未分化/去分化子宫内膜癌的临床病理学特征及治疗研究

Clinicopathological features and treatment of undifferentiated/dedifferentiated endometrial carcinoma

目的探讨未分化/去分化子宫内膜癌(UEC/DEC)患者的临床病理学特征及该病患者的诊断、治疗和结局。方法选取2018年1月至2022年3月于南京医科大学第一附属医院妇科就诊,并确诊为UEC/DEC的11例患者为研究对象。其中,8例为DEC患者(No.1~2、4~10),3例为UEC患者(No.3~4、11),回顾性分析这11例患者的临床特点、病理学与分子特征及诊疗结局。本研究遵循的程序符合南京医科大学第一附属医院伦理委员会制定的伦理学标准,得到该委员会批准(伦审号:2021-SR-239),并与患者本人或其家属签署临床研究知情同意书。结果①11例患者的主要临床表现均为阴道不规则出血。②UEC细胞在光学显微镜下,形态学上未分化组分(UC)呈实性片状小圆形至多角形,细胞形态单一,细胞核大,染色质丰富,核分裂象多见;细胞黏附性差,缺乏分化特征。免疫组织化学(IHC)染色提示细胞角蛋白(CK)、上皮细胞膜抗原(EMA)、雌激素受体(ER)、配对盒8基因(Pax8)、波形蛋白(vimentin)呈阴性或局灶阳性表达,E-钙黏素(cadherin)不表达;与低级别子宫内膜样癌成分界限清晰。③对8例UEC和DEC患者进行错配修复(MMR)蛋白检测,6例呈完整状态,2例呈缺失状态。④11例患者术后病理学检查结果提示,国际妇产科联盟(FIGO)Ⅰ~Ⅱ期为6例,Ⅲ~Ⅳ期为5例。⑤11例患者均接受手术治疗,手术过程顺利并且术后恢复良好,术中及术后均无并发症发生。除1例FIGOⅠA期的患者外,其余患者术后均接受放、化疗。⑥对这11例患者随访至2022年3月31日,目前存活的9例患者中,总体生存(OS)期最长者达34个月,中位OS期为10.5个月。2例死亡患者分别为FIGOⅢB期及ⅢC2期者。结论UEC/DEC具有侵袭性强、患者预后差等特点,需临床及病理医师对该病临床病理学特征有充分的认识,进行准确诊断,实施综合治疗。

Objective To explore the clinicopathological features,diagnosis,treatment and outcomes of undifferentiated/dedifferentiated endometrial carcinoma(UEC/DEC)in order to provide a basis for clinical decision-making.Methods Eleven patients diagnosed as UEC/DEC from January 2018 to March 2022 in the Department of Gynecology of the First Affiliated Hospital of Nanjing Medical University were enrolled in the study.The data including clinical,pathological,molecular features were retrospectively analyzed to investigate the diagnosis,treatment and outcomes of UEC/DEC.This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Nanjing Medical University(Approval No.QYFYWZll26841).Informed consents were obtained from all those patients.Results①Among 11 cases with pathologically confirmed UEC/DEC were identified,including 3 cases of UEC and 8 cases of DEC.The main clinical manifestation is abnormal vaginal bleeding.②Morphologically,undifferentiated components(UC)of UEC/DEC were composed of solid sheet-like ovoid or polygonal de-cohesive cells with uniform vesicular nuclei,abundant chromatin,lack of glandular differentiation and presenting sharp boundaries from low-grade cancer components.Immunohistochemistry(IHC)stain showed predominantly focal or complete loss expression of cytokeratin(CK),epithelial membrane antigen(EMA),estrogen receptor(ER),paired box protein(Pax8),vimentin and E-cadherin in the UC components.③Mismatch repair(MMR)protein status of the tumor were performed on 8 cases.Two cases showed MMR deficiency,while the remaining 6 cases showed normal MMR status.④Six cases presented with FIGO stageⅠ-Ⅱ,whereas 5 cases were FIGO stageⅢ-Ⅳ.⑤All patients underwent surgery,and the operation process and postoperative recovery all were good.There were no complications during and after the operation.Only 1 patient with FIGO stageⅠA received postoperative adjuvant therapy.⑥These 11 patients were followed up to March 31,2022.On the follow-up,the longest overall survival(OS)time was 34 months,and median OS time was 10.5 months.Two patients died of the disease with FIGO stageⅢB andⅢC2,respectively,and 9 patients were disease-free.Conclusions UEC/DEC presents highly aggressive behavior and poor prognosis.It is crucial for clinicians and pathologists to fully understand its clinicopathological and molecular features,to establish accurate diagnosis and appropriate treatment.