Turkish Journal of Pathology

Türk Patoloji Dergisi

Turkish Journal of Pathology

Turkish Journal of Pathology

2013, Vol 29, Num, 3     (Pages: 241-245)

“Pure” Primary Large Cell Neuroendocrine Carcinoma of the Urinary Bladder

Teresa PUSİOL 1, Maria Grazia ZORZI 1, Doriana MORICHETTI 1

1 S. Maria del Carmine Hospital, Anatomic Pathology, ROVERETO, ITALY

DOI: 10.5146/tjpath.2013.01189
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Introduction

Dear Editors,

Large Cell Neuroendocrine Carcinoma (LCNC) is defined in the urinary bladder, as in other sites, as a high-grade neoplasm exhibiting neuroendocrine features at the hematoxylin and eosin level, and high mitotic activity and evidence of neuroendocrine diff erentiation at the immunohistochemical level. Recently we observed a case of LCNC of the bladder in a 68-year-old man. The patient presented with gross hematuria of two weeks duration in October 2011. No significant clinical history was found. Urinary cytology identified malignant cells (Figure 1). Chest radiography and computerized tomography of the abdomen and pelvis showed no evidence of other primary tumours. A contrast total body CT revealed a 3x4 cm mass in the dome of the urinary bladder. Transurethral resection (TR) and subsequently radical cystoprostatectomy (CP) with bilateral lymphadenectomy (L) were performed in December 2012. The macroscopic examination of the CP revealed a 2.8x2.2 cm mass situated on the dome with infiltration of muscularis propria (Figure 2). Histologically the tumour showed organoid nesting, trabecular growth, rosettes and perilobular palisading patterns, suggesting a neuroendocrine diff erentiation. The tumour cells were large, with moderate cytoplasm. Nucleoli were frequent and prominent. Mitotic count was 12 per mm2. Large zones of necrosis were found (Figure 3). The tumour invaded the deep muscularis propria. The 56 lymph nodes were free of disease (pT2bN0). Immunohistochemical staining showed that the tumour neuroendocrine components were positive for cytokeratin 7 and for neuroendocrine markers such as neurone specific enolase (NSE) and CD 56. The PET TC total body revealed diff use liver and bone metastases in April 2013. Radiotherapy (R), chemotherapy (Ch) and adjuvant Ch were administered.

We read with great interest Sarı et al.’s paper[1] “Large cell neuroendocrine carcinoma of urinary bladder; case presentation”. The literature review of this authors is incomplete. The legend of Table I should be modified and replaced with “Published cases of pure (6 cases) or mixed (8 cases) bladder large cell neuroendocrine carcinoma”. In fact Sarı et al. included mixed tumours with the LCNC component. We examined all published pure bladder LCNC cases with exclusion of mixed neoplasms in order to establish the clinical-pathological, immunohistochemical, prognostic features of the disease[1-11]. In our review we excluded the case reported by Abenoza et al.[12]. These authors described a primary mixed adenocarcinomaneuroendocrine carcinoma of the urinary bladder of probable urachal origin. Neuroendocrine diff erentiation was confirmed by ultrastructural (neurosecretory granules) and immunohistochemical studies (chromogranin and neuronspecific enolase). Two local recurrences and multiple metastases consisted exclusively of the neuroendocrine component. The patient died 30 months aft er diagnosis with widely metastatic neuroendocrine carcinoma.

Figure 1: Urinary cytology identified malignant cells (x20 PAP).

Figure 2: The macroscopic examination of the cystoprostatectomy revealed a 2.8x2.2 cm mass situated on the dome with infiltration of muscularis propria.

Figure 3: Histologically the tumour showed organoid nesting, trabecular growth, rosettes and perilobular palisading patterns, suggesting neuroendocrine diff erentiation. The tumour cells were large, with moderate cytoplasm. Nucleoli were frequent and prominent. Mitotic count was 12 per mm2 (x40 H&E).

Table I: Pure large-cell neuroendocrine bladder carcinoma: review of the literature

Table I: Continuation

Evans et al. case[13] case was not considered because only less than 5% of the total tumour volume was adenocarcinoma. Dundr et al.’s case[14] was excluded because the tumour showed neuroendocrine markers (chromogranin A, NSE, and synaptophysin), but lymphoepithelioma-like features were found and a high-grade papillary transitional cell carcinoma was present in the overlying mucosa. The neoplasm reported by Li et al.[15] is a mixed malignancy composed of large cell neuroendocrine and mesenchymal components. Quek et al.[16] reported 25 neuroendocrine tumours of the bladder including 5 cases of LCNC of which 3 had a secondary urothelial cell carcinoma component. However, this authors did not describe the clinical-pathological, and prognostic features and these cases have therefore been excluded in present literature review. Trimeche et al.[17] described a mixed tumour composed 95% by LCNC and a high-grade urothelial invasive part (5%). Consequently the present case has not been considered in our review of “pure” LCNC. Akamatsu et al.[18] reported a case of LCNC with the presence of squamous cell carcinoma and urothelial carcinoma. This case is a bladder mixed malignant tumour. Engles et al.[19] reported one case of bladder malignancy composed of high-grade urothelial carcinoma, small cell carcinoma and LCNBC. Hata and Tasaki[20] described LCNBC localised on the anterior wall associated with urothelial carcinoma and primary lung cancer.

In conclusion pure LCNC of the bladder is a very aggressive malignancy, unresponsive to therapy.

Reference

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