| Background and ObjectiveCervical cancer is one of the leading causes of cancer death in women.Worldwide,cervical cancer ranks fourth in the most common malignant tumors in women,with approximately 530,000 new cases each year,of which 270,000 are fatal.About 85% of cervical cancer deaths worldwide occurring in less developed or developing countries.Compared with developed countries,the mortality rate of cervical cancer in developing and economically backward countries is 18 times higher.Cervical cancer is the second most common cancer among women living in underdeveloped areas.It is estimated that there are 570,000 new cases in 2018(84% of new global cases),accounting for 7.5% of all female cancer deaths.About 201,000 women died of cervical cancer in 2018.Comprehensive management of cervical cancer includes primary prevention(inoculation of HPV vaccine),secondary prevention(regular screening and active treatment of cervical precancerous lesions),tertiary prevention(early diagnosis and treatment of invasive cervical cancer)and palliative care.The World Health Organization recommends prophylactic vaccination against HPV 16 and 18,which is now approved for use in many countries.Clinical trials and post-marketing surveillance have shown that HPV vaccines are very safe and can effectively prevent HPV infection.It is worth noting that routine cervical cancer screening is still required after HPV vaccine inoculation.Neuroendocrine neoplasm may occur in the uterine cervix;it accounts for 0.5-1% of all malignant tumors of the uterine cervix.It is generally accepted that the integration of HPV into the host genome is the single most important event in evolution of cervical carcinomas.Almost all neuroendocrine carcinomas of the cervix are associated with HPV 18 or seldom HPV 16.Neuroendocrine carcinomas most likely develop from neuroendocrine cells occurring in the normal endocervix or from stimulated multipotential reserve cells of the endocervical epithelium undergoing neuroendocrine metaplasia and hyperplasia.Neuroendocrine tumors of uterine cervix are divided into small and large cell type as well as carcinoid and atypical carcinoid.Small cell neuroendocrine carcinoma of the uterine cervix is a rare tumor with a highly aggressive clinical course and poor prognosis due to the high frequency of lymph node involvement at an early stage.It is important to differentiate small cell carcinoma of the uterine cervix from other malignant tumors of the cervix.Morphological features,cytopathology and histopathology as well as the immunocytochemistry studies play important roles in making an accurate diagnosis.Clinically,abnormal vaginal bleeding is the most commonly reported symptoms.In spite of the neuroendocrine origin of this tumor,the clinical carcinoid syndrome in the neuroendocrine tumors of the cervix is very unusual;but on the other hand,a primary carcinoid tumor other than the cervix,with direct secretion of its mediators into the systemic circulation could be responsible for the carcinoid syndrome.The distinction of squamous,glandular an d neuroendocrine carcinomas of the cervix is clinically significant for at least two reasons.First,a poorly differentiated carcinoma of glandular origin,even with early invasion,is likely to have a worse prognosis than a similar squamous tumor.Second,neuroendocrine carcinomas are inherently more aggressive than their squamous counterparts and are managed with different protocols.Expression of chromogranin A,synaptophysin,and various other proteins involved in the formation of neurosecretory granules or CD 56,a neural cell adhesion molecule,can be used as markers of neuroendocrine differentiation,as in neuroendocrine carcinomas of other organs.Neuroendocrine carcinomas of the cervix are regarded as highly aggressive tumors with subclinical hematogenous and lymphatic metastases frequently even in early disease.Neuroendocrine features in poorly differentiated carcinomas of the cervix indicate a poor outcome.Sixty-five percent of patients with cervical non-small cell neuroendocrine carcinomas die within 3 years of diagnosis.To investigate the clinicopathological features,treatment methods and survival of cervical neuroendocrine carcinoma(NECUC),and to analyze the prognostic factors Materials and MethodsThe clinical case data of 28 NECUC patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to November 2017 were collected.The median age of the patients was 45.5 years old(28-64 years old);clinical stage: according to the 2009 International Stage of Obstetrics and Gynecology(FIGO)staging,12 cases of IB1,4 cases of IB2,6 cases of IIA1,IIA2 6 cases.Among them,pathological type: 13 cases of small cell carcinoma,2 cases of large cell carcinoma,13 cases of mixed type cancer;10 cases of local tumor diameter of the cervix: >4 cm,and 18 cases of ≤4 cm.Twenty-eight patients with NECUC underwent extensive uterine resection plus pelvic(or para-aortic)lymphadenectomy,of which 8 patients retained bilateral ovaries and 21 patients with deep interstitial invasion of the cervix(invasive depth ≥ 1/2).17 cases of lymphatic vascular involvement(LVSI),4 cases of pelvic and/or para-aortic lymph node metastasis;10 patients received neoadjuvant chemotherapy before surgery(1 to 3 courses),all patients received postoperative Adjuvant chemotherapy(3 to 6 courses),10 patients received postoperative adjuvant radiotherapy.The follow-up deadline was December 2017 and the median follow-up time was 18.5 months(range 5 to 42 months).The survival and recurrence of NECUC patients were retrospectively analyzed,and the prognostic factors were explored.ResultsOf the 28 NECUC patients,11 died during the follow-up period.During the follow-up period,10 patients with NECUC had recurrence and metastasis,and the median recurrence and metastasis time was 14 months(range 3 to 37 months).Recurrence and metastasis: 1 case of lung metastasis,1 case of bone metastasis,1 case of brain metastasis,1 case of pelvic lymph node metastasis,6 of which were multiple metastases(>2 metastatic sites).Of the 10 patients with recurrence and metastasis,5 had died and 5 had tumor-bearing survival,3 of which were treated within 2 years,and the follow-up time was short.Univariate survival analysis showed that clinical stage,cervical tumor diameter,tumor composition(specifically referred to as single type and mixed type cancer),pelvic and/or para-aortic lymph node metastasis were significantly associated with the prognosis of patients with NECUC(P<0.05),that is,clinical Stages ≥ IB2,cervical local tumor diameter > 4cm,tumor components for single cancer,pelvic and/or para-aortic lymph node metastasis were relatively poor prognosis.However,patients’ age,cervical deep interstitial invasion,LVSI,neoadjuvant chemotherapy,postoperative adjuvant radiotherapy,tumor recurrence and metastasis,and whether or not the ovaries remain during surgery,there was no significant correlation with the prognosis of patients with NECUC(P>0.05).Conclusion1.Neuroendocrine carcinoma of the uterine cervix is highly invasive,and the prognosis is worse.This study shows that clinical stage ≥ IB2,cervical local tumor diameter > 4cm,tumor components for single cancer,pelvic and/or para-aortic lymph node metastasis is high risk factors for prognosis.2.There was no significant correlation with the prognosis of patients with NECUC,such as:postoperative adjuvant radiotherapy.so it is necessary to be cautious in the clinical selection of postoperative adjuvant radiotherapy. |
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