|Year : 2015 | Volume
| Issue : 2 | Page : 136-138
Primary small cell neuroendocrine carcinoma of the urinary bladder
Geetha Aravind Chilari1, Shailaja Prabhala1, Srinivas Gutta2, Jayashankar Erukkambattu1
1 Department of Pathology, Kamineni Academy of Medical Sciences and Research Centre, Hyderabad, Andhra Pradesh, India
2 Department of Urology, Kamineni Academy of Medical Sciences and Research Centre, Hyderabad, Andhra Pradesh, India
|Date of Web Publication||12-Jun-2015|
Dr. Geetha Aravind Chilari
Plot No. 29b, H. No. 11-13-999, Road No. 2, Green Hills Colony, Kothapet, Saroor Nagar, Hyderabad - 500 035, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Primary small cell neuroendocrine carcinomas of the urinary bladder are rare, highly aggressive tumors and diagnosed mainly at advanced stages. Herein, we report a case of a 75-year-old man who presented with acute urinary retention and was found to have an infiltrative growth in the bladder. Histopathology and immunohistochemistry (IHC) were diagnostic of primary small cell neuroendocrine carcinoma. This case is being presented because of its rarity and highlighting the importance of histopathology and IHC in differentiating clinical mimics and making accurate diagnosis.
Keywords: Immunohistochemistry, primary neuroendocrine carcinoma, urinary bladder
|How to cite this article:|
Chilari GA, Prabhala S, Gutta S, Erukkambattu J. Primary small cell neuroendocrine carcinoma of the urinary bladder. J NTR Univ Health Sci 2015;4:136-8
|How to cite this URL:|
Chilari GA, Prabhala S, Gutta S, Erukkambattu J. Primary small cell neuroendocrine carcinoma of the urinary bladder. J NTR Univ Health Sci [serial online] 2015 [cited 2020 Jan 23];4:136-8. Available from: http://www.jdrntruhs.org/text.asp?2015/4/2/136/158604
| Introduction|| |
Primary small cell neuroendocrine carcinomas of the urinary bladder account for less than1% of all bladder tumors. It was first reported by Cramer in 1981.  It usually coexists with urothelial carcinoma in elderly patients. Hematuria is the most common symptom. The cell of origin is thought to be multipotent stem cell. Histology and immunohistochemistry (IHC) are crucial for the diagnosis. Herein, we report a case of primary small cell neuroendocrine carcinoma of the urinary bladder.
| Case report|| |
A 75-year-old male presented with dyspnea and acute urinary retention to Department of Nephrology. History of hematuria and cigarette smoking was present. He is a known case of hypertension and diabetes. Computerized tomography (CT) (kidney, ureter, and bladder) scan revealed mass at base of the bladder infiltrating the prostate and retroperitoneal lymphadenopathy. No evidence of metastatic disease was found except for retroperitoneal lymph node enlargement. He was referred to urology for cystoscopy and further management. Cystoscopy revealed huge growth in bladder with extension into prostatic urethra. Bilateral vesicoureteric junctions were not visualized. Clinically, urothelial malignancy was considered, and biopsy of the mass was carried out. Patient succumbed to death after biopsy before definitive treatment was initiated.
| Pathological findings|| |
Histopathological findings revealed bladder mucosa with urothelial lining and underlying invasive lesion arranged in the form of nests and sheets composed of small round malignant cells with scant cytoplasm, pyknotic round to oval nuclei and evenly dispersed stippled chromatin [Figure 1]a and b. Mitoses were high [Figure 1]c. There were large areas of necrosis. Based on morphology, possibility of neuroendocrine carcinoma is suspected.
|Figure 1: Hematoxylin and eosin staining of the biopsy specimen. (a) Urothelial mucosa with underlying lesion composed of sheets of monomorphic cells (×40). (b) Small cells with hyperchromatic nuclei (×100). (c) Mitotic figures (×400)|
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Immunohistochemistry [Table 1], was done with synaptophysin [Figure 2]a, neuron-specific enolase (NSE) [Figure 2]b, chromogranin [Figure 2]c, cytokeratin (CK)7, CK20, prostate specific antigen (PSA), Ki-67 [Figure 2]d, which confirmed the diagnosis. Based on morphology and IHC results, diagnosis of small cell neuroendocrine carcinoma was made.
|Figure 2: Immunohistochemistry with (a) synaptophysinpositive (×100), (b) neuron-specific enolase-positive (×100), (c) chromogranin-positive (×100), and (d) Ki-67 labeling index 90% (×100)|
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| Discussion|| |
Primary small cell neuroendocrine carcinoma of the bladder (SCCB) is an extremely rare bladder malignancy with a mean frequency of 0.7% and a range between 0.35% and 1.8%. ,,,,, Less than 1000 cases of SCCB have been diagnosed and reported in the literature. The majority of patients are male, with male:female ratio of 5:1, and a range between 1:1 and 16:1. ,,,,,,, Mean age at time of first diagnosis is 67 years; ranging between 32 and 91 years. ,,
The origin of SCCB is not well defined. There is a hypothesis that they may arise from neuroendocrine cells within normal or metaplastic urothelium.  The most accepted hypothesis proposes the origin of SCCB may be a multipotential common stem cell within the urothelium that can differentiate into various cell types depending on the influence of a specific transformation or progression-related genes. ,, This may explain the coexistence of SCCB with transitional cell carcinoma (TCC) but fails to explain the low incidence of concomitant carcinoma in situ.
The clinical features of SCCB are similar to those of bladder TCC with gross hematuria being the most common symptom (63-88% of the cases) ,, followed by dysuria. , Urinary obstruction, abdominal pain, urinary tract infection, and weight loss were occasionally reported ,, along with rare cases of paraneoplastic syndromes such as ectopic adrenocorticotropic hormone secretion and hypercalcemia. , In our case, presentation was acute urinary retention with previous history of intermittent hematuria.
At cystoscopy, the tumor size can range from 4 to 10 cm and the tumor is usually located in the lateral wall and fundus of the bladder while rarely occurring in the trigone within a bladder diverticulum.  Grossly, these tumors are polypoid lesions and are sometimes ulcerated.  In our case, tumor was large, occupying the entire bladder with areas of ulceration on cystoscopy.
Microscopically, the lesions were composed of nests of small round malignant cells with scant cytoplasm, pyknotic round to oval nuclei and evenly dispersed "salt and pepper chromatin". The mitotic rate was high (>10 mitotic figures/10 high-power fields) in 57% of the cases. Tumor rosettes were seen in 23.5% of the cases. Tumor necrosis was present in the majority of the cases. Crush artefact (Azzopardi effect) was found in 78.4% of the cases. Vascular invasion was present in 16.7% of the cases.  In our case, the tumor showed similar histomorphology. Tumor rosettes and vascular invasion were not identified in our case.
In Abrahams study, mixtures of SCCB with TCC was present in 70% of the cases, while mixtures of SCCB with adenocarcinoma and squamous carcinoma were present only in 8% and 10% of the cases respectively.  In our case, there was no association with other tumor types on biopsy.
Immunohistochemistry results show positive staining with the following antigens: NSE (88.5%), chromogranin (50%), synaptophysin (72.4%), serotonin, CK, S-100 protein, thyroid transcription factor-1 in 40%, epidermal growth factor receptor (30%), and C-KIT (27%). ,,, SCCB can also show positive staining with the epithelial markers: CK7, and epithelial membrane antigen in 41%, and 77.7% of the cases, respectively.
In our case, neuroendocrine markers were intensely positive in all tumor cells. CK7 and CK20 were negative ruling out possible co-existing TCC in the biopsy sample. PSA was negative ruling out prostatic metastasis.
The management of SCCB should involve pathologists, surgeons, radiotherapists, and oncologists. Various treatment modalities include radical resection, radiotherapy and chemotherapy. In our case, the patient was old with concomitant medical problems. Based on the literature available, we conclude that small cell neuroendocrine tumors of the urinary bladder, behave aggressively with a grave prognosis.
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[Figure 1], [Figure 2]