[Clinicopathological features of differentiated-type dysplasia of the esophagus].

Objective: To investigate the clinicopathological features of differentiated-type (squamous) dysplasia of the esophagus. Methods: A total of 184 cases of esophageal differentiated-type dysplasia were collected retrospectively at People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), and Beijing Chaoyang Hospital, Capital Medical University, China from 2016 to 2019. Their histological characteristics and immunophenotypes were analyzed, and related literature was reviewed. Results: The median age of the 184 patients was 65 years (range 39-83 years), while the ratio of men to women was 1.7∶1.0. There were 17 cases in the upper esophagus, 143 in the middle esophagus and 24 in the lower esophagus. The median diameter of the dysplasia was 15 mm (range 2-50 mm). According to the Paris classification, 2 cases were 0-Ⅰ, 25 cases were 0-Ⅱa, 70 cases were 0-Ⅱb, 74 cases were 0-Ⅱb and 0-Ⅱc and 13 cases were 0-Ⅱc. Macroscopically, the lesional mucosa was reddish with rough surface and white moss; capillary abnormality was found on narrow-band imaging. Histologically, dysplastic cells had distinct features of squamous epithelium, with abundant eosinophilic cytoplasm, round to irregular nuclei, coarse chromatin, obvious nucleolus, and conspicuous mitoses. The cellularity was increased, the arrangement of cells was disordered, and the polarity of cells in basal layer was lost. When the dysplasia did not completely spread to the whole layer of squamous epithelium, a clear boundary was often formed between the dysplasia and the normal epithelium above it. The neoplastic epithelial protrusions often grew toward the lamina propria and were accompanied by conspicuous inflammatory cell reaction at its frontal edge. Sometimes, abnormal mature single epithelial cells or cell clusters infiltrated into the lamina propria. There were high-grade dysplasia of the common type and superficial invasive squamous cell carcinoma in 98 cases of differentiated-type dysplasia. Immunohistochemical staining showed that the mutation rate of TP53 was 47.7% (53/111). The median of Ki-67 labeling index was 50.0% (range 10%-80%), while that of basal tumor cells was 12/HPF (range 3-65/HPF). The abnormal distribution pattern of Ki-67 was seen in 111 (100%) cases. According to the initial pathological diagnosis, there were 16 cases of low-grade intraepithelial neoplasia, 37 cases of atypical epithelial cells and 131 cases of high-grade intraepithelial neoplasia and superficial invasive squamous cell carcinoma. Conclusions: The morphology of differentiated-type dysplasia of the esophagus is unique. Characteristics of highly differentiated dysplastic cells suggest that they may represent a differentiated type in the morphological lineage of esophageal squamous (high-grade) dysplasia. When the knowledge of the lesion is insufficient, it is easy to be misdiagnosed or missed in pathologic examination.

[Spindle cell type squamous dysplasia of the esophagus: a clinicopathological analysis].

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.

[Clinicopathological features of basal cell layer type high-grade squamous dysplasia of the esophagus].

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.

[Pathological characteristics of colorectal adenoma with submucosal pseudoinvasion].

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.

Autoantibody against integrin αv ß3 contributes to thrombocytopenia by blocking the migration and adhesion of megakaryocytes.

Essentials The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. We analyzed the role of anti-αvß3 autoantibody in the pathogenesis of ITP in patients. Anti-αvß3 autoantibody impeded megakaryocyte migration and adhesion to the vascular niche. Anti-αv ß3 autoantibody potentially contributes to the pathogenesis of refractory ITP. SUMMARY: Background The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. Anti-αvß3 integrin autoantibody is detected in chronic ITP patients, but its contribution to ITP is still unclear. Objectives To clarify the potential role of anti-αvß3 integrin autoantibody in chronic ITP and the related mechanism. Methods Relationship between levels of anti-αvß3 autoantibody and platelets in chronic ITP patients was evaluated. The influence of anti-αvß3 antibody on megakaryocyte (MK) survival, differentiation, migration and adhesion was assessed, and the associated signal pathways were investigated. Platelet recovery and MKs' distribution were observed in an ITP mouse model pretreated with different antibodies. Result In this study, we showed that the anti-αvß3 autoantibody usually coexists with anti-αIIbß3 autoantibody in chronic ITP patients, and patients with both autoantibodies have lower platelets. In in vitro studies, we showed that the anti-αvß3 antibody had no significant effect on the survival and proliferation of MKs, whereas it decreased formations of proplatelet significantly. Anti-αvß3 antibody impeded stromal cell derived facor-1 alpha (SDF-1α)- mediated migration and inhibited the phosphorylation of protein kinase B. Anti-αvß3 antibody significantly inhibited MKs' adhesion to endothelial cells and Fibrogen. The phosphorylation of focal adhesion kinase and proto-oncogene tyrosine-protein kinase Src induced by adhesion was inhibited when MKs were pretreated with anti-αvß3 antibody. In in vivo studies, we showed that injection with anti-αv antibody delayed platelet recovery in a mouse model of ITP. Conclusions These findings demonstrate that the autoantibody against integrin αv ß3 may aggravate thrombocytopenia in ITP patients by impeding MK migration and adhesion to the vascular niche, which provides new insights into the pathogenesis of ITP.