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      Bladder pseudo-tumor: case report of vesical tamm-horsfall protein deposit


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          INTRODUCTION Urothelial carcinomas (UC) are malignant tumors that correspond to more than 90% of the bladder tumors (1). The main sign of UC is hematuria, however with the routine use of imaging exams, more patients are being diagnosed whilst asymptomatic. On ultrasonography (US), UCs present as a focal bladder wall thickening and/or a polypoid lesion (2). Nevertheless, these findings may be due to several other malignant and non-malignant differential diagnoses, such as nephrogenic adenoma, inverted papilloma, leiomyoma, amyloidosis, glandular cystitis, endometriosis, bladder xanthoma, among others (3–6). Cystoscopy is the gold standard procedure to investigate patients with suspicion of any bladder neoplasia. Our objective is to report a case of Tamm-Hosrsfall protein deposit in the bladder wall, mimicking a vesical UC. CASE REPORT A 51-year-old asymptomatic man, with no history of hematuria, underwent to a routine US. The exam demonstrated a bladder with regular walls, except for an area of focal thickening and a nodular lesion in the bladder floor, close to the right ureteral meatus (Figure-1). Serum and urinary laboratory tests were normal. Figure 1 A: US with an area of focal thickening in the bladder floor (arrow); B: The focal thickening in the bladder floor is close to the ureteral meatus (arrow show the ureteric jet in US doppler); C: Nodular lesion in the bladder floor, close to the focal thickening (arrow). Cystoscopy found three elevated lesions in the right lateral vesical wall, each one with about 0.5cm, all of which with intact mucosa. Additionally, there was an ipsilateral ulcerated peri-meatal lesion (Figure-2). All lesions were cold-cup biopsied and the pathological analysis revealed deposition of an eosinophilic proteinaceous substance throughout the mucosa and around the vessels. This was also associated with a mixed inflammatory process at the lamina propria, without evidence of cellular atypia (Figures 3 and 4). The search for infectious agents and amyloid protein (red-congo) were negative. The findings led to the diagnosis of Tamm-Horsfall protein deposition (THP). The patient remained asymptomatic and had no complications following the procedure. Figure 2 (cystoscopy) – A) right peri-meatal region, which is evidencing ulcerated lesion (thick arrow) and lesions elevated with intact mucosa (narrow arrow); B) Image focused on elevated lesions (thick arrow); C) image focused on ulcerated lesion. Figure 3 Hematoxylin and Eosin (H&E) stain - Bladder biopsy: deposits of eosinofilic material in the lamina propria (arrows). Figure 4 Periodic Acid Schif (PAS) stain: eosinofilic material deposits strongly positive by the PAS stain. DISCUSSION The THP is a high molecular weight glycoprotein synthesized in the ascending portion of the Henle loop, and in the distal convoluted tubule. THP is abundant in normal human urine. Its actual physiological function remains unknown, but there is a hypothesis about a possible protective factor against urinary tract infections, lithogenesis, and some nephropathies (7–9). The etiology for THP deposit is still unclear, however it is most likely related to mucosal changes, such as inflammation and necrosis (7–9). A series of three patients with atypical THP mimichking tumor at the peri-pelvic and peri-renal fat tissues has been reported. In addition to the initial bladder carcinoma diagnostic hypothesis, renal pelvic neoplasia and urinary tuberculosis were also suspected (10). Another report presented a patient with a ureteral lesion associated with hydronephrosis, which suggested a tumor, but exactly like our case, histology favored THP deposition (11). A large study consisting of 247 bladder biopsies and 15 specimens of cystectomy identified the presence of THP deposition in the bladder tissue in 18 cases (6.9%). The cystectomy cases presented positive biopsies for THP deposition in 60% of the patients, higher than isolated biopsies (3.6%). The author describes a typical pathological finding characterized by whitish masses with discrete eosinophilic deposition (12). However, our patient, beyond the THP deposits mimicking a bladder tumor, did not present any other bladder pathology or symptoms. There are reports that have identified association between bladder wall THP deposition and interstitial cystitis (13, 14). Additionally, patients with interstitial cystitis have been reported to have changes in THP when compared to control groups. Our case demonstrates that THP deposition in the bladder may be one of the differential diagnoses for bladder lesions, mainly when the lesion does not have the usual papillary aspect and appears to be in a sub-urothelial layer.

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          The global epidemiology of bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection

          We tested the hypotheses that the global incidence of bladder cancer was increasing but its mortality was reducing and its incidence was positively correlated with country-specific socioeconomic development. We retrieved data on age-standardized incidence and mortality rates/100,000 from the GLOBOCAN database in 2012. Temporal patterns were examined for 39 countries from the Cancer Incidence in Five Continents volumes I-X and other national registries. We evaluated the correlation between the incidence/mortality rates and Human Development Index (HDI)/ logarithmic values of Gross Domestic Product per capita (GDP). The average annual percent change of the incidence and mortality rates in the most recent 10 years was examined by joinpoint regression analysis. The highest incidence rates were observed in Southern Europe, Western Europe and North America. The mortality rates were the highest in Western Asia and Northern Africa. The incidence was positively correlated with HDI (r = 0.66 [men]; r = 0.50 [women]) and to a lesser extent logarithmic values of GDP per capita (r = 0.60 [men]; r = 0.50 [women], all p < 0.01). Many European countries experienced incidence rise. A substantial mortality reduction was observed in most countries, yet increases in mortality rates were observed in the Philippines and Iceland. These findings identified countries where more preventive actions are required.
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            Role of Imaging in the Local Staging of Urothelial Carcinoma of the Bladder

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              Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infection.

              Urinary tract infection (UTI) is the most common nonepidemic bacterial infection in humans, representing a constant danger for the host. Both innate and adaptive components of the immune system as well as stromal cells including bladder epithelium are involved in the prevention and clearance of UTI. However, the particular properties of the urogenital tract, which does not comprise typical physical barriers like a mucus or ciliated epithelium, necessitate soluble mediators with potent immunomodulatory capabilities. One candidate molecule capable of both mediating direct antimicrobial activity and alerting immune cells is the evolutionary conserved Tamm-Horsfall protein (THP). Tamm-Horsfall protein is exclusively produced by the kidney in the distal loop of Henle; however, its definite physiological function remains elusive. Mounting evidence indicates that beyond a mere direct antimicrobial activity, THP exerts potent immunoregulatory activity. Furthermore, the genetic ablation of the THP gene leads to severe infection and lethal pyelonephritis in an experimental model of UTI. Recent data are provided demonstrating that THP links the innate immune response with specific THP-directed cell-mediated immunity. In light of these novel findings we discuss the particular role of THP as a specialized defence molecule. We propose an integrated model of protective mechanisms against UTI where THP acts by two principle nonmutually exclusive mechanisms involving the capture of potentially dangerous microbes and the ability of this peculiar glycoprotein to induce robust protective immune responses against uropathogenic bacteria.

                Author and article information

                Int Braz J Urol
                Int Braz J Urol
                International Brazilian Journal of Urology : official journal of the Brazilian Society of Urology
                Sociedade Brasileira de Urologia
                20 February 2020
                May-Jun 2020
                : 46
                : 3
                : 477-480
                [1 ] orgnameHospital Israelita Albert Einstein São Paulo SP Brasil originalHospital Israelita Albert Einstein, São Paulo, SP, Brasil
                [2 ] orgnameFaculdade de Medicina do ABC orgdiv1Disciplina de Urologia Santo André SP Brasil originalDisciplina de Urologia, Faculdade de Medicina do ABC, Santo André, SP, Brasil
                Author notes
                Correspondence address: Marcelo Langer Wroclawski, MD, PhD, Hospital Israelita Albert Einstein, Rua: Iguatemi, 192 / 43-44 São Paulo, SP, Brasil. Cep: 01451-010 Fax: + 55 11 31682130, E-mail: urologia.marcelo@ 123456gmail.com

                CONFLICT OF INTEREST

                None declared.

                Author information

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 11 August 2019
                : 17 September 2019
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 14, Pages: 4
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