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*

Objective:To investigate the correlation of CD8 positive tumor-infiltrating lymphocytes (CD8 + TIL) density and programmed-death receptor ligand 1 (PD-L1) expression in rectal cancer with clinicopathological characteristics and prognosis of patients after neoadjuvant chemoradiotherapy. Methods:The clinicopathological data of 166 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgery in the Beijing Chao-Yang Hospital, Capital Medical University from January 2015 to December 2018 were retrospectively analyzed. CD8 + TIL density and PD-L1 expression were detected by using immunohistochemistry. The correlation of CD8 + TIL density and PD-L1 expression with clinicopathological characteristics of patients after neoadjuvant chemoradiotherapy was analyzed. Kaplan-Meier method was used to analyze the disease-free survival (DFS) and Cox regression risk model was used to make univariate and multivariate analysis of the influencing factors for DFS. Results:Among 166 LARC patients, 81 cases (48.8%) had high density of CD8 + TIL, 85 cases (51.2%) had low density of CD8 + TIL; 63 cases (38.0%) had PD-L1 expression, and 103 cases (62.0%) had non-expression of CD8 + TIL. The expression rate of PD-L1 in CD8 + TIL high density group was higher than that in CD8 + TIL low density group [50.6% (41/81) vs. 25.9%(22/85), χ2 = 10.78, P < 0.001]. According to the density of CD8 + TIL and PD-L1 expression, immunophenotype was divided among 4 groups; the 3-year DFS rate of the CD8 + TIL high density /PD-L1 expression group was 87.1%, which was higher than that of the other groups (CD8 + TIL low density /PD-L1 expression group was 72.8%, CD8 + TIL high density /PD-L1 non-expression group was 67.0%, CD8 + TIL low density /PD-L1 non-expression group was 64.3%), and the difference was statistically significant ( P < 0.05). Univariate analysis showed that tumor differentiation degree, TNM stage, CD8 + TIL density, PD-L1 expression and CD8 + TIL density /PD-L1 expression were correlated with the DFS of patients (all P < 0.05). Multivariate analysis results showed that CD8 + TIL high density /PD-L1 expression was an independent protective factor for DFS ( HR = 0.049, 95% CI 0.005-0.497, P = 0.011), while TNM stage 3 was an independent risk factor for DFS ( HR = 2.752,95% CI 1.300-5.825, P = 0.008). Conclusions:In LARC after neoadjuvant therapy, CD8 + TIL density is positively correlated with the expression of PD-L1, and the high density of CD8 + TIL/PD-L1 expression is an independent influencing factor for good prognosis, suggesting that these patients may benefit from the immunotherapy.

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.

The pursuit of minimally invasive biopsy and targeted treatment as well as technical progress have boosted the extensive clinical usages of fine needle puncture cell/tissue acquisition technology in recent years. How to rationally use the limited fine needle puncture materials which are usually minimal and fragmented, while making pathological diagnosis, accomplish the auxiliary tests of immune phenotype, molecular features and other tests required by the clinician, and comprehensively improve the diagnostic benefits of fine needle puncture material is a big challenge facing the pathology community. Up to now, there has been no successful experience that can be learned from abroad. Some suggestions for the further improvement of diagnostic efficacy of fine needle puncture specimens from the aspects of sub-specialty cooperation and comprehensive utilization of the materials are put forward based on the progress trend in pathology and the current situation in China.
China

Humans ; Biopsy, Fine-Needle ; Cytodiagnosis ; Pathology, Clinical ; Image-Guided Biopsy

Objective:To investigate the pathomorphological characteristics of colorectal adenoma with submucosal pseudoinvasion and to summarize the corresponding pseudoinvasion patterns.Methods:The clinicopathological data of 9 cases of colorectal adenoma were collected at 989 Hospital of PLA Joint Logistics Support Force (4 cases) and Beijing Chaoyang Hospital, Capital Medical University (5 cases), from 2016 to 2019. retrospectively, and the histomorphological characteristics and immunophenotypes were analyzed, and discussed in light of the relevant literature.Results:There were 8 cases of adenoma with stalk. Tumor glands were found in the submucosa at the head end of adenoma, similar to infiltrating adenocarcinoma. The structure and cellular morphology of submucosal glands were very similar to the intramucosal tumor while the local submucosal tumor showed continuity with the intramucosal tumor. The submucosal tumors were lobule-like or nest-like with clear boundary. The outline of the gland was smooth and blunt-round, and there was loose fibromyxoid stroma around the gland, similar to the mucosa propria stroma. Some cases of the submucosal glands were cystic dilated with mucocele formation and hemosiderin deposition. One case with broad stalk-base showed an elevated adenoma with local high grade dysplasia involved in the aggregated lymphoid nodule, forming the lymphoglandular complexes, simulating invasive adenocarcinoma with associated submucosal lymphoid aggregates. Submucosal cancer tissue and intramucosal cancer tissue had continuity, and their morphology was the same. The submucosal tumor was round in the outline, smooth and blunt in the edge, and surrounded by lymphoid tissue. There was no stromal response around the gland to promote the proliferation of connective tissue, neither was there single-cell or small-cell cluster, sharp angle branch of gland, or vascular infiltration.Conclusions:There are two unique morphological patterns in colorectal adenoma with submucosal pseudoinvasion. Morphologically, the data show that one is lobular-like pattern, and the other is lymphoglandular complexes-like pattern. The main features of the two patterns are the same-morphology and continuity of submucosal tumor and intramucosal tumor. The pushed glands were surrounded by the intrinsic membrane stroma and muscularis mucosae in proper order, lacking the typical morphological characteristics of invasive adenocarcinoma.

Objective:To investigate the clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus.Methods:Fifty-two cases of basal cell layer type high-grade squamous dysplasia of the esophagus were collected at PLA Joint Logistics Support Force 989 Hospital (34 cases) and Beijing Chaoyang Hospital (18 cases) from 2009 to 2019. The clinical, histological and immunohistochemical features were characterized. Related literature was also reviewed.Results:The median age of the 52 patients was 64 years (range 43-72 years). There were 35 men and 17 women, with a male to female ratio of 2.1∶1.0. There were 8 cases in the upper esophagus, 41 in the middle esophagus and 3 in the lower esophagus. According to the Paris Classification, 24 cases were 0-Ⅱb and 28 cases were 0-Ⅱc. Endoscopic examination showed that the color of the lesions was red and the edge was irregular. The narrow band imaging showed that the lesions were brown, and the microvascular abnormalities on the mucosal surface were observed with high magnification. Iodine staining of the lesions showed no or light staining and irregular border. Histologically, the basal layer of squamous epithelium was hypercellular, with large and hyperchromatic nuclei, and disordered cell arrangement. A high proportion of the cases showed a down-growth pattern and associated invasive squamous cell carcinoma. The immunohistochemical staining of 37 cases showed that the mutation rate of p53 was 48.6% (18/37), the median of Ki-67 labeling index was 60% (range 20%-90%), the median of Ki-67 labeling index of the basal tumor cells was 26/HPF (range 5-70/HPF), and the rate of abnormal Ki-67 distribution pattern was 37(100.0%). According to the initial pathological diagnosis, there were 8 cases of low-grade intraepithelial neoplasia, 2 cases of atypical epithelial cells and 42 cases of high-grade intraepithelial neoplasia.Conclusions:The basal cell layer type high-grade squamous dysplasia of the esophagus has a unique morphology. The dysplasia is mainly limited to the lower half part of the squamous epithelium. With marked cytological atypia and prominent invasiveness pattern, it is likely to develop into invasive squamous cell carcinoma at an early stage of the disease. The rate of pathologic misdiagnosis (such as low-grade lesion) is high. The p53 mutation and Ki-67 abnormal distribution pattern are helpful features for confirming the diagnosis of such high-grade dysplasia.

Objective:To investigate the value of chromosomes 7 and 8 polysomy in circulating tumor cells (CTCs) for the diagnosis of non-small cell lung cancer, and the correlation of CTCs with clinical pathological characteristics and epidermal growth factor receptor (EGFR) mutations in cancer tissue.Methods:Fifty-seven patients with non-small cell lung cancer and 21 patients with benign lung diseases were enrolled at Beijing Chaoyang Hospital, Capital Medical University, Beijing, China from November 2017 to October 2020. Negative enrichment combined with immunofluorescence in situ hybridization (imFISH) was used to identify CTCs polysomy on chromosomes 7 and 8. EGFR mutations in 56 lung cancer patients was detected using ARMS-PCR.Results:CTCs were detected in 93.0% (53/57) of non-small cell lung cancers and 28.6% (6/21) benign lung lesions. The difference between lung cancer patients and the control cohort was statistically significant ( P<0.01). Receive operator curve (ROC) analyses showed that, when the cut-off value was 1 cell/3.2 mL, Youden index had the highest sensitivity of 93.0% and specificity of 71.4% (AUC=0.906, 95% CI:0.833-0.980, P<0.01). The positive rate of CTCs in stage Ⅲ-Ⅳ cancers was significantly higher than that in stage Ⅰ-Ⅱ ( P=0.023). No significant correlation was observed between positive rate of CTCs or chromosome polysomy and age, gender, smoking status, pathologic types and EGFR mutation status. The number of CTCs in EGFR mutated group was higher than that in the non-mutated group (6.5±1.1 vs. 3.7±0.7, P=0.045). The detection rate for CTCs ≥5 in the EGFR mutated group was also higher than the EGFR non-mutated group (52.0% vs. 19.4%, P=0.010). Conclusion:Detection of CTCs with chromosomes 7 and 8 polysomy has potential value in auxiliary diagnosis of non‐small cell lung cancer, and the number of CTCs is correlated to TNM stage and EGFR gene mutation status.

Objective:To investigate the clinicpathological features of basal cell type dysplasia of the esophagus.Methods:The clinicopathological data of 71 cases of basal cell type dysplasia of esophagus were collected at the People′s Liberation Army Joint Logistics Support Force 989 Hospital, from 2009 to 2019, and the histomorphologic characteristics and immunophenotype were evaluated. The relevant literature was reviewed.Results:The ratio of male to female patients was 1.6∶1.0, and the median age was 65 years (range 48-81 years). The tumors were located in the upper segment of the esophagus in four cases (5.6%), the middle segment in 54 cases (76.1%), and the lower segment in 13 cases (18.3%).The median maximal tumor diameter was 12.0 mm (range 3-42 mm). According to Paris Classification, 0-Ⅱb accounted for 42.3% (30/71) of the cases. Under endoscope, the lesions were reddish with abnormal mucosal microvessels. Histologically, the neoplastic cells were small, with a high nuclear-cytoplasmic ratio, similar to basal cells, and uniform in morphology. The structural atypia was characterized by dense and disordered tumor cells, loss of basal cell polarity, and absence of normal squamous differentiation gradient. In 10 cases, the tumors were confined to the lower part of the epithelium. The tumor cells were smaller and more uniform in shape, and extend to the superficial lamina propria. Sixty-one tumors involved at least the entire layer of the upper cortex. There were 31 cases of neoplasms with superficial invasive carcinoma. The types of neoplasms included typical squamous cell carcinoma, basaloid squamous cell carcinoma, small cell neuroendocrine carcinoma, squamous cell carcinoma with sebaceous adenoid carcinoma, and differentiation of glandular/ductal epithelioid carcinoma. Immunohistochemical staining showed that the mutant expression rate of p53 protein was 41.5% (17/41). All 41 cases (100.0%) showed abnormal distribution pattern of Ki-67. According to the initial pathologic diagnosis, there were 18 cases of low grade dysplasia, 12 cases of atypical epithelial cells, and 41 cases of high grade dysplasia and superficially invasive carcinoma.Conclusions:Basal cell type dysplasia has unique morphologic characteristics and represents a tumor subtype in the morphologic lineage of esophageal squamous dysplasia. Tumor cells of basal cell type dysplasia, especially those distributed only in the lower part of the stratified squamous epithelium, may be tumor stem cells at the earliest stage of esophageal carcinogenesis and have multidirectional differentiation potential. When the tumor is confined to the lower part of the stratified squamous epithelium, it does not meet the diagnostic criteria for esophageal squamous dysplasia as defined by the current WHO classification.

Objective:To investigate the clinicopathological features and significance of spindle cell type squamous dysplasia of the esophagus.Methods:The clinicopathological data of 37 cases of spindle cell type squamous dysplasia of esophagus were collected retrospectively at People′s Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from 2009 to 2019. The histological and immunohistochemical characteristics were analyzed, with a literature review.Results:The median age of the 37 patients was 65 years (range 47-81 years), while the ratio of men to women was 1.5∶1.0. There were 4 cases in the upper esophagus, 31 in the middle esophagus and 2 in the lower esophagus. The median diameter of the lesions was 14 mm (range 3-40 mm). According to the Paris classification, 11 cases were 0-Ⅱa, 14 cases were 0-Ⅱb, 3 cases were 0-Ⅱb and 0-Ⅱa, and 9 cases were 0-Ⅱc. Under endoscope, the lesional mucosa was reddish. The micro-vessels were dilated, with various shapes and density. Histologically, tumor cells and nuclei were spindle shaped or elongated spindle shaped, with considerable homogeneity, dark nuclei and delicate or slightly thickened chromatin. The mitosis was conspicuous, and atypic mitoses were seen; the cytoplasm was acidophilic, and the intercellular bridge was obvious. The cells were dense and often lost polarity, but still arranged in parallel, mostly perpendicular to the basement membrane. Spindle cells often involved the whole layer of epithelium, with no gradient maturation and differentiation of normal squamous epithelium. The tumor was well demarcated. The spindle cells often invaded lamina propria. There were 15 cases with focal high-grade dysplasia and superficial invasive squamous cell carcinoma. Immunohistochemical staining showed that the mutation rate of p53 was 41.4% (12/29), the median of Ki-67 labeling index was 40% (range 20%-80%), and the abnormal distribution pattern of Ki-67 was 29 (100%). According to the initial pathological diagnosis, there were 6 cases of low-grade dysplasia, 4 cases of atypical epithelial cells and 27 cases of high-grade dysplasia and superficial invasive squamous cell carcinoma.Conclusions:Spindle tumor cells have moderate to severe atypia, and some tumors show invasive pattern. P53 mutation and Ki-67 abnormal distribution pattern indicate that they are high-grade dysplasia of esophageal squamous epithelium. The unique characteristics of spindle tumor cells suggest that they may represent a spindle cell subtype in the morphological spectrum of esophageal squamous dysplasia. When the knowledge of the lesion is insufficient, it can be easily misdiagnosed or missed.