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Metachronous primary urothelial carcinoma following small cell carcinoma of the urinary bladder A 69-year-old male presented to our rural urology practice with macroscopic haematuria for investigation in April 2011. He is an ex-smoker of 30 years and has no other risk factors for bladder cancer. His urine cytology was positive for malignancy, and an ultrasound with subsequent computed tomography (CT) urogram revealed a 5-cm heterogeneous echogenic mass protruding from the right wall of his urinary bladder. At cystoscopy, the mass was located on the right side of the dome of the bladder, and histopathology from transurethral resection specimen (Figs 1,2) revealed a pathological stage T2 small cell carcinoma of the bladder (SCCB). Staging CT Fig. 1. (a) Haematoxylin and eosin staining of small cell carcinoma of the bladder with typical features of small round cells in sheets and nests with round to oval nuclei and scant cytoplasm. (b) Comparison of haematoxylin and eosin staining of the subsequent high-grade papillary urothelial carcinoma.
Fig. 2. Immunohistochemistry staining showing cellular expression of (a) chromogranin A and (b) synaptophysin in small cell carcinoma of the bladder, and absent of staining with (c) chromogranin A and (d) synaptophysin in urothelial carcinoma.
© 2014 Royal Australasian College of Surgeons
and positron emission tomography scan revealed a metabolically active right pelvic lymph node in keeping with metastatic nodal disease (Fig. 3). Following discussion at our multidisciplinary meeting, the patient was started on six cycles of chemotherapy (carboplatin and etoposide) with concurrent radiotherapy. Re-staging CT in November 2011 showed a reduction in the right lateral bladder wall thickening with no lymphadenopathy or metastasis. On subsequent surveillance cystoscopy with transurethral resection of previous scar and random bladder biopsies, there was no evidence of malignancy.
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ANZ J Surg •• (2014) ••–••
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Images for surgeons
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He developed macroscopic haematuria again 2 years following his initial diagnosis, and was found to have positive urine cytology but an unremarkable CT urogram. Rigid cystoscopy revealed a 5-cm superficial looking tumour on the right lateral wall. Histopathology of transurethral resection specimen (Fig. 1) revealed a high-grade papillary urothelial carcinoma with extensive carcinoma-in-situ component without stromal or muscularis propria invasion (i.e. grade 3 pTa and carcinoma in situ). He underwent an induction course of Bacillus Calmette–Guérin, and 3 months later his urine cytology and rigid cystoscopy with random bladder biopsies did not reveal any further evidence of malignancy. SCCB is rare and comprises less than 1% of all bladder cancer.1,2 Metachronous urothelial carcinoma following bladder-preserving management such as this case is even rarer, with only three cases reported previously.2 These cases highlight the importance of regular surveillance cystoscopy in these patients, despite a lack of clear follow-up protocol for patients with SCCB. SCCB is an aggressive tumour and frequently presents as locally advanced or metastatic disease.1,3 It carries a poor 5-year survival ranging from 16% to 40%,1,3 with patients with extensive disease (TxNxM1 or TxN2-3M0) doing worse than those with limited disease (T1-4N0-1M0).4,5 Risk factors for SCCB include smoking, male sex, advanced age and Caucasian origin.4,5 Because of its rarity, current knowledge of the disease is limited to small retrospective studies at major academic centres. Diagnosis of SCCB on histopathology is by characteristic features such as uniformly small, round to oval cells with sparse cytoplasm and overlapping nuclei.1 Immunohistochemistry staining for neuron specific enolase, synaptophysin, chromogranin and CAM5.2 can also aid the diagnosis.3 SCCB frequently coexists with another nonSCCB bladder tumour, ranging from 68% to 88%.1,3 Most commonly, SCCB coexists with urothelial carcinoma, but infrequently also with squamous cell carcinoma or adenocarcinoma.1,3 Management of SCCB involves a multimodality approach and differs for limited versus extensive disease.5 Chemotherapy is the
Fig. 3. (a) Ultrasound and (b) computed tomography (CT) scan showing the right-sided bladder mass. (c) Positron emission tomography (PET) scan and (d) PET-CT scan showing fluorodeoxyglucose avid node in the right pelvis.
mainstay of treatment to improve survival,6 as surgery alone without chemotherapy is often inadequate.5 Cystectomy may not improve survival;1 therefore, a bladder-preserving tri-modality treatment of chemoradiotherapy and transurethral resection of bladder tumour (TURBT) with the option of cystectomy on recurrence is a reasonable management for limited disease.2,5,7 In a retrospective study involving 17 patients with limited SCCB disease treated with sequential chemoradiotherapy following transurethral resection of bladder tumour, Bex et al. showed a median overall survival of 32.5 months.7 Another study by Lohrisch et al. showed a median survival of 41 months in a similar group of patients.2 For extensive SCCB disease, management is generally with cisplatin-based chemotherapy.5 Although poorly reported in the literature, metachronous primary bladder malignancies can occur in patients with SCCB managed with bladder-preserving treatment. In the study by Lohrisch et al. looking at chemoradiotherapy for SCCB, three of five surviving patients developed metachronous urothelial carcinoma on followup.2 This can be treated conventionally for urothelial carcinomas,2 and Lohrisch et al. showed a 38- and 104-month survival of the two patients who underwent TURBT for their urothelial carcinoma following SCCB.2 One patient underwent cystectomy, who eventually died from small cell carcinoma of the lung.2 Clinicians should be aware of the risk of metachronous primary bladder malignancy in SCCB patients managed with bladderpreserving treatment. Patients should undergo frequent surveillance cystoscopy similar to the follow-up after bladder-preserving management of urothelial carcinoma. Metachronous urothelial carcinoma can be managed conventionally with a potential for a good outcome.
References 1. Cheng L, Pan CX, Yang XJ et al. Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients. Cancer 2004; 101: 957–62.
© 2014 Royal Australasian College of Surgeons
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2. Lohrisch C, Murray N, Pickles T, Sullivan L. Small cell carcinoma of the bladder: long term outcome with integrated chemoradiation. Cancer 1999; 86: 2346–52. 3. Abrahams NA, Moran C, Reyes AO, Siefker-Radtke A, Ayala AG. Small cell carcinoma of the bladder: a contemporary clinicopathological study of 51 cases. Histopathology 2005; 46: 57–63. 4. Koay EJ, Teh BS, Paulino AC, Butler EB. A surveillance, epidemiology, and end results analysis of small cell carcinoma of the bladder: epidemiology, prognostic variables, and treatment trends. Cancer 2011; 117: 5325–33. 5. Thota S, Kistangari G, Daw H, Spiro T. A clinical review of small-cell carcinoma of the urinary bladder. Clin. Genitourin. Cancer 2013; 11: 73–7. 6. Mackey JR, Au HJ, Hugh J, Venner P. Genitourinary small cell carcinoma: determination of clinical and therapeutic factors associated with survival. J. Urol. 1998; 159: 1624–9.
© 2014 Royal Australasian College of Surgeons
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7. Bex A, de Vries R, Pos F, Kerst M, Horenblas S. Long-term survival after sequential chemoradiation for limited disease small cell carcinoma of the bladder. World J. Urol. 2009; 27: 101–6.
Henry H. I. Yao,* MBBS Kevin Chu,* MBBChir, MRCS Christopher Hallot,† MBChB, FRCPA Jonathan Lewin,* FRACS (Urol) *Department of Urology, Albury Wodonga Health, Albury, New South Wales, Australia and †Pathology, Border Pathology, Albury, New South Wales, Australia doi: 10.1111/ans.12832
Metachronous primary urothelial carcinoma following small cell carcinoma of the urinary bladder A 69-year-old male presented to our rural urology practice with macroscopic haematuria for investigation in April 2011. He is an ex-smoker of 30 years and has no other risk factors for bladder cancer. His urine cytology was positive for malignancy, and an ultrasound with subsequent computed tomography (CT) urogram revealed a 5-cm heterogeneous echogenic mass protruding from the right wall of his urinary bladder. At cystoscopy, the mass was located on the right side of the dome of the bladder, and histopathology from transurethral resection specimen (Figs 1,2) revealed a pathological stage T2 small cell carcinoma of the bladder (SCCB). Staging CT Fig. 1. (a) Haematoxylin and eosin staining of small cell carcinoma of the bladder with typical features of small round cells in sheets and nests with round to oval nuclei and scant cytoplasm. (b) Comparison of haematoxylin and eosin staining of the subsequent high-grade papillary urothelial carcinoma.
Fig. 2. Immunohistochemistry staining showing cellular expression of (a) chromogranin A and (b) synaptophysin in small cell carcinoma of the bladder, and absent of staining with (c) chromogranin A and (d) synaptophysin in urothelial carcinoma.
© 2014 Royal Australasian College of Surgeons
and positron emission tomography scan revealed a metabolically active right pelvic lymph node in keeping with metastatic nodal disease (Fig. 3). Following discussion at our multidisciplinary meeting, the patient was started on six cycles of chemotherapy (carboplatin and etoposide) with concurrent radiotherapy. Re-staging CT in November 2011 showed a reduction in the right lateral bladder wall thickening with no lymphadenopathy or metastasis. On subsequent surveillance cystoscopy with transurethral resection of previous scar and random bladder biopsies, there was no evidence of malignancy.
(a)
(b)
(a)
(c)
(b)
(d)
ANZ J Surg •• (2014) ••–••
2
Images for surgeons
(a)
(b)
(c)
(d)
He developed macroscopic haematuria again 2 years following his initial diagnosis, and was found to have positive urine cytology but an unremarkable CT urogram. Rigid cystoscopy revealed a 5-cm superficial looking tumour on the right lateral wall. Histopathology of transurethral resection specimen (Fig. 1) revealed a high-grade papillary urothelial carcinoma with extensive carcinoma-in-situ component without stromal or muscularis propria invasion (i.e. grade 3 pTa and carcinoma in situ). He underwent an induction course of Bacillus Calmette–Guérin, and 3 months later his urine cytology and rigid cystoscopy with random bladder biopsies did not reveal any further evidence of malignancy. SCCB is rare and comprises less than 1% of all bladder cancer.1,2 Metachronous urothelial carcinoma following bladder-preserving management such as this case is even rarer, with only three cases reported previously.2 These cases highlight the importance of regular surveillance cystoscopy in these patients, despite a lack of clear follow-up protocol for patients with SCCB. SCCB is an aggressive tumour and frequently presents as locally advanced or metastatic disease.1,3 It carries a poor 5-year survival ranging from 16% to 40%,1,3 with patients with extensive disease (TxNxM1 or TxN2-3M0) doing worse than those with limited disease (T1-4N0-1M0).4,5 Risk factors for SCCB include smoking, male sex, advanced age and Caucasian origin.4,5 Because of its rarity, current knowledge of the disease is limited to small retrospective studies at major academic centres. Diagnosis of SCCB on histopathology is by characteristic features such as uniformly small, round to oval cells with sparse cytoplasm and overlapping nuclei.1 Immunohistochemistry staining for neuron specific enolase, synaptophysin, chromogranin and CAM5.2 can also aid the diagnosis.3 SCCB frequently coexists with another nonSCCB bladder tumour, ranging from 68% to 88%.1,3 Most commonly, SCCB coexists with urothelial carcinoma, but infrequently also with squamous cell carcinoma or adenocarcinoma.1,3 Management of SCCB involves a multimodality approach and differs for limited versus extensive disease.5 Chemotherapy is the
Fig. 3. (a) Ultrasound and (b) computed tomography (CT) scan showing the right-sided bladder mass. (c) Positron emission tomography (PET) scan and (d) PET-CT scan showing fluorodeoxyglucose avid node in the right pelvis.
mainstay of treatment to improve survival,6 as surgery alone without chemotherapy is often inadequate.5 Cystectomy may not improve survival;1 therefore, a bladder-preserving tri-modality treatment of chemoradiotherapy and transurethral resection of bladder tumour (TURBT) with the option of cystectomy on recurrence is a reasonable management for limited disease.2,5,7 In a retrospective study involving 17 patients with limited SCCB disease treated with sequential chemoradiotherapy following transurethral resection of bladder tumour, Bex et al. showed a median overall survival of 32.5 months.7 Another study by Lohrisch et al. showed a median survival of 41 months in a similar group of patients.2 For extensive SCCB disease, management is generally with cisplatin-based chemotherapy.5 Although poorly reported in the literature, metachronous primary bladder malignancies can occur in patients with SCCB managed with bladder-preserving treatment. In the study by Lohrisch et al. looking at chemoradiotherapy for SCCB, three of five surviving patients developed metachronous urothelial carcinoma on followup.2 This can be treated conventionally for urothelial carcinomas,2 and Lohrisch et al. showed a 38- and 104-month survival of the two patients who underwent TURBT for their urothelial carcinoma following SCCB.2 One patient underwent cystectomy, who eventually died from small cell carcinoma of the lung.2 Clinicians should be aware of the risk of metachronous primary bladder malignancy in SCCB patients managed with bladderpreserving treatment. Patients should undergo frequent surveillance cystoscopy similar to the follow-up after bladder-preserving management of urothelial carcinoma. Metachronous urothelial carcinoma can be managed conventionally with a potential for a good outcome.
References 1. Cheng L, Pan CX, Yang XJ et al. Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients. Cancer 2004; 101: 957–62.
© 2014 Royal Australasian College of Surgeons
Images for surgeons
2. Lohrisch C, Murray N, Pickles T, Sullivan L. Small cell carcinoma of the bladder: long term outcome with integrated chemoradiation. Cancer 1999; 86: 2346–52. 3. Abrahams NA, Moran C, Reyes AO, Siefker-Radtke A, Ayala AG. Small cell carcinoma of the bladder: a contemporary clinicopathological study of 51 cases. Histopathology 2005; 46: 57–63. 4. Koay EJ, Teh BS, Paulino AC, Butler EB. A surveillance, epidemiology, and end results analysis of small cell carcinoma of the bladder: epidemiology, prognostic variables, and treatment trends. Cancer 2011; 117: 5325–33. 5. Thota S, Kistangari G, Daw H, Spiro T. A clinical review of small-cell carcinoma of the urinary bladder. Clin. Genitourin. Cancer 2013; 11: 73–7. 6. Mackey JR, Au HJ, Hugh J, Venner P. Genitourinary small cell carcinoma: determination of clinical and therapeutic factors associated with survival. J. Urol. 1998; 159: 1624–9.
© 2014 Royal Australasian College of Surgeons
3
7. Bex A, de Vries R, Pos F, Kerst M, Horenblas S. Long-term survival after sequential chemoradiation for limited disease small cell carcinoma of the bladder. World J. Urol. 2009; 27: 101–6.
Henry H. I. Yao,* MBBS Kevin Chu,* MBBChir, MRCS Christopher Hallot,† MBChB, FRCPA Jonathan Lewin,* FRACS (Urol) *Department of Urology, Albury Wodonga Health, Albury, New South Wales, Australia and †Pathology, Border Pathology, Albury, New South Wales, Australia doi: 10.1111/ans.12832
