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CORRESPONDENCE
Year : 2018  |  Volume : 14  |  Issue : 10  |  Page : 785-788

Primary large cell neuroendocrine carcinoma of the prostate in a hormone naive patient: A case report from Taiwan


1 Department of Urology, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan
2 Department of Oncology, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan
3 Department of Pathology, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan

Date of Web Publication24-Sep-2018

Correspondence Address:
Chen-Hsun Ho
Department of Urology, Taipei Medical University-Shuang Ho Hospital, No. 291 Jhongjheng Road, Jhonghe, New Taipei 23561
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.180685

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 > Abstract 


Large cell neuroendocrine carcinoma (LCNEC) of the prostate is extremely rare. Previously reported cases in the literature were almost exclusively developed in men receiving androgen deprivation therapy for prostate adenocarcinoma. We herein present a case of de novo LCNEC: A 66-year-old male was incidentally diagnosed as LCNEC after he underwent transurethral resection of prostate. The stage was T4N1M1. Therefore, the patient was treated with 6 cycles of cisplatin and etoposide in the following 6 months, which achieved a partial remission. He gave up the chance to eradicate the residual mass. Three months later, the tumor progressed rapidly. In conclusion, LCNEC is a rare prostate cancer. Our experience shows that chemotherapy with etoposide and cisplatin is effective to achieve a significant remission. However, LCNEC is highly malignant in nature, postchemotherapy surgery for the residual mass should be considered.

Keywords: Large cell, neuroendocrine tumor, transurethral resection of the prostate


How to cite this article:
Tzou KY, Cheng WH, Lee WH, Ho CH. Primary large cell neuroendocrine carcinoma of the prostate in a hormone naive patient: A case report from Taiwan. J Can Res Ther 2018;14, Suppl S3:785-8

How to cite this URL:
Tzou KY, Cheng WH, Lee WH, Ho CH. Primary large cell neuroendocrine carcinoma of the prostate in a hormone naive patient: A case report from Taiwan. J Can Res Ther [serial online] 2018 [cited 2020 Oct 31];14:785-8. Available from: https://www.cancerjournal.net/text.asp?2018/14/10/785/180685




 > Introduction Top


Large cell neuroendocrine carcinoma (LCNEC) is very rare and accounts for <0.5% of all diagnosed prostate carcinomas.[1] Only scanty case reports of LCNEC had been published.[2],[3],[4] Moreover, majority of cases result from previously treated prostate adenocarcinoma, and reports of de novo LCNEC of prostate have been extremely limited.[5],[6],[7] Little is known about the clinical course and the effective treatment plan for LCNEC of prostate. We herein report a rare case of de novo LCNEC and its response to chemotherapy.


 > Case Report Top


The 66-year-old male underwent transurethral resection of prostate because of lower urinary tract symptoms. The preoperative prostate-specific antigen (PSA) levels were 2.44 ng/mL. There is no medical and family history of malignancy. The pathologic examination of the surgical specimen revealed LCNEC of the prostate, involving more than 90% of prostate tissue. Microscopically, it showed solid sheets, trabeculae, and smaller nests of tumor cells with high nuclear cytoplasmic ratio, eosinophilic cytoplasm, and brisk mitotic activity. Large areas of tumor necrosis are noted [Figure 1]a and [Figure 1]b. Conventional acinar adenocarcinoma of prostate was not found. Immunohistochemical (IHC) stains showed diffusely positive for pan-cytokeratin, and synaptophysin [Figure 1]c and [Figure 1]d. It was focally positive for Ki-67, chromogranin, p53, and c-Myc, thyroid transcription factor-1 (TTF-1) [Figure 2]. Stains for CK7, CK20, androgen receptor (AR), PSA, p504S, p63, GATA-3, vimentin, and CD45 were negative. The results of IHC stain were summarized in [Table 1]. A computed tomography scan (CT scan) of the abdomen and pelvis [Figure 3] revealed an irregular soft mass measuring about 12 cm in diameter with pelvic wall invasion. On the basis of above finding, initial tumor, node, metastasis stage is pT4N1M1. The patient underwent 6 cycles of chemotherapy with cisplatin and etoposide. The postchemotherapy CT scan [Figure 4] showed that the tumor was obvious shrinkage, measuring about 4 cm in diameter. He refused to receive the recommended cystoprostatectomy. Three months later, he presented with abdominal pain and distention. CT scan showed progressively advanced prostate carcinoma with intestinal, ureters, and pelvic wall invasion [Figure 5].
Figure 1: Histological features of the large cell neuroendocrine carcinoma of prostate (a) Low power view showed diffuse solid sheets, trabeculae and smaller nests of tumor cells (H and E, ×100). (b) High power view showed high nuclear cytoplasmic ratio with prominent nucleoli, eosinophilic cytoplasm, and brisk mitotic activity (H and E, ×400). (c) Immunohistochemical stains showed diffuse positive for synaptophysin and (d) CK (×400)

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Figure 2: Immunohistochemistry stain of the large cell neuroendocrine carcinoma show focally positive for c-Myc (a), Ki-67 (b), thyroid transcription factor-1 (c), and p53 (d) (×400)

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Table 1: Summary of Immunohistochemical stains

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Figure 3: Computed tomography axial view of pelvis shows an irregular prostate mass (arrowhead) with left lateral wall of bladder and rectum (arrow) invasion

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Figure 4: Computed tomography axial view of pelvis shows decreased size of irregular prostate mass (arrowhead) with left lateral wall of bladder invasion. And rectum (arrow) is intact

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Figure 5: Computed tomography axial view of pelvis shows progression of prostate mass with intestinal and pelvic wall invasion

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 > Discussion Top


Neuroendocrine tumors of prostate are rare and account for 1% to 5% of all prostate cancer.[2] Most common classification is small cell carcinoma, whereas larger cell carcinoma is extremely scanty.[8] Neuroendocrine differentiation in prostatic carcinoma is most commonly presented in the form of scattered or clusters of cells with neuroendocrine features. The presentation of pure neuroendocrine tumor is rarest.[2] In 2003, the Prostate Cancer Foundation Panel reached a consensus for diagnosis of LCENC, that is the tumor cells should show morphologic evidence of neuroendocrine differentiation characterized by large nests with peripheral palisading and IHC stain should express at least one neuroendocrine marker.[5] The pathologic manifestations of our case fit these criteria.

These kind of prostate tumors could arise from consequence of the selective pressure of androgen deprivation therapy (ADT),[2],[3],[4] metastasis from lung cancer,[9],[10] or de novo growth.[5],[6],[11] Most reported LCNEC of prostate had been treated with long-term ADT. Evans et al. ever reported six of seven LCNEC of prostate had mixed adenocarcinoma and treated with ADT in his series.[2] He thought LCNEC proliferation from adenocarcinoma occur by clonal progression under the suppression effect of ADT. However, it could arise de novo via direct transformation without ADT exposure although it is extremely rare. There is only few case of de novo LCNEC reported. LCNEC is considered androgen resistant because of selection pressure of ADT. In contrast, de novo LCNEC may retain androgen dependence and respond to ADT, which were ever reported by Azad et al. and Acosta-Gonzalez et al.[5],[7] However we did not find androgen receptor expression in the IHC staining of our case. Since primary LCNEC is rare in prostate, metastasis from other origin, such as lung, should be ruled out before designated as primary prostatic LCNEC. It is still debated that whether TTF-1 could be used for differentiated primary extrapulmonary origin from metastasis of lung.[12],[13]

Due to limited case reports, the treatment of prostate LCNEC is still unclear. Some study suggested treatments of neuroendocrine tumor of prostate according to that of neuroendocrine tumor of lung. That is to say, it could be treated with platinum-containing combination chemotherapy, including combination of carboplatin, and docetaxel, or combination of cisplatin and etoposide.[14] Because LCNEC is one kind of neuroendocrine tumor, we hence used this regimen of chemotherapy. In our case, chemotherapy with cisplatin and etoposide seems to have very effective initially although the residual tumor relapsed after 3 months later. However, our case provided an implication that chemotherapy alone is not adequate in spite of well initial response with chemotherapy. We proposed multimodality treatment is necessary for controlling the disease progression.

IHC stain plays a critical role in the diagnosis of LCNEC. Nevertheless, it not only helps clinicians realize biology of this rare tumor but also provides some suggestions of treatment. For instance, IHC stain revealed high Ki-67 expression in our case. Ki-67 that expressed by cycling cells may have important therapeutic and prognostic implications. That is most of the cytotoxic chemotherapy agents are very effective in tumors with high proliferative rates. Nevertheless, some study reported that ADT is still effective in patient with AR expression.[7]

LCNEC is very aggressive and poor prognosis. However, limited published data make it difficult to know whether de novo LCNEC had different clinical prognosis from post-ADT LCNEC now although some study reported better prognosis of de novo than post-ADT LCNEC.[5]


 > Conclusion Top


LCNEC is a rare prostate cancer. Our experience shows that chemotherapy with etoposide and cisplatin is effective to achieve a significant remission. However, LCNEC is highly malignant in nature, and a multimodality treatment may be necessary.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Lima MV, Nogueira C, Oliveira JA, Muniz Neto FJ, Franco M, Tavora F. Prostatic carcinomas with neuroendocrine differentiation diagnosed in needle biopsies, a morphologic study of 7 cases among 465 sequential biopsies in a tertiary cancer center. Int Braz J Urol 2011;37:598-604.  Back to cited text no. 1
    
2.
Evans AJ, Humphrey PA, Belani J, van der Kwast TH, Srigley JR. Large cell neuroendocrine carcinoma of prostate: A clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. Am J Surg Pathol 2006;30:684-93.  Back to cited text no. 2
    
3.
Patel R, Faiena I, Geltzeiler J. Large cell differentiation of metastatic prostate cancer after androgen deprivation therapy. Can J Urol 2015;22:7752-4.  Back to cited text no. 3
    
4.
Moratalla Charcos LM, Pastor Navarro T, Cortes Vizcaino V, Osca Garcia JM, Gil Salom M. Large-cell neuroendocrine carcinoma of prostate. Case report. Arch Esp Urol 2013;66:368-71.  Back to cited text no. 4
    
5.
Acosta-Gonzalez G, Qin J, Wieczorek R, Melamed J, Deng FM, Zhou M, et al. De novo large cell neuroendocrine carcinoma of the prostate, case report and literature review. Am J Clin Exp Urol 2014;2:337-42.  Back to cited text no. 5
    
6.
Okoye E, Choi EK, Divatia M, Miles BJ, Ayala AG, Ro JY. De novo large cell neuroendocrine carcinoma of the prostate gland with pelvic lymph node metastasis: A case report with review of literature. Int J Clin Exp Pathol 2014;7:9061-6.  Back to cited text no. 6
    
7.
Azad AA, Jones EC, Chi KN. Metastatic large-cell neuroendocrine prostate carcinoma: Successful treatment with androgen deprivation therapy. Clin Genitourin Cancer 2014;12:e151-3.  Back to cited text no. 7
    
8.
di Sant'Agnese PA. Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications. Cancer 1992;70 1 Suppl: 254-68.  Back to cited text no. 8
    
9.
Shimizu K, Goto T, Maeshima A, Oyamada Y, Kato R. Prostatic metastasis of pulmonary large cell neuroendocrine carcinoma. J Cancer 2012;3:96-9.  Back to cited text no. 9
    
10.
Yoo JH, Lee JH, Kim EK, Hong YK, Lee Y, Jeong HC. Prostatic metastasis of large cell neuroendocrine carcinoma of the lung. Respirology 2009;14:772-5.  Back to cited text no. 10
    
11.
Lin D, Tan AJ, De Sousa AF, Singh-Rai R. A rare case of large cell neuroendocrine carcinoma. BMJ Case Rep 2014;2014. pii: Bcr2014206403.  Back to cited text no. 11
    
12.
Agoff SN, Lamps LW, Philip AT, Amin MB, Schmidt RA, True LD, et al. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors. Mod Pathol 2000;13:238-42.  Back to cited text no. 12
    
13.
Ordóñez NG. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol 2000;24:1217-23.  Back to cited text no. 13
    
14.
Aparicio AM, Harzstark AL, Corn PG, Wen S, Araujo JC, Tu SM, et al. Platinum-based chemotherapy for variant castrate-resistant prostate cancer. Clin Cancer Res 2013;19:3621-30.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1]



 

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