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Delayed diagnosis of bladder cancer in a patient with autosomal dominant polycystic kidney disease

1 Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo; Departmentof Medical Oncology/Hematology, Kakogawa Central City Hospital, Hyogo, Japan
2 Departmentof Medical Oncology/ Hematology, Kakogawa Central City Hospital, Hyogo, Japan

Date of Submission24-Jun-2022
Date of Decision12-Jul-2022
Date of Acceptance14-Jul-2022
Date of Web Publication04-Oct-2022

Correspondence Address:
Hirotaka Suto,
Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo 135-8550
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_1310_22

 > Abstract 

Approximately 50% of autosomal dominant polycystic kidney disease (ADPKD) patients have gross hematuria, but few cases of bladder cancer complications are known. We report a case of a 49-year-old female ADPKD patient with bladder cancer, who was presented to our hospital 4 months after the onset of gross hematuria. A computed tomography (CT) scan showed a bladder mass, enlarged pelvic and left inguinal lymph nodes, multiple liver cysts, and a polycystic kidney. Based on family history, CT scan results, and lymph node biopsy, we diagnosed the patient with uroplakin III-negative bladder cancer with squamous metaplasia and ADPKD. The patient was treated with systemic chemotherapy but died 2 months after the definitive diagnosis. The delayed diagnosis was disastrous, and malignancy should be considered in the differential diagnosis when symptoms suggestive of malignancy such as hematuria appear. Particularly, uroplakin III-negative advanced bladder cancer has a poor prognosis and requires early diagnosis and treatment.

Keywords: Autosomal dominant polycystic kidney disease, bladder cancer, gross hematuria

How to cite this URL:
Suto H, Inui Y, Nishikawa S, Okamura A. Delayed diagnosis of bladder cancer in a patient with autosomal dominant polycystic kidney disease. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=357837

 > Introduction Top

Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited renal disease, leads to end-stage renal failure.[1],[2] Gross hematuria is present in approximately 50% of ADPKD patients, most of which have a benign etiology.[1],[3]

Bladder cancer is more common in men, and hematuria is also a typical hallmark.[4] However, genetic predispositions, such as ADPKD complications, have rarely been reported. Therefore, hematuria in ADPKD patients may be considered a benign etiology and may delay the diagnosis of bladder cancer. We herein report a case of ADPKD with bladder cancer that had a disastrous outcome because of delayed diagnosis.

 > Case Report Top

A 49-year-old female patient presented with lower abdominal pain and gross hematuria in May 202X but remained untreated. In September 202X, the patient visited our hospital and underwent a computed tomography (CT) scan, which showed a bladder mass, enlarged pelvic lymph nodes and an enlarged left inguinal lymph node, multiple liver cysts, and a polycystic kidney [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. The patient was a non-smoker and had no relevant medical history. However, the patient's father and brother had previously been diagnosed with polycystic kidney disease. The findings of the physical examination at the first visit were as follows: body temperature, 36.0°C; heart rate, 100 beats per minute; blood pressure, 96/66 mmHg; respiratory rate, 16 breaths per minute; eyelid conjunctiva, pallor; no heart murmur; a flat, soft, and tender abdomen; bilateral leg edema; and a 2 cm large non-tender and immobile lymph node in the left inguinal area. Laboratory tests showed the following: hemoglobin, 7.4 g/dL; C-reactive protein, 6.8 mg/dL; and creatinine, 1.27 mg/dL. Urine test showed occult blood 3+. T2-weighted magnetic resonance imaging (MRI) showed a heterogeneous low-signal coarse mass protruding into the bladder [Figure 2]. CT scan, MRI, and cystoscopy findings were consistent with bladder cancer. Histological examination of the left inguinal lymph node showed carcinoma cells with a high degree of squamous metaplasia [Figure 3]a. Immunohistochemical (IHC) expression of p40 was confirmed [Figure 3]b, but IHC staining was negative for uroplakin III [Figure 3]c. Based on imaging and pathology findings, we finally diagnosed the patient with stage IVA (UICC TNM 8th edition) bladder cancer with squamous metaplasia. In addition, CT showed bilateral kidneys with more than five cysts on one side, and this patient's father and brother have been diagnosed with ADPKD. Therefore, we also diagnosed this patient with ADPKD based on the Japanese ADPKD diagnostic criteria [Table 1]. In October 202X, we initiated gemcitabine and carboplatin (GCb) combination therapy. However, the patient died in December 202X because of increased inflammatory response, anemia, and thrombocytopenia associated with the progression of bladder cancer. Written informed consent was obtained from the patient's family for the publication of this paper.
Figure 1: Plain CT findings of the abdomen at initial visit: (a) bladder mass (red arrow) and enlarged pelvic lymph nodes (yellow arrow); (b) enlarged left inguinal lymph node (yellow arrow); (c) multiple liver cysts; (d) polycystic kidney

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Figure 2: Abdominal sagittal T2-weighted MRI shows a heterogeneous low-signal coarse mass protruding into the bladder (red arrow)

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Figure 3: Histopathological examination of the left inguinal lymph node; hematoxylin and eosin staining shows (a) carcinoma cells, a high degree of squamous metaplasia, ×100. IHC staining shows (b) strong expression of p40, ×100; (c) negative expression of uroplakin III, ×100

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Table 1: Japanese Autosomal dominant polycystic kidney disease diagnostic criteria

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 > Discussion Top

We presented a case of ADPKD with bladder cancer that led to a definitive diagnosis approximately 5 months after the onset of gross hematuria and to death approximately 2 months after diagnosis.

The gene responsible for ADPKD is PKD1 or PKD2, which reportedly has no association with urologic tumors such as renal cell carcinoma or bladder cancer.[1],[5] Patients with ADPKD have a high incidence of renal cell carcinoma, which causes the disease because of maintenance dialysis,[6] and the cumulative incidence of bladder cancer in Japanese women is less than 1%.[4] Thus, the probability of bladder cancer complications in Japanese women with ADPKD who are not on maintenance dialysis is low. More than 50% of adult patients with polycystic kidney disease develop microscopic or macroscopic hematuria.[7] Most of these cases are because of urinary tract infections and ruptured renal cysts.[8] Therefore, hematuria and abdominal distention were diagnosed as symptoms associated with cystic lesions, which might lead to a delay in the diagnosis and treatment of bladder cancer.

In this case, the bladder cancer progressed faster than usual, leading to death in a relatively short period: 7 months from symptom onset and 2 months from diagnosis. The combination of gemcitabine and cisplatin (GC) is one of the standard treatments for stage IV bladder cancer, with a reported overall response rate (ORR) of 51% and a median progression-free survival (mPFS) of 6.9 months and a median overall survival (mOS) of 13.4 months.[9] ADPKD patients with gross hematuria, as in the present case, often have impaired renal functions.[8] Therefore, they are often cisplatin-ineligible, but they are eligible for combination therapy with GCb. Previous studies showed that GCb regimens for stage IV bladder cancer have ORR of 46%, mPFS of 5.8 months, and mOS of 11.0 months.[9] Although the ORR and mPFS of the GCb regimen are not significantly inferior to those of the GC regimen, the GCb regimen was not effective at all in this case, resulting in rapid disease progression. The poor prognosis of this case might be related to the negative IHC expression of uroplakin III. In bladder cancers with squamous metaplasia, IHC expression of uroplakin III is often negative. In advanced bladder cancer, uroplakin III-negative cases have a poorer prognosis than uroplakin III-positive cases.[10] Our patient also had bladder cancer with squamous cell transformation and was negative for uroplakin III, which might have resulted in a poor prognosis.

In conclusion, even in the case of hereditary diseases that are not associated with malignancy, such as ADPKD, malignancy should be considered in the differential diagnosis when symptoms suggestive of malignancy such as hematuria appear. In particular, advanced bladder cancer in uroplakin III-negative patients requires early diagnosis and treatment because of its rapid progression and poor prognosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.


The authors would like to thank Mr. Toshinori Kuriyama of the Clinical Laboratory, Kakogawa Central City Hospital, for his cooperation in conducting this study.

In addition, Editage (www.editage.com) provided English proofreading.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

Grantham JJ. Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med 2008;359:1477-85.  Back to cited text no. 1
Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet 2007;369:1287-301.  Back to cited text no. 2
Masoumi A, Reed-Gitomer B, Kelleher C, Bekheirnia MR, Schrier RW. Developments in the management of autosomal dominant polycystic kidney disease. Ther Clin Risk Manag 2008;4:393-407.  Back to cited text no. 3
Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, Kiemeney L, et al. Bladder cancer: Epidemiology, staging and grading, and diagnosis. Urology 2005;66(Suppl 1):4-34.  Back to cited text no. 4
Seeger-Nukpezah T, Geynisman DM, Nikonova AS, Benzing T, Golemis EA. The hallmarks of cancer: Relevance to the pathogenesis of polycystic kidney disease. Nat Rev Nephrol 2015;11:515-34.  Back to cited text no. 5
Jilg CA, Drendel V, Bacher J, Pisarski P, Neeff H, Drognitz O, et al. Autosomal dominant polycystic kidney disease: Prevalence of renal neoplasias in surgical kidney specimens. Nephron Clin Pract 2013;123:13-21.  Back to cited text no. 6
Delaney VB, Adler S, Bruns FJ, Licinia M, Segel DP, Fraley DS. Autosomal dominant polycystic kidney disease: Presentation, complications, and prognosis. Am J Kidney Dis 1985;5:104-11.  Back to cited text no. 7
Dedi R, Bhandari S, Turney JH, Brownjohn AM, Eardley I. Lesson of the week: Causes of haematuria in adult polycystic kidney disease. BMJ 2001;323:386-7.  Back to cited text no. 8
Powles T, van der Heijden MS, Castellano D, Galsky MD, Loriot Y, Petrylak DP, et al. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (Danube): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2020;21:1574-88.  Back to cited text no. 9
Huang HY, Shariat SF, Sun TT, Lepor H, Shapiro E, Hsieh JT, et al. Persistent uroplakin expression in advanced urothelial carcinomas: Implications in urothelial tumor progression and clinical outcome. Hum Pathol 2007;38:1703-13.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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