Neoplasms characterized by the expression of markers of neuroendocrine differentiation in neoplastic cells are defined as neuroendocrine neoplasms. A case of neuroendocrine carcinomas (NECs) with a small amount of papillary adenocarcinoma and significantly vacuolar nucleus at the esophagogastric junction was reported in this article. A 77-year-old male had dysphagia for one week. Endoscopy revealed early-stage esophagogastric junction carcinoma, and biopsy was diagnosed as poorly differentiated carcinoma. Endoscopic submucosal dissection was performed. Histologically, the papillary adenocarcinoma progresses from typically branching papillary structures (well-differentiated) to hyperplasia of the lining epithelium of the papilla to form a cribriform structure (moderately differentiated), to solid area lacking papillary structures (poorly differentiated). There was a continuous process, and during this process, the vacuoles in the nuclei of tumor cells showed progressive changes from mild to obvious and finally to significant vacuoles. The tumor was mainly composed of solid areas (about 95%), with single cell, large cell, round or oval to irregular nuclei, and significantly vacuolar nuclei, nuclei with larger vacuoles appeared in a loop, a few thin weakly basophilic or weakly eosinophilic fine particles could be seen in the vacuoles, and the vacuoles had rough edges. The nucleus chromatin at the outer edge of the vacuoles was fine particles, and mitosis was common (20-30/mm²), atypical mitosis could be seen, and nucleoli could be seen easily, the cytoplasm was weakly eosinophilic, and the boundaries of cells were unclear. The cells were arranged in a nested, trabecular, or diffuse sheet shape, with some arranged in a glandular tube shape. Tumor thrombus was found in the vein of submucosa; the interstitial tissue rich in capillaries within the tumor was accompanied by a large number of neutrophil infiltration. Immunohistochemical staining showed that the solid area of the tumor was positive for synaptophysin (Syn) and chromogranin A (CgA), while papillary adenocarcinoma was negative. Mucin 5AC (MUC5AC) was diffusely positive in papillary adenocarcinoma, while the proportion of positive cells in the solid area of the tumor was about 10% to 15%. In a word, this case showed the extreme situation of the vacuolar nuclear characteristics of NECs, extremely rare, in a sense, this case expanded the boundary of the morphological spectrum of NECs. Understanding the extreme vacuolar features of this nucleus is helpful to make a correct pathological diagnosis.
Humans ; Male ; Esophagogastric Junction/pathology* ; Aged ; Carcinoma, Neuroendocrine/pathology* ; Vacuoles/pathology* ; Esophageal Neoplasms/pathology* ; Cell Nucleus/pathology* ; Adenocarcinoma, Papillary/pathology* ; Stomach Neoplasms/pathology*

China is a country with high incidence of digestive tract tumors.The three major digestive tract tumors,represented by gastric cancer,esophageal cancer,and colon cancer,seriously threaten the health of our people.This article reviewed the challenges faced in the pathological development of early gastrointestinal cancer,the changes in di-agnostic criteria for early gastrointestinal cancer,and the research progress on molecular subtyping of advanced gastro-intestinal cancer.In the diagnosis of early gastrointestinal cancer,pathologists should closely collaborate with clinical practice,improve the accuracy of early gastrointestinal cancer diagnosis through continuous learning and practice,make reasonable use of relevant molecular pathological methods to assist in guiding clinical treatment,and closely monitor the latest research progress of gastrointestinal tumors.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Purpose To investigate the independent risk factors for early papillary gastric adenocarcinoma(EP-GA)and construct a diagnostic nomogram.Methods A retrospective analysis was performed on the clinicopathologi-cal characteristics of 325 cases of early differentiated gastric adenocarcinoma.Taking EPGA as the case group and early well-moderately differentiated tubular gastric adenocarcinoma(ETGA)as the control group,the independent risk fac-tors for the occurrence of EPGA were identified through univariate and multivariate analyses,and a nomogram was con-structed.The diagnostic performance of the nomogram was evaluated using the receiver operating characteristic(ROC)curves,Hosmer-Lemeshow goodness-of-fit tests,and calibration curves.Results Among the 325 cases of early differ-entiated gastric adenocarcinoma,there were 121 cases of EPGA and 204 cases of ETGA.Univariate analysis showed that elevated appearance(56.3％),ulcer formation(11.5％),tumor maximum diameter of 2.15(1.60,3.00)cm,moderately-differentiated(55.2％),submucosal invasion(21.9％),lymphovascular invasion(10.4％),high ex-pression of MUC5AC(75.0％),microsatellite instability-high(15.6％),and wild-type expression of p53(59.4％)were significantly associated with an increased risk of EPGA.Multivariate analysis revealed that gross appearance,ul-cer formation,tumor maximum diameter,and the expression of MUC5AC was independent risk factors for EPGA.A di-agnostic nomogram was constructed,and the area under the ROC curve(AUC)was calculated.In the training and val-idation cohorts,the AUC values were 0.847(95％CI=0.799-0.896)and 0.830(95％CI=0.733-0.927),re-spectively.The Hosmer-Lemeshow goodness-of-fit tests showed that x2=13.498,P=0.096,and x2=7.138,P=0.415,respectively.Conclusion The nomogram,based on independent risk factors,exhibits good accuracy for diag-nosing EPGA and can help pathologists in achieving rapid and precise EPGA diagnosis.

China is a country with high incidence of digestive tract tumors.The three major digestive tract tumors,represented by gastric cancer,esophageal cancer,and colon cancer,seriously threaten the health of our people.This article reviewed the challenges faced in the pathological development of early gastrointestinal cancer,the changes in di-agnostic criteria for early gastrointestinal cancer,and the research progress on molecular subtyping of advanced gastro-intestinal cancer.In the diagnosis of early gastrointestinal cancer,pathologists should closely collaborate with clinical practice,improve the accuracy of early gastrointestinal cancer diagnosis through continuous learning and practice,make reasonable use of relevant molecular pathological methods to assist in guiding clinical treatment,and closely monitor the latest research progress of gastrointestinal tumors.

Purpose To investigate the expression of chromogranin A(CgA)in gastroenteropancreatic neuroendo-crine neoplasms(GEP-NENs)and its relationship with clinicopathological features.Methods The clinicopathological data of GEP-NENs diagnosed in the Department of Pathology,Beijing Chao-yang Hospital,Capital Medical University from May 2011 to December 2024 were retrospectively analyzed.Immunohistochemical staining was applied to evaluate the expression of CgA,and the patients were divided into CgA(+)group and CgA(-)group.Differences in clinico-pathological features between the 2 groups were compared.Results The age of 229 patients ranged from 21 to 89 years,with an average age of 54.4 years.The most common primary site was the rectum(56.8％,130/229),fol-lowed by the stomach(16.6％,38/229),pancreas(14.4％,33/229),small intestine(6.1％,14/229),and colon(6.1％,14/229).There were 206 cases of single lesion and 23 cases of multiple lesions(number of tumors ≥2).There were 153 cases of G1(66.8％),29 cases of G2(12.7％),7 cases of G3(3.1％),and 40 cases of neuroendocrine carcinoma(NEC,17.5％).The positive rates of CgA in G1,G2,G3,and NEC groups were 37.2％,75.8％,71.4％,and 65.0％,respectively,with statistically significant differences(P＜0.001).The positive rates of CgA in T1,T2,T3,and T4 were 37.2％,83.3％,75.9％,and 57.7％,respectively,with statistically significant differences(P＜0.001).There were significant differences in age,vascular invasion,lymph node metasta-sis,and number of tumors between CgA(+)group and CgA(-)group(P＜0.001),but there was no significant difference in sex,tumor location,Syn,and CD56 expression between the two groups(P=0.595,P=0.098,P=0.173,P=0.557).Conclusion Immunohistochemical antibody CgA is a useful marker for GEP-NENs.CgA positiv-ity may be a poor prognostic factor for GEP-NENs patients.

Purpose To investigate the independent risk factors for early papillary gastric adenocarcinoma(EP-GA)and construct a diagnostic nomogram.Methods A retrospective analysis was performed on the clinicopathologi-cal characteristics of 325 cases of early differentiated gastric adenocarcinoma.Taking EPGA as the case group and early well-moderately differentiated tubular gastric adenocarcinoma(ETGA)as the control group,the independent risk fac-tors for the occurrence of EPGA were identified through univariate and multivariate analyses,and a nomogram was con-structed.The diagnostic performance of the nomogram was evaluated using the receiver operating characteristic(ROC)curves,Hosmer-Lemeshow goodness-of-fit tests,and calibration curves.Results Among the 325 cases of early differ-entiated gastric adenocarcinoma,there were 121 cases of EPGA and 204 cases of ETGA.Univariate analysis showed that elevated appearance(56.3％),ulcer formation(11.5％),tumor maximum diameter of 2.15(1.60,3.00)cm,moderately-differentiated(55.2％),submucosal invasion(21.9％),lymphovascular invasion(10.4％),high ex-pression of MUC5AC(75.0％),microsatellite instability-high(15.6％),and wild-type expression of p53(59.4％)were significantly associated with an increased risk of EPGA.Multivariate analysis revealed that gross appearance,ul-cer formation,tumor maximum diameter,and the expression of MUC5AC was independent risk factors for EPGA.A di-agnostic nomogram was constructed,and the area under the ROC curve(AUC)was calculated.In the training and val-idation cohorts,the AUC values were 0.847(95％CI=0.799-0.896)and 0.830(95％CI=0.733-0.927),re-spectively.The Hosmer-Lemeshow goodness-of-fit tests showed that x2=13.498,P=0.096,and x2=7.138,P=0.415,respectively.Conclusion The nomogram,based on independent risk factors,exhibits good accuracy for diag-nosing EPGA and can help pathologists in achieving rapid and precise EPGA diagnosis.

For over a decade, Chinese cytopathologist has participated in the compilation of international reporting systems and subsequently promoted them widely in China; The clinical diagnostic level has significantly increased and has been widely recognized by clinical doctors in the industry; Dozens of clinical research papers have been published in international SCIE journals, among which the unique arrangement of cancer cell escape patterns was first discovered by Chinese cytology experts; Molecular detection methods are widely used in cytological specimens, and the differentiation between transient and persistent cervical HPV infection has achieved ideal results in the laboratory; The urgent need for standardized standards in clinical diagnosis has been resolved through expert consensus; Artificial intelligence assisted cervical cytology diagnosis has been applied in the screening of cervical cancer in a few hospitals and local areas.

For over a decade, Chinese cytopathologist has participated in the compilation of international reporting systems and subsequently promoted them widely in China; The clinical diagnostic level has significantly increased and has been widely recognized by clinical doctors in the industry; Dozens of clinical research papers have been published in international SCIE journals, among which the unique arrangement of cancer cell escape patterns was first discovered by Chinese cytology experts; Molecular detection methods are widely used in cytological specimens, and the differentiation between transient and persistent cervical HPV infection has achieved ideal results in the laboratory; The urgent need for standardized standards in clinical diagnosis has been resolved through expert consensus; Artificial intelligence assisted cervical cytology diagnosis has been applied in the screening of cervical cancer in a few hospitals and local areas.

Purpose To investigate the clinicopathological and histological features of non-small cell lung cancer(NSCLC)patients with high expression of PD-L1 and positive driver muta-tion.Methods The clinical data of 141 patients with PD-L1 high expression and driver mutation-positive NSCLC were col-lected.Immunohistochemical methods,ARMS-PCR,and next-generation sequencing(NGS)were used to detect PD-L1 ex-pression and driver gene mutations.The clinicopathological fea-tures were analyzed and the related literatures were reviewed.Results There were 141 cases NSCLC patients with high ex-pression of PD-L1 in tumor cells,of which 57 cases were≥50％,＜60％;≥60％,＜70％in 18 cases;≥70％,＜80％in 35 cases;≥80％in 31 cases.Among 141 cases NSCLC patients with high PD-L1 expression,53 cases(37.6％)had driver gene mutations,including 4 cases BRAF 15 exon mutations,9 cases MET-associated mutations,17 cases EGFR-associated mutations,16 cases KRAS 2 exon mutations,4 cases EML4-ALK fusion mutations,and 3 cases other rare mu-tations.The high expression of PD-L1 and the occurrence of driver gene mutation were related to the gender,smoking history and pathological type of patients(P＜0.05).MET-related mu-tations and KRAS 2 exon mutations were more common in males than in females.All BRAF 15 exon mutations were female.The mean percentage of PD-L1 expression was highest in patients with MET mutation,KRAS 2 exon mutation,and 3 cases rare mutations.In 33 cases with BRAF 15 exon mutation,MET am-plification or mutation,EGFR-related mutation,and 3 cases oth-er rare mutations,PD-L1 was highly expressed in solid,glandu-lar,and micropapillary tumor cells.In 20 cases with KRAS 2 exon mutation and EML4-ALK fusion mutation,PD-L1 was highly expressed in solid nested tumor cells.Conclusion In NSCLC,high expression of PD-L1 and positive driver gene mu-tation are negatively correlated with the degree of tumor differen-tiation.In the poorly differentiated surgical specimens of lung adenocarcinoma,solid,micropapillary,or glandular tubular tumor tissues should be selected as far as possible for PD-L1 ex-pression and driver gene mutation detection.