结直肠混合性腺-神经内分泌癌的临床病理特征与诊疗分析

Analysis of clinicopathologic characteristics and diagnosis/treatment of colorectal mixed adeno‑neuroendocrine carcinoma

背景与目的:混合性腺-神经内分泌癌(MANEC)是一种发病率极低,恶性程度高的恶性肿瘤。近年来,肠道MANEC的发病率有一定的增长趋势。本研究总结了近10余年来收治的结直肠MANEC病例的临床病理资料及诊疗经过,以期提高对该病的认识,从而规范其治疗及管理。方法:回顾性分析2010年1月—2023年3月中南大学湘雅医院13例经手术标本的病理及免疫组化确诊为结直肠MANEC的患者的临床资料。结果:13例结直肠MANEC的患者中,男性10例(76.9%),平均年龄为65.1岁,最常见的主诉为便血及大便性状改变,体格检查发现阳性体征的概率为61%,所有患者都通过CT或MRI发现肠壁增厚,并通过内镜发现肿块并以此获得术前的组织病理报告,但仅有2例在术前的病理报告中提示存在神经内分泌成分,加行以18F-奥曲肽(18F-OC)为显像剂的PET/CT全身断层显像,提示肠壁增厚处及周围淋巴结存在生长抑素受体表达增高。13例患者均行手术治疗,其中3例行术前新辅助治疗。术后的临床分级为Ⅲ、Ⅳ期占多数(84.6%),肠旁淋巴结和肝脏为常见的转移部位,肿块的平均大小为4 cm×3.4 cm×2.6 cm,84.6%(11/13)为溃疡型肿块,12例(92.2%)为中低分化腺癌。7例患者接受了术后药物治疗,获得8例患者的具体生存期,平均生存期为20.6个月,中位生存期为13.5个月,有2例的术后生存期超过3年。结论:结直肠MANEC的预后普遍偏差,生存期可能主要与临床病理分期及有无远处转移相关。术前病理正确诊断率较低,以奥曲肽为显像剂的PET/CT可增加该类疾病的检出率。治疗原则为手术治疗为主,化疗为辅,联合针对神经内分泌癌与腺癌两种成分的化疗方案是否更有优势,以及免疫治疗对于晚期结直肠MANEC的疗效均有待进一步临床试验验证。

Background and Aims:Mixed adeno-neuroendocrine carcinoma(MANEC)is a rare and highly malignant tumor.In recent years,the incidence of colorectal MANEC has shown a certain growth trend.This study summarizes the clinicopathologic data as well as the diagnosis and treatment process of colorectal MANEC cases treated over the past decade,with the aim of increasing awareness of this disease and thereby standardizing its treatment and management.Methods:The clinical data of 13 patients diagnosed with colorectal MANEC through pathological and immunohistochemical examination of surgical specimens from January 2010 to March 2023 were retrospectively analyzed.Results:Among the 13 patients with colorectal MANEC,10 were male(76.9%),with an average age of 65.1 years.The most common complaints were bloody stools and changes in stool characteristics,with 61%of patients showing positive physical signs.All patients were found to have thickening of the bowel wall through CT or MRI,and a mass was detected through endoscopy,which led to preoperative histopathological reports.However,only 2 cases had a preoperative pathological report indicating the presence of neuroendocrine components,and additional whole-body PET/CT imaging using 18Foctreotide(18F-OC)as the imaging agent indicated increased somatostatin receptor expression in the thickened bowel wall and surrounding lymph nodes.All 13 patients underwent surgical treatment,with 3 cases receiving preoperative neoadjuvant therapy.The majority of patients were classified as stageⅢorⅣafter surgery(84.6%).Common sites of metastasis included per-intestinal lymph nodes and the liver.The average tumor size was 4 cm×3.4 cm×2.6 cm,and 84.6%(11/13)of tumors were ulcerative.In 92.2%of cases,the tumors were moderately to poorly differentiated adenocarcinomas.Seven patients received postoperative drug therapy.The survival periods for 8 patients were obtained,and the average survival was 20.6 months with a median survival of 13.5 months.Two patients had a postoperative survival exceeding 3 years.Conclusion:Colorectal MANEC has a generally unfavorable prognosis,and survival may be primarily associated with clinical pathological stage and the presence of distant metastasis.The preoperative pathological diagnosis rate is relatively low,and the use of octreotide-based PET/CT imaging can increase the detection rate of this disease.The main treatment approach is surgery,with chemotherapy as an adjuvant therapy.Further clinical studies are needed to determine whether a combination chemotherapy regimen targeting both the neuroendocrine and adenocarcinoma components,as well as immunotherapy,can provide advantages in the treatment of advanced colorectal MANEC.