Int Urol Nephrol DOI 10.1007/s11255-014-0691-4
UROLOGY - CASE REPORT
AFP-producing urothelial carcinoma of the bladder: a case report Jianan Ye • Xianlin Xu • Min Fan • Dong Xue Qianfeng Zhuang
•
Received: 9 October 2013 / Accepted: 28 February 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract We report a case of urothelial carcinoma of the urinary bladder with concurrent alpha-fetoprotein (AFP) elevation. A 60-year-old male was admitted for gross hematuria. Subsequent analyses revealed elevated serum AFP levels (970.20 ng/ml). He had no history of hepatitis, and hepatobiliary disease was not detected on computed tomography or ultrasound. Carcino-embryonic antigen was normal. The patient underwent radical cystectomy and was found to have a high-grade urothelial carcinoma of bladder on pathology. In addition, immunohistochemical staining of the tumor cells showed strong AFP positivity. Postoperatively, serum AFP levels decreased gradually to normal. In summary, urothelial carcinoma of the urinary bladder with AFP elevation is rare, and the mechanism and prognosis require further exploration. Keywords Alpha-fetoprotein Urinary bladder Urothelial carcinoma
Introduction Alpha-fetoprotein (AFP) is derived from embryonic stem cells and gradually disappears approximately 2 weeks after birth. Elevated serum AFP levels later in life are primarily seen in patients with hepatocellular carcinoma or germ cell tumors, gastric cancer, pancreatic cancer, lung cancer, and other tumors [1]. Urothelial carcinoma of the urinary J. Ye X. Xu (&) M. Fan D. Xue Q. Zhuang Department of Surgical Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, Jiangsu, China e-mail: [email protected] J. Ye e-mail: [email protected]
bladder with AFP elevation is rare and has been rarely reported. Here, we report a case of bladder urothelial carcinoma with elevated AFP.
Case presentation A 60-year-old man with recurrent gross hematuria for 3 years was found to have bladder-occupying lesions on B-ultrasound examination and presented to our institution in September 2012. There were no obvious abnormalities on physical examination of the liver, spleen, and genitourinary system. Urinalysis was abnormal (RBC 1,918.0/ll, leukocytes 7,295.0/ll, positive protein). There were no abnormalities on routine blood and fecal testing, including liver, renal, and coagulation function. Hepatitis B and C titers were negative. PSA and carcino-embryonic antigen (CEA) levels were within a normal range. Serum AFP was 970.20 ng/ml and remained elevated at 886.40 ng/ml three days after admission. There were no abnormalities on radiographic examinations of the alimentary and reproductive systems (Fig. 1). Pelvic computed tomography (CT) showed a bladder tumor measuring 3.7 9 4.5 9 2.4 cm (Fig. 2). Cystoscopy revealed a contracted bladder, filled with a cauliflower-like mass. Biopsy demonstrated invasive high-grade urothelial carcinoma. Before surgery, it was not clear whether the stage was pT1 or pT2 even after biopsy. However, the basal part of tumor was wide on cystoscopy, and the stage was suggestive of pT2 on CT, so we integrated all aspects and chose radical cystectomy. After radical cystectomy, a high-grade urothelial carcinoma of the bladder with invasion of lamina propria and muscularis propria (Fig. 3) was found. Immunohistochemical staining for AFP was strongly positive with more than 60 % of tumor cells staining positively for
123
Int Urol Nephrol
Fig. 3 Pathological analysis of bladder urothelial carcinoma. H&E staining of tissue sections revealed a high-grade urothelial carcinoma of bladder with lamina propria invasion, 9400
Fig. 1 CT scan of the abdomen, without detectable liver lesions
Fig. 4 Strongly positive AFP expression in urothelial carcinoma of the bladder by immunohistochemistry Fig. 2 CT scan of the bladder with extensive shadowing in the bladder
AFP (Fig. 4). And tumor cells were also strongly positive for p63 (Fig. 5), supporting urothelial origin. Serum AFP levels drastically decreased postoperatively (174.90 ng/ml in the first week, 83.06 ng/ml in the second week, 21.38 ng/ ml in the fourth week, 5.32 ng/ml in the sixth week, and 2.15 ng/ml in the twenty-fifth week). Liver function was always normal throughout his hospital course.
Discussion Serum AFP is considered to be a specific tumor marker for primary liver cancer, especially when levels are above
123
200 ng/ml [2]. Elevated serum AFP may also occur in viral hepatitis, liver cirrhosis, and gastric, pancreatic, lung, and embryonic gonad tumors [3]. Pectasides et al. retrospectively evaluated serum tumor markers for urothelial carcinoma of the bladder and concluded that AFP is not an effective marker for the diagnosis and monitoring of bladder cancer [4]. In our case, serum AFP was high and remained elevated until after radical cystectomy. Preoperatively, we eliminated the common conditions that would lead to AFP elevation. CEA, CA19-9, and CA125 levels were all within normal range. There were no abnormalities on radiographic examination, except for bladder cancer. Postoperatively, serum AFP levels decreased gradually and returned to normal in six weeks. Immunohistochemical staining of the
Int Urol Nephrol
year, we could not easily determine the prognosis and survival time, but we would closely follow-up.
Conclusion An AFP-producing urothelial carcinoma of the bladder is extremely rare. While we presume that the source of the serum AFP was from the bladder cancer, the nature of this phenomenon is still unknown. Whether an elevated AFP is relevant to the prognosis of bladder urothelial carcinoma remains unclear and requires further exploration.
Fig. 5 The p63 immunostaining is positive, 9200
bladder cancer specimen was strongly positive for AFP; thus, we presume the bladder cancer lesions to be the source of the serum AFP. AFP-producing urothelial carcinomas of the bladder are rare. According to the published literature, this is the third case of urothelial carcinoma of the urinary bladder with AFP elevation [5, 6]. As far as we know, serum AFP is not commonly used to detect bladder cancer. Thus, the rare case reports may be due to the fact that AFP testing is not routinely performed in bladder cancer. Erdemir et al. reported that bladder urothelial carcinomas with squamous or glandular differentiation behave more aggressively and have a poorer prognosis than general urothelial tumors [7]. In this case, postoperative pathological finding and the p63 positivity indicate the urothelial origin of the tumor, the patient has been followed for over a year now, and the disease did not progress obviously. Carcinomas with hepatoid features, regardless of AFP level, have a poor prognosis [8]. It is also reported that an AFP-producing transitional cell carcinoma (TCC), with lung and bone metastases, is aggressive and carries a poor prognosis [5]. And the survival time in 69 % of patients with TCC treated with concurrent chemoradiotherapy was three years [9]. Up to now, only one case of AFP-producing TCC was successfully controlled by radiotherapy alone reported by Shiga et al. [10]. In our case, the relevant examination before operation did not show tumor metastasis, and postoperative pathology also indicated negative margin, so the patient did not undergo any chemotherapy or radiotherapy. As the current follow-up time was only over a
Conflict of interest None of the contributing authors have any conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.
References 1. El-Bahrawy M (2011) Alpha-fetoprotein-producing non-germ cell tumors of the urological system. Rev Urol 13:14–19 2. Gupta S, Bent S, Kohlwes J (2003) Test characteristics of afetoprotein for detecting hepatocellular carcinoma in patients with hepatitis CA systematic review and critical analysis. Ann Intern Med 139:46–50 3. Willder JM, Thomson AM, Grigor KM, Howard G, Stewart GD (2012) A unique case of an alpha-fetoprotein-producing lung cancer with testicular metastasis. Can Urol Assoc J 6:364 4. Pectasides D, Bafaloucos D, Antoniou F, Gogou L, Economides N, Varthalitis J, Dimitriades M, Kosmidis P, Athanassiou A (1996) TPA, TATI, CEA, AFP, [beta]-HCG, PSA, SCC, and CA 19-9 for monitoring transitional cell carcinoma of the bladder. Am J Clin Oncol 19:271–277 5. Lu C-H, Chou W-C, Hung Y-S, Yeh K-Y, Sheu S, Liaw C–C (2009) Alpha-fetoprotein-producing transitional cell carcinoma of the urinary bladder: a case report. Int Urol Nephrol 41:567–570 6. Yamada K, Fujioka Y, Ebihara Y, Kiriyama I, Suzuki H, Akimoto M (1994) Alpha-fetoprotein producing undifferentiated carcinoma of the bladder. J Urol 152:958–960 7. Erdemir F, Tunc M, Ozcan F, Parlaktas BS, Uluocak N, Kılıcaslan I, Gokce O (2007) The effect of squamous and/or glandular differentiation on recurrence, progression and survival in urothelial carcinoma of bladder. Int Urol Nephrol 39:803–807 8. Ishikura H, Fujii H, Kakuta Y, Yoshiki T, Ishiguro T, Enatsu C, Kanda M (1991) Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment. Cancer 67:3051–3056 9. Chen W-C, Liaw C–C, Chuang C-K, Chen M-F, Chen C-S, Lin PY, Chang P-L, Chu S-H, Wu C-T, Hong J-H (2003) Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. Int J Radiat Oncol Biol Phys 56:726–733 10. Shiga Y, Kawai K, Shimazui T, Iijima T, Noguchi M, Akaza H (2004) Case of a-fetoprotein-producing transitional cell carcinoma of the renal pelvis. Int J Urol 11:117–118
123
UROLOGY - CASE REPORT
AFP-producing urothelial carcinoma of the bladder: a case report Jianan Ye • Xianlin Xu • Min Fan • Dong Xue Qianfeng Zhuang
•
Received: 9 October 2013 / Accepted: 28 February 2014 Ó Springer Science+Business Media Dordrecht 2014
Abstract We report a case of urothelial carcinoma of the urinary bladder with concurrent alpha-fetoprotein (AFP) elevation. A 60-year-old male was admitted for gross hematuria. Subsequent analyses revealed elevated serum AFP levels (970.20 ng/ml). He had no history of hepatitis, and hepatobiliary disease was not detected on computed tomography or ultrasound. Carcino-embryonic antigen was normal. The patient underwent radical cystectomy and was found to have a high-grade urothelial carcinoma of bladder on pathology. In addition, immunohistochemical staining of the tumor cells showed strong AFP positivity. Postoperatively, serum AFP levels decreased gradually to normal. In summary, urothelial carcinoma of the urinary bladder with AFP elevation is rare, and the mechanism and prognosis require further exploration. Keywords Alpha-fetoprotein Urinary bladder Urothelial carcinoma
Introduction Alpha-fetoprotein (AFP) is derived from embryonic stem cells and gradually disappears approximately 2 weeks after birth. Elevated serum AFP levels later in life are primarily seen in patients with hepatocellular carcinoma or germ cell tumors, gastric cancer, pancreatic cancer, lung cancer, and other tumors [1]. Urothelial carcinoma of the urinary J. Ye X. Xu (&) M. Fan D. Xue Q. Zhuang Department of Surgical Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, Jiangsu, China e-mail: [email protected] J. Ye e-mail: [email protected]
bladder with AFP elevation is rare and has been rarely reported. Here, we report a case of bladder urothelial carcinoma with elevated AFP.
Case presentation A 60-year-old man with recurrent gross hematuria for 3 years was found to have bladder-occupying lesions on B-ultrasound examination and presented to our institution in September 2012. There were no obvious abnormalities on physical examination of the liver, spleen, and genitourinary system. Urinalysis was abnormal (RBC 1,918.0/ll, leukocytes 7,295.0/ll, positive protein). There were no abnormalities on routine blood and fecal testing, including liver, renal, and coagulation function. Hepatitis B and C titers were negative. PSA and carcino-embryonic antigen (CEA) levels were within a normal range. Serum AFP was 970.20 ng/ml and remained elevated at 886.40 ng/ml three days after admission. There were no abnormalities on radiographic examinations of the alimentary and reproductive systems (Fig. 1). Pelvic computed tomography (CT) showed a bladder tumor measuring 3.7 9 4.5 9 2.4 cm (Fig. 2). Cystoscopy revealed a contracted bladder, filled with a cauliflower-like mass. Biopsy demonstrated invasive high-grade urothelial carcinoma. Before surgery, it was not clear whether the stage was pT1 or pT2 even after biopsy. However, the basal part of tumor was wide on cystoscopy, and the stage was suggestive of pT2 on CT, so we integrated all aspects and chose radical cystectomy. After radical cystectomy, a high-grade urothelial carcinoma of the bladder with invasion of lamina propria and muscularis propria (Fig. 3) was found. Immunohistochemical staining for AFP was strongly positive with more than 60 % of tumor cells staining positively for
123
Int Urol Nephrol
Fig. 3 Pathological analysis of bladder urothelial carcinoma. H&E staining of tissue sections revealed a high-grade urothelial carcinoma of bladder with lamina propria invasion, 9400
Fig. 1 CT scan of the abdomen, without detectable liver lesions
Fig. 4 Strongly positive AFP expression in urothelial carcinoma of the bladder by immunohistochemistry Fig. 2 CT scan of the bladder with extensive shadowing in the bladder
AFP (Fig. 4). And tumor cells were also strongly positive for p63 (Fig. 5), supporting urothelial origin. Serum AFP levels drastically decreased postoperatively (174.90 ng/ml in the first week, 83.06 ng/ml in the second week, 21.38 ng/ ml in the fourth week, 5.32 ng/ml in the sixth week, and 2.15 ng/ml in the twenty-fifth week). Liver function was always normal throughout his hospital course.
Discussion Serum AFP is considered to be a specific tumor marker for primary liver cancer, especially when levels are above
123
200 ng/ml [2]. Elevated serum AFP may also occur in viral hepatitis, liver cirrhosis, and gastric, pancreatic, lung, and embryonic gonad tumors [3]. Pectasides et al. retrospectively evaluated serum tumor markers for urothelial carcinoma of the bladder and concluded that AFP is not an effective marker for the diagnosis and monitoring of bladder cancer [4]. In our case, serum AFP was high and remained elevated until after radical cystectomy. Preoperatively, we eliminated the common conditions that would lead to AFP elevation. CEA, CA19-9, and CA125 levels were all within normal range. There were no abnormalities on radiographic examination, except for bladder cancer. Postoperatively, serum AFP levels decreased gradually and returned to normal in six weeks. Immunohistochemical staining of the
Int Urol Nephrol
year, we could not easily determine the prognosis and survival time, but we would closely follow-up.
Conclusion An AFP-producing urothelial carcinoma of the bladder is extremely rare. While we presume that the source of the serum AFP was from the bladder cancer, the nature of this phenomenon is still unknown. Whether an elevated AFP is relevant to the prognosis of bladder urothelial carcinoma remains unclear and requires further exploration.
Fig. 5 The p63 immunostaining is positive, 9200
bladder cancer specimen was strongly positive for AFP; thus, we presume the bladder cancer lesions to be the source of the serum AFP. AFP-producing urothelial carcinomas of the bladder are rare. According to the published literature, this is the third case of urothelial carcinoma of the urinary bladder with AFP elevation [5, 6]. As far as we know, serum AFP is not commonly used to detect bladder cancer. Thus, the rare case reports may be due to the fact that AFP testing is not routinely performed in bladder cancer. Erdemir et al. reported that bladder urothelial carcinomas with squamous or glandular differentiation behave more aggressively and have a poorer prognosis than general urothelial tumors [7]. In this case, postoperative pathological finding and the p63 positivity indicate the urothelial origin of the tumor, the patient has been followed for over a year now, and the disease did not progress obviously. Carcinomas with hepatoid features, regardless of AFP level, have a poor prognosis [8]. It is also reported that an AFP-producing transitional cell carcinoma (TCC), with lung and bone metastases, is aggressive and carries a poor prognosis [5]. And the survival time in 69 % of patients with TCC treated with concurrent chemoradiotherapy was three years [9]. Up to now, only one case of AFP-producing TCC was successfully controlled by radiotherapy alone reported by Shiga et al. [10]. In our case, the relevant examination before operation did not show tumor metastasis, and postoperative pathology also indicated negative margin, so the patient did not undergo any chemotherapy or radiotherapy. As the current follow-up time was only over a
Conflict of interest None of the contributing authors have any conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.
References 1. El-Bahrawy M (2011) Alpha-fetoprotein-producing non-germ cell tumors of the urological system. Rev Urol 13:14–19 2. Gupta S, Bent S, Kohlwes J (2003) Test characteristics of afetoprotein for detecting hepatocellular carcinoma in patients with hepatitis CA systematic review and critical analysis. Ann Intern Med 139:46–50 3. Willder JM, Thomson AM, Grigor KM, Howard G, Stewart GD (2012) A unique case of an alpha-fetoprotein-producing lung cancer with testicular metastasis. Can Urol Assoc J 6:364 4. Pectasides D, Bafaloucos D, Antoniou F, Gogou L, Economides N, Varthalitis J, Dimitriades M, Kosmidis P, Athanassiou A (1996) TPA, TATI, CEA, AFP, [beta]-HCG, PSA, SCC, and CA 19-9 for monitoring transitional cell carcinoma of the bladder. Am J Clin Oncol 19:271–277 5. Lu C-H, Chou W-C, Hung Y-S, Yeh K-Y, Sheu S, Liaw C–C (2009) Alpha-fetoprotein-producing transitional cell carcinoma of the urinary bladder: a case report. Int Urol Nephrol 41:567–570 6. Yamada K, Fujioka Y, Ebihara Y, Kiriyama I, Suzuki H, Akimoto M (1994) Alpha-fetoprotein producing undifferentiated carcinoma of the bladder. J Urol 152:958–960 7. Erdemir F, Tunc M, Ozcan F, Parlaktas BS, Uluocak N, Kılıcaslan I, Gokce O (2007) The effect of squamous and/or glandular differentiation on recurrence, progression and survival in urothelial carcinoma of bladder. Int Urol Nephrol 39:803–807 8. Ishikura H, Fujii H, Kakuta Y, Yoshiki T, Ishiguro T, Enatsu C, Kanda M (1991) Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment. Cancer 67:3051–3056 9. Chen W-C, Liaw C–C, Chuang C-K, Chen M-F, Chen C-S, Lin PY, Chang P-L, Chu S-H, Wu C-T, Hong J-H (2003) Concurrent cisplatin, 5-fluorouracil, leucovorin, and radiotherapy for invasive bladder cancer. Int J Radiat Oncol Biol Phys 56:726–733 10. Shiga Y, Kawai K, Shimazui T, Iijima T, Noguchi M, Akaza H (2004) Case of a-fetoprotein-producing transitional cell carcinoma of the renal pelvis. Int J Urol 11:117–118
123
