EBV-positive small cell neuroendocrine carcinoma of nasopharynx as a probably unique subtype of neuroendocrine carcinoma: a clinicopathologic study of three cases and literature review.
Humans
Male
Female
Carcinoma, Neuroendocrine
/ virology
Nasopharyngeal Neoplasms
/ virology
Middle Aged
Epstein-Barr Virus Infections
/ complications
Nasopharyngeal Carcinoma
/ virology
Immunohistochemistry
Biomarkers, Tumor
/ analysis
Herpesvirus 4, Human
/ isolation & purification
Carcinoma, Small Cell
/ virology
Adult
Aged
Biology
Clinicopathology
Epstein-Barr virus
Nasopharynx
Small cell neuroendocrine carcinoma
Journal
Diagnostic pathology
ISSN: 1746-1596
Titre abrégé: Diagn Pathol
Pays: England
ID NLM: 101251558
Informations de publication
Date de publication:
24 Jul 2024
24 Jul 2024
Historique:
received:
27
05
2024
accepted:
13
07
2024
medline:
26
7
2024
pubmed:
26
7
2024
entrez:
25
7
2024
Statut:
epublish
Résumé
There is currently scarcity of information on small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx). It is believed that this type of cancer is not associated with Epstein-Barr virus (EBV) infection and is indistinguishable from classic SCNEC occurring in other organs. Herein we provided 3 cases of nasopharyngeal mass in our hospital, two males and one female. On admission, these patients were considered nasopharyngeal carcinoma with lymph node metastasis, and one of them had liver metastasis. The nasopharyngeal mucosal tissues were biopsied for pathological examination including immunohistochemistry and in situ hybridization. PubMed database was searched for articles about SCNEC-nasopharynx published up to April 2024 in any language. The 3 cases had similar histological features of SCNEC in other organs but differed in rich- tumor-infiltrating lymphocytes (TILs). All of them stained for pancytokeratin (panCK) and epidermal growth factor receptor (EGFR). Case 1 and Case 2 diffusely expressed insulinoma-associated protein 1(INSM-1) and synaptophysin (Syn), Case 3 strongly stained for CD56 and Syn. Immunostaining of all 3 cases for p40, p63, TTF-1, CK20, S-100 and NUT showed negative. BRG-1, INI-1 and Rb were retained. And p53 all showed wild-type expression. The Ki-67 labeling indiced of case 1, 2, and 3 were 80%, 90%, and 80%, respectively. In situ hybridization showed strong and uniform nuclear positivity of EBV-encoded small RNAs (EBER) in the neoplastic cells of 3 cases. EBV-positive SCNEC-nasopharynx was exactly rare. The origin of this tumor is still controversial. It may originate from EBV-infected mucosal epithelium like nasopharyngeal carcinoma. Based on our cases and relevant literature, we found EBV-positive SCNEC-nasopharynx as a probably site-specific subtype of SCNEC with differing pathogenetic mechanism. The subtype not only virus positivity but also that it was associated with TILs and did not show p53 or Rb alterations by immunohistochemistry. It may be more responsive to treatment and have a better prognosis than classic SCNEC. We will continue to follow-up these patients and collect additional cases to further understand the unique biology of this rare solid tumor.
Sections du résumé
BACKGROUND
BACKGROUND
There is currently scarcity of information on small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx). It is believed that this type of cancer is not associated with Epstein-Barr virus (EBV) infection and is indistinguishable from classic SCNEC occurring in other organs.
MATERIALS AND METHODS
METHODS
Herein we provided 3 cases of nasopharyngeal mass in our hospital, two males and one female. On admission, these patients were considered nasopharyngeal carcinoma with lymph node metastasis, and one of them had liver metastasis. The nasopharyngeal mucosal tissues were biopsied for pathological examination including immunohistochemistry and in situ hybridization. PubMed database was searched for articles about SCNEC-nasopharynx published up to April 2024 in any language.
RESULT
RESULTS
The 3 cases had similar histological features of SCNEC in other organs but differed in rich- tumor-infiltrating lymphocytes (TILs). All of them stained for pancytokeratin (panCK) and epidermal growth factor receptor (EGFR). Case 1 and Case 2 diffusely expressed insulinoma-associated protein 1(INSM-1) and synaptophysin (Syn), Case 3 strongly stained for CD56 and Syn. Immunostaining of all 3 cases for p40, p63, TTF-1, CK20, S-100 and NUT showed negative. BRG-1, INI-1 and Rb were retained. And p53 all showed wild-type expression. The Ki-67 labeling indiced of case 1, 2, and 3 were 80%, 90%, and 80%, respectively. In situ hybridization showed strong and uniform nuclear positivity of EBV-encoded small RNAs (EBER) in the neoplastic cells of 3 cases.
CONCLUSION
CONCLUSIONS
EBV-positive SCNEC-nasopharynx was exactly rare. The origin of this tumor is still controversial. It may originate from EBV-infected mucosal epithelium like nasopharyngeal carcinoma. Based on our cases and relevant literature, we found EBV-positive SCNEC-nasopharynx as a probably site-specific subtype of SCNEC with differing pathogenetic mechanism. The subtype not only virus positivity but also that it was associated with TILs and did not show p53 or Rb alterations by immunohistochemistry. It may be more responsive to treatment and have a better prognosis than classic SCNEC. We will continue to follow-up these patients and collect additional cases to further understand the unique biology of this rare solid tumor.
Identifiants
pubmed: 39049067
doi: 10.1186/s13000-024-01526-w
pii: 10.1186/s13000-024-01526-w
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Case Reports
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
101Informations de copyright
© 2024. The Author(s).
Références
Ozgur Mete, Bruce M Wenig. Update from the 5th edition of the World Health Organization Classification of Head and Neck Tumors: overview of the 2022 WHO classification of head and neck neuroendocrine neoplasms. Head and neck pathology. 2022 ,16(1): 123–142. http:// https://doi.org/10.1007/s12105-022-01435-8
Zhenjian Cai, Mei Lin, Angel I Blanco, Jing Liu, Hui Zhu. Epstein-Barr virus-positive large cell neuroendocrine carcinoma of the nasopharynx: report of one case and review of the literature. Head and Neck Pathology. 2019, 13(3):313–317. http:// https://doi.org/10.1007/s12105-018-0963-x
Jason K Wasserman, Sylvia Papp, Andrew J Hope, Bayardo Perez-Ordóñez. Epstein-Barr virus-positive large cell neuroendocrine carcinoma of the nasopharynx: report of a case with complete clinical and radiological response after combined chemoradiotherapy. Head and neck pathology. 2018, 12(4):587–591. http:// https://doi.org/10.1007/s12105-017-0883-1
I-Hung Lin, Chung-Feng Hwang, Hsiu-Yu Huang, Chih-Yen Chien. Small cell carcinoma of the nasopharynx. Acta oto-laryngologica. 2007,127(2):206–208. http:// https://doi.org/10.1080/00016480500401027
Deviprasad Shetty, Rajeshwari Aroor, Tahir Mohammed, Adarsha T. V, Gangadhara Somayaji. Small-cell neuroendocrine carcinoma originating from the lateral nasopharyngeal wall. Ear, nose, throat J. 2008;87(11):E1-3.
pubmed: 19006052
Mohebbi Ali Reza, Daneshi Ahmad, Emami Ali Reza. Nasopharyngeal neuroendocrine carcinoma: a case report? Ear, nose, throat J. 2008;87(12):E14.
pubmed: 19105129
Georges F Hatoum, Brandon Patton, Cristiane Takita, May Abdel-Wahab, Kelly LaFave, Donald Weed, Isildinha M Reis. Small cell carcinoma of the head and neck: the university of Miami experience. International journal of radiation oncology, biology, physics. 2009 ,74(2):477–481. http:// https://doi.org/10.1016/j.ijrobp.2008.08.014
Li-yu Lee, Kai-ping Chang, Cheng-Lung Hsu, Tse-Ching Chen, Tseng-tong Kuo. Small-cell neuroendocrine carcinoma of the nasopharynx: report of a rare case lacking association with Epstein-Barr virus. International journal of surgical pathology. 2011, 19(2):199–202. http:// https://doi.org/10.1177/1066896908316904
Shunyu N Brian, Lynrah Zaren, Goyal Amit, Raphal Vandana. Small-cell neuroendocrine carcinoma of nasopharynx. Clinical Rhinology. 2012;5(3):130–1.
doi: 10.5005/jp-journals-10013-1134
Artur Aguiar, Manuel Jacome, Isabel Azevedo, Eurico Monteiro, Vera Castro. Small-cell neuroendocrine carcinoma originating from the nasopharynx: report of a rare case. Reports of practical oncology and radiotherapy. 2015, 2(3):e3814. http:// https://doi.org/10.17795/rro-3814 .
Shigeo Takahashi, Takenori Miyashita, Hiroshi Hoshikawa, Reiji Haba, Taro Togami, Toru Shibata. Accelerated hyperfractionated radiotherapy for small cell carcinoma of the nasopharynx. Head & neck. 2015, 37(5): E63–5. http:// https://doi.org/10.1002/hed.23888
Daniela Azevedo, Elisabete Rios, Lurdes Vendeira, Cristina Sarmento.Small cell neuroendocrine carcinoma of the nasopharynx: a rare case report. Autopsy & case reports. 2017 ,7(1) : 31–35. http:// https://doi.org/10.4322/acr.2017.002
Bellahammou K, Lakhdissi A, Akkar O, Kouhen F, Rais F, Dahraoui S, M’rabti H, Errihani H. Small-cell neuroendocrine carcinoma of nasopharynx: a case report. International Journal of Surgery and Medicine. 2017, 3(2):132–135. http:// https://doi.org/10.5455/ijsm.nasopharynx-carcinoma
Nishu Bhardwaj, Aanchal Kakkar, David Victor Kumar Irugu. Small cell neuroendocrine carcinoma: a rare nasopharyngeal malignancy with aggressive clinical course. Indian journal of otolaryngology and head and neck surgery : official publication of the association of otolaryngologists of india. 2018, 70(3):454–458. http:// https://doi.org/10.1007/s12070-018-1344-1
Takahiro Wakasaki, Ryuji Yasumatsu, Muneyuki Masuda, Mioko Matsuo, Akihiro Tamae, Kazuhiko Kubo, Ryunosuke Kogo, Ryutaro Uchi, Masahiko Taura, Takashi Nakagawa. Small cell carcinoma in the head and neck. The Annals of otology, rhinology, and laryngology 2019 ,128(11):1006–1012. http:// https://doi.org/10.1177/0003489419853601
Yu-Ling Zhou, Ying-Peng Peng, Qiao-Dan Liu, Xian-Zhen Chen, Jianzhong He, Wei Wei, Gui-Hua Zhong, Ya-Qin Zhang, Ye Liu, Jia-Ying Pan, Shao-Yan Feng, Zhi-Gang Liu. Clinical characteristics and prognosis of small cell carcinoma in the nasopharynx: a population-based study. Cancer control : journal of the Moffitt Cancer Center. 2022, 29:10732748221087075. http:// https://doi.org/10.1177/10732748221087075
Massimo Mesolella, Salvatore Allosso, Silvia Varricchio, Daniela Russo, Sara Pignatiello, Sarah Buono, Gaetano Motta. Small-cell carcinoma of nasopharynx: a case report of unusual localization. Ear, nose, & throat journal. 2023 , 102(1):NP13-NP18 . http:// https://doi.org/10.1177/0145561320973780
C Z Fan, H N Li, L J Dai, Z Li. Epstein-Barr virus-positive small cell neuroendocrine carcinoma of the nasopharynx: report of a case. Zhonghua bing li xue za zhi (Chinese journal of pathology). 2024, 53(1):86–88. http:// https://doi.org/10.3760/cma.j.cn112151-20230901-00117
Sai Wah Tsao, Chi Man Tsang, Kwok Wai Lo. Epstein-Barr virus infection and nasopharyngeal carcinoma. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2017, 372 (1732). http:// https://doi.org/10.1098/rstb.2016.0270
Kelli B Pointer, Huaising C Ko, Jeffrey V Brower, Matthew E Witek, Randall J Kimple, Ricardo V Lloyd, Paul M Harari, Andrew M Baschnagel. Small cell carcinoma of the head and neck: an analysis of the National Cancer Database. Oral oncology. 2017, 69:92–98. http:// https://doi.org/10.1016/j.oraloncology.2017.04.009
Jennifer L Hunt, Leon Barnes, Asterios Triantafyllou, Douglas R Gnepp, Kenneth O Devaney, Göran Stenman, Gyorgy B Halmos, Justin A Bishop, Alena Skálová, Stefan M Willems, Henrik Hellquist, Alessandra Rinaldo, Alfio Ferlito. Well-differentiated neuroendocrine carcinoma of the larynx: confusion of terminology and uncertainty of early studies. Advances in anatomic pathology. 2019, 26(4): 246–250 . http:// https://doi.org/10.1097/PAP.0000000000000236
Elenaé Vázquez-Ulloa, Marcela Lizano, Marika Sjöqvist, Leslie Olmedo-Nieva, Adriana Contreras-Paredes. Deregulation of the notch pathway as a common road in viral carcinogenesis. Reviews in medical virology. 2018, 28(5):e1988 . http:// https://doi.org/10.1002/rmv.1988
Julie George, Jing Shan Lim, Se Jin Jang, Yupeng Cun, Luka Ozretić, Gu Kong, Frauke Leenders, Xin Lu, Lynnette Fernández-Cuesta, Graziella Bosco, Christian Müller, Ilona Dahmen, Nadine S Jahchan, Kwon-Sik Park, Dian Yang, Anthony N Karnezis, Dedeepya Vaka, Angela Torres, Maia Segura Wang, Jan O Korbel, Roopika Menon, Sung-Min Chun, Deokhoon Kim, Matt Wilkerson, Neil Hayes, David Engelmann, Brigitte Pützer, Marc Bos, Sebastian Michels, Ignacija Vlasic, Danila Seidel, Berit Pinther, Philipp Schaub, Christian Becker, Janine Altmüller, Jun Yokota, Takashi Kohno, Reika Iwakawa, Koji Tsuta, Masayuki Noguchi, Thomas Muley, Hans Hoffmann, Philipp A Schnabel, Iver Petersen, Yuan Chen, Alex Soltermann, Verena Tischler, Chang-min Choi, Yong-Hee Kim, Pierre P Massion, Yong Zou, Dragana Jovanovic, Milica Kontic, Gavin M Wright, Prudence A Russell, Benjamin Solomon, Ina Koch, Michael Lindner, Lucia A Muscarella, Annamaria la Torre, John K Field, Marko Jakopovic, Jelena Knezevic, Esmeralda Castaños-Vélez, Luca Roz, Ugo Pastorino, Odd-Terje Brustugun, Marius Lund-Iversen, Erik Thunnissen, Jens Köhler, Martin Schuler, Johan Botling, Martin Sandelin, Montserrat Sanchez-Cespedes, Helga B Salvesen, Viktor Achter, Ulrich Lang, Magdalena Bogus, Peter M Schneider, Thomas Zander, Sascha Ansén, Michael Hallek, Jürgen Wolf, Martin Vingron, Yasushi Yatabe, William D Travis, Peter Nürnberg, Christian Reinhardt, Sven Perner, Lukas Heukamp, Reinhard Büttner, Stefan A Haas, Elisabeth Brambilla, Martin Peifer, Julien Sage, Roman K Thomas.Comprehensive genomic profiles of small cell lung cancer. Nature, 2015 ,524 (7563): 47–53 . http:// https://doi.org/10.1038/nature14664
Xintong Peng, Yanling Zhou, Yongguang Tao, Shuang Liu. Nasopharyngeal carcinoma: the role of the EGFR in epstein-barr virus infection. Pathogens (Basel, Switzerland) . 2021, 10 (9). http:// https://doi.org/10.3390/pathogens10091113
Elena Levantini, Giorgia Maroni, Marzia Del Re, Daniel G Tenen. EGFR signaling pathway as therapeutic target in human cancers. Seminars in cancer biology 2022, 85:253–275. http:// https://doi.org/10.1016/j.semcancer.2022.04.002
Enrico Caliman, Sara Fancelli, Giulia Petroni, Marta Rita Gatta Michelet, Federica Cosso, Carlotta Ottanelli, Francesca Mazzoni, Luca Voltolini, Serena Pillozzi, Lorenzo Antonuzzo. Challenges in the treatment of small cell lung cancer in the era of immunotherapy and molecular classification. Lung cancer (Amsterdam, Netherlands) . 2023, 175:88–100. http:// https://doi.org/10.1016/j.lungcan.2022.11.014
L Bonanno, A Pavan, M V Dieci, E Di Liso, M Schiavon, G Comacchio, I Attili, G Pasello, F Calabrese, F Rea, A Favaretto, M Rugge, V Guarneri, M Fassan, P F Conte. The role of immune microenvironment in small-cell lung cancer: distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytes. European journal of cancer. 2018, 101:191–200. http:// https://doi.org/10.1016/j.ejca.2018.06.023