Objective: To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment. Methods: A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples. Results: The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor's surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34βE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC (P=0.002), TP63 (P=0.002), CDKN1C (P=0.002) and NFE2L2 (P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway (P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway (P=0.013) and PI3K pathway (P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion: Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.
目的： 探讨伴导管分化的食管癌临床病理学特征及分子遗传学特征，为其诊治积累经验。 方法： 收集宁波市临床病理诊断中心2011年6月至2022年12月确诊的伴导管分化的食管癌17例，整理临床及病理诊断信息，通过HE切片观察其组织学特征，选择肿瘤组织区域获取DNA，采用二代测序技术检测并分析肿瘤标本中的基因突变情况。 结果： 17例病例，男性16例，女性1例；患者年龄54~77岁，中位年龄66岁。其中9例以伴导管分化的癌为主，肿瘤表面鳞状上皮均伴有高级别上皮内瘤变，肿瘤与异型鳞状上皮有移行，局灶伴有不同程度的鳞状细胞癌成分（<10%）；另外8例肿瘤主体为不同分化程度的鳞状细胞癌或基底样鳞状细胞癌或肉瘤样癌，局灶区域为伴导管分化的癌（<10%）；伴导管分化区域的肿瘤细胞主要呈小管状排列，小管呈双层结构，即管腔内层细胞和外层细胞。免疫组织化学结果显示肿瘤性小管外层细胞表达p63、p40、细胞角蛋白（CK）5/6、CK34βE12，内层细胞表达CK7。与文献报道的食管鳞状细胞癌相比较，本组病例中MYC（P=0.002）、TP63（P=0.002）、CDKN1C（P=0.002）和NFE2L2（P=0.045）等基因突变发生频率更低；信号通路层面，NOTCH信号通路（P=0.041）突变发生频率更高，而NRF2通路（P=0.013）和PI3K通路（P=0.009）突变相对于食管鳞状细胞癌发生频率更低。 结论： 伴导管分化的食管癌是一种形态学特殊的食管癌，分子改变与普通的食管鳞状细胞癌也存在明显差异。.