The micropapillary variant of urothelial carcinoma (MPUC) is an aggressive form of urothelial carcinoma with high metastatic potential and a poor prognosis. Although various therapies have been reported, there is still no established treatment strategy for MPUC due to its rarity. The incidence of urinary tract malignancies is higher in patients undergoing hemodialysis (HD) than in healthy individuals. Here, we report the case of an 82-year-old man on HD with end-stage kidney disease who visited our hospital for macrohematuria. Cystoscopy followed by computed tomography and urine cytology revealed a sessile papillary tumor around the left bladder wall. We performed transurethral resection of the bladder tumor. Based on histopathological and imaging findings indicative of clinical-stage T3N0M0 MPUC, we performed radical cystectomy. Histopathology revealed a pathological stage T4aN0M0 MPUC. Two months after the cystectomy, the patient complained of constipation and painful defecation due to local recurrence and rectal invasion. While colostomy was performed to improve defecation 3 months after cystectomy, he did not receive any chemotherapy due to his progressively worsening general condition. Six months after cystectomy, he died following rapid metastases. Our findings, in this case, confirm that bladder cancer in HD patients tends to be pathologically more advanced. Therefore, regular screening is recommended for its early detection in HD patients

Fukawa, Tomoya

Fukuta, Kyotaro

Iihara, Kiyotaka

Inai, Tohru

Izaki, Hirofumi

Kanayama, Hiro-Omi

Kanda, Kazuya

Kudo, Eiji

Moriyama, Takahiro

Nakanishi, Ryoichi

Sutou, Yasushi

Takahashi, Masayuki

Yamaguchi, Kunihisa

Yamamoto, Yasuyo

English

Tokushima University Institutional Repository

© 2022 The Author(s).Published by S. Karger AG, BaselCase ReportCase Rep Oncol 2022;15:462–468Micropapillary Variant of Urothelial Carcinoma in a Hemodialysis PatientKyotaro Fukuta a    Kiyotaka Iihara b    Takahiro Moriyama a    Ryoichi Nakanishi c    Hirofumi Izaki c    Kazuya Kanda c    Tohru Inai c    Eiji Kudo d    Tomoya Fukawa e    Kunihisa Yamaguchi e    Yasuyo Yamamoto e    Masayuki Takahashi e    Yasushi Sutou a    Hiro-Omi Kanayama eaDepartment of Urology, Tsurugi Municipal Handa Hospital, Tsurugi, Japan; bJapan Department of Urology, Fukuoka Shin Mizumaki Hospital, Kitakyushu, Japan; cDepartment of Urology, Tokushima Prefectural Central Hospital, Tokushima, Japan; dDepartment of Pathology, Tokushima Prefectural Central Hospital, Tokushima, Japan; eDepartment of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, JapanKeywordsBladder cancer · Micropapillary variant · Hemodialysis · Urothelial carcinoma · CystectomyAbstractThe micropapillary variant of urothelial carcinoma (MPUC) is an aggressive form of urothelial carcinoma with high metastatic potential and a poor prognosis. Although various therapies have been reported, there is still no established treatment strategy for MPUC due to its rarity. The incidence of urinary tract malignancies is higher in patients undergoing hemodialysis (HD) than in healthy individuals. Here, we report the case of an 82-year-old man on HD with end-stage kidney disease who visited our hospital for macrohematuria. Cystoscopy followed by computed tomography and urine cytology revealed a sessile papillary tumor around the left bladder wall. We performed transurethral resection of the bladder tumor. Based on histo-pathological and imaging findings indicative of clinical-stage T3N0M0 MPUC, we performed radical cystectomy. Histopathology revealed a pathological stage T4aN0M0 MPUC. Two months after the cystectomy, the patient complained of constipation and painful defecation due to local recurrence and rectal invasion. While colostomy was performed to improve def-ecation 3 months after cystectomy, he did not receive any chemotherapy due to his progres-sively worsening general condition. Six months after cystectomy, he died following rapid me-tastases. Our findings, in this case, confirm that bladder cancer in HD patients tends to be pathologically more advanced. Therefore, regular screening is recommended for its early detection in HD patients.© 2022 The Author(s).Published by S. Karger AG, BaselReceived: March 4, 2022Accepted: March 29, 2022Published online: April 28, 2022Correspondence to: Kyotaro Fukuta, k.fukuta0429 @ gmail.comwww.karger.com/croThis article is licensed under the Creative Commons Attribution-NonCommercial 4.0 Interna tional License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.DOI: 10.1159/000524430463Case Rep Oncol 2022;15:462–468Fukuta et al.: Micropapillary Variant of UC in an HD Patientwww.karger.com/cro© 2022 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000524430IntroductionThe micropapillary variant of urothelial carcinoma (MPUC) was first described by Amin et al [1]. A rare and aggressive variant of urothelial carcinoma (UC), MPUC, has high meta-static potential. Although various therapies have been reported, they are based mainly on small, single-center experiences due to the disease’s rarity. Moreover, despite the treatment of metastatic UC have recently revolutionized chemotherapy and immune checkpoint inhib-itors (ICIs) [2–4], sometimes, patients could not administer systemic chemotherapy because of their aggressive clinical courses. Hence, an optimal treatment strategy for MPUC remains to be established.The incidence of urological malignancies is higher in hemodialysis (HD) patients than in healthy individuals [5]. In HD patients, the detection of bladder cancer is often delayed because of oliguria or anuria [5]. Here, we report a case of MPUC in an HD patient.Case PresentationAn 82-year-old man who had been on maintenance HD for 10 months due to chronic renal failure with nephrosclerosis visited our hospital for macroscopic hematuria. Cystoscopy revealed a sessile papillary tumor and edematous changes around the left wall of the bladder (Fig. 1a). Computed tomography (CT) revealed left hydronephrosis and a bladder tumor involving the left ureteral orifice (Fig. 1b). Urine cytology was classified as class 3b, and UC was suspected. Transurethral resection of the bladder tumor was performed. Histopatho-logical evaluation and CT findings revealed invasive MPUC (clinical-stage T3N0M0). Two months after the initial diagnosis, laparoscopic radical cystectomy and bilateral ureteral ligation were performed. However, due to adhesions involving the pelvic floor and significant extravesical invasion, these procedures could not be completed laparoscopically. Histopa-thology revealed pathological stage T4aN0M0 MPUC (UC, 5%; micropapillary variant, 95%) a bFig. 1. Cystoscopy and abdominal CT findings at the initial diagnosis. a Cystoscopy shows a sessile papillary tumor and edematous changes around the left wall. b CT shows left hydronephrosis due to the bladder tumor invading the left ureteral orifice (yellow arrow).464Case Rep Oncol 2022;15:462–468Fukuta et al.: Micropapillary Variant of UC in an HD Patientwww.karger.com/cro© 2022 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000524430(Fig. 2) and incidental prostate adenocarcinoma (Gleason score 4 + 4, pathological stage T2a). Although there were no perioperative complications, the patient complained of constipation and pain on defecation due to local recurrence and invasion of the rectum 2 months after cystectomy (Fig. 3a). As his general condition progressively worsened with the rapid progression of the disease, he could not undergo chemotherapy. Colostomy was performed to improve defecation 3 months after cystectomy. However, the patient died 6 months after cystectomy due to rapid metastases (Fig. 3b).DiscussionMPUC is a rare variant that accounts for 0.7–2.2% of bladder cancers [6]. The histopath-ological features of MPUC are similar to those of papillary serous carcinoma of the ovary, with delicate filiform processes and infiltrating clusters of micropapillary aggregates without central vascular cores [7]. Although the optimal treatment for MPUC remains controversial, immediate radical cystectomy is considered the best option to improve prognosis, regardless of muscle invasion [7]. In addition, despite the efficacy of ICIs for metastatic UC has been reported [2–4], the efficacy of ICIs for MPUC remains unclear. However, the 5-year survival rate of patients with MPUC is ≤25%, even after cystectomy, chemotherapy, and radiotherapy [6]. Previous reports indicate that the proportion of MPUC determined histopathologically is a prognostic indicator, with >50% micropapillary variant associated with increased mortality [8, 9]. In the present case, the proportion of micropapillary variant was 95%, which might account for the aggressive clinical course. Further cases of MPUC need to be accumulated to establish more effective treatments.The risk of all malignant tumors is 1.4–4.5 times higher in HD patients than in healthy subjects [10]. Gastrointestinal malignancies account for 44% of all malignant tumors in HD patients, followed by urological malignancies (15.4%) [5], and renal-cell carcinoma is a particular complication in these patients. Bladder cancer is the second most common urological malignancy worldwide. Why the incidence of urological malignancies is higher in HD patients remains unclear, although chronic urinary infections, weakened immune system, malnutrition, and DNA damage have been reported as possible etiologies [11]. Bladder cancer in HD patients is often diagnosed at an advanced stage [5]. Yonemura et al. [10] reported muscle invasion in 39 of 80 bladder cancer cases in HD patients. The histological type was a bFig. 2. Macroscopic and microscopic findings at cystectomy. a Macroscopically, tumors can be seen all around the bladder with significant extravesical invasion. b Hematoxylin and eosin staining show the malignant cells arranged in small papillary clusters in clear spaces with a high incidence of lymphovascular and vascular in-vasion (red arrow). The proportions were 95% micropapillary variant and 5% UC465Case Rep Oncol 2022;15:462–468Fukuta et al.: Micropapillary Variant of UC in an HD Patientwww.karger.com/cro© 2022 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000524430identifiable in 70 of the 80 cases, with UC accounting for 67 cases, including 4 cases of divergent differentiation and variant histologies [10]. Additionally, the proportion of divergent differentiation and variant histologies in HD patients was equivalent to that in healthy subjects [10]. Table 1 summarizes the reports of 13 bladder cancer cases with divergent and/or variant histologies in patients undergoing HD. In most of these cases, the disease was detected in the advanced stage, and 10 of the 13 cases had muscle-invasive bladder cancer. To the best of our knowledge, this is the first report of MPUC in a patient on HD.The high incidence of muscle-invasive bladder cancer in HD patients is thought to be due to the poor awareness of oliguria or anuria symptoms. Although urinary cytology helps diagnose UC in patients on HD, adequate urine output is required [18]. Thus, additional imaging evaluations may be essential for diagnosing UC in HD patients with anuria. Yonemura et al. [10] recommended that screening for malignant tumors using CT and ultrasonography should be considered at least once a year in these patients. Cystoscopy is helpful in the early detection and diagnosis of bladder cancer. However, because it is invasive, urologists must judge whether it should be performed immediately as a screening procedure in cases without a history of bladder cancer. Satoh et al. [19] and Lin et al. [20] have reported the detection of bladder cancer in several cases within 1 year of starting HD. Therefore, screening for bladder cancer with urine cytology, ultrasonography, and CT should be considered shortly after starting HD and performed at least once a year. Further cases are required to determine the screening for bladder cancer in HD patients.abFig. 3. CT findings at 2 months after cystectomy and clinical course. a Local recurrence was confirmed at the pelvic floor (red arrow), associated with annular thickening of the rectal wall (yellow circle). Constipation and defecation pain was believed to be caused by bladder cancer invading the rectum. b Clinical course. After local recurrence and invasion to the rectum appeared, colostomy was performed to improve defecation symptoms. However, local recurrence progressed rapidly, and he gradually felt perineal pain due to skin me-tastases at 3 months after cystectomy.466Case Rep Oncol 2022;15:462–468Fukuta et al.: Micropapillary Variant of UC in an HD Patientwww.karger.com/cro© 2022 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000524430Table 1. Clinical and pathological details of HD patients with divergent differentiation and variant histologiesNo.AuthorAge, yearsGenderDuration of HDHistologyPathologicalT stageFollow-up, monthsSurvival data1Ryoji et al. [12]72M30UC with glandular differentiation3UnknownUnknown2Ryoji et al. [12]44F125UC with squamous/glandular differentiationUnknown4DOD3Ryoji et al. [12]61M6UC with glandular differentiationUnknownUnknownUnknown4Ryoji et al. [12]61M6Adenocarcinoma40.6DOD5Ryoji et al. [12]41M15Squamous-cell carcinoma3b15DOD6Ryoji et al. [12]53F12UC with squamous differentiation3bUnknownNED7Ryoji et al. [12]72M32UC with glandular differentiation3b1.5DOC8Shirai et al. [13]65F15UC with sarcomatoid variant4a6NED9Siqueira et al. [14]58MUnknownUC with sarcomatoid variant4a6DOD10Yonemura et al. [10]82M75UC with small-cell carcinoma21.5DOC11Isono et al. [15]69F21UC with clear-cell variant120NED12Ishii et al. [16]56M204UC with small-cell carcinoma4a19DOD13Jassim et al. [17]59FUnknownUC with clear-cell variant336NED14Fukuta (2022)82M10UC with micropapillary variant4a6DODDOD, died of disease; NED, no evidence of disease; DOC, death due to complications.467Case Rep Oncol 2022;15:462–468Fukuta et al.: Micropapillary Variant of UC in an HD Patientwww.karger.com/cro© 2022 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000524430In this case, the patient developed gross hematuria 10 months after starting HD, and MPUC was first diagnosed using CT, cystoscopy, and urine cytology. Although no metastasis was detected at the time of diagnosis, MPUC being an aggressive variant of UC, the patient died of rapid disease progression 6 months after cystectomy. In addition, the limitation of this case report include bladder cancer with divergent and/or variant histologies in HD patients have been accumulated by several case reports due to its rarity. Since UC includes aggressive variants such as MPUC, careful screening is warranted for improved prognosis, especially in HD patients.ConclusionIn conclusion, the detection of bladder cancer in HD patients is often delayed because of oliguria or anuria, resulting in disease progression. Bladder cancer often includes aggressive variant histologies such as MPUC. Therefore, regular screening for HD patients is recom-mended for the early detection of bladder cancer.Statement of EthicsEthical approval was not required for this study in accordance with local or national guidelines. Written informed consent for publication of this case report and any accompa-nying images was obtained from the next of kin.Conflict of Interest StatementThe authors declare no conflict of interest.Funding SourcesThe authors received no funds for this article.Author ContributionsKyotaro Fukuta reviewed the literature and drafted the manuscript. Kiyotaka Iihara, Takhahiro Moriyama, Ryoichi Nakanishi, Hirofumi Izaki, Kazuya Kanda, Tohru Inai, and Yasushi Sutou performed the surgery. Tomoya Fukawa, Kunihisa Yamaguchi, Yasuyo Yamamoto, Masayuki Takahashi, and Hiro-Omi Kanayama critically revised the manuscript. Kyotaro Fukuta, Kiyotaka Iihara, Hirofumi Izaki, and Eiji Kudo performed examinations before and after surgery, provided photographs, and drafted the first version of the manu-script. All the authors approved the final manuscript.Data Availability StatementAll data generated or analyzed in this study are included in this article. Further inquiries can be directed to the corresponding authors.468Case Rep Oncol 2022;15:462–468Fukuta et al.: Micropapillary Variant of UC in an HD Patientwww.karger.com/cro© 2022 The Author(s). Published by S. Karger AG, BaselDOI: 10.1159/000524430References 1 Amin MB, Ro JY, el-Sharkawy T, Lee KM, Troncoso P, Silva EG, et al. 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Micropapillary Variant of UC in an HD Patient

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Micropapillary Variant of UC in an HD Patient

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