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Published in:

01-06-2016

Neuroendocrine Tumors of the Prostate: Emerging Insights from Molecular Data and Updates to the 2016 World Health Organization Classification

Authors: David S. Priemer, Rodolfo Montironi, Lisha Wang, Sean R. Williamson, Antonio Lopez-Beltran, Liang Cheng

Published in: Endocrine Pathology | Issue 2/2016

Abstract

Neuroendocrine neoplasms of the prostate represent a multifarious group of tumors that exist both in pure forms and associated with prostatic adenocarcinoma. Morphologically, neuroendocrine cells in prostate neoplasms can range from being indistinguishable from surrounding prostate adenocarcinoma cells to having high-grade neuroendocrine appearances similar to neuroendocrine malignancies of other organs. On the molecular level, neuroendocrine malignancies arising in the setting of prostate adenocarcinoma have been the subject of a large amount of recent research, most of which has supported the conclusion that neuroendocrine malignancy within the prostate develops as a transdifferentiation from prostate adenocarcinoma. There has not, however, been substantial investigation into rare, pure neuroendocrine malignancies and the possibility that these tumors may have a different cell of origin and molecular genesis. Here, we discuss the morphologic spectrum of malignant neuroendocrine prostate neoplasms and review the most recent molecular data on the subject of malignant neuroendocrine differentiation in prostatic adenocarcinoma. In reflection of the most recent data, we also discuss diagnostic classification of prostate neuroendocrine tumors with reference to the 2016 World Health Organization (WHO) classification. We discuss the reporting of these tumors, placing emphasis on the differentiation between pure and mixed neuroendocrine malignancies so that, in the least, they can be easily identified for the purposes of future clinical and laboratory-based investigation. Finally, we suggest a designation for an unclassifiable (or not otherwise specified) high-grade neuroendocrine prostate malignancy whose features do not easily place it into one of the WHO diagnostic entities.

Bostwick DG, Cheng L. Urologic Surgical Pathology, third edition, Elsevier, Philadelphia, PA, 2014.

Santoni M, Conti A, Burattini L, Berardi R, Scarpelli M, Cheng L, Lopez-Beltran A, Cascinu S and Montironi R. Neuroendocrine differentiation in prostate cancer: novel morphological insights and future therapeutic perspectives. Biochim Biophys Acta. 2014; 1846(2):630–637.

Xing N, Qian J, Bostwick D, Bergstralh E and Young CY. Neuroendocrine cells in human prostate over-express the anti-apoptosis protein survivin. Prostate. 2001; 48(1):7–15.

Fisher KW, Montironi R, Lopez Beltran A, Moch H, Wang L, Scarpelli M, Williamson SR, Koch MO and Cheng L. Molecular foundations for personalized therapy in prostate cancer. Curr Drug Targets. 2015; 16(2):103–114.

Moch H, Humphrey PA, Ulbright TM and Reuter VE. (2016). WHO Classification of Tumours of the Urinary System and Male Genital Organ: World Health Organization).

Adlakha H and Bostwick DG. Paneth cell-like change in prostatic adenocarcinoma represents neuroendocrine differentiation: report of 30 cases. Hum Pathol. 1994; 25(2):135–139.

Abrahamsson PA, Cockett AT and di Sant’Agnese PA. Prognostic significance of neuroendocrine differentiation in clinically localized prostatic carcinoma. Prostate Suppl. 1998; 8:37–42.

Ahlgren G, Pedersen K, Lundberg S, Aus G, Hugosson J and Abrahamsson PA. Regressive changes and neuroendocrine differentiation in prostate cancer after neoadjuvant hormonal treatment. Prostate. 2000; 42(4):274–279.

Allen FJ, Van Velden DJ and Heyns CF. Are neuroendocrine cells of practical value as an independent prognostic parameter in prostate cancer? Br J Urol. 1995; 75(6):751–754.

10.

Aprikian AG, Cordon-Cardo C, Fair WR and Reuter VE. Characterization of neuroendocrine differentiation in human benign prostate and prostatic adenocarcinoma. Cancer. 1993; 71(12):3952–3965.

11.

Aprikian AG, Cordon-Cardo C, Fair WR, Zhang ZF, Bazinet M, Hamdy SM and Reuter VE. Neuroendocrine differentiation in metastatic prostatic adenocarcinoma. J Urol. 1994; 151(4):914–919.

12.

Bubendorf L, Sauter G, Moch H, Schmid HP, Gasser TC, Jordan P and Mihatsch MJ. Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy. J Pathol. 1996; 178(4):437–441.

13.

Casella R, Bubendorf L, Sauter G, Moch H, Mihatsch MJ and Gasser TC. Focal neuroendocrine differentiation lacks prognostic significance in prostate core needle biopsies. J Urol. 1998; 160(2):406–410.

14.

Cohen MK, Arber DA, Coffield KS, Keegan GT, McClintock J and Speights VO, Jr. Neuroendocrine differentiation in prostatic adenocarcinoma and its relationship to tumor progression. Cancer. 1994; 74(7):1899–1903.

15.

Ishida E, Nakamura M, Shimada K, Tasaki M and Konishi N. Immunohistochemical analysis of neuroendocrine differentiation in prostate cancer. Pathobiology. 2009; 76(1):30–38.

16.

Jeetle SS, Fisher G, Yang ZH, Stankiewicz E, Moller H, Cooper CS, Cuzick J, Berney DM and Trans-Atlantic Prostate G. Neuroendocrine differentiation does not have independent prognostic value in conservatively treated prostate cancer. Virchows Arch. 2012; 461(2):103–107.

17.

Noordzij MA, van der Kwast TH, van Steenbrugge GJ, Hop WJ and Schroder FH. The prognostic influence of neuroendocrine cells in prostate cancer: results of a long-term follow-up study with patients treated by radical prostatectomy. Int J Cancer. 1995; 62(3):252–258.

18.

Segawa N, Mori I, Utsunomiya H, Nakamura M, Nakamura Y, Shan L, Kakudo K and Katsuoka Y. Prognostic significance of neuroendocrine differentiation, proliferation activity and androgen receptor expression in prostate cancer. Pathol Int. 2001; 51(6):452–459.

19.

Shariff AH and Ather MH. Neuroendocrine differentiation in prostate cancer. Urology. 2006; 68(1):2–8.

20.

Speights VO, Jr., Cohen MK, Riggs MW, Coffield KS, Keegan G and Arber DA. Neuroendocrine stains and proliferative indices of prostatic adenocarcinomas in transurethral resection samples. Br J Urol. 1997; 80(2):281–286.

21.

Tamas EF and Epstein JI. Prognostic significance of paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate. Am J Surg Pathol. 2006; 30(8):980–985.

22.

Tan MO, Karaoglan U, Celik B, Ataoglu O, Biri H and Bozkirli I. Prostate cancer and neuroendocrine differentiation. Int Urol Nephrol. 1999; 31(1):75–82.

23.

Weinstein MH, Partin AW, Veltri RW and Epstein JI. Neuroendocrine differentiation in prostate cancer: enhanced prediction of progression after radical prostatectomy. Hum Pathol. 1996; 27(7):683–687.

24.

Cheville JC, Tindall D, Boelter C, Jenkins R, Lohse CM, Pankratz VS, Sebo TJ, Davis B and Blute ML. Metastatic prostate carcinoma to bone: clinical and pathologic features associated with cancer-specific survival. Cancer. 2002; 95(5):1028–1036.

25.

Jiborn T, Bjartell A and Abrahamsson PA. Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment. Urology. 1998; 51(4):585–589.

26.

Krijnen JL, Bogdanowicz JF, Seldenrijk CA, Mulder PG and van der Kwast TH. The prognostic value of neuroendocrine differentiation in adenocarcinoma of the prostate in relation to progression of disease after endocrine therapy. J Urol. 1997; 158(1):171–174.

27.

Epstein JI, Amin MB, Beltran H, Lotan TL, Mosquera JM, Reuter VE, Robinson BD, Troncoso P and Rubin MA. Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol. 2014; 38(6):756–767.

28.

Aparicio A, Tzelepi V, Araujo JC, Guo CC, Liang S, Troncoso P, Logothetis CJ, Navone NM and Maity SN. Neuroendocrine prostate cancer xenografts with large-cell and small-cell features derived from a single patient’s tumor: morphological, immunohistochemical, and gene expression profiles. Prostate. 2011; 71(8):846–856.

29.

Kaur G, Singh B, Beltran H, Akhtar NH, Nanus DM and Tagawa ST. Circulating tumor cell (CTC) enumeration in patients with metastatic neuroendocrine prostate cancer (NEPC) and castration-resistant prostate cancer (CRPC). J Clin Oncol. 2014; (32):abstr 204.

30.

Beltran H, Jendrisak A, Landers M, Mosquera JM, Kossai M, Louw J, Krupa R, Graf RP, Schreiber NA, Nanus DM, Tagawa ST, Marrinucci D, Dittamore R and Scher HI. The Initial Detection and Partial Characterization of Circulating Tumor Cells in Neuroendocrine Prostate Cancer. Clin Cancer Res. 2015.

31.

Beltran H, Rickman DS, Park K, Chae SS, Sboner A, MacDonald TY, Wang Y, Sheikh KL, Terry S, Tagawa ST, Dhir R, Nelson JB, de la Taille A, Allory Y, Gerstein MB, Perner S, et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 2011; 1(6):487–495.

32.

Nadal R, Schweizer M, Kryvenko ON, Epstein JI and Eisenberger MA. Small cell carcinoma of the prostate. Nat Rev Urol. 2014; 11(4):213–219.

33.

Yuan TC, Veeramani S and Lin MF. Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells. Endocr Relat Cancer. 2007; 14(3):531–547.

34.

Abrahamsson PA. Neuroendocrine cells in tumour growth of the prostate. Endocr Relat Cancer. 1999; 6(4):503–519.

35.

Abrahamsson PA. Neuroendocrine differentiation in prostatic carcinoma. Prostate. 1999; 39(2):135–148.

36.

Berruti A, Mosca A, Porpiglia F, Bollito E, Tucci M, Vana F, Cracco C, Torta M, Russo L, Cappia S, Saini A, Angeli A, Papotti M, Scarpa RM and Dogliotti L. Chromogranin A expression in patients with hormone naive prostate cancer predicts the development of hormone refractory disease. J Urol. 2007; 178(3 Pt 1):838–843; quiz 1129.

37.

Bonkhoff H. Neuroendocrine cells in benign and malignant prostate tissue: morphogenesis, proliferation, and androgen receptor status. Prostate Suppl. 1998; 8:18–22.

38.

Bonkhoff H, Wernert N, Dhom G and Remberger K. Relation of endocrine-paracrine cells to cell proliferation in normal, hyperplastic, and neoplastic human prostate. Prostate. 1991; 19(2):91–98.

39.

Hirano D, Okada Y, Minei S, Takimoto Y and Nemoto N. Neuroendocrine differentiation in hormone refractory prostate cancer following androgen deprivation therapy. Eur Urol. 2004; 45(5):586–592; discussion 592.

40.

Mucci NR, Akdas G, Manely S and Rubin MA. Neuroendocrine expression in metastatic prostate cancer: evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. Hum Pathol. 2000; 31(4):406–414.

41.

Clegg N, Ferguson C, True LD, Arnold H, Moorman A, Quinn JE, Vessella RL and Nelson PS. Molecular characterization of prostatic small-cell neuroendocrine carcinoma. Prostate. 2003; 55(1):55–64.

42.

Kadakia KC, Tomlins SA, Sanghvi SK, Cani AK, Omata K, Hovelson DH, Liu CJ and Cooney KA. Comprehensive serial molecular profiling of an “N of 1” exceptional non-responder with metastatic prostate cancer progressing to small cell carcinoma on treatment. J Hematol Oncol. 2015; 8(1):109.

43.

Hansel DE, Nakayama M, Luo J, Abukhdeir AM, Park BH, Bieberich CJ, Hicks JL, Eisenberger M, Nelson WG, Mostwin JL and De Marzo AM. Shared TP53 gene mutation in morphologically and phenotypically distinct concurrent primary small cell neuroendocrine carcinoma and adenocarcinoma of the prostate. Prostate. 2009; 69(6):603–609.

44.

Lapuk AV, Wu C, Wyatt AW, McPherson A, McConeghy BJ, Brahmbhatt S, Mo F, Zoubeidi A, Anderson S, Bell RH, Haegert A, Shukin R, Wang Y, Fazli L, Hurtado-Coll A, Jones EC, et al. From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer. J Pathol. 2012; 227(3):286–297.

45.

Tan HL, Sood A, Rahimi HA, Wang W, Gupta N, Hicks J, Mosier S, Gocke CD, Epstein JI, Netto GJ, Liu W, Isaacs WB, De Marzo AM and Lotan TL. Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. Clin Cancer Res. 2014; 20(4):890–903.

46.

Tzelepi V, Zhang J, Lu JF, Kleb B, Wu G, Wan X, Hoang A, Efstathiou E, Sircar K, Navone NM, Troncoso P, Liang S, Logothetis CJ, Maity SN and Aparicio AM. Modeling a lethal prostate cancer variant with small-cell carcinoma features. Clin Cancer Res. 2012; 18(3):666–677.

47.

Borges GT, Vencio EF, Quek SI, Chen A, Salvanha DM, Vencio RZ, Nguyen HM, Vessella RL, Cavanaugh C, Ware CB, Troisch P and Liu AY. Conversion of Prostate Adenocarcinoma to Small Cell Carcinoma-Like by Reprogramming. J Cell Physiol. 2016.

48.

Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA and Chinnaiyan AM. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005; 310(5748):644–648.

49.

Guo CC, Dancer JY, Wang Y, Aparicio A, Navone NM, Troncoso P and Czerniak BA. TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate. Hum Pathol. 2011; 42(1):11–17.

50.

Han B, Mehra R, Lonigro RJ, Wang L, Suleman K, Menon A, Palanisamy N, Tomlins SA, Chinnaiyan AM and Shah RB. Fluorescence in situ hybridization study shows association of PTEN deletion with ERG rearrangement during prostate cancer progression. Mod Pathol. 2009; 22(8):1083–1093.

51.

Lotan TL, Gupta NS, Wang W, Toubaji A, Haffner MC, Chaux A, Hicks JL, Meeker AK, Bieberich CJ, De Marzo AM, Epstein JI and Netto GJ. ERG gene rearrangements are common in prostatic small cell carcinomas. Mod Pathol. 2011; 24(6):820–828.

52.

Scheble VJ, Braun M, Wilbertz T, Stiedl AC, Petersen K, Schilling D, Reischl M, Seitz G, Fend F, Kristiansen G and Perner S. ERG rearrangement in small cell prostatic and lung cancer. Histopathology. 2010; 56(7):937–943.

53.

Schelling LA, Williamson SR, Zhang S, Yao JL, Wang M, Huang J, Montironi R, Lopez-Beltran A, Emerson RE, Idrees MT, Osunkoya AO, Man YG, Maclennan GT, Baldridge LA, Comperat E and Cheng L. Frequent TMPRSS2-ERG rearrangement in prostatic small cell carcinoma detected by fluorescence in situ hybridization: the superiority of fluorescence in situ hybridization over ERG immunohistochemistry. Hum Pathol. 2013; 44(10):2227–2233.

54.

Williamson SR, Zhang S, Yao JL, Huang J, Lopez-Beltran A, Shen S, Osunkoya AO, MacLennan GT, Montironi R and Cheng L. ERG-TMPRSS2 rearrangement is shared by concurrent prostatic adenocarcinoma and prostatic small cell carcinoma and absent in small cell carcinoma of the urinary bladder: evidence supporting monoclonal origin. Mod Pathol. 2011; 24(8):1120–1127.

55.

Mounir Z, Lin F, Lin VG, Korn JM, Yu Y, Valdez R, Aina OH, Buchwalter G, Jaffe AB, Korpal M, Zhu P, Brown M, Cardiff RD, Rocnik JL, Yang Y and Pagliarini R. TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation. Oncogene. 2015; 34(29):3815–3825.

56.

Wang L, Williamson SR, Zhang S, Huang J, Montironi R, Davison DD, Wang M, Yao JL, Lopez-Beltran A, Osunkoya AO, MacLennan GT, Baldridge LA, Du X and Cheng L. Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma. Mol Carcinog. 2015; 54(9):900–907.

57.

Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL and Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001; 61(9):3550–3555.

58.

Mosquera JM, Beltran H, Park K, MacDonald TY, Robinson BD, Tagawa ST, Perner S, Bismar TA, Erbersdobler A, Dhir R, Nelson JB, Nanus DM and Rubin MA. Concurrent AURKA and MYCN gene amplifications are harbingers of lethal treatment-related neuroendocrine prostate cancer. Neoplasia. 2013; 15(1):1–10.

59.

Vlachostergios PJ and Papandreou CN. Targeting neuroendocrine prostate cancer: molecular and clinical perspectives. Front Oncol. 2015; 5:6.

60.

Park K, Chen Z, MacDonald TY, Siddiqui J, Ye H, Erbersdobler A, Shevchuk MM, Robinson BD, Sanda MG, Chinnaiyan AM, Beltran H, Rubin MA and Mosquera JM. Prostate cancer with Paneth cell-like neuroendocrine differentiation has recognizable histomorphology and harbors AURKA gene amplification. Hum Pathol. 2014; 45(10):2136–2143.

61.

Pignon JC, Grisanzio C, Geng Y, Song J, Shivdasani RA and Signoretti S. p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc Natl Acad Sci U S A. 2013; 110(20):8105–8110.

62.

Yao JL, Madeb R, Bourne P, Lei J, Yang X, Tickoo S, Liu Z, Tan D, Cheng L, Hatem F, Huang J and Anthony di Sant’Agnese P. Small cell carcinoma of the prostate: an immunohistochemical study. Am J Surg Pathol. 2006; 30(6):705–712.

63.

Hu Y, Ippolito JE, Garabedian EM, Humphrey PA and Gordon JI. Molecular characterization of a metastatic neuroendocrine cell cancer arising in the prostates of transgenic mice. J Biol Chem. 2002; 277(46):44462–44474.

64.

Garabedian EM, Humphrey PA and Gordon JI. A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells. Proc Natl Acad Sci U S A. 1998; 95(26):15382–15387.

65.

Kaplan-Lefko PJ, Chen TM, Ittmann MM, Barrios RJ, Ayala GE, Huss WJ, Maddison LA, Foster BA and Greenberg NM. Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model. Prostate. 2003; 55(3):219–237.

66.

Zhou Z, Flesken-Nikitin A, Corney DC, Wang W, Goodrich DW, Roy-Burman P and Nikitin AY. Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 2006; 66(16):7889–7898.

67.

Parimi V, Goyal R, Poropatich K and Yang XJ. Neuroendocrine differentiation of prostate cancer: a review. Am J Clin Exp Urol. 2014; 2(4):273–285.

68.

Sun Y, Niu J and Huang J. Neuroendocrine differentiation in prostate cancer. Am J Transl Res. 2009; 1(2):148–162.

69.

Puccetti L, Supuran CT, Fasolo PP, Conti E, Sebastiani G, Lacquaniti S, Mandras R, Milazzo MG, Dogliani N, De Giuli P and Fasolis G. Skewing towards neuroendocrine phenotype in high grade or high stage androgen-responsive primary prostate cancer. Eur Urol. 2005; 48(2):215–221; Discussion 221–213.

70.

Tarle M, Ahel MZ and Kovacic K. Acquired neuroendocrine-positivity during maximal androgen blockade in prostate cancer patients. Anticancer Res. 2002; 22(4):2525–2529.

71.

Bollito E, Berruti A, Bellina M, Mosca A, Leonardo E, Tarabuzzi R, Cappia S, Ari MM, Tampellini M, Fontana D, Gubetta L, Angeli A and Dogliotti L. Relationship between neuroendocrine features and prognostic parameters in human prostate adenocarcinoma. Ann Oncol. 2001; 12 Suppl 2:S159-164.

72.

Cohen RJ, Glezerson G and Haffejee Z. Neuro-endocrine cells--a new prognostic parameter in prostate cancer. Br J Urol. 1991; 68(3):258–262.

73.

So JS, Gordetsky J and Epstein JI. Variant of prostatic adenocarcinoma with Paneth cell-like neuroendocrine differentiation readily misdiagnosed as Gleason pattern 5. Hum Pathol. 2014; 45(12):2388–2393.

74.

Giordano S, Tolonen T, Tolonen T, Hirsimaki S and Kataja V. A pure primary low-grade neuroendocrine carcinoma (carcinoid tumor) of the prostate. Int Urol Nephrol. 2010; 42(3):683–687.

75.

Goulet-Salmon B, Berthe E, Franc S, Chanel S, Galateau-Salle F, Kottler M, Mahoudeau J and Reznik Y. Prostatic neuroendocrine tumor in multiple endocrine neoplasia Type 2B. J Endocrinol Invest. 2004; 27(6):570–573.

76.

Whelan T, Gatfield CT, Robertson S, Carpenter B and Schillinger JF. Primary carcinoid of the prostate in conjunction with multiple endocrine neoplasia IIb in a child. J Urol. 1995; 153(3 Pt 2):1080–1082.

77.

Wang W and Epstein JI. Small cell carcinoma of the prostate. A morphologic and immunohistochemical study of 95 cases. Am J Surg Pathol. 2008; 32(1):65–71.

78.

Deorah S, Rao MB, Raman R, Gaitonde K and Donovan JF. Survival of patients with small cell carcinoma of the prostate during 1973–2003: a population-based study. BJU Int. 2012; 109(6):824–830.

79.

Agoff SN, Lamps LW, Philip AT, Amin MB, Schmidt RA, True LD and Folpe AL. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors. Mod Pathol. 2000; 13(3):238–242.

80.

Cheuk W, Kwan MY, Suster S and Chan JK. Immunostaining for thyroid transcription factor 1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas. Arch Pathol Lab Med. 2001; 125(2):228–231.

81.

Jones TD, Kernek KM, Yang XJ, Lopez-Beltran A, MacLennan GT, Eble JN, Lin H, Pan CX, Tretiakova M, Baldridge LA and Cheng L. Thyroid transcription factor 1 expression in small cell carcinoma of the urinary bladder: an immunohistochemical profile of 44 cases. Hum Pathol. 2005; 36(7):718–723.

82.

Kaufmann O and Dietel M. Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites. Histopathology. 2000; 36(5):415–420.

83.

Li AF, Li AC, Hsu CY, Li WY, Hsu HS and Chen JY. Small cell carcinomas in gastrointestinal tract: immunohistochemical and clinicopathological features. J Clin Pathol. 2010; 63(7):620–625.

84.

Lu J, Xue LY, Lu N, Zou SM, Liu XY and Wen P. Superficial primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical analysis of 15 cases. Dis Esophagus. 2010; 23(2):153–159.

85.

McCluggage WG, Kennedy K and Busam KJ. An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly TTF1 positive and which may express CK20 and P63. Am J Surg Pathol. 2010; 34(4):525–532.

86.

Yun JP, Zhang MF, Hou JH, Tian QH, Fu J, Liang XM, Wu QL and Rong TH. Primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical features of 21 cases. BMC Cancer. 2007; 7:38.

87.

Simon RA, di Sant’Agnese PA, Huang LS, Xu H, Yao JL, Yang Q, Liang S, Liu J, Yu R, Cheng L, Oh WK, Palapattu GS, Wei J and Huang J. CD44 expression is a feature of prostatic small cell carcinoma and distinguishes it from its mimickers. Hum Pathol. 2009; 40(2):252–258.

88.

Wang CC, De Marzo AM, Lotan TL and Epstein JI. Overlap of CD44 expression between prostatic small cell carcinoma and acinar adenocarcinoma. Hum Pathol. 2015; 46(4):554–557.

89.

Tsai H, Morais CL, Alshalalfa M, Tan HL, Haddad Z, Hicks J, Gupta N, Epstein JI, Netto GJ, Isaacs WB, Luo J, Mehra R, Vessella RL, Karnes RJ, Schaeffer EM, Davicioni E, et al. Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas. Clin Cancer Res. 2015; 21(24):5619–5629.

90.

Freeman C, Berg JW and Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer. 1972; 29(1):252–260.

91.

Patel DR, Gomez GA, Henderson ES and Gamarra M. Primary prostatic involvement in non-Hodgkin lymphoma. Urology. 1988; 32(2):96–98.

92.

Sarris A, Dimopoulos M, Pugh W and Cabanillas F. Primary lymphoma of the prostate: good outcome with doxorubicin-based combination chemotherapy. J Urol. 1995; 153(6):1852–1854.

93.

Nandedkar MA, Palazzo J, Abbondanzo SL, Lasota J and Miettinen M. CD45 (leukocyte common antigen) immunoreactivity in metastatic undifferentiated and neuroendocrine carcinoma: a potential diagnostic pitfall. Mod Pathol. 1998; 11(12):1204–1210.

94.

Mackey JR, Au HJ, Hugh J and Venner P. Genitourinary small cell carcinoma: determination of clinical and therapeutic factors associated with survival. J Urol. 1998; 159(5):1624–1629.

95.

Evans AJ, Humphrey PA, Belani J, van der Kwast TH and 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(6):684–693.

96.

Humphrey PA. Histological variants of prostatic carcinoma and their significance. Histopathology. 2012; 60(1):59–74.

97.

Okoye E, Choi EK, Divatia M, Miles BJ, Ayala AG and 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(12):9061–9066.

98.

Beltran H, Tomlins S, Aparicio A, Arora V, Rickman D, Ayala G, Huang J, True L, Gleave ME, Soule H, Logothetis C and Rubin MA. Aggressive variants of castration-resistant prostate cancer. Clin Cancer Res. 2014; 20(11):2846–2850.

Title: Neuroendocrine Tumors of the Prostate: Emerging Insights from Molecular Data and Updates to the 2016 World Health Organization Classification
Authors: David S. Priemer
Rodolfo Montironi
Lisha Wang
Sean R. Williamson
Antonio Lopez-Beltran
Liang Cheng
Publication date: 01-06-2016
Publisher: Springer US
Published in: Endocrine Pathology / Issue 2/2016
Print ISSN: 1046-3976
Electronic ISSN: 1559-0097
DOI: https://doi.org/10.1007/s12022-016-9421-z

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