Final Diagnosis (Slide show after references)
The overall findings include chronic polypoid ureteritis, nephrogenic adenoma and amyloidosis which appear to obstruct the lumen resulting in ureteral obstruction and hydronephrosis.
Amyloidosis is a heterogenous group of disorders caused by deposition of misfolded proteins as insoluble eosinophilic material in the extracellular tissues of the body, leading to impairment of organ function . The amyloid deposits can be systemic or localized. Localized amyloidosis accounts for 10-20% of cases [2-3]. It can be seen in many organs including the genitourinary system, most commonly as an incidental finding in the seminal vesicles. Ureteric involvement by amyloidosis is exceedingly rare and only a few cases have been reported in the literature [4-6]. It occurs predominantly in females with a female to male ratio of 1.9:1. The mean age at diagnosis is 58 years (range, 17-81 years) and the majority of patients present with flank pain, followed by hematuria .
On imaging, there are no specific findings to detect amyloidosis; however, the possibility could be suspected when the lesion is visualized as a hypointensity on T2‐weighted MRI images and no obvious mass effect is appreciated . Because of its non-specific clinical and radiologic findings, malignancy is usually the primary clinical impression and radical surgery, including nephroureterectomy, is not unusual .
The etiology of amyloidosis is not fully understood. In the ureter, it has been postulated that chronic and recurrent inflammation associated with migration of lymphoplasmacytic cells may result in an aberrant monoclonal proliferation with the local secretion of light chains, which may then be transformed to amyloid by lysosomal degradation . The presence of a lymphoplasmacytic infiltrate, although polyclonal as highlighted by kappa and lambda light chain immunostains, was prominent in our case; the co-existence of amyloidosis and nephrogenic adenoma has not been previously reported.
Nephrogenic adenoma (NA) is an uncommon benign tumor-like lesion that is most often seen in the urinary bladder . Location in the ureter ranges from 4-8% of reported cases [10-11]. Nephrogenic adenoma occurs in patients with chronic bladder inflammation or previous genitourinary surgery. Multiple hypotheses have been postulated, including that nephrogenic adenomas are metaplastic alterations of urothelial tissue, and hence called “nephrogenic metaplasia”. Another hypothesis postulates that NA develops from seeding and implantation of renal tubular cells due to renal disease or hypoxic conditions. This hypothesis is supported by the identification of nephrogenic adenomas in renal-transplant recipients from opposite sex where the NA cells share the same FISH chromosomal characteristics of renal tubular cells of the donor transplanted kidney .
On histologic examination, NA can show variety of growth patterns including tubules (most common), cysts, papillae, and focal solid growth. It is mostly limited to the lamina propria; however, superficial involvement of muscularis mucosae has been reported, especially in large lesions . The tubules are infrequently surrounded by thick basement membrane in an edematous, inflamed stroma. The tubules are lined by a single cell layer of cuboidal, columnar or flattened cells with hobnailed nuclei . Although enlarged nuclei and prominent nucleoli may be observed in some cases, significant nuclear atypia, including presence of mitosis, is rare . Immunohistochemically, nephrogenic adenoma is consistently positive for PAX2, PAX8, CK7, aquaporin-1, MUC1, vimentin and variably positive for p504S (α-methylacyl-CoA-racemase, AMACR) .
In summary, multiple benign and reactive lesions were present in our case including nephrogenic adenoma and amyloidosis in a background of lymphoplasmacytic inflammation leading to chronic ureteritis. It’s unclear what lesion antecedes the other, but it is possible that the chronic and recurrent irritation and inflammation led to localized amyloidosis with subsequent trapping of renal tubular cells with the development of nephrogenic adenoma, further complicating the ureteric obstruction.
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