oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2020-19-5-97-107oncotomsk-1584Research ArticleОБЗОРЫREVIEWSНЕЙРОЭНДОКРИННЫЕ ОПУХОЛИ ШЕЙКИ МАТКИNEUROENDOCRINE TUMORS OF THE CERVIXСафроноваК. В.SafronovaK. V.

аспирант отделения онкогинекологии, 197758, пос. Песочный, ул. Ленинградская, 68;

кафедра онкологии, 191015, г. Санкт-Петербург, ул. Кирочная, 41

MD, Postgraduate, Gynecological Oncology Department, 68, Leningradskaya Street, Pesochny, 19775, St-Petersburg;

Oncology Department, 41, Kirochnaya Street, 191015, St-Petersburg

kristina-skalli@yandex.ruАртемьеваА. С.ArtemievaA. S.

кандидат медицинских наук, руководитель научной лаборатории морфологии опухолей, заведующая патологоанатомическим отделением с прозектурой,

197758, пос. Песочный, ул. Ленинградская, 68

MD, PhD, Head of Laboratory of Cancer Morphology, Head of Pathology Department,

68, Leningradskaya Street, Pesochny, 19775, St-Petersburg

НюганенА. О.NuganenA. O.

врач-патологоанатом, 

197758, пос. Песочный, ул. Ленинградская, 68

MD, Pathologist,

68, Leningradskaya Street, Pesochny, 19775, St-Petersburg

КутушеваГ. Ф.KutushevaG. F.

доктор медицинских наук, профессор кафедры акушерства и гинекологии,

197022, г. Санкт-Петербург, ул. Льва Толстого, 6–8

MD, PhD, Professor, Department of Obstetrics and Gynecology,

6–8, Lev Tostoy Street, 197022, St-Petersburg

ЧугловаД. А.ChuglovaD. A.

врач-патологоанатом,

197758, пос. Песочный, ул. Ленинградская, 68

MD, Pathologist,

68, Leningradskaya Street, Pesochny, 19775, St-Petersburg

МикаяН. А.MikayaN. A.

кандидат медицинских наук, заведующий отделением онкогинекологии, 

197758, пос. Песочный, ул. Ленинградская, 68

MD, PhD, Head of Gynecologic Oncology Department,

68, Leningradskaya Street, Pesochny, 19775, St-Petersburg

БерлевИ. В.BerlevI. V.

доктор медицинских наук, профессор, руководитель научного отделения онкогинекологии, 197758, пос. Песочный, ул. Ленинградская, 68;

заведующий кафедрой акушерства и гинекологии, 191015, г. Санкт-Петербург, ул. Кирочная, 41

MD, PhD, Professor, Head of Gynecologic Oncology Department, 68, Leningradskaya Street, Pesochny, 19775, St-Petersburg;

Head of Department of Obstetrics and Gynecology, 41, Kirochnaya Street, 191015, St-Petersburg

УрманчееваА. Ф.UrmancheevaA. F.

доктор медицинских наук, профессор, ведущий научный сотрудник отделения онкогинекологии, 197758, пос. Песочный, ул. Ленинградская, 68;

профессор кафедры онкологии, 191015, г. Санкт-Петербург, ул. Кирочная, 41

MD, PhD, Professor, Leading Researcher, Gynecologic Oncology Department, 68, Leningradskaya Street, Pesochny, 19775, St-Petersburg;

Professor of Oncology Department, 41, Kirochnaya Street, 191015, St-Petersburg

БеляевА. М.BelyaevA. M.

доктор медицинских наук, профессор, директор,197758, пос. Песочный, ул. Ленинградская, 68;

заведующий кафедрой онкологии, 191015, г. Санкт-Петербург, ул. Кирочная, 41

MD, PhD, Professor, Director, 68, Leningradskaya Street, Pesochny, 19775, St-Petersburg

Head of Oncology Department, 41, Kirochnaya Street, 191015, St-Petersburg

УльрихЕ. А.UlrichE. A.

доктор медицинских наук, профессор, врач отделения онкогинекологии, 191015, г. Санкт-Петербург, ул. Кирочная, 41;

профессор кафедры акушерства и гинекологии с курсом гинекологии детского возраста, 194100, г. Санкт-Петербург, ул. Литовская, 2

MD, PhD, Professor, Gynecologic Oncology Department, 68, Leningradskaya Street, Pesochny, 19775, St-Petersburg;

41, Kirochnaya Street, 191015, St-Petersburg;

Professor of the Department of Obstetrics and Gynecology, 2, Litovskaya Street, 194100, St-Petersburg

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава России; ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава РоссииРоссияN.N. Petrov National Medical Research Center of Oncology; I.I. Mechnikov Northwestern State Medical UniversityRussian FederationФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииРоссияN.N. Petrov National Medical Research Center of OncologyRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава РоссииРоссияI.P. Pavlov First Saint Petersburg State Medical UniversityRussian FederationФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава России 197758, пос. Песочный, ул. Ленинградская, 68 ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России; ФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава РоссииРоссияN.N. Petrov National Medical Research Center of Oncology; I.I. Mechnikov Northwestern State Medical University; Saint Petersburg State Pediatric Medical UniversityRussian Federation20202810202019597107Copyright © Сафронова К.В., Артемьева А.С., Нюганен А.О., Кутушева Г.Ф., Чуглова Д.А., Микая Н.А., Берлев И.В., Урманчеева А.Ф., Беляев А.М., Ульрих Е.А., 20202020Сафронова К.В., Артемьева А.С., Нюганен А.О., Кутушева Г.Ф., Чуглова Д.А., Микая Н.А., Берлев И.В., Урманчеева А.Ф., Беляев А.М., Ульрих Е.А.Safronova K.V., Artemieva A.S., Nuganen A.O., Kutusheva G.F., Chuglova D.A., Mikaya N.A., Berlev I.V., Urmancheeva A.F., Belyaev A.M., Ulrich E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/1584

Цель исследования – обобщение имеющихся данных об особенности этиологии и диагностики, клинической картине и различных подходах в лечении нейроэндокринных опухолей шейки матки.

Материал и методы

Материал и методы. Поиск соответствующих источников производился в системах PubMed и cochrane Library, анализировались публикации с 1980 по 2019 г., 53 из которых были использованы для написания данного обзора. Также в публикации освещены 6 случаев собственных наблюдений в НМИЦ онкологии им. Н.Н. Петрова.

Результаты

Результаты. Нейроэндокринные опухоли (НЭО) являются крайне редкими и агрессивными злокачественными новообразованиями нижнего женского полового тракта, среди которых НЭО шейки матки встречаются чаще всего. Из-за редкости этих опухолей в настоящее время отсутствуют стандарты по лечению, основанные на проспективных, хорошо спланированных клинических исследованиях. По этим причинам НЭО представляют собой актуальную проблему для клиницистов. По данным собственных наблюдений, в НМИЦ онкологии им. Н.Н. Петрова средний возраст пациенток (n=6) составил 46 лет, возрастной диапазон 32–71 год; распределение по гистотипу: крупноклеточная нейроэндокринная карцинома – 4, мелкоклеточная нейроэндокринная карцинома – 2 пациентки. Одна пациентка с IIIA стадией выбыла из наблюдения; из 5 прослеженных 2 пациентки с IIIA и IIB стадией умерли от прогрессирования заболевания через 6 и 11 мес соответственно, 1 пациентка с IB1 стадией после комбинированного лечения находится в ремиссии 16 мес. Две пациентки со IIB стадией в настоящее время продолжают получать первичное лечение.

Заключение

Заключение. Основная клиническая проблема заключается в редкой встречаемости данного гистологического подтипа опухоли шейки матки. Выбор тактики лечения решается мультидисциплинарно и требует дальнейших исследований. 

The purpose of the study was to summarize the available data on etiology, diagnosis, clinical symptoms and signs as well as on various approaches to the treatment of neuroendocrine cervical tumors.

Material and Methods

Material and Methods. The relevant sources were searched in the PubMed and cochrane Library systems, and publications from 1980 to 2019 were analyzed, 53 of which were used to write this review. We also included 6 case reports from N.N. Petrov National Research Center of Oncology.

Results

Results. Neuroendocrine tumors (NETs) are extremely rare and aggressive malignancies of the female genital tract, among which NETs of the cervix are the most common. Due to the rarity of these tumors, there are currently no treatment standards based on prospective, well-planned clinical trials. For these reasons, NETs present a significant therapeutic challenge for clinicians. Case reports. Six patients ranged in age from 32 to 71 years, with a median age of 46 years, were diagnosed with large-cell neuroendocrine carcinoma (4 patients) and small-cell neuroendocrine carcinoma (2 patients). One patient with stage IIIA dropped out of the follow-up schedule. Out of 5 followed up patients, 2 patients with stage IIIA and IIB died of disease progression after 6 and 11 months, respectively. One patient with stage IB1 is in remission for 16 months. Two patients with stage IIB continue to receive primary treatment.

Conclusion

Conclusion. Neuroendocrine carcinoma of the cervix is a rare variant of cervical cancer. The choice of treatment options is decided only by a multidisciplinary team of doctors, and further research is required. 

нейроэндокринные карциномынейроэндокринные неоплазиинейроэндокринные опухолишейка маткиneuroendocrine carcinomasneuroendocrine neoplasiasneuroendocrine tumorscervixReferencesTavassoli F.A., Devilee P. Pathology and genetics of tumors of the breast and female genital organs. WHO, IARC Press. Verh Dtsch Ges Pathol 2002; 86: 116–9.Tavassoli F.A., Devilee P. Pathology and genetics of tumors of the breast and female genital organs. WHO, IARC Press. Verh Dtsch Ges Pathol 2002; 86: 116–9.Kurman R.J., Carcangiu M.L., Herrington C.S. WHO classification of tumours of the female reproductive organs. Lyon IARC Press, 2014. 540 p.Kurman R.J., Carcangiu M.L., Herrington C.S. WHO classification of tumours of the female reproductive organs. Lyon IARC Press, 2014. 540 p.Ambros R.A., Park J.S., Shah K.V., Kurman R.J. Evaluation of histologic, morphometric, and immunohistochemical criteria in the differential diagnosis of small cell carcinomas of the cervix with particular reference to human papillomavirus types 16 and 18. Mod Pathol. 1991 Sep; 4(5): 586–93.Ambros R.A., Park J.S., Shah K.V., Kurman R.J. Evaluation of histologic, morphometric, and immunohistochemical criteria in the differential diagnosis of small cell carcinomas of the cervix with particular reference to human papillomavirus types 16 and 18. Mod Pathol. 1991 Sep; 4(5): 586–93.Gadducci A., Carinelli S., Aletti G. Neuroendrocrine tumors of the uterine cervix: A therapeutic challenge for gynecologic on- cologists. Gynecol Oncol. 2017 Mar; 144(3): 637–646. doi: 10.1016/j.ygyno.2016.12.003.Gadducci A., Carinelli S., Aletti G. Neuroendrocrine tumors of the uterine cervix: A therapeutic challenge for gynecologic on- cologists. Gynecol Oncol. 2017 Mar; 144(3): 637–646. doi: 10.1016/j.ygyno.2016.12.003.Kim J.Y., Hong S.M., Ro J.Y. Recent updates on grading and classification of neuroendocrine tumors. Ann Diagn Pathol. 2017 Aug; 29: 11–16. doi: 10.1016/j.anndiagpath.2017.04.005.Kim J.Y., Hong S.M., Ro J.Y. Recent updates on grading and classification of neuroendocrine tumors. Ann Diagn Pathol. 2017 Aug; 29: 11–16. doi: 10.1016/j.anndiagpath.2017.04.005.Guadagno E., De Rosa G., Del Basso De Caro M. Neuroendocrine tumours in rare sites: differences in nomenclature and diagnostics - a rare and ubiquitous histotype. J Clin Pathol. 2016 Jul; 69(7): 563–74. doi: 10.1136/jclinpath-2015-203551.Guadagno E., De Rosa G., Del Basso De Caro M. Neuroendocrine tumours in rare sites: differences in nomenclature and diagnostics - a rare and ubiquitous histotype. J Clin Pathol. 2016 Jul; 69(7): 563–74. doi: 10.1136/jclinpath-2015-203551.Salvo G., Gonzalez Martin A., Gonzales N.R., Frumovitz M. Updates and management algorithm for neuroendocrine tumors of the uterine cervix. Int J Gynecol Cancer. 2019 Jul; 29(6): 986–995. doi: 10.1136/ijgc-2019-000504.Salvo G., Gonzalez Martin A., Gonzales N.R., Frumovitz M. Updates and management algorithm for neuroendocrine tumors of the uterine cervix. Int J Gynecol Cancer. 2019 Jul; 29(6): 986–995. doi: 10.1136/ijgc-2019-000504.Klimstra D.S., Modlin I.R., Coppola D., Lloyd R.V., Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010; 39(6): 707–12. doi: 10.1097/MPA.0b013e3181ec124e.Klimstra D.S., Modlin I.R., Coppola D., Lloyd R.V., Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010; 39(6): 707–12. doi: 10.1097/MPA.0b013e3181ec124e.Guadagno E., De Rosa G., Del Basso De Caro M. Neuroendocrine tumours in rare sites: differences in nomenclature and diagnostics-a rare and ubiquitous histotype. J Clin Pathol. 2016; 69(7): 563–74. doi: 10.1136/jclinpath-2015-203551.Guadagno E., De Rosa G., Del Basso De Caro M. Neuroendocrine tumours in rare sites: differences in nomenclature and diagnostics-a rare and ubiquitous histotype. J Clin Pathol. 2016; 69(7): 563–74. doi: 10.1136/jclinpath-2015-203551.Travis W.D., Brambilla E., Burke A.P., Marx A., Nicholson A.G. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol. 2015 Sep; 10(9): 1240–1242. doi: 10.1097/JTO.0000000000000663.Travis W.D., Brambilla E., Burke A.P., Marx A., Nicholson A.G. Introduction to The 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. J Thorac Oncol. 2015 Sep; 10(9): 1240–1242. doi: 10.1097/JTO.0000000000000663.Chen J., Macdonald O.K., Gaffney D.K. Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix. Obstet Gynecol. 2008 Jun; 111(6): 1394–402. doi: 10.1097/AOG.0b013e318173570b.Chen J., Macdonald O.K., Gaffney D.K. Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix. Obstet Gynecol. 2008 Jun; 111(6): 1394–402. doi: 10.1097/AOG.0b013e318173570b.Margolis B., Tergas A.I., Chen L., Hou J.Y., Burke W.M., Hu J.C., Ananth C.V., Neugut A.I., Hershman D.L., Wright J.D. Natural history and outcome of neuroendocrine carcinoma of the cervix. Gynecol Oncol. 2016 May; 141(2): 247–254. doi: 10.1016/j.ygyno.2016.02.008.Margolis B., Tergas A.I., Chen L., Hou J.Y., Burke W.M., Hu J.C., Ananth C.V., Neugut A.I., Hershman D.L., Wright J.D. Natural history and outcome of neuroendocrine carcinoma of the cervix. Gynecol Oncol. 2016 May; 141(2): 247–254. doi: 10.1016/j.ygyno.2016.02.008.Abeler V.M., Holm R., Nesland J.M., Kjørstad K.E. Small cell carcinoma of the cervix. A clinicopathologic study of 26 patients. Cancer. 1994; 73(3): 672–7. doi: 10.1002/1097-0142(19940201)73:33.0.co;2-r.Abeler V.M., Holm R., Nesland J.M., Kjørstad K.E. Small cell carcinoma of the cervix. A clinicopathologic study of 26 patients. Cancer. 1994; 73(3): 672–7. doi: 10.1002/1097-0142(19940201)73:33.0.co;2-r.Toki T., Katayama Y., Motoyama T. Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro-invasive squamous cell carcinoma and adenocarcinoma in situ. Pathol Int. 1996 Jul; 46(7): 520–5. doi: 10.1111/j.1440-1827.1996.tb03648.x.Toki T., Katayama Y., Motoyama T. Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro-invasive squamous cell carcinoma and adenocarcinoma in situ. Pathol Int. 1996 Jul; 46(7): 520–5. doi: 10.1111/j.1440-1827.1996.tb03648.x.Hara H., Ishii E., Hondo T., Nakagawa M., Teramoto K., Oyama T. Cytological features of atypical carcinoid combined with adenocarcinoma of the uterine cervix. Diagn Cytopathol. 2012 Aug; 40(8): 724–8. doi: 10.1002/dc.21657. PMID: 21394936.Hara H., Ishii E., Hondo T., Nakagawa M., Teramoto K., Oyama T. Cytological features of atypical carcinoid combined with adenocarcinoma of the uterine cervix. Diagn Cytopathol. 2012 Aug; 40(8): 724–8. doi: 10.1002/dc.21657. PMID: 21394936.Muñoz N., Bosch F.X., de Sanjosé S., Herrero R., Castellsagué X., Shah K.V., Snijders P.J., Meijer C.J.; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003 Feb 6; 348(6): 518–27. doi: 10.1056/NEJMoa021641.Muñoz N., Bosch F.X., de Sanjosé S., Herrero R., Castellsagué X., Shah K.V., Snijders P.J., Meijer C.J.; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003 Feb 6; 348(6): 518–27. doi: 10.1056/NEJMoa021641.de Sanjose S., Quint W.G., Alemany L., Geraets D.T., Klaustermeier J.E., Lloveras B., Tous S., Felix A., Bravo L.E., Shin H.R., Vallejos C.S., de Ruiz P.A., Lima M.A., Guimera N., Clavero O., Alejo M., LlombartBosch A., Cheng-Yang C., Tatti S.A., Kasamatsu E., Iljazovic E., Odida M., Prado R., Seoud M., Grce M., Usubutun A., Jain A., Suarez G.A., Lombardi L.E., Banjo A., Menéndez C., Domingo E.J., Velasco J., Nessa A., Chichareon S.C., Qiao Y.L., Lerma E., Garland S.M., Sasagawa T., Ferrera A., Hammouda D., Mariani L., Pelayo A., Steiner I., Oliva E., Meijer C.J., Al-Jassar W.F., Cruz E., Wright T.C., Puras A., Llave C.L., Tzardi M., Agorastos T., Garcia-Barriola V., Clavel C., Ordi J., Andújar M., Castellsagué X., Sánchez G.I., Nowakowski A.M., Bornstein J., Muñoz N., Bosch F.X.; Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010; 11(11): 1048–56. doi: 10.1016/S1470-2045(10)70230-8.de Sanjose S., Quint W.G., Alemany L., Geraets D.T., Klaustermeier J.E., Lloveras B., Tous S., Felix A., Bravo L.E., Shin H.R., Vallejos C.S., de Ruiz P.A., Lima M.A., Guimera N., Clavero O., Alejo M., LlombartBosch A., Cheng-Yang C., Tatti S.A., Kasamatsu E., Iljazovic E., Odida M., Prado R., Seoud M., Grce M., Usubutun A., Jain A., Suarez G.A., Lombardi L.E., Banjo A., Menéndez C., Domingo E.J., Velasco J., Nessa A., Chichareon S.C., Qiao Y.L., Lerma E., Garland S.M., Sasagawa T., Ferrera A., Hammouda D., Mariani L., Pelayo A., Steiner I., Oliva E., Meijer C.J., Al-Jassar W.F., Cruz E., Wright T.C., Puras A., Llave C.L., Tzardi M., Agorastos T., Garcia-Barriola V., Clavel C., Ordi J., Andújar M., Castellsagué X., Sánchez G.I., Nowakowski A.M., Bornstein J., Muñoz N., Bosch F.X.; Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010; 11(11): 1048–56. doi: 10.1016/S1470-2045(10)70230-8.Alejo M., Alemany L., Clavero O., Quiros B., Vighi S., Seoud M., Cheng-Yang C., Garland S.M., Juanpere N., Lloreta J., Tous S., Klaustermeier J.E., Quint W., Bosch F.X., de Sanjosé S., Lloveras B.; RIS HPV TT study group. Contribution of Human papillomavirus in neuroendocrine tumors from a series of 10,575 invasive cervical cancer cases. Papillomavirus Res. 2018; 5: 134–142. doi: 10.1016/j.pvr.2018.03.005.Alejo M., Alemany L., Clavero O., Quiros B., Vighi S., Seoud M., Cheng-Yang C., Garland S.M., Juanpere N., Lloreta J., Tous S., Klaustermeier J.E., Quint W., Bosch F.X., de Sanjosé S., Lloveras B.; RIS HPV TT study group. Contribution of Human papillomavirus in neuroendocrine tumors from a series of 10,575 invasive cervical cancer cases. Papillomavirus Res. 2018; 5: 134–142. doi: 10.1016/j.pvr.2018.03.005.Lai C.H., Chang C.J., Huang H.J., Hsueh S., Chao A., Yang J.E., Lin C.T., Huang S.L., Hong J.H., Chou H.H., Wu T.I., Huang K.G., Wang C.C., Chang T.C. Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery. J Clin Oncol. 2007 Aug 20; 25(24): 3628–34. doi: 10.1200/JCO.2007.11.2995.Lai C.H., Chang C.J., Huang H.J., Hsueh S., Chao A., Yang J.E., Lin C.T., Huang S.L., Hong J.H., Chou H.H., Wu T.I., Huang K.G., Wang C.C., Chang T.C. Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery. J Clin Oncol. 2007 Aug 20; 25(24): 3628–34. doi: 10.1200/JCO.2007.11.2995.Kasuga Y., Miyakoshi K., Nishio H., Akiba Y., Otani T., Fukutake M., Ikenoue S., Ochiai D., Matsumoto T., Tanaka K., Minegishi K., Kuji N., Roberts R., Aoki D., Tanaka M. Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis. BJOG. 2017; 124(11): 1729–1735. doi: 10.1111/1471-0528.14688.Kasuga Y., Miyakoshi K., Nishio H., Akiba Y., Otani T., Fukutake M., Ikenoue S., Ochiai D., Matsumoto T., Tanaka K., Minegishi K., Kuji N., Roberts R., Aoki D., Tanaka M. Mid-trimester residual cervical length and the risk of preterm birth in pregnancies after abdominal radical trachelectomy: a retrospective analysis. BJOG. 2017; 124(11): 1729–1735. doi: 10.1111/1471-0528.14688.Castle P.E., Pierz A., Stoler M.H. A systematic review and metaanalysis on the attribution of human papillomavirus (HPV) in neuroendocrine cancers of the cervix. Gynecol Oncol. 2018; 148(2): 422–9. doi: 10.1016/j.ygyno.2017.12.001.Castle P.E., Pierz A., Stoler M.H. A systematic review and metaanalysis on the attribution of human papillomavirus (HPV) in neuroendocrine cancers of the cervix. Gynecol Oncol. 2018; 148(2): 422–9. doi: 10.1016/j.ygyno.2017.12.001.Howitt B.E., Kelly P., McCluggage W.G. Pathology of Neuroendocrine Tumours of the Female Genital Tract. Curr Oncol Rep. 2017 Sep; 19(9): 59. doi: 10.1007/s11912-017-0617-2.Howitt B.E., Kelly P., McCluggage W.G. Pathology of Neuroendocrine Tumours of the Female Genital Tract. Curr Oncol Rep. 2017 Sep; 19(9): 59. doi: 10.1007/s11912-017-0617-2.Giorgadze T., Kanhere R., Pang C., Ganote C., Miller L.E., Tabaczka P., Brown E., Husain M. Small cell carcinoma of the cervix in liquid-based Pap test: utilization of split-sample immunocytochemical and molecular analysis. Diagn Cytopathol. 2012 Mar; 40(3): 214–9. doi: 10.1002/dc.21542.Giorgadze T., Kanhere R., Pang C., Ganote C., Miller L.E., Tabaczka P., Brown E., Husain M. Small cell carcinoma of the cervix in liquid-based Pap test: utilization of split-sample immunocytochemical and molecular analysis. Diagn Cytopathol. 2012 Mar; 40(3): 214–9. doi: 10.1002/dc.21542.McCluggage W.G., Kennedy K., Busam K.J. 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 Apr; 34(4): 525–32. doi: 10.1097/PAS.0b013e3181d1d457.McCluggage W.G., Kennedy K., Busam K.J. 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 Apr; 34(4): 525–32. doi: 10.1097/PAS.0b013e3181d1d457.Houghton O., McCluggage W.G. The expression and diagnostic utility of p63 in the female genital tract. Adv Anat Pathol. 2009 Sep; 16(5): 316–21. doi: 10.1097/PAP.0b013e3181b507c6.Houghton O., McCluggage W.G. The expression and diagnostic utility of p63 in the female genital tract. Adv Anat Pathol. 2009 Sep; 16(5): 316–21. doi: 10.1097/PAP.0b013e3181b507c6.Chan J.K., Tsui W.M., Tung S.Y., Ching R.C. Endocrine cell hyperplasia of the uterine cervix. A precursor of neuroendocrine carcinoma of the cervix? Am J Clin Pathol. 1989 Dec; 92(6): 825–30. doi: 10.1093/ajcp/92.6.825.Chan J.K., Tsui W.M., Tung S.Y., Ching R.C. Endocrine cell hyperplasia of the uterine cervix. A precursor of neuroendocrine carcinoma of the cervix? Am J Clin Pathol. 1989 Dec; 92(6): 825–30. doi: 10.1093/ajcp/92.6.825.Deng G.H., Zhang X., Wu L.Y. Clinicopathological analysis of nine cases of small cell carcinoma of the uterine cervix. Zhonghua Zhong Liu Za Zhi. 2010 Mar; 32(3): 199–202.Deng G.H., Zhang X., Wu L.Y. Clinicopathological analysis of nine cases of small cell carcinoma of the uterine cervix. Zhonghua Zhong Liu Za Zhi. 2010 Mar; 32(3): 199–202.Albores-Saavedra J., Gersell D., Gilks C.B., Henson D.E., Lindberg G., Santiago H., Scully R.E., Silva E., Sobin L.H., Tavassoli F.J., Travis W.D., Woodruff J.M. Terminology of endocrine tumors of the uterine cervix: results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute. Arch Pathol Lab Med. 1997 Jan; 121(1): 34–9.Albores-Saavedra J., Gersell D., Gilks C.B., Henson D.E., Lindberg G., Santiago H., Scully R.E., Silva E., Sobin L.H., Tavassoli F.J., Travis W.D., Woodruff J.M. Terminology of endocrine tumors of the uterine cervix: results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute. Arch Pathol Lab Med. 1997 Jan; 121(1): 34–9.Lojek M.A., Fer M.F., Kasselberg A.G., Glick A.D., Burnett L.S., Julian C.G., Greco F.A., Oldham R.K. Cushing’s syndrome with small cell carcinoma of the uterine cervix. Am J Med. 1980; 69(1): 140–4. doi: 10.1016/0002-9343(80)90513-6.Lojek M.A., Fer M.F., Kasselberg A.G., Glick A.D., Burnett L.S., Julian C.G., Greco F.A., Oldham R.K. Cushing’s syndrome with small cell carcinoma of the uterine cervix. Am J Med. 1980; 69(1): 140–4. doi: 10.1016/0002-9343(80)90513-6.Ishibashi-Ueda H., Imakita M., Yutani C., Ohmichi M., Chiba Y., Kubo T., Waki M. Small cell carcinoma of the uterine cervix with syndrome of inappropriate antidiuretic hormone secretion. Mod Pathol. 1996 Apr; 9(4): 397–400.Ishibashi-Ueda H., Imakita M., Yutani C., Ohmichi M., Chiba Y., Kubo T., Waki M. Small cell carcinoma of the uterine cervix with syndrome of inappropriate antidiuretic hormone secretion. Mod Pathol. 1996 Apr; 9(4): 397–400.Koch C.A., Azumi N., Furlong M.A., Jha R.C., Kehoe T.E., Trowbridge C.H., O’Dorisio T.M., Chrousos G.P., Clement S.C. Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. J Clin Endocrinol Metab. 1999 Nov; 84(11): 4209–13. doi: 10.1210/jcem.84.11.6126.Koch C.A., Azumi N., Furlong M.A., Jha R.C., Kehoe T.E., Trowbridge C.H., O’Dorisio T.M., Chrousos G.P., Clement S.C. Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. J Clin Endocrinol Metab. 1999 Nov; 84(11): 4209–13. doi: 10.1210/jcem.84.11.6126.Boruta D.M.2nd, Schorge J.O., Duska L.A., Crum C.P., Castrillon D.H., Sheets E.E. Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix. Gynecol Oncol. 2001; 81(1): 82–7. doi: 10.1006/gyno.2000.6118.Boruta D.M.2nd, Schorge J.O., Duska L.A., Crum C.P., Castrillon D.H., Sheets E.E. Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix. Gynecol Oncol. 2001; 81(1): 82–7. doi: 10.1006/gyno.2000.6118.Wang H.L., Lu D.W. Detection of human papillomavirus DNA and expression of p16, Rb, and p53 proteins in small cell carcinomas of the uterine cervix. Am J Surg Pathol. 2004; 28(7): 901–8. doi: 10.1097/00000478-200407000-00009.Wang H.L., Lu D.W. Detection of human papillomavirus DNA and expression of p16, Rb, and p53 proteins in small cell carcinomas of the uterine cervix. Am J Surg Pathol. 2004; 28(7): 901–8. doi: 10.1097/00000478-200407000-00009.Kuroda N., Wada Y., Inoue K., Ohara M., Mizuno K., Toi M., Tanaka A., Wani Y., Yanai H. Smear cytology findings of large cell neuroendocrine carcinoma of the uterine cervix. Diagn Cytopathol. 2013; 41(7): 636–9. doi: 10.1002/dc.21834.Kuroda N., Wada Y., Inoue K., Ohara M., Mizuno K., Toi M., Tanaka A., Wani Y., Yanai H. Smear cytology findings of large cell neuroendocrine carcinoma of the uterine cervix. Diagn Cytopathol. 2013; 41(7): 636–9. doi: 10.1002/dc.21834.Dongol S., Tai Y., Shao Y., Jiang J., Kong B. A retrospective clinicopathological analysis of small-cell carcinoma of the uterine cervix. Mol Clin Oncol. 2014 Jan; 2(1): 71–75. doi: 10.3892/mco.2013.193.Dongol S., Tai Y., Shao Y., Jiang J., Kong B. A retrospective clinicopathological analysis of small-cell carcinoma of the uterine cervix. Mol Clin Oncol. 2014 Jan; 2(1): 71–75. doi: 10.3892/mco.2013.193.Hoskins P.J., Wong F., Swenerton K.D., Pike J.A., Manji M., McMurtrie E., Acker B., Le Riche J. Small cell carcinoma of the cervix treated with concurrent radiotherapy, cisplatin, and etoposide. Gynecol Oncol. 1995; 56(2): 218–25. doi: 10.1006/gyno.1995.1035.Hoskins P.J., Wong F., Swenerton K.D., Pike J.A., Manji M., McMurtrie E., Acker B., Le Riche J. Small cell carcinoma of the cervix treated with concurrent radiotherapy, cisplatin, and etoposide. Gynecol Oncol. 1995; 56(2): 218–25. doi: 10.1006/gyno.1995.1035.Hoskins P.J., Swenerton K.D., Pike J.A., Lim P., Aquino-Parsons C., Wong F., Lee N. Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combined-modality regimen of involved-field irradiation and platinum-based combination chemotherapy. J Clin Oncol. 2003 Sep 15; 21(18): 3495–501. doi: 10.1200/JCO.2003.01.501.Hoskins P.J., Swenerton K.D., Pike J.A., Lim P., Aquino-Parsons C., Wong F., Lee N. Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combined-modality regimen of involved-field irradiation and platinum-based combination chemotherapy. J Clin Oncol. 2003 Sep 15; 21(18): 3495–501. doi: 10.1200/JCO.2003.01.501.Chang T.C., Lai C.H., Tseng C.J., Hsueh S., Huang K.G., Chou H.H. Prognostic factors in surgically treated small cell cervical carcinoma followed by adjuvant chemotherapy. Cancer. 1998 Aug 15; 83(4): 712–8. doi: 10.1002/(sici)1097-0142(19980815)83:43.0.co;2-v.Chang T.C., Lai C.H., Tseng C.J., Hsueh S., Huang K.G., Chou H.H. Prognostic factors in surgically treated small cell cervical carcinoma followed by adjuvant chemotherapy. Cancer. 1998 Aug 15; 83(4): 712–8. doi: 10.1002/(sici)1097-0142(19980815)83:43.0.co;2-v.Viswanathan A.N., Deavers M.T., Jhingran A., Ramirez P.T., Levenback C., Eifel P.J. Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence. Gynecol Oncol. 2004 Apr; 93(1): 27–33. doi: 10.1016/j.ygyno.2003.12.027.Viswanathan A.N., Deavers M.T., Jhingran A., Ramirez P.T., Levenback C., Eifel P.J. Small cell neuroendocrine carcinoma of the cervix: outcome and patterns of recurrence. Gynecol Oncol. 2004 Apr; 93(1): 27–33. doi: 10.1016/j.ygyno.2003.12.027.Zivanovic O., Leitao M.M.Jr., Park K.J., Zhao H., Diaz J.P., Konner J., Alektiar K., Chi D.S., Abu-Rustum N.R., Aghajanian C. Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy. Gynecol Oncol. 2009 Mar; 112(3): 590–3. doi: 10.1016/j.ygyno.2008.11.010.Zivanovic O., Leitao M.M.Jr., Park K.J., Zhao H., Diaz J.P., Konner J., Alektiar K., Chi D.S., Abu-Rustum N.R., Aghajanian C. Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy. Gynecol Oncol. 2009 Mar; 112(3): 590–3. doi: 10.1016/j.ygyno.2008.11.010.Chan J.K., Loizzi V., Burger R.A., Rutgers J., Monk B.J. Prognostic factors in neuroendocrine small cell cervical carcinoma: a multivariate analysis. Cancer. 2003; 97: 568–574.Chan J.K., Loizzi V., Burger R.A., Rutgers J., Monk B.J. Prognostic factors in neuroendocrine small cell cervical carcinoma: a multivariate analysis. Cancer. 2003; 97: 568–574.Wang K.L., Chang T.C., Jung S.M., Chen C.H., Cheng Y.M., Wu H.H., Liou W.S., Hsu S.T., Ou Y.C., Yeh L.S., Lai H.C., Huang C.Y., Chen T.C., Chang C.J., Lai C.H. Primary treatment and prognostic factors of small cell neuroendocrine carcinoma of the uterine cervix: a Taiwanese Gynecologic Oncology Group study. Eur J Cancer. 2012; 48(10): 1484–94. doi: 10.1016/j.ejca.2011.12.014.Wang K.L., Chang T.C., Jung S.M., Chen C.H., Cheng Y.M., Wu H.H., Liou W.S., Hsu S.T., Ou Y.C., Yeh L.S., Lai H.C., Huang C.Y., Chen T.C., Chang C.J., Lai C.H. Primary treatment and prognostic factors of small cell neuroendocrine carcinoma of the uterine cervix: a Taiwanese Gynecologic Oncology Group study. Eur J Cancer. 2012; 48(10): 1484–94. doi: 10.1016/j.ejca.2011.12.014.Bermúdez A., Vighi S., García A., Sardi J. Neuroendocrine cervical carcinoma: a diagnostic and therapeutic challenge. Gynecol. Oncol. 2001; 82: 32–39.Bermúdez A., Vighi S., García A., Sardi J. Neuroendocrine cervical carcinoma: a diagnostic and therapeutic challenge. Gynecol. Oncol. 2001; 82: 32–39.Sheets E.E., Berman M.L., Hrountas C.K., Liao S.Y., DiSaia P.J. Surgically treated, early-stage neuroendocrine small-cell cervical carcinoma. Obstet Gynecol. 1988 Jan; 71(1): 10–14.Sheets E.E., Berman M.L., Hrountas C.K., Liao S.Y., DiSaia P.J. Surgically treated, early-stage neuroendocrine small-cell cervical carcinoma. Obstet Gynecol. 1988 Jan; 71(1): 10–14.Nasu K., Hirakawa T., Okamoto M., Nishida M., Kiyoshima C., Matsumoto H., Takai N., Narahara H. Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery. Rare Tumors. 2011 Mar 30; 3(1): e6. doi: 10.4081/rt.2011.e6.Nasu K., Hirakawa T., Okamoto M., Nishida M., Kiyoshima C., Matsumoto H., Takai N., Narahara H. Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery. Rare Tumors. 2011 Mar 30; 3(1): e6. doi: 10.4081/rt.2011.e6.Krivak T.C, McBroom J.W., Sundborg M.J., Crothers B., Parker M.F. Large cell neuroendocrine cervical carcinoma: a report of two cases and review of the literature. Gynecol Oncol. 2001; 82(1): 187–91. doi: 10.1006/gyno.2001.6254.Krivak T.C, McBroom J.W., Sundborg M.J., Crothers B., Parker M.F. Large cell neuroendocrine cervical carcinoma: a report of two cases and review of the literature. Gynecol Oncol. 2001; 82(1): 187–91. doi: 10.1006/gyno.2001.6254.Gilks C.B., Young R.H., Gersell D.J., Clement P.B. Large cell neuroendocrine [corrected] carcinoma of the uterine cervix: a clinicopathologic study of 12 cases. Am J Surg Pathol. 1997 Aug; 21(8): 905–14. doi: 10.1097/00000478-199708000-00004.Gilks C.B., Young R.H., Gersell D.J., Clement P.B. Large cell neuroendocrine [corrected] carcinoma of the uterine cervix: a clinicopathologic study of 12 cases. Am J Surg Pathol. 1997 Aug; 21(8): 905–14. doi: 10.1097/00000478-199708000-00004.Sato Y., Shimamoto T., Amada S., Asada Y., Hayashi T. Large cell neuroendocrine carcinoma of the uterine cervix: a clinicopathological study of six cases. Int J Gynecol Pathol. 2003 Jul; 22(3): 226–30. doi: 10.1097/01.PGP.0000071046.12278.D1.Sato Y., Shimamoto T., Amada S., Asada Y., Hayashi T. Large cell neuroendocrine carcinoma of the uterine cervix: a clinicopathological study of six cases. Int J Gynecol Pathol. 2003 Jul; 22(3): 226–30. doi: 10.1097/01.PGP.0000071046.12278.D1.Embry J.R., Kelly M.G., Post M.D., Spillman M.A. Large cell neuroendocrine carcinoma of the cervix: prognostic factors and survival advantage with platinum chemotherapy. Gynecol Oncol. 2011 Mar; 120(3): 444–8. doi: 10.1016/j.ygyno.2010.11.007.Embry J.R., Kelly M.G., Post M.D., Spillman M.A. Large cell neuroendocrine carcinoma of the cervix: prognostic factors and survival advantage with platinum chemotherapy. Gynecol Oncol. 2011 Mar; 120(3): 444–8. doi: 10.1016/j.ygyno.2010.11.007.Rhemtula H., Grayson W., van Iddekinge B., Tiltman A. Large-cell neuroendocrine carcinoma of the uterine cervix--a clinicopathological study of five cases. S Afr Med J. 2001 Jun; 91(6): 525–8.Rhemtula H., Grayson W., van Iddekinge B., Tiltman A. Large-cell neuroendocrine carcinoma of the uterine cervix--a clinicopathological study of five cases. S Afr Med J. 2001 Jun; 91(6): 525–8.Emerson R.E., Michael H., Wang M., Zhang S., Roth L.M., Cheng L. Cervical Carcinomas With Neuroendocrine Differentiation: A Report of 28 Cases With Immunohistochemical Analysis and Molecular Genetic Evidence of Common Clonal Origin With Coexisting Squamous and Adenocarcinomas. Int J Gynecol Pathol. 2016 Jul; 35(4): 372–84. doi: 10.1097/PGP.0000000000000254.Emerson R.E., Michael H., Wang M., Zhang S., Roth L.M., Cheng L. Cervical Carcinomas With Neuroendocrine Differentiation: A Report of 28 Cases With Immunohistochemical Analysis and Molecular Genetic Evidence of Common Clonal Origin With Coexisting Squamous and Adenocarcinomas. Int J Gynecol Pathol. 2016 Jul; 35(4): 372–84. doi: 10.1097/PGP.0000000000000254.Futagami M., Yokoyama Y., Mizunuma H. Presentation of a patient with pT2bN1M0 small cell carcinoma of the uterine cervix who obtained long-term survival with maintenance chemotherapy, and literature-based discussion. Eur J Gynaecol Oncol. 2011; 32(1): 99–102.Futagami M., Yokoyama Y., Mizunuma H. Presentation of a patient with pT2bN1M0 small cell carcinoma of the uterine cervix who obtained long-term survival with maintenance chemotherapy, and literature-based discussion. Eur J Gynaecol Oncol. 2011; 32(1): 99–102.Yoseph B., Chi M., Truskinovsky A.M., Dudek A.Z. Large-cell neuroendocrine carcinoma of the cervix. Rare Tumors. 2012 Jan 2; 4(1): e18. doi: 10.4081/rt.2012.e18.Yoseph B., Chi M., Truskinovsky A.M., Dudek A.Z. Large-cell neuroendocrine carcinoma of the cervix. Rare Tumors. 2012 Jan 2; 4(1): e18. doi: 10.4081/rt.2012.e18.

The authors declare that there are no conflicts of interest present.