Case Report
Urologia Internationalis
Received: February 7, 2013 Accepted after revision: July 16, 2013 Published online: January 30, 2014
Urol Int 2016;96:370–372 DOI: 10.1159/000355089
Carcinosarcoma of the Female Urethra L. D’Arrigo A. Costa F. Fraggetta M. Pennisi P. Pepe F. Aragona Urology Unit and Pathology Unit, Cannizzaro Hospital, Catania, Italy
Abstract Carcinosarcoma is a rare malignant tumor with a biphasic morphology characterized by the presence of a malignant epithelial and mesenchymal component. It has been reported in many organs, including the genitourinary tract. We describe a case of a 47-year-old woman admitted to our hospital for history of recurrent urinary tract infection, dysuria and discharge of bloody fluid from the urethra at the end of urination. A tender palpable mass under the anterior vaginal wall was found and pathological examination showed a urethral carcinosarcoma. The histopathogenetic hypothesis and clinical management were considered in this report. © 2014 S. Karger AG, Basel
Introduction
Carcinosarcoma (CS) is a rare malignant tumor with a biphasic morphology characterized by the presence of a malignant epithelial and mesenchymal component. It has © 2014 S. Karger AG, Basel 0042–1138/14/0963–0370$39.50/0 E-Mail [email protected] www.karger.com/uin
been reported in many organs, including the genitourinary tract. Although many cases of CS of the renal pelvis, bladder and prostate have been reported, to the best of our knowledge, only 4 cases of CS have been described in the female urethra. Herein, we report an additional case of CS of the female urethra focusing on the clinical and pathological features together with a brief literature review.
Case Report A 47-year-old woman was admitted to our hospital because of a recent history of recurrent urinary tract infection, dysuria and discharge of bloody fluid from the urethra at the end of urination. On physical examination, a tender mass was palpable under the anterior vaginal wall. A needle transvaginal biopsy was performed and a histological diagnosis of poorly differentiated carcinoma with a clear cell component was rendered. Serum tumor markers were within the normal limit including PSA and carbohydrate antigen 19-9 (CA19-9). Pelvic MRI showed a solid mass, approximately 5 cm in diameter, arising from the proximal urethra and infiltrating superiorly the bladder neck and the posterior bladder wall and distally the anterior vaginal wall up to the vulvar rim (online suppl. fig. 1; for online supplementary material, see www. karger.com/doi/10.1159/000355089). PET demonstrated that the mass was metabolically active (online suppl. fig. 2).
Letterio D’Arrigo, MD Urology Unit, Cannizzaro Hospital Via Messina 829 IT–95127 Catania (Italy) E-Mail eliodarrigo @ libero.it
Downloaded by: Univ.of Adelaide 129.127.145.240 - 11/5/2017 4:20:19 PM
Key Words Carcinosarcoma · Urethral neoplasms · Epithelial and mesenchymal tumors
Table 1. Reported cases of CS of the urethra in women
Patient [ref.]
Age
Symptoms
Location and extent of tumor at presentation
Treatment
1 [3]
61
difficulty urinating
smooth mass at vaginal examination; mass surrounding the urethra
tumor excision by transperineal 1 year, bone metastasis approach; cystostomy; local radiotherapy (50 Gy)
presumably died of disease
2 [4]
62
frequency difficulty urinating; dyspareunia
firm, tender urethral mass
anterior exenteration and ileal conduit
2 years
no evidence of disease
3 [5]
50
urinary tract infection; urinary retention
urethral mass
anterior exenteration and ileal conduit
26-month local radiation 50 Gy to the recurrence sites
not reported
bleeding in the genital region
tumor arose from the urinary meatus
urethrectomy and suprapubic cystostomy
not reported
not reported
frequent UTI; bloody urethral discharge
firm, tender urethral mass fixed to anterior vaginal wall
neodjuvant chemo- and radiotherapy; anterior exenteration with pelvic lymphadenectomy and continent urinary reservoir
salvage chemotherapy died 18 months for local recurrence 6 months after surgery following surgery
Present case
47
On the basis of clinical findings and imaging, a neoadjuvant chemotherapy (cisplatin 40 mg/m2/week for 1 month) and irradiation (46 Gy to the pelvis) was started elsewhere. The patient was deferred for delayed surgery after 30 days and a radical anterior pelvic exenteration (cystourethrectomy and hysterectomy with total vaginectomy), bilateral pelvic lymph node dissection and continent urinary diversion via an ileocecal urinary reservoir (Tiflis pouch) was performed. Pathological examination revealed the presence of a gray-whitish polypoid mass, measuring 4.5 cm in the maximum diameter, encasing the urethra. On the cut surface, the tumor partially involved the vagina whereas the uterus and the urinary bladder were unremarkable. Histologically the tumor presented a polypoid growth pattern (online suppl. fig. 3) and was manly composed of a poorly differentiated carcinoma consisting of high-grade serous carcinoma with psammoma bodies (online suppl. fig. 4). The tumor presented either an infiltrative growth pattern or a well-recognized papillary component lined by a serous or clear cell component. Areas of a malignant heterologous component (chondrosarcoma) were interspersed within the serous carcinoma (online suppl. fig. 5). The tumor infiltrated the whole urethra reaching the anterior vaginal wall; the bladder, uterus and ovaries were not involved by the tumor and no metastases were found in 18 pelvic nodes. A final diagnosis of CS with a heterologous component of CS was rendered. At 6 months follow-up, pelvic MRI and PET showed two local recurrences and a chemotherapy protocol (gemcitabine 1,000 mg, paclitaxel 80 mg/m2 and cisplatin 50 mg/m2) was started; unfortunately, the patient died 18 months following surgery.
Carcinosarcoma of the Female Urethra
Status
Discussion
Primary neoplasms of the female urethra are rare; tumor histology varies depending on the anatomic site of origin. The squamous cell carcinomas are by far the most common, accounting for up to 70% of the primary urethral carcinomas [1], and are usually located in the distal urethra, whereas transitional cell carcinomas and adenocarcinomas are the most common in the proximal tract. CS is a malignant tumor containing carcinomatous and sarcomatous components. It is not to be confused with sarcomatoid carcinoma, which is a carcinoma that exhibits a prominent spindle cell component, although the distinction is not clinically relevant because their biological behavior and outcome are similar. The most common site of CS in the genitourinary tract is the bladder (65%) followed by the prostate (15.7%), kidney (4%) and ureter (7.9%) [2]. CS of the female urethra is extremely rare, with only 4 cases reported in the literature [3–6] (table 1). Therefore, no data concerning epidemiology and incidence of this tumor are available. CS of the uterus is an uncommon cancer accounting for 1–3% of all cancers of uterus. These rare cancers have a poor prognosis and a third of these cancers have already spread beyond the uterus at the time of diagnosis. AlUrol Int 2016;96:370–372 DOI: 10.1159/000355089
371
Downloaded by: Univ.of Adelaide 129.127.145.240 - 11/5/2017 4:20:19 PM
4 [6]
Follow-up
though the histogenesis of the malignant mixed tumors is still being debated, the multiclonal hypothesis proposes an origin from two or more undifferentiated stem cells (convergence hypothesis); the monoclonal hypothesis suggests that CS derives from a single totipotential tumor stem cell that differentiates into separate epithelial and mesenchymal cells (divergence hypothesis). Evidence of the monoclonal origin of systemic CS supports the divergent tumor theory [7]. The urothelial origin of these tumors was also hypothesized and a transitional form of malignancies associated with the presence of a pseudostratified epithelium reminiscent of the urothelium was also found in some tumors [8]. Radiation exposure has been suggested as a predisposing factor for the development of CS of the bladder [9]; however, in the reported cases of female urethra CS (including our own), none had a history of radiation exposure. The rarity of female urethral tumors has contributed to the absence of a standardized approach to the management and follow-up of these patients. Most urethral cancers in females are locally advanced when detected and involve the proximal third or the entire urethra. When surgery is planned, extensive resection is necessary, including total cystourethrectomy, with pelvic lymph node dissection and removal of the vagina. Inguinal lymph node dissection is not recommended in the absence of palpable disease in the groin. However, even extensive
surgery often fails and local recurrence after surgery alone is reported in 60–100% of cases [10]. Irradiation as a single modality therapy produces an unacceptably high morbidity rate and low tumor control rate. A combination protocol of chemotherapy and irradiation followed by surgery is reported to achieve a better local control, although it does not improve the overall survival [11]. In our case the chemotherapy protocol was in accordance with the dose utilized for the treatment of transitional carcinomas [12]. The prognosis is poor – of the reported cases, only 1 patient [4] was free of disease at the 2-year follow-up.
Conclusion
CS is a rare malignant tumor with a bad prognosis. The rarity of these tumors has contributed to the absence of a standardized approach to the management and follow-up of these patients. The surgical treatment with extensive resection is preferable but a local recurrence is high. Irradiation therapy has a low tumor control rate. A multimodal treatment with chemo- and radiotherapy seem to offer a better local control of disease but does not improve survival. In our case, even the neoadjuvant treatment with chemo- and radiotherapy did not improved the prognosis.
References
372
Urol Int 2016;96:370–372 DOI: 10.1159/000355089
5 Liu J, Wu H: Carcinosarcoma of female urethra with melanocytic differentiation. Int J Clin Exp Pathol 2011;4:206–209. 6 Komai Y, Urushibara M, Saito K, Sakai K, Morimoto S: A case of sarcomatoid carcinoma in the region of the female urethra. Nihon Hinyokika Gakkai Zasshi 2005;96:650–653. 7 Thompson L, Chang B, Barsky SH: Monoclonal origin of malignant mixed tumors (carcinosarcoma): evidence for a divergent histogenesis. Am J Surg Pathol 1996;20:277–285. 8 Oliva E, Amin MB, Jimenez R, Young RH: Clear cell carcinoma of the urinary bladder: a report and comparison of four tumors of mullerian origin and nine of probable urothelial origin with discussion of histogenesis and diagnostic problems. Am J Surg Pathol 2002;26: 190–197. 9 Lahoti C, Schinella R, Rangwala AF, Lee M, Mizrachi H: Carcinosarcoma of urinary bladder: report of 5 cases with immunohistologic study. Urology 1994;43:389–393.
10 Di Marco DS, Di Marco CS, Zincke H, Webb MJ, Bass S E, Slezakc JM, Lightner DJ: Surgical treatment for local control of female urethral carcinoma. Urol Oncol 2004;22:404–409. 11 Dalbagni G, Zhang Z-F, Lacombe L, Herr HW: Female urethral carcinoma: an analysis of treatment outcome and a plea for a standardized management strategy. Br J Urol 1998;82:835–841. 12 Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R: Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987. J Clin Oncol 2012;30:1107–1113.
D’Arrigo/Costa/Fraggetta/Pennisi/Pepe/ Aragona
Downloaded by: Univ.of Adelaide 129.127.145.240 - 11/5/2017 4:20:19 PM
1 Bermejo CE, Basler JW: Carcinoma of the urethra; in Hamdy FC, Basler JW, Catalona WJ (eds): Management of Urologic Malignancies. London, Churchill Livingstone, 2002, p 525. 2 Frank I, Takahashi S, Tsukamoto T, Lieber M: Genitourinary sarcomas and carcinosarcomas in adults; in Vogelzang NJ, Scardino PT, Shipley WU, Coffey DS (eds): Genitourinary Oncology, ed 2. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 1101–1119. 3 Konno N, Mori M, Kurooka Y, Kameyama S, Homma Y, Moriyama N, Tajima A, Murayama T, Kawabe K: Carcinosarcoma in the region of female urethra. Int J Urol 1997;4:229– 231. 4 Jayamohan Y, Urs L, Rowland R, Woolums S, Lele SM: Periurethral carcinosarcoma. A report of 2 cases with a review of the literature. Arch Pathol Lab Med 2005;129:e91–e93.
Urologia Internationalis
Received: February 7, 2013 Accepted after revision: July 16, 2013 Published online: January 30, 2014
Urol Int 2016;96:370–372 DOI: 10.1159/000355089
Carcinosarcoma of the Female Urethra L. D’Arrigo A. Costa F. Fraggetta M. Pennisi P. Pepe F. Aragona Urology Unit and Pathology Unit, Cannizzaro Hospital, Catania, Italy
Abstract Carcinosarcoma is a rare malignant tumor with a biphasic morphology characterized by the presence of a malignant epithelial and mesenchymal component. It has been reported in many organs, including the genitourinary tract. We describe a case of a 47-year-old woman admitted to our hospital for history of recurrent urinary tract infection, dysuria and discharge of bloody fluid from the urethra at the end of urination. A tender palpable mass under the anterior vaginal wall was found and pathological examination showed a urethral carcinosarcoma. The histopathogenetic hypothesis and clinical management were considered in this report. © 2014 S. Karger AG, Basel
Introduction
Carcinosarcoma (CS) is a rare malignant tumor with a biphasic morphology characterized by the presence of a malignant epithelial and mesenchymal component. It has © 2014 S. Karger AG, Basel 0042–1138/14/0963–0370$39.50/0 E-Mail [email protected] www.karger.com/uin
been reported in many organs, including the genitourinary tract. Although many cases of CS of the renal pelvis, bladder and prostate have been reported, to the best of our knowledge, only 4 cases of CS have been described in the female urethra. Herein, we report an additional case of CS of the female urethra focusing on the clinical and pathological features together with a brief literature review.
Case Report A 47-year-old woman was admitted to our hospital because of a recent history of recurrent urinary tract infection, dysuria and discharge of bloody fluid from the urethra at the end of urination. On physical examination, a tender mass was palpable under the anterior vaginal wall. A needle transvaginal biopsy was performed and a histological diagnosis of poorly differentiated carcinoma with a clear cell component was rendered. Serum tumor markers were within the normal limit including PSA and carbohydrate antigen 19-9 (CA19-9). Pelvic MRI showed a solid mass, approximately 5 cm in diameter, arising from the proximal urethra and infiltrating superiorly the bladder neck and the posterior bladder wall and distally the anterior vaginal wall up to the vulvar rim (online suppl. fig. 1; for online supplementary material, see www. karger.com/doi/10.1159/000355089). PET demonstrated that the mass was metabolically active (online suppl. fig. 2).
Letterio D’Arrigo, MD Urology Unit, Cannizzaro Hospital Via Messina 829 IT–95127 Catania (Italy) E-Mail eliodarrigo @ libero.it
Downloaded by: Univ.of Adelaide 129.127.145.240 - 11/5/2017 4:20:19 PM
Key Words Carcinosarcoma · Urethral neoplasms · Epithelial and mesenchymal tumors
Table 1. Reported cases of CS of the urethra in women
Patient [ref.]
Age
Symptoms
Location and extent of tumor at presentation
Treatment
1 [3]
61
difficulty urinating
smooth mass at vaginal examination; mass surrounding the urethra
tumor excision by transperineal 1 year, bone metastasis approach; cystostomy; local radiotherapy (50 Gy)
presumably died of disease
2 [4]
62
frequency difficulty urinating; dyspareunia
firm, tender urethral mass
anterior exenteration and ileal conduit
2 years
no evidence of disease
3 [5]
50
urinary tract infection; urinary retention
urethral mass
anterior exenteration and ileal conduit
26-month local radiation 50 Gy to the recurrence sites
not reported
bleeding in the genital region
tumor arose from the urinary meatus
urethrectomy and suprapubic cystostomy
not reported
not reported
frequent UTI; bloody urethral discharge
firm, tender urethral mass fixed to anterior vaginal wall
neodjuvant chemo- and radiotherapy; anterior exenteration with pelvic lymphadenectomy and continent urinary reservoir
salvage chemotherapy died 18 months for local recurrence 6 months after surgery following surgery
Present case
47
On the basis of clinical findings and imaging, a neoadjuvant chemotherapy (cisplatin 40 mg/m2/week for 1 month) and irradiation (46 Gy to the pelvis) was started elsewhere. The patient was deferred for delayed surgery after 30 days and a radical anterior pelvic exenteration (cystourethrectomy and hysterectomy with total vaginectomy), bilateral pelvic lymph node dissection and continent urinary diversion via an ileocecal urinary reservoir (Tiflis pouch) was performed. Pathological examination revealed the presence of a gray-whitish polypoid mass, measuring 4.5 cm in the maximum diameter, encasing the urethra. On the cut surface, the tumor partially involved the vagina whereas the uterus and the urinary bladder were unremarkable. Histologically the tumor presented a polypoid growth pattern (online suppl. fig. 3) and was manly composed of a poorly differentiated carcinoma consisting of high-grade serous carcinoma with psammoma bodies (online suppl. fig. 4). The tumor presented either an infiltrative growth pattern or a well-recognized papillary component lined by a serous or clear cell component. Areas of a malignant heterologous component (chondrosarcoma) were interspersed within the serous carcinoma (online suppl. fig. 5). The tumor infiltrated the whole urethra reaching the anterior vaginal wall; the bladder, uterus and ovaries were not involved by the tumor and no metastases were found in 18 pelvic nodes. A final diagnosis of CS with a heterologous component of CS was rendered. At 6 months follow-up, pelvic MRI and PET showed two local recurrences and a chemotherapy protocol (gemcitabine 1,000 mg, paclitaxel 80 mg/m2 and cisplatin 50 mg/m2) was started; unfortunately, the patient died 18 months following surgery.
Carcinosarcoma of the Female Urethra
Status
Discussion
Primary neoplasms of the female urethra are rare; tumor histology varies depending on the anatomic site of origin. The squamous cell carcinomas are by far the most common, accounting for up to 70% of the primary urethral carcinomas [1], and are usually located in the distal urethra, whereas transitional cell carcinomas and adenocarcinomas are the most common in the proximal tract. CS is a malignant tumor containing carcinomatous and sarcomatous components. It is not to be confused with sarcomatoid carcinoma, which is a carcinoma that exhibits a prominent spindle cell component, although the distinction is not clinically relevant because their biological behavior and outcome are similar. The most common site of CS in the genitourinary tract is the bladder (65%) followed by the prostate (15.7%), kidney (4%) and ureter (7.9%) [2]. CS of the female urethra is extremely rare, with only 4 cases reported in the literature [3–6] (table 1). Therefore, no data concerning epidemiology and incidence of this tumor are available. CS of the uterus is an uncommon cancer accounting for 1–3% of all cancers of uterus. These rare cancers have a poor prognosis and a third of these cancers have already spread beyond the uterus at the time of diagnosis. AlUrol Int 2016;96:370–372 DOI: 10.1159/000355089
371
Downloaded by: Univ.of Adelaide 129.127.145.240 - 11/5/2017 4:20:19 PM
4 [6]
Follow-up
though the histogenesis of the malignant mixed tumors is still being debated, the multiclonal hypothesis proposes an origin from two or more undifferentiated stem cells (convergence hypothesis); the monoclonal hypothesis suggests that CS derives from a single totipotential tumor stem cell that differentiates into separate epithelial and mesenchymal cells (divergence hypothesis). Evidence of the monoclonal origin of systemic CS supports the divergent tumor theory [7]. The urothelial origin of these tumors was also hypothesized and a transitional form of malignancies associated with the presence of a pseudostratified epithelium reminiscent of the urothelium was also found in some tumors [8]. Radiation exposure has been suggested as a predisposing factor for the development of CS of the bladder [9]; however, in the reported cases of female urethra CS (including our own), none had a history of radiation exposure. The rarity of female urethral tumors has contributed to the absence of a standardized approach to the management and follow-up of these patients. Most urethral cancers in females are locally advanced when detected and involve the proximal third or the entire urethra. When surgery is planned, extensive resection is necessary, including total cystourethrectomy, with pelvic lymph node dissection and removal of the vagina. Inguinal lymph node dissection is not recommended in the absence of palpable disease in the groin. However, even extensive
surgery often fails and local recurrence after surgery alone is reported in 60–100% of cases [10]. Irradiation as a single modality therapy produces an unacceptably high morbidity rate and low tumor control rate. A combination protocol of chemotherapy and irradiation followed by surgery is reported to achieve a better local control, although it does not improve the overall survival [11]. In our case the chemotherapy protocol was in accordance with the dose utilized for the treatment of transitional carcinomas [12]. The prognosis is poor – of the reported cases, only 1 patient [4] was free of disease at the 2-year follow-up.
Conclusion
CS is a rare malignant tumor with a bad prognosis. The rarity of these tumors has contributed to the absence of a standardized approach to the management and follow-up of these patients. The surgical treatment with extensive resection is preferable but a local recurrence is high. Irradiation therapy has a low tumor control rate. A multimodal treatment with chemo- and radiotherapy seem to offer a better local control of disease but does not improve survival. In our case, even the neoadjuvant treatment with chemo- and radiotherapy did not improved the prognosis.
References
372
Urol Int 2016;96:370–372 DOI: 10.1159/000355089
5 Liu J, Wu H: Carcinosarcoma of female urethra with melanocytic differentiation. Int J Clin Exp Pathol 2011;4:206–209. 6 Komai Y, Urushibara M, Saito K, Sakai K, Morimoto S: A case of sarcomatoid carcinoma in the region of the female urethra. Nihon Hinyokika Gakkai Zasshi 2005;96:650–653. 7 Thompson L, Chang B, Barsky SH: Monoclonal origin of malignant mixed tumors (carcinosarcoma): evidence for a divergent histogenesis. Am J Surg Pathol 1996;20:277–285. 8 Oliva E, Amin MB, Jimenez R, Young RH: Clear cell carcinoma of the urinary bladder: a report and comparison of four tumors of mullerian origin and nine of probable urothelial origin with discussion of histogenesis and diagnostic problems. Am J Surg Pathol 2002;26: 190–197. 9 Lahoti C, Schinella R, Rangwala AF, Lee M, Mizrachi H: Carcinosarcoma of urinary bladder: report of 5 cases with immunohistologic study. Urology 1994;43:389–393.
10 Di Marco DS, Di Marco CS, Zincke H, Webb MJ, Bass S E, Slezakc JM, Lightner DJ: Surgical treatment for local control of female urethral carcinoma. Urol Oncol 2004;22:404–409. 11 Dalbagni G, Zhang Z-F, Lacombe L, Herr HW: Female urethral carcinoma: an analysis of treatment outcome and a plea for a standardized management strategy. Br J Urol 1998;82:835–841. 12 Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R: Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987. J Clin Oncol 2012;30:1107–1113.
D’Arrigo/Costa/Fraggetta/Pennisi/Pepe/ Aragona
Downloaded by: Univ.of Adelaide 129.127.145.240 - 11/5/2017 4:20:19 PM
1 Bermejo CE, Basler JW: Carcinoma of the urethra; in Hamdy FC, Basler JW, Catalona WJ (eds): Management of Urologic Malignancies. London, Churchill Livingstone, 2002, p 525. 2 Frank I, Takahashi S, Tsukamoto T, Lieber M: Genitourinary sarcomas and carcinosarcomas in adults; in Vogelzang NJ, Scardino PT, Shipley WU, Coffey DS (eds): Genitourinary Oncology, ed 2. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 1101–1119. 3 Konno N, Mori M, Kurooka Y, Kameyama S, Homma Y, Moriyama N, Tajima A, Murayama T, Kawabe K: Carcinosarcoma in the region of female urethra. Int J Urol 1997;4:229– 231. 4 Jayamohan Y, Urs L, Rowland R, Woolums S, Lele SM: Periurethral carcinosarcoma. A report of 2 cases with a review of the literature. Arch Pathol Lab Med 2005;129:e91–e93.
