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CASE REPORT  
Year : 2020  |  Volume : 63  |  Issue : 2  |  Page : 298-300
A rare case of small cell neuroendocrine tumor of the urinary bladder


1 Department of Urology, Lourdes Hospital, Kochi, Kerala, India
2 Department of Pathology, Lourdes Hospital, Kochi, Kerala, India

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Date of Web Publication18-Apr-2020
 

   Abstract 


Small cell neuroendocrine tumor of the bladder is a rare tumor characterized by poor differentiation and high aggressiveness. Very few cases worldwide have been reported till date. Recent literature shows equivalent survival data for localized disease treated with chemoradiotherapy combined with either bladder sparing surgery or radical cystectomy. We report a case of small cell neuroendocrine carcinoma of the bladder diagnosed after transurethral resection of bladder tumor, then followed by adjuvant chemotherapy for six cycles and awaiting radical cystectomy.

Keywords: Immunohistochemistry, neuroendocrine tumor, small cell carcinoma, transurethral resection of bladder tumor

How to cite this article:
Praveen B, Varghese J, Krishnamoorthy H, Pillai BS. A rare case of small cell neuroendocrine tumor of the urinary bladder. Indian J Pathol Microbiol 2020;63:298-300

How to cite this URL:
Praveen B, Varghese J, Krishnamoorthy H, Pillai BS. A rare case of small cell neuroendocrine tumor of the urinary bladder. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 May 30];63:298-300. Available from: http://www.ijpmonline.org/text.asp?2020/63/2/298/282710





   Introduction Top


Small cell carcinoma (SmCC) belongs to a family of neuroendocrine tumors (NETs). NETs of the bladder include small cell neuroendocrine carcinoma, large cell neuroendocrine carcinoma, well-differentiated NET, and paragangliomas. Only ~150 cases have been reported in the literature to date to the best of our knowledge.


   Case History Top


A 50-year-old male was admitted with complaints of frank hematuria and passage of clots for 1 week, Ultrasonography of the abdomen showed apolypoidal lesion measuring 3 × 3 cm near the right vesicoureteric junction with moderate hydroureteronephrosis, computed tomography (CT) urogram showed mildly enhancing vesicoureteric junction polypoidal lesion of size 3.8 × 3.4 cm causing moderate hydroureteronephrosis, and no retroperitoneal or mesenteric lymphadenopathy was seen [Figure 1]. There was no evidence of distant metastasis on metastatic workup. The patient underwent transurethral resection of bladder tumor (TURBT); intraoperatively, a 4-cm polypoidal lesion at the right lateral wall near to the right ureteric orifice was seen. histopathological examination (HPE) - S/O small cell neuroendocrine carcinoma with deep muscle invasion [Figure 2]. On immunohistochemistry, the cells were immunoreactive to CD56, chromogranin, and synaptophysin with Ki-67 90% and non-immunoreactive to CK7, CK20, TTK1, and uroplakin, consistent with small cell neuroendocrine variety [Figure 3].
Figure 1: Contrast Enhanced CT Abdomen(a) Contrast film showing HUN. (b) Precontrast film showing HUN. (c) Contrast film showing enhancing bladder lesion. (d) Precontrast film showing bladder lesion

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Figure 2: Histopathological Examination(a) Cells arranged in nests, sheets cords, and ribbon-like basiloid variety. (b) Focal rosette-like formation with necrosis. (c) Low-power HE stain. (d) High-power HE stain

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Figure 3: Immunohistochemistry(a) Synaptophysin. (b) Chromogranin.

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   Discussion Top


SmCC of the bladder is a rare histologic variant and accounts for less than 1% of all bladder malignancies.[1],[2] It has been postulated that bladder SmCC may develop from malignant transformation of Kulchitsky-type neuroendocrine cells in the bladder mucosa.[3] Indeed, a recent study demonstrated that microRNA-145 transformed conventional Urothelial carcinoma (UC) cells to pluripotent stem cells with subsequent differentiation into neuroendocrine, glandular, squamous lineages.[4] A third theory proposed that bladder SmCC and UC may share a common clonal origin – a multipotential, undifferentiated cell (or cancer stem cell) based on the fact that most SmCCs coexist with conventional UC in the bladder.[5]

Microscopically, SmCC of the bladder shows sheets and large nests of malignant cells with round to oval nuclei, scant cytoplasm, and a high nuclear/cytoplasmic ratio, resembling SmCC of the lung. The nuclei show finely stippled chromatin and numerous mitotic figures but lack prominent nucleoli. Coagulative necrosis and nuclear molding are commonly seen.[6] In our case, microscopy examination showed similar morphology and characteristic features.

Poorly differentiated UC may show solid sheets of immature cells with large nuclei and scant cytoplasm, mimicking SmCC, but it shows a distinct immunohistochemical profile from SmCC. SmCC is by far the most common NET in the bladder and typically expresses neuroendocrine markers, such as CD56, synaptophysin, chromogranin, and neuron-specific enolase, but a lack of expression of these markers does not exclude the diagnosis of SmCC. But in our case, the cells were immunoreactive to markers of neuroendocrine differentiation with Ki-67 90% and non-immunoreactive to CK7, CK20, TTK1, and uroplakin.

SmCC of the bladder is an aggressive disease which usually presents at an advanced stage with frequent metastases. When the disease is localized to the bladder, SmCC does not have a significantly different clinical outcome from conventional urothelial carcinoma. However, when the disease develops metastasis, SmCC shows a significantly worse prognosis than UC. In a study done by Wang et al., the median survival time for the patients who underwent neoadjuvant chemotherapy before cystectomy was 38 months, but the median survival time for patients who did not receive neoadjuvant chemotherapy was only 12 months. Long-term survival (>60 months) was observed in patients who had disease localized to the bladder and received neoadjuvant chemotherapy.[7]

Indeed, neoadjuvant chemotherapy followed by radical cystectomy can lead to a long-term survival in patients who have SmCC limited to the bladder.[8] In our case, the patient had completed adjuvant chemotherapy of six cycles in 6 months with cisplatin and iphosphamide and is being advised radical cystectomy, for which the patient is not willing at present. Cystoscopy and CT urogram done at 6 months showed normal study with no recurrence at site of previous TURBT, no regional lymph node, or distant metastasis.

In conclusion, it is important to differentiate SmCC from other malignant neoplasms in the bladder in view of its aggressiveness and presentation at advanced stage with frequent metastasis. Due to the rarity of SmCC of the urinary bladder, more clinical trials are required for further characterization of tumor and its appropriate management. Till then, treatment of SmCC of the urinary bladder will continue to mirror that of small cell lung cancer. Identification of new molecular markers for early diagnosis and the development of novel targeted therapies will aid in improvement of survival in future.

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 Top

1.
Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: Prostate and bladder tumours. Eur Urol 2016;70:106-19.  Back to cited text no. 1
    
2.
Cheng L, Pan CX, Yang XJ, Lopez-Beltran A, MacLennan GT, Lin H, et al. Small cell carcinoma of the urinary bladder: A clinicopathologic analysis of 64 patients. Cancer 2004;101:957-62.  Back to cited text no. 2
    
3.
Cramer SF, Aikawa M, Cebelin M. Neurosecretory granules in small cell invasivecarcinoma of the urinary bladder. Cancer 1981;47:724-30.  Back to cited text no. 3
    
4.
Davis BH, Ludwig ME, Cole SR, Lorenzini P, Reuter VE, Rosai J. Small cell neuroendocrine carcinoma of the urinary bladder: Report of three cases with ultrastructural analysis. Ultrastruct Pathol 1983;4:197-204.  Back to cited text no. 4
    
5.
Blomjous CE, Vos W, De Voogt HJ, Van der Valk P, Meijer CJ. Small cell carcinoma of the urinary bladder: A clinicopathologic, morphometric, immunohistochemical, and ultrastructural study of 18 cases. Cancer 1989;64:1347-57.  Back to cited text no. 5
    
6.
Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: A global overview and recent trends. Eur Urol 2017;71:96-108.  Back to cited text no. 6
    
7.
Wang G, Xiao L, Zhang M, Kamat AM, Siefker-Radtke A, Dinney CP, et al. Small cell carcinoma of the urinary bladder: A clinicopathologic and immunohistochemical analysis of 81 cases. Hum Pathol 2018;79:57-65.  Back to cited text no. 7
    
8.
Bryant CM, Dang LH, Stechmiller BK, Gilbert SM, Morris CG, Zlotecki RA. Treatment of small cell carcinoma of the bladder with chemotherapy and radiation after transurethral resection of a bladder tumor. Am J Clin Oncol 2016; 39:69-75.  Back to cited text no. 8
    

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Correspondence Address:
Jophy Varghese
Department of Pathology, Lourdes Hospital, Kochi - 682 012, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_692_18

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    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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