birefringence" in the mass "apple green birefringence" in the mass (Congo red, 100X)
Case 3 - Figure 14 - Polarized Congo red stain demonstrating "apple green birefringence" in the mass (Congo red, 200X)


Diagnosis
Primary Cerebral Amyloidoma

Discussion
The precise nature of amyloid fibrils and their cellular origin was a mystery from the 18th century until the 1970's. A unifying biochemical principle has emerged that "amyloid" consists of polymerized proteins that share a common secondary structure: beta-pleated sheets. Approximately 30 proteins are susceptible to increased folding of the polypeptide backbone into an increased beta sheet form, which leads to fibril formation, polymerization, and deposition. The clinical features of amyloid deposition disorders depend on the cellular origin and nature of the deposited protein. The nomenclature of the amyloid proteins has evolved to reflect the particular precursor protein that leads to the polymerized protein deposition. The current standardized nomenclature consists of the letter "A" (representing "Amyloid") followed by an abbreviation of the name of precursor protein. For example, amyloid resulting from the deposition of immunoglobulin light chain is designated " AL" – "A" for "Amyloid" and "L" for "light chain." For up-to-date information on this topic, see reference number 22 (textbook) and the following website:

http://www.emedicine.com/med/topic3377.htm

The following table can be found at the above website:

Table 1. Human Amyloidoses

Type Fibril Protein Main Clinical Settings
Systemic Immunoglobulin light chains Plasma cell disorders
Transthyretin Familial amyloidosis, senile cardiac amyloidosis
A amyloidosis Inflammation-associated amyloidosis, familial Mediterranean fever
Beta2-microglobulin Dialysis-associated amyloidosis
Immunoglobulin heavy chains Systemic amyloidosis
Hereditary Fibrinogen alpha chain Familial systemic amyloidosis
Apolipoprotein AI Familial systemic amyloidosis
Lysozyme Familial systemic amyloidosis
Central nervous system Beta protein precursor Alzheimer syndrome, Down syndrome, hereditary cerebral hemorrhage with amyloidosis (Dutch)
Prion protein Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia
Cystatin C hereditary cerebral hemorrhage with amyloidosis (Icelandic)
Ocular Gelsolin Familial amyloidosis (Finnish)
Lactoferrin Familial corneal amyloidosis
Keratoepithelin Familial corneal dystrophies
Localized Calcitonin Medullary thyroid carcinoma
Amylin* Insulinoma, type 2 diabetes
Atrial natriuretic factor amyloidosis Isolated atrial amyloidosis
Prolactin Pituitary amyloid
Keratin Cutaneous amyloidosis
Medin Aortic amyloidosis in elderly people

* Islet amyloid polypeptide amyloidosis

"Amyloidomas" are rare causes of mass lesions in the central nervous system and constitute the rarest form of central nervous system amyloidosis. In a recent report and review of the literature, Tabatabai et al. [19] analyzed 11 cases of primary cerebral amyloidoma [1, 2, 4, 5, 6, 7, 8, 9, 13, 14, 19]. The review included patients with an age span of 26 to 76 and whose clinical presentation ranged from asymptomatic to seizure disorders, psychiatric symptoms and cognitive decline. The series included several cases of amyloid deposition localized to the trigeminal (gasserian) ganglion (one cause of trigeminal neuralgia), skull base, and, less commonly, the orbit, sacrum, soft tissues of the legs and nasopharynx. Spine and other bony sites were also represented [12, 18]. Several additional cases of solitary CNS amyloidoma that were not cited in the review have been reported [3, 10, 20], and there are a few cases in the radiology literature [16, 17].

Amyloid deposition in the central nervous system has been reported in association with multiple myeloma [11]. Neurologic complications of multiple myeloma are diverse and include direct compression (radiculopathy, cord compression, or tumor at the base of the skull or cervical spine), infiltrative lesions (peripheral neuropathy), and even autoimmune peripheral neuropathies [21].

More commonly, amyloid is associated with Alzheimer's Disease (AD). Amyloid in AD is deposited in diffuse and core plaques, and also within leptomeningeal and cortical blood vessels. Vascular amyloid deposition can result in lobar hemorrhage. Amyloid-related lobar hemorrhage can be seen in association with amyloid angiopathy alone or in association with AD (see table above).

The diagnosis of amyloidoma can be made cytologically by fine needle aspiration with or without touch or "squash" preparations [15, 20], or through histologic examination of specimens obtained by peripheral nerve biopsy, stereotactic biopsy, craniotomy or autopsy. Patients who have been newly diagnosed with amyloidoma should undergo evaluation for systemic amyloidosis and for multiple myeloma [21].

References

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  8. Eriksson L, Sletten K, Benson L, Westermark P. Tumor-like localized amyloid of the brain is derived from immunoglobulin light chain. Scand J Immunol 1993. 37:623-626.

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  12. Dee CH, Missirian RJ, Chernoff IJ. Primary Amyloidoma of the Spine: A case report and review of the literature. Spine 1998 February; 23(4):497-500.

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  15. Parker JR, Powell S, Chevea-Barrios P, Haykal HA, Ostrowski ML. Aspiration biopsy findings in amyloid tumor of the cervical vertebra. A case report. Acta Cytol 2001 May-June; 45(3):399-403.

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  17. Gandhi D, Wee R, Goyal M. CT and MR imaging of intracerebral amyloidoma: a case report and review of the literature. Am J Neuroradiol 2003 March; 24:519-522.

  18. Belber CJ and Graham DL. Multiple myeloma-associated solitary epidural amyloidoma of C2-C3 without bony connection or myelopathy; case report and review of the literature. Surg Neurol 2004 Dec; 62(6):506-9.

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  20. Dispenzieri A, Kyle RA. Neurological aspects of multiple myeloma and related disorders. Best Pract Res Clin Haematol. 2005; 18(4):673-88.

  21. Meir K, Maly B, Shoshan Y, Maly A, Soffer D. Cerebral amyloidoma diagnosed intraoperatively with squash preparations: a case report. Acta Cytol. 2005 Mar-Apr; 49(2):195-8.

  22. Sipe, JD (editor) Amyloid Proteins: The Beta Sheet Conformation and Disease (Hardcover textbook). November 2005; John Wiley and Sons, 79pgs. ISBN: 352731072X