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| CASE REPORT |
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| Year : 2022 | Volume
: 13
| Issue : 2 | Page : 85-88 |
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Small cell carcinoma - Urinary bladder
Isha Shah, Dhara Patel, U Suryanarayana
Department of Radiotherapy, GCRI, Ahmedabad, Gujarat, India
| Date of Submission | 07-Nov-2021 |
| Date of Acceptance | 17-Dec-2021 |
| Date of Web Publication | 09-Feb-2022 |
Correspondence Address:
Dr. Isha Shah
Department of Radiotherapy, GCRI, Ahmedabad, Gujarat
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jrcr.jrcr_50_21
Primary small-cell neuroendocrine carcinoma of the urinary bladder is a rare type of poorly differentiated and highly aggressive tumor. It accounts for <0.7% of all cancers arising from the bladder. Small-cell carcinoma of the urinary bladder is frequently found in conjunction with other histologic types such as urothelial carcinoma (transitional cell carcinoma [TCC]), squamous cell carcinoma, and adenocarcinoma. Although the tumor shares similar histological features like small-cell carcinoma originating from other sites of the body, its clinical picture is very similar to conventional TCC of the urinary bladder. Unknown etiology and pathogenesis makes its diagnosis and treatment difficult. Here, we report a case of small-cell carcinoma of the urinary bladder, its clinical presentation, pathological characteristics, behavior, management, and outcome.
Keywords: Bladder carcinoma, extrapulmonary small-cell carcinoma, small-cell carcinoma, urinary bladder
How to cite this article:
Shah I, Patel D, Suryanarayana U. Small cell carcinoma - Urinary bladder. J Radiat Cancer Res 2022;13:85-8 |
| Introduction | |  |
Neuroendocrine carcinoma includes carcinoid tumors, large cell carcinomas, and small-cell carcinomas. It commonly occurs in the respiratory tract and gastrointestinal systems. Small-cell carcinoma primarily arising from the urinary bladder is extremely rare, with a mean frequency of 0.7% and a range between 0.35% and 1.8%.[1] The reported incidence is <1–9/1,000,000 population. Transitional cell carcinoma (TCC) of the urinary bladder is predominantly seen in sixth- to seventh-decade males. The mean age at the time of diagnosis is 67 years. Like TCC, smoking history is also associated with many patients with small-cell carcinoma of the bladder.
Neuroendocrine tumors (NETs) frequently arise from epithelial cells rich in enterochromaffin cells, such as the gastrointestinal tract. Respiratory tract develops from the gastrointestinal bud, so the lung is also a site of NETs. A small number of chromaffin cells can be found in the bladder and prostate.[2]
Its presenting symptoms are similar to those of conventional urothelial carcinoma, whereas its prognosis is poorer with frequent metastasis.[3] The management of this highly aggressive and poorly differentiated tumor is challenging because it is refractory to treatment. In previously published studies, different treatment strategies, surgery, chemotherapy, and radiotherapy either alone or as a part of combined therapy have been used as the treatment.[4],[5]
| Case Report | | |
A 58-year-old male presented to the urology department with complaints of painless hematuria and difficulty in passing urine for the past 15 days. The patient had a history of cigarette smoking for 20 years. Urine examination showed red blood cells (RBCs) (4–7 RBC's/high power field). Ultrasonography and contrast-enhanced computed tomography scan of the abdomen and pelvis showed 82 mm × 78 mm × 78 mm lesion in the right anterolateral wall of the urinary bladder, involving all layers and reaching up to the base of the bladder. Cystoscopy and transurethral resection of bladder tissue was performed. Histopathological examination was suggestive of small-blue-round-cell tumor along with the few cells of urothelial carcinoma. Immunohistochemistry was positive for synaptophysin, CD 56, CK (positive by urothelial component), epithelial membrane antigen (EMA) (positive by urothelial component), and cytokeratin marker CAM 5.2 (positive by urothelial component). Ki67 was >90% which confirmed the diagnosis of mixed small-cell carcinoma (90%) and high-grade urothelial carcinoma (10%) invading lamina propria and deep muscles extensively.
After ruling out metastasis to lung and brain, the patient had undergone four cycles of carboplatin and etoposide chemotherapy. In postchemotherapy, contrast-enhanced computed tomography (CECT) scan of the abdomen and pelvis was done for response evaluation which showed significant reduction in the size of bladder mass (35 mm × 21 mm × 31 mm).
According to the bladder conservation protocol, the patient was offered curative chemoradiotherapy. As small-cell carcinoma has high metastatic potential, after evaluating complete history, examination, and proper workup with ruling out any metastasis to lung and brain by contrast-enhanced computed tomography (CT) of the thorax and magnetic resonance imaging of the brain, we planned curative concurrent chemoradiation therapy with 60 Gy radiotherapy in 30 fractions with anteroposterior and posteroanterior portals with comfortably full bladder, as 2 Gy per fraction, for 5 days a week over 6 weeks with weekly carboplatin. After 20 fractions of the radiotherapy, CT scan of the patient was taken which showed tumor regression, as shown in the [Figure 1]. | Figure 1: Computed tomography scan showing lesion in the right wall of the urinary bladder
Click here to view |
After 1 month, adjuvant carboplatin and etoposide chemotherapy was offered. After 3 months of concurrent chemoradiotherapy, MRI abdomen and pelvis was done which was suggestive of complete resolution of tumor as shown in [Figure 2] and [Figure 3]. | Figure 2: Posttreatment magnetic resonance imaging image showing no residual lesion in the right wall of the urinary bladder
Click here to view |
| Discussion | | |
Small-cell carcinoma is a type of NET which is highly malignant and most commonly arises within the lung. When the primary site is outside the lungs and pleural space, it is called an extrapulmonary small-cell carcinoma. Outside the respiratory tract, small-cell carcinoma can appear in the pancreas, liver, gastrointestinal tract, cervix, prostate, and rarely in the urinary bladder.[6] It arises from the neuroendocrine cells. It occurs due to genetic mutations such as p53 mutation, Myc amplification, and PTEN mutation. Histologically, its classical feature is to show small round or oval blue cells with minimal cytoplasm.
Several theories have been postulated to explain the development of these tumors. Widely accepted theory is that small-cell carcinoma of the bladder (SCCB) originates from a multipotent stem cell. Multipotent stem cell origin explains coexistence of SCCB with other bladder malignancies such as TCC. As seen in our case, this theory explains the existence of SCCB with TCC, and the positivity of cytokeratin, EMA, and CAMS2 of the immunohistochemical staining. CAMS2 is present in both urothelial carcinoma and small-cell carcinoma, but staining is punctate along the membrane in the urothelial carcinoma and perinuclear in small-cell carcinoma. Neuroendocrine cells are most commonly positive for neuron-specific enolase (25%–100%), chromogranin A (22%–89%), synaptophysin (67%–76%), CD 57, CD 56, and protein gene product 9.5. Due to field effect by a common carcinogen, multicentricity of this tumor is well explained. In this case, smoking has been shown to be associated with the development of this tumor. The second theory postulates that these tumors arise from neuroendocrine cells that are normally found among the urothelial cells. It is assumed that they are cells similar to the enterochromaffin cells in the gut. This theory supported that the neuroendocrine cells do not proliferate by themselves but create a fertile environment that encourages tumor growth, differentiation, and angiogenesis by releasing growth factors and neuropeptides such as serotonin, 5-hydroxytryptamine, somatostatin, and bombesin.[3] The third and last theory suggests that NETs frequently arise from epithelium rich in enterochromaffin cells such as the gastrointestinal tract. As the respiratory tract develops from the gastrointestinal bud, the lung is also a site of NETs. A small number of chromaffin cells can be found in the bladder and prostate, which counts for the urinary bladder NETs.[3]
Clinical features are similar to those of bladder TCC. The most common symptom is the gross hematuria noted in 63%–88% of the SCCB.[1] Dysuria has been reported as the next most common symptom. Urinary obstruction, abdominal pain, urinary tract infection, and weight loss have been reported sometimes. Rare cases of paraneoplastic syndromes such as ectopic adrenocorticotropic hormone secretion and hypercalcemia have also been reported.[1]
Small-cell carcinoma of the urinary bladder is a rare pathology, and the data regarding the treatment are very less, so we currently have no standard of treatment. Options for the treatment are extrapolated from small-cell carcinoma of the lung, especially regarding the chemotherapy options, but not regarding the surgical ones.[3]
Treatment options are chemotherapy alone, neoadjuvant chemotherapy followed by cystectomy, cystectomy followed by adjuvant chemotherapy, cystectomy alone, transurethral resection of the bladder (TURBT) alone, radiotherapy alone, and concurrent or sequential chemotherapy and radiotherapy.[3] In the studies found in the literature, TURBT alone was an inadequate method of control of the disease due to its aggressive nature, even in limited disease. The national comprehensive cancer network's guidelines recommend resection and chemotherapy with or without radiotherapy for nonlocally advanced tumors, radiotherapy and chemotherapy for locoregionally advanced disease and chemotherapy alone for metastatic disease.[7] The chemotherapy regimens are used based on the extent of disease. Mixed small-cell carcinoma responds to MVAC regimen (methotrexate, vinblastine, Adriamycin, and cisplatin), pure small-cell carcinoma responds to cisplatin–etoposide or etoposide or ifosfamide/doxorubicin regimen.[8]
Radiation was used in combination with chemotherapy. Chemotherapy regimens used in combination with radiotherapy were carboplatin–etoposide. According to a study conducted by Chau[9] for treatment outcomes for squamous cell carcinoma of the bladder, results from the 409 patients showed that patients have a poor prognosis overall, but survival is improved in those able to receive chemotherapy and with organ-confined disease. Brain metastases are rare. Other studies showed that patients with limited disease receiving chemoradiation had 1 month more survival than those receiving chemotherapy alone. Hence, in this case, neoadjuvant chemotherapy followed by chemoradiotherapy was used as a treatment protocol.
| Conclusion | | |
Small-cell carcinoma of the urinary bladder is a rare and fatal disease. Its presenting age, sex predilection, symptoms, and gross morphology are similar to those of urothelial carcinoma, whereas its biologic behavior is much more aggressive when compared with urothelial carcinoma. Metastasis is common and the prognosis is poor.
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.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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| 2. | Ghervan L, Zaharie A, Ene B, Elec FI. Small-cell carcinoma of the urinary bladder: Where do we stand? Clujul Med 2017;90:13-7. |
| 3. | Zhao X, Flynn EA. Small cell carcinoma of the urinary bladder: A rare, aggressive neuroendocrine malignancy. Arch Pathol Lab Med 2012;136:1451-9. |
| 4. | Çamtosun A, Çelik H, Altıntaş R, Akpolat N. Primary small cell carcinoma in urinary bladder: A rare case. Case Rep Urol 2015;2015:789806. |
| 5. | Chen Z, Liu Q, Chen R, Liu Z, Li M, Ling Q, et al. Clinical analysis of small cell carcinoma of the bladder in Chinese: Nine case reports and literature reviews. World J Surg Oncol 2017;15:33. |
| 6. | Berniker AV, Abdulrahman AA, Teytelboym OM, Galindo LM, Mackey JE. Extrapulmonary small cell carcinoma: Imaging features with radiologic-pathologic correlation. Radiographics 2015;35:152-63. |
| 7. | Siddiqui EJ, Shabbir MA, Mikhailidis DP, Mumtaz FH, Thompson CS. The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation. BJU Int 2006;97:634-9. |
| 8. | Flaig TW, Spiess PE, Agarwal N, Bangs R, Boorjian SA, Buyyounouski MK, et al. Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2020;18:329-54. |
| 9. | Chau C, Rimmer Frcr Y, Choudhury PhD A, Leaning Frcr D, Law A, Enting D, et al. Treatment outcomes for small cell carcinoma of the bladder: Results from a UK patient retrospective cohort study. Int J Radiat Oncol Biol Phys 2021;110:1143-50. |
[Figure 1], [Figure 2], [Figure 3]
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