Pharyngeal amyloidomas: Variable appearance on imaging

Abstract

Amyloidomas are rare tumor-like depositions of abnormally folded, insoluble proteins that may be seen in the setting of systemic amyloidosis or as isolated tumoral deposits. Focal, isolated amyloidomas carry an excellent prognosis whereas systemic amyloidoses do not. The ability to identify or suggest amyloidoma on imaging studies may help direct laboratory testing and eventual diagnosis. Amyloidomas involving the head and neck have been variably described from homogeneously T2 hypointense to iso-slightly hyperintense relative to skeletal muscle. Herein we present two patients with pharyngeal submucosal amyloidomas of differing sizes and imaging characteristics to emphasize their potential widely variable imaging appearance and broaden our knowledge of these rare lesions.

Introduction

Amyloidomas are rare soft tissue manifestations of amyloid deposition disorders. They may be the result of a systemic (amyloidosis) or local process. When found in the head and neck region the larynx is the most common site, with nasopharynx, orbits, palate and lymph nodes locations less common.^1,2 Most head and neck amyloidomas are small at time of diagnosis, and for these lesions T2 hypointensity is often described as the most characteristic imaging finding. We present two patients with pharyngeal submucosal amyloidomas that differed greatly in size and imaging findings to further our understanding of this entity.

Case reports

Case 1

A 55-year-old female had a history of right neck extramedullary plasmacytoma treated with external beam radiation in 2011. Serial positron emission tomography/computed tomography (PET/CT) and contrast-enhanced neck CT examinations for plasmacytoma surveillance revealed no evidence of recurrence as recently as July 2013. She presented in March 2016 to an outside institution with a new complaint of progressive snoring. Physical exam revealed a firm right tonsillar region mass and PET/CT was ordered for further lesion evaluation. PET/CT demonstrated bilateral pharyngeal submucosal mass lesions (right larger than left), with heterogeneously increased F-18 fluorodeoxyglucose (FDG) uptake, greatest within the more superior aspect of both lesions (Figure 1(a)). The patient was referred to our institution for further evaluation and treatment. Post-contrast neck CT revealed large bilateral, well-defined nasopharynx and oropharynx retropharyngeal space masses, containing tiny calcifications on the left. The masses enhanced heterogeneously, greater on the right (Figure 1(b)). On subsequent neck magnetic resonance imaging (MRI), these large masses appeared heterogeneous on all pulse sequences. The upper aspect of these masses, corresponding with greatest PET FDG uptake, appeared T2 and T1 mildly hyperintense relative to muscle (Figures 1(c) and (d)) with intense, near uniform enhancement on T1 post-contrast images (Figure 1(e)). The lower masses, demonstrating less FDG uptake on PET/CT, appeared T2 and T1 mildly hypointense relative to muscle (Figures 1(c) and (d)), with less intense, heterogeneous T1 post-contrast enhancement (Figure 1(e)).

Figure 1.

A 55-year-old female with bilateral retropharyngeal amyloidomas. PET/CT coronal image (a) demonstrates heterogeneous FDG uptake, with greatest FDG uptake within the amyloidomas’ upper nasopharyngeal component (thick arrows) and geographic regions of low FDG uptake within the lower lesions (thin arrows) at the oropharynx level. Contrast-enhanced neck CT axial image (b) at the upper oropharynx level reveals well-defined bilateral retropharyngeal masses, containing tiny calcifications on the left (small black arrow). On CT these masses demonstrate variable contrast enhancement that is more homogeneous and intense on the right (thick white arrow) than the left (thin white arrow). MRI coronal T2 (c), T1 (d) and post-contrast T1 (e)-weighted images demonstrate amyloidoma heterogeneity, with their upper FDG avid component appearing T2 and mildly T1 hyperintense relative to muscle with marked post-contrast enhancement (thick arrows). The inferior amyloidoma components (thin arrows), with predominant low FDG uptake, are mildly T2 and T1 hypointense to muscle, with heterogeneous, less intense contrast enhancement. Pathology slide (H/E stain, 10× magnification) (f) from oropharynx level biopsy of the right pharyngeal lesion demonstrates a heavy background of eosinophilia (black arrow) with scant plasma cells, and a focal collection of plasma cells within its superior aspect (thick white arrow).

PET/CT: positron emission tomography/computed tomography; FDG: F-18 fluorodeoxyglucose; MRI: magnetic resonance imaging; H/E: hematoxylin and eosin.

The larger right retropharyngeal mass was biopsied transorally at the oropharynx level. Pathology revealed a heavy background of eosinophilia with scant plasma cells seen (Figure 1(f)). Congo red stain was positive for amyloid deposition. Liquid chromatography tandem mass spectrometry was performed on peptides extracted from the specimen and revealed a profile consistent with light-chain (AL) amyloid. The plasma cells that were present did not show evidence of a monoclonal population or plasmacytoma recurrence.

Bone marrow biopsy three weeks later showed no evidence for plasma cell dyscrasia and no amyloid deposition. Peripheral blood draw revealed elevated kappa light chains consistent with amyloidosis. Subsequent rectal biopsy at an outside facility demonstrated no plasma cell proliferative disorder or evidence for amyloid deposition. Renal, hepatic and cardiac functions were normal. The patient was treated with autologous stem cell transplant almost four months after biopsy. At three months post-stem cell transplant she is alive and doing well.

Case 2

A 48-year-old female presented with a five-year history of vague malaise, leg weakness, extremity numbness and throat soreness. On physical exam a cyst-like swelling with intact overlying mucosa was noted adjacent to the right Eustachian tube. Retrospective review of an outside enhanced head CT showed asymmetric enlargement of the right torus tubarius with small calcifications (Figure 2(a)). MRI revealed an anterior right torus tubarius submucosal mass that on T2-weighted images appeared mildly hyperintense relative to muscle (Figure 2(b)). The lesion appeared T1 isointense relative to muscle (Figure 2(c)), and non-enhancing on T1 post-contrast images (Figure 2(d)).

Figure 2.

A 48-year-old female with nasopharyngeal submucosal amyloidoma. Contrast-enhanced CT axial image (a) reveals a submucosal non-enhancing lesion (thick arrow) containing two small calcifications (thin arrow) contiguous with an enlarged torus tubarius.

MRI axial T2 (b), T1 (c) and post-contrast T1-weighted (d) images demonstrate the amyloidoma (arrow) relative to muscle to be T2 hyperintense, T1 isointense and non-enhancing.

CT: computed tomography; MRI: magnetic resonance imaging.

Biopsy of this nasopharynx submucosal lesion revealed amyloid deposition without significant plasma cell population consistent with amyloidoma. A bone marrow and fat aspirate failed to show evidence for systemic amyloidosis. Serum light chains were within normal limits. Follow-up imaging in 2012 revealed slight enlargement but unchanged imaging characteristics of the nasopharyngeal lesion. The patient remained asymptomatic from this lesion.

Discussion

Systemic amyloidosis may be an immunogenic, familial, or reactive disorder of amyloid deposition defined by the type of protein being deposited (amyloid A (AA), AL, etc.).^1,3 Systemically, it can manifest as dysfunction in single or multiple organ systems including the gastrointestinal, cardiac, central nervous system, and kidneys. AL amyloidosis is the most common sub-type of systemic amyloidosis. When AL amyloidosis affects the head and neck it most commonly involves the tongue, causing diffuse enlargement (AA and transthyretin (ATTR) subtypes are not associated with tongue enlargement).³

Amyloidomas, focal tumor-like depositions of amyloid, are exceedingly rare but have been reported in almost every organ system including the lung, breast, gastrointestinal tract, abdomen, extremities, and central nervous system.⁴ These focal depositions may be associated with systemic diseases such as multiple myeloma or plasma cell dyscrasias, focal processes such as a plasmacytoma, infectious/inflammatory disease, or have no distinguishable underlying cause. It is important to determine if there is a systemic cause for the focal deposition as systemic amyloidosis portends a poorer prognosis than an isolated amyloidoma.⁵ One study found the overall most common sites for amyloidomas to be the mediastinum and abdomen, although others have reported a preference for skull and spinal involvement.^2,6 These conflicting statements likely reflect the limited sample size in this rare disease.

In the head and neck, amyloidomas tend to occur twice as frequently in the larynx as in any other location, typically on the false vocal cords.¹ The orbits are the second most common site and amyloidomas involving the nasopharynx, nasal passages, skull base, tonsil, lymph nodes, and brachial plexus have been described in case reports.^1,7 There is a strong 3:1 male to female ratio with peak occurrences from 35 to 60 years of age for the focal form. Although amyloidomas are considered a benign entity, aggressive local behavior and osseous erosions may be seen.⁸

Histopathological evaluation of amyloidomas biopsies typically demonstrates plasma cells in a heavily eosinophilic background. The eosinophilic background will display green birefringence on Congo red stain under polarized light to confirm the presence of the beta-pleated sheets consistent with amyloid.⁹ The thought that amyloidomas may represent “burned out” plasmacytomas in some cases has been suggested, and is an intriguing hypothesis in our first patient, who had a previously irradiated plasmacytoma in close proximity.¹⁰

On CT, amyloidomas have previously been described as a well-defined submucosal, homogenous mass, frequently with punctate or dense calcifications.¹¹ While our pharyngeal amyloidomas appeared similar to previous reports on unenhanced CT, the large retropharyngeal lesions in patient 1 enhanced heterogeneously.

The MRI appearance of amyloidomas involving head and neck soft tissues and the skull base have been variably described in previous reports as homogenous to mildly heterogeneous on T1- and T2-weighted sequences, with homogeneous post-contrast enhancement.¹² Lesions tended to appear isointense to muscle on T1, and iso- to mildly hyperintense to muscle on T2-weighted images. On MRI, the smaller nasopharynx submucosal lesion in case 2 appeared homogeneous, slightly hyperintense to muscle on T2-weighted images, and had no contrast enhancement. The large retropharyngeal masses in case 1 appeared heterogeneous on all sequences. The more inferior portion of this amyloidoma at the oropharynx level appeared T2 hypointense relative to muscle, with less intense, heterogeneous T1 post-contrast enhancement and less FDG uptake on PET; while more superior nasopharynx lesion was mildly T2 hyperintense with respect to muscle, demonstrated near homogeneous T1 post-contrast enhancement and greater FDG avidity on PET.^13,14 Amyloidoma FDG avidity has been previously described in a few case reports.^15,16 Increased FDG uptake on PET-CT was associated with concentrated plasma cells in a patient with coexisting nasopharynx amyloidoma and extramedullary plasmacytoma.¹⁶ Transoral biopsy of patient 1’s retropharyngeal mass at the oropharynx level largely contained amyloid with scant non-monoclonal plasma cells most consistent with an isolated amyloidoma. While this patient had no evidence of recurrent extramedullary plasmacytoma, the greater FDG uptake and intense, homogeneous MRI post-contrast enhancement within the upper aspect, this amyloidoma at the nasopharynx level suggest a greater concentration of plasma cells in this region. These findings suggest that amyloidoma FDG uptake, MRI signal intensity, and post-contrast enhancement may be related to plasma cell concentration.

Other lesions demonstrating homogeneous, mild T2 hyperintensity and lack of contrast enhancement similar to patient 2’s nasopharyngeal submucosal amyloidoma include subacute hematomas or lipomas.¹⁷ The less common heterogeneous T2 signal intensity, T1 post-contrast enhancement and avid FDG uptake of our first amyloidoma may mimic more common malignant pathologies found in this region such as squamous cell carcinoma or sarcoma.

Amyloidomas are rare focal tumor-like depositions of abnormally folded proteins that may or may not be related to a systemic disease. It is critical to distinguish isolated forms from those involved in systemic processes as the treatment and outcomes are extremely divergent. Correctly identifying or suggesting differential amyloidomas may help expedite the clinical diagnosis and treatment of either form. Herein we emphasize the variable PET/CT and MRI appearance of pharyngeal amyloidomas, with heterogeneous T2 signal and variable contrast enhancement noted in this series.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.