Case report on ureteral amyloidosis that was incidentally diagnosed in a patient with malignant lymphoma

Abstract

Herein, we report a rare case of localized ureteral amyloidosis in a patient with malignant lymphoma. A 73-year-old female patient visited our institution for a comprehensive examination and treatment of malignant lymphoma. Contrast-enhanced computed tomography scan and magnetic resonance imaging revealed left hydronephrosis and a left lower ureteral mass. These findings suggested either ureteral amyloidosis or a ureteral carcinoma with significant fibrosis. Cystoscopic biopsy was performed, and the patient was pathologically diagnosed with ureteral amyloidosis. Renal renography revealed left renal dysfunction. However, the patient was asymptomatic. Hence, the patient should be followed-up for ureteral amyloidosis. Computed tomography scan were performed every 3 months, and after approximately 1 year, there was no evidence of mass enlargement. This case highlights the rarity of ureteral amyloidosis and the importance of imaging diagnosis in clinical practice.

Introduction

Amyloidosis is a group of diseases caused by the accumulation of insoluble amyloid fibrils in tissues, leading to organ dysfunction. Ureteral amyloidosis is rare, accounting for 25% of urinary tract amyloidoses, and often presents with symptoms associated with ureteral obstruction and hematuria, which should be differentiated from neoplastic lesions.

By 2023, 80 cases of ureteral amyloidosis had been reported in Japan [3]. Herein, we report a case of ureteral amyloidosis that was incidentally detected during examination of a malignant lymphoma, mainly based on imaging findings. The lesion was believed to be a localized ureteral amyloidosis based on its course and the presence of chronic hydronephrosis. Further, a literature review was performed. This report aims to highlight the clinical and imaging findings of a rare case of localized ureteral amyloidosis and discuss its differentiation from neoplastic lesions.

Case report

A 73-year-old female patient visited our institution due to a rapidly growing left cervical lymph node. The patient had no medical history of note. She also had no other symptoms, including hematuria or back pain, other than enlarged cervical lymph nodes.

An excision was performed, and the patient was pathologically diagnosed with diffuse large B-cell lymphoma (DLBCL).

To further examine the patient, contrast-enhanced computed tomography (CT) scan was performed. Results revealed a circumferential thickening of the left lower ureter with left hydronephrosis and left renal parenchymal atrophy with enhancement. The thickened wall was iso-dense to the muscle, without an evident contrast effect (Fig. 1). Magnetic resonance imaging showed an extremely low signal wall thickening on T2-weighted imaging (T2WI) and the lumen of the thickened wall was smooth. And diffusion-weighted imaging (DWI) showed not highly intense. (Fig. 2). ¹⁸F-fluorodeoxyglucose positron emission tomography/CT scan was performed. Results showed no significant FDG accumulation (maximum standardized uptake value = 2.3) (Fig. 3). Based on these imaging findings, ureteral amyloidosis or urothelial carcinoma with strong fibrosis was suspected. However, the patient did not present with malignant lymphoma lesions on other regions. Renal renographic scintigraphy was also performed, and results showed that the left kidney was hypofunctioning.

Fig. 1.

(A) Coronal contrast-enhanced computed tomography (CT) scan showed no evident contrast enhancement effect in the thickened left ureteral wall (arrow). (B) Coronal contrast-enhanced CT scan showed left hydronephrosis and left renal atrophy (arrowhead).

Fig. 2.

(A) On axial T2-weighted imaging (T2WI), the left lower ureteral mass (arrow) exhibited a strong low signal intensity than that of the muscle, and the lumen of the thickened wall was smooth. (B) On axial T1-weighted imaging (T1WI), the mass (arrow) exhibited a low signal intensity. (C) On axial diffusion-weighted imaging (DWI), the mass (arrow) was not highly intense.

Fig. 3.

¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT scan only revealed a mild FDG accumulation in the left lower ureteral mass (maximum standardized uptake value = 2.3) (arrow).

Before starting the treatment for malignant lymphoma, cystoscopic biopsy of the left ureteral mass was conducted to obtain a diagnosis. Results revealed an elevated lesion with an orange tone at the left ureteral orifice without evident mucosal changes. Cut cold biopsy of the elevated lesion was performed. Histopathologically, there was no malignant finding in the ureteral epithelium. However, the amyloid deposits in the submucosal stroma presented as orange-colored granules on direct fast scarlet staining and apple green birefringence on polarized light microscopy (Fig. 4). These findings were very typical of amyloid deposition.Additional immunostaining was performed, and the patient tested negative for amyloid A, κ-chain, λ-chain, and transthyretin. Based on these findings, the left ureteral mass was diagnosed as ureteral amyloidosis. The patient had complete response 6 months after the treatment for DLBCL. Thereafter, recurrence was not observed. CT scan were performed every 3 months,and the size of the left ureteral mass did not increase within 1 year.

Fig. 4.

(A) Hematoxylin & Eosin (H&E) staining showed an amorphous eosinophilic material in the submucosa of the ureter, and there were no malignant findings in the ureteral epithelium. (B) The direct fast scarlet (DFS) staining had positive results (as evidenced by the presence of orange granules), and it revealed submucosal amyloid deposits. (C) Polarized light microscopy showed an apple green birefringence of amyloids.

Discussion

Amyloidosis is a group of diseases characterized by the deposition of amyloid fibrils, which are insoluble proteins that form due to various factors, leading to organ dysfunction due to their accumulation extracellularly in various tissues [1]. It is classified into systemic amyloidosis and localized amyloidosis, with localized amyloidosis accounting for 10%-20% of cases [2]. The common sites of localized amyloidosis are generally the respiratory, skin, and urinary tracts. Urinary tract amyloidosis occurs mainly in the renal pelvis, ureters, bladder, and urethra, with over half of cases involving bladder amyloidosis and 25% involving ureteral amyloidosis [[1], [2], [3]]. In the urogenital tract, amyloid deposits are most frequently found in the renal parenchyma in cases of systemic amyloidosis. Meanwhile, localized amyloid deposition in the urinary tract, particularly in the ureter, is extremely rare [4].

Typical imaging findings in ureteral amyloidosis reflect fibrosis-rich amyloid deposited in the ureteral submucosal stroma. Amyloid protein is known to have a T2 shortening effect, which results in circumferential or nodular ureteral wall thickening with a low T2WI signal.

Although there are no coherent reports on imaging findings on DWI in ureteral amyloidosis, there is a report of a patient who, like our case, lacked diffusion restriction, which was useful in differentiating ureteral carcinoma [4].

The contrast effect is mild, and the lumen remains smooth and calcified in some cases. These findings can be also useful in differentiating ureteral amyloidosis from ureteral carcinoma [[2], [3], [4]]. Some reports indicate that wall thickening occurs in the lower ureter in about half of all cases, and this case was typical of such cases. However, in a previous report, a long continuous lesion from the pelvic-ureteric junction to the upper ureter (with a smooth lumen) was observed [4].

In our case, the patient presented with the typical imaging findings. However, inflammation often causes various contrast effects, signal elevation on T2WI and diffusion-weighted imaging, often complicating the differentiation of amyloidosis from malignant tumors [[2], [3], [4]].

In addition, there was no increase in FDG accumulation in this case, which we consider atypical for ureteral carcinoma. There are no consistent reports on FDG accumulation in ureteral amyloidosis, but it is generally accepted that FDG accumulation occurs in immunoreactive cells (macrophages, monocytes and leucocytes) and other cells in amyloidosis [6]. Therefore, the presence of inflammation may cause FDG uptake, making it difficult to differentiate amyloidosis from malignancy.

Ureteral amyloidosis can be treated with local excision when surgical treatment is performed. However, in the past, many cases have been unnecessarily treated with total nephroureteral resection because of difficulty in preoperative diagnosis and misdiagnosis as ureteral carcinoma, especially in cases where biopsy was not performed [4,5]. Therefore, it is very important to suggest a benign mass such as ureteral amyloidosis preoperatively on imaging, which may lead to biopsy and appropriate renal preservation.

In this case, the patient's left kidney was already dysfunctional, and the patient was asymptomatic. In addition, the patient required immediate treatment for malignant lymphoma. Therefore, this patient was followed up with no treatment for ureteral amyloidosis, and this patient was followed up with CT scans every 3 months. Although no appropriate follow-up protocol is currently defined, regular follow-up is necessary because there have been reports of cases of recurrence in patients with resected ureteral amyloidosis [3].

In this case, ureteral amyloidosis was detected incidentally during examination for DLBCL. There are known cases of amyloidosis associated with B-cell lymphoma especially immunoglobulin light chain amyloidosis (AL type amyloidosis), and the mechanism involves the deposition of monoclonally proliferated immunoglobulins in the organs [1,2,7]. However, the association between the 2 diseases in this patient is weak as immunohistochemistry did not show the deposition of AL amyloid protein (κ, λ chains). Further, the presence of kidney atrophy indicates chronic ureteral amyloidosis. The rapid increase in the size of DLBCL does not likely precede the amyloidosis and cause the amyloidotic lesion, as in this case. Therefore, the ureteral mass was an incidental finding.

Conclusion

Ureteral amyloidosis is a rare disease. Appropriate diagnosis of ureteral amyloidosis on imaging may help avoid overtreatment, such as nephrectomy.

Therefore, it is important to consider ureteral amyloidosis, especially in the setting of a low-signal mass on T2WI.

Patient consent

Informed consent was obtained for the publication of this case report.

Author contributions

All authors had substantial contributions to the manuscript, and they approved the final version of the article that should be published.