CT and MRI Features of Localized Peritumoral Amyloidosis in a Patient with Head and Neck Mucosa-Associated Lymphoid Tissue Lymphoma: A Case Report.

Amyloidosis has been reported to be associated with non-Hodgkin lymphoma. Amyloidosis and lymphoma can be related in two ways: lymphoma-associated systemic amyloidosis and peritumoral amyloidosis with lymphoma. We report a rare case of peritumoral amyloidosis in a patient with head and neck mucosa-associated lymphoid tissue lymphoma. On CT, the oropharyngeal mass showed an irregularly shaped soft-tissue density with multifocal amorphous calcifications and heterogeneous enhancement. On MRI, the mass showed heterogeneous low signal intensity on both T1- and T2-weighted images. On contrast-enhanced MR images, the mass showed good enhancement with several inner non-enhancing foci. Concurrent pathologies, such as peritumoral amyloidosis, should be considered when calcifications are noted in patients with pre-treatment lymphoma. Copyrights

INTRODUCTION

The amyloidosis is a rare, slow and progressive disease characterized by extracellular eosinophilic deposition and accumulation of abnormally folded and insoluble protein (amyloid) (1). Amyloidosis can be classified by anatomic distribution. It may be systemic (multiorgan involvement) or localized (single organ involvement). It can present as focal, tumor-like lesion (amyloidoma) or diffuse infiltrative pattern (1).

The frequency of head and neck involvement ranges from 12%–90% (2). The most common site is the tongue, followed by the larynx and thyroid (2). Amyloidoma is extremely rare, but it has been described in almost every organ (1). In contrast, oropharyngeal amyloidosis is exceedingly rare (3), with only seven case reports of in the last 30 years (4).

There are several cases describing the association between lymphoma and amyloid deposition, representatively two entities of “lymphoma associated systemic amyloidosis” and “peritumoral amyloidosis with lymphoma”. The systemic amyloidosis is predominantly associated with lymphoplasmacytic lymphoma and multiorgan involvement. On the other hand, patients with peritumoral amyloidosis with lymphoma [mostly associated with mucosa-associated lymphoid tissue (MALT) lymphoma] are reported to have peritumoral amyloid deposits and predominantly single organ involvement (5).

In this report, we describe a rare case of concurrent oropharyngeal amyloidosis and MALT lymphoma, which could be classified as peritumoral amyloidosis with lymphoma.

CASE REPORT

A 60-year-old female visited our hospital for tongue swelling and foreign-body sensation in the throat. During physical examination, a mass was found in the left tongue base. She had never smoked. Laboratory studies were not remarkable.

CT revealed an irregularly shaped high-density mass lesion with amorphous calcifications involving the left lingual tonsil, left palatine tonsil, left tongue base, the soft palate and uvula (Fig. 1A). After contrast administration, heterogeneous enhancement was noted (Fig. 1A). In addition, a less than 1 cm sized high attenuated lesion with calcification was present at the left lower eyelid (Fig. 1B). For the oropharyngeal mass, venous malformation was considered as a differential diagnosis due to the presence of calcifications. However, the possibility of systemic lymphoproliferative disease such as lymphoma could not be excluded due to the presence of the concurrent eyelid lesion. The patient underwent excisional biopsy for the oropharyngeal mass. The pathologic report revealed a MALT lymphoma. After excision, PET-CT and contrast-enhanced MRI were performed for further evaluation. PET-CT revealed a residual hypermetabolic mass suggestive of residual lymphoma with involvement in the left oropharynx. Mild fluorodeoxyglucose uptake was also noted in the left neck level I, II lymph nodes and in the inferior aspect of left eyeball, suspicious for lymphoma involvement. There was no evidence of lymphoma involvement in the other areas of the body. On contrast enhanced MRI, residual mass lesion involving the left palatine tonsil, soft palate, uvula, and the left side tongue base was suspected. The mass showed heterogeneous low signal intensity on T1 and T2 weighted images (Fig. 1C) and showed strong enhancement with internal non-enhancing foci on enhanced T1 weighted images (Fig. 1C). A repeated biopsy of the oropharyngeal mass and excisional biopsy for the orbital mass was performed. The pathology report revealed chronic inflammation with degenerative eosinophilic material in the oropharynx and left eyelid masses, without evidence of residual lymphoma. The patient was followed in the outpatient clinic without adjuvant therapy. Follow up MR image during 2 years showed a slow but progressive increase in the size of the oropharyngeal mass, therefore a repeated excisional biopsy was performed.

Fig. 1

A peritumoral amyloidosis in a patient with MALT lymphoma in a 60-year-old female, presenting with tongue swelling and foreign-body sensation in the throat.

A. The pre-contrast neck scan (left) shows an oropharyngeal mass with multiple amorphous calcification (arrow). Heterogeneous enhancement (arrow) is observed on the contrast-enhanced images (right).

B. The pre-contrast neck scan (left) shows dense calcification (arrow) of the orbital mass. Heterogeneous enhancement (arrow) is observed on the contrast-enhanced images (right).

C. A tonsillar and soft-palate mass (arrows) of heterogeneous low signal intensity on the T1-weighted (left) and T2-weighted (middle) images. The contrast-enhanced MR image (right) reveals a well-enhanced mass (arrow) with internal low-signal foci.

MALT = mucosa-associated lymphoid tissue

D. On hamatoxylin and eosion staining, the specimen consists of several pieces of eosinophilic amorphous material (left upper image). This material is located within the subepithelial area (right upper image). A few clusters of plasma cells surrounded by this deposition are also noted (left middle image). Dystrophic calcification is observed (right middle image). The amorphous eosinophilic deposition stains salmon-pink with congo red (left lower image) and shows apple-green birefringence under the polarized microscope (right lower image).

E. On follow-up MRI after radiotherapy, the tonsillar and soft-palate mass (arrows) also show heterogeneous low signal intensity on T1- and T2-weighted images (left, middle). The CE MR image (right) also reveals a well-enhanced mass (arrow) with internal low-signal foci. There is no significant change in the size of the lesion.

CE = contrast-enhanced, MALT = mucosa-associated lymphoid tissue

Biopsy specimen of the mass confirmed the presence of peritumoral amyloidosis with lymphoma (Fig. 1D). Histologically, the specimen consisted of amorphous eosinophilic material, a few plasma cell clusters and calcification. The material was accumulated at subepithelial connective tissue. It was salmon-pink on congo-red stain and shows a typical apple-green birefringence when viewed under cross-polarized light. This result confirmed the diagnosis of amyloidosis. The plasma cell clusters surrounded by amyloid deposition and showed Kappa chain monoclonality, suggesting recurrent lymphoma. Multifocal dystrophic calcifications were also noted in this specimen.

The patient underwent radiotherapy for recurrent lymphoma. Follow up MRI after radio-therapy showed no significant change in size and signal intensities of the lesion (Fig. 1E).

On retrospective pathologic review, the initial biopsy specimens of the oropharynx and orbit were also consistent with peritumoral amyloidosis with lymphoma.

This study was approved by the Institutional Review Board of our institution and the requirement for informed consent was waived (IRB No. 2020-07-022-001).

DISCUSSION

Amyloidosis of the head and neck usually occurs in the setting of primary amyloidosis (2). Localized amyloidosis in the head and neck is extremely rare (1), with the larynx and orbits the most frequently involved sites (1). Oropharyngeal amyloidosis is even rarer (4). On CT, it appears as a well-defined submucosal homogeneous mass, except for areas of calcification (23), with varying degrees of enhancement (4). The calcifications range from subtle psammomatous to well-defined foci (3). On MRI, amyloidosis has a signal intensity similar to that of skeletal muscle (3). It may show low signal intensity both on T1 weighted images and T2 weighted images, because of the molecular structure of amyloid. The compact and complex environment of the amyloid may allow increase chance for dissipation of coherent resonance, resulting in a loss of signal intensity (6). In addition, decreased water mobility in an area of densely packed protein is expected within the highly organized amyloid protein (6). Given the high vascularity of the lesion and the fragility of its vessels, it may show marked enhancement and slow washout (3). To our knowledge, in the last 20 years there have been only five case reports of amyloidosis of the palate (7) but none have described the MRI findings of amyloidosis of the palate.

There are two entities of “lymphoma associated systemic amyloidosis” and “peritumoral amyloidosis with lymphoma” (5). Previous studies have suggested that peritumoral and systemic amyloidosis are distinct disease entities, in which peritumoral amyloidosis with MALT lymphoma show indolent behavior with rare progression to disseminated disease. MALT lymphoma associated with amyloid deposition is considered as a result of immunoglobulin or immunoglobulin light chains deposition produced in MALT lymphoma (8).

Systemic amyloidosis is a life-threatening disease which can cause progressive organ failure (8). The presence of amyloid deposition could lead to difficulties in the differential diagnosis of lymphoma with non-tumorous condition (8). Clinical consensus criteria have been established to differentiate systemic amyloidosis from localized amyloid deposition (8). In addition to histologic evidence of amyloidosis, it includes evidence of organ dysfunction such as organomegaly or abnormal laboratory finding (8). In contrast to the cases of systemic amyloidosis, our case demonstrated amyloid deposits localized to involved sites of MALT lymphoma. In addition there is no laboratory finding that suggests organ dysfunction.

The fact that lymphoma relapses often contained amyloid, but amyloid was never encountered in sites not involved by lymphoma is described (8). So, amyloid-containing specimens in patient with lymphoma, the possibility of sampling error and excisional biopsy should be considered (9). The treatment may vary according to stage and involvement site, including excision alone, localized radiotherapy, rituximab, and other chemotherapy (8). Cases of multiple recurrences were described in many cases (8).

In general, radiologically demonstrable calcifications in lymphoma are considered to be a consequence of previous treatment, usually radiotherapy or, less commonly, chemotherapy (9). Pre-treatment calcifications are rarely reported in lymphoma, and it is regarded as a consequence of hypercalcemia (9). In our patient, the laboratory findings were grossly normal. Therefore, in patients with pre-treatment lymphoma and normal laboratory findings, calcifications detected on CT could be a clue of a concurrent peritumoral amyloidosis in the background of MALT lymphoma showing plasmacytic differentiation.

In conclusion, peritumoral amyloidosis with lymphoma could demonstrate a heterogeneous high density mass with calcifications and well enhancement on CT. On MR imaging, the mass showed low signal intensity on both T1 and T2 weighted images. Calcifications on imaging in a patient with lymphoma could suggest a second concurrent pathology, such as peritumoral amyloidosis.