Interferon regulatory factor 4(IRF4)plays an important role in B-cell development and differentiation.Large B-cell lymphoma with IRF4 gene rearrangement(LBCL-IRF4)is a germinal center derived mature B-cell lym-phoma,initially classified as a special provisional type of follicular lymphoma.With advancing research and under-standing,LBCL-IRF4 has been shown to differ from classic follicular lymphoma(cFL),pediatric follicular lymphoma(PTFL)and diffuse large B-cell lymphoma(DLBCL).The latest fifth edition of the World Health Organization(WHO)classification of hematopoietic and lymphoid tissue tumors has officially classified this tumor as a distinct type under large B cell lymphoma.To gain a more comprehensive understanding of this tumor,this paper reviews the re-search progress on the clinicopathological and molecular genetic characteristics of LBCL-IRF4.

Interferon regulatory factor 4(IRF4)plays an important role in B-cell development and differentiation.Large B-cell lymphoma with IRF4 gene rearrangement(LBCL-IRF4)is a germinal center derived mature B-cell lym-phoma,initially classified as a special provisional type of follicular lymphoma.With advancing research and under-standing,LBCL-IRF4 has been shown to differ from classic follicular lymphoma(cFL),pediatric follicular lymphoma(PTFL)and diffuse large B-cell lymphoma(DLBCL).The latest fifth edition of the World Health Organization(WHO)classification of hematopoietic and lymphoid tissue tumors has officially classified this tumor as a distinct type under large B cell lymphoma.To gain a more comprehensive understanding of this tumor,this paper reviews the re-search progress on the clinicopathological and molecular genetic characteristics of LBCL-IRF4.

Objective: To investigate the clinical features, morphological characteristics, immunophenotype, and differential diagnosis of goblet cell adenocarcinoma (GCA) in the digestive system. Methods: The clinicopathological data, morphological characteristics, immunophenotypes of 22 cases of GCA in the digestive system diagnosed from January 2010 to January 2021 were collected. Meanwhile, 25 cases of neuroendocrine neoplasm (NEN) and 24 cases of adenocarcinoma were used as controls. Relevant literature was also reviewed. Results: There were 16 males and 6 females, aged from 36 to 79 years with an average of 56 years. The anatomical sites of the 22 GCA were mostly appendix (17 cases) and occasionally extra-appendix (5 cases), including 3 cases in stomach, 1 case in duodenum and 1 case in anal. All 17 cases of appendiceal GCA were pure GCA. Among the 5 cases of extra-appendiceal GCA, One case of gastric GCA was pure, two cases of gastric GCA with NEN or adenocarcinoma, duodenal GCA with NEN and adenocarcinoma, anal GCA with NEN.Low-grade GCAs were composed of goblet, Paneth and neuroendocrine cells, which were arranged in intestinal crypt tubular or cluster structures and distributed in the wall of digestive system. The tubular and cluster structures lacked adhesion. Goblet cells were columnar, located in the base, with clear cytoplasm, small nuclei, inconspicuous atypia, and uncommon mitoses. Extracellular mucus and signet-ring cells with nuclear variations could be seen in some cases. Nerve fiber bundle invasion and tumor thrombus in vessels were often present. High-grade GCAs lacked tubular and cluster structures, and their histological structures were more complex. Tumor cells expressed mixed neuroendocrine and glandular epithelial markers. Similar to the expression patterns of synaptophysin and chromogranin A, CD200 and INSM1 were also dot-like or patch-positive in GCA. Conclusions: GCA is an infrequent tumor of the digestive system and shows the bi-directional differentiation characteristics of neuroendocrine and glandular epithelium. Accurate diagnosis and staging are related to its prognosis.
Adenocarcinoma/pathology* ; Appendiceal Neoplasms/surgery* ; Carcinoid Tumor/surgery* ; Chromogranin A ; Female ; Goblet Cells/pathology* ; Humans ; Male ; Neuroendocrine Tumors/pathology* ; Repressor Proteins ; Synaptophysin

Objective:To investigate the expression and diagnostic values of CD200 and insulinoma associated protein 1 (INSM1) in gastrointestinal and pancreatic neuroendocrine neoplasm (GIP-NEN).Methods:The expression of CD200, INSM1, Syn and CgA was detected in 69 cases of GIP-NEN, 66 cases of gastrointestinal and pancreatic non-neuroendocrine neoplasm (GIP-nonNEN) and 16 cases of metastatic neuroendocrine neoplasm by immunohistochemistry, to compare the values of CD200, INSM1, Syn, CgA and their combinations in diagnosing GIP-NEN. Receiver operating characteristics (ROC) curve was used.Results:The immunoreactivity of CD200 was present in the cytoplasma and/or membrane of the neoplasms cells, the positive expression rates in GIP-NEN and GIP-nonNEN were significantly different ( P<0.01). The sensitivity and specificity of CD200 for diagnosing GIP-NEN were 95.7% and 78.8%, respectively. There was significant difference of the positive rates of CD200 between neuroendocrine tumor and neuroendocrine carcinoma ( P=0.05). The immunoreactivity of INSM1 was present in the nuclei of neoplasms cells. The positive expression rates in GIP-NEN and GIP-nonNEN were significantly different ( P<0.01). The sensitivity and specificity of INSM1 for diagnosis of GIP-NEN were 85.5% and 95.5%, respectively. There were also significantly different positive rates of INSM1 between neuroendocrine tumor and neuroendocrine carcinoma, as well as between G1 and G3 neuroendocrine tumors ( P<0.05). There was no difference in the area under ROC curve (AUC) of single stain of CD200, INSM1, Syn or CgA (0.857, 0.907, 0.890 and 0.833, respectively, P>0.05). The sensitivity of combined CD200+INSM1 stains for diagnosing GIP-NEN was significantly higher than that of Syn+CgA (85.5% vs. 63.8%, P<0.05). The AUC of two combinations were 0.962 and 0.925, respectively, which were not statistically different ( P>0.05). Conclusions:CD200 and INSM1 are two novel markers of neuroendocrine neoplasm, which aid to diagnosis for GIP-NEN and exclude its mimickers. They are associated with tumor grades. Combining both as an immunohistochemical panel shows high sensitivity and specificity. Thus, the combined panel can be utilized as useful supplement for Syn and CgA.

Objective:To evaluate the interobserver variation of pathologists in the morphological evaluation of non-invasive follicular thyroid neoplasm with papillary-like nuclear features(NIFTP).Methods:Nine pathologists from different regions in China were selected to evaluate the digital slides of 30 cases of NIFTP. Three score system was applied, including nuclear size and shape, membrane irregularity, and chromatin features. Individual histologic features were scored as either present(1)or absent(0). A total score of 0 or 1 was considered inadequate for the diagnosis of NIFTP and a total score of 2 or 3 was considered sufficient for the diagnosis of NIFTP.Results:Overall, 9 doctors had weak consistency in the interpretation of the 30 cases(Kappa value 0.081 4), in which the interpretation of the membrane irregularity had the best consistency(Kappa value 0.193 6)and the interpretation of nuclear size and shape revealed the worst consistency(Kappa value 0.102 2). The overall consistency of the evaluation from the 7 senior pathologists was better than that of all the pathologists(Kappa value 0.134 1), but it was still weak. The consistency of nuclear membrane irregularity(Kappa value 0.267 4)and nuclear chromatin features(Kappa value 0.257 3)was weak, but much better than that of nuclear size and shape(Kappa value 0.073 0). The interobserver consistency in our study was lower than that in Asian study generally. However, the judgement on membrane irregularity in our senior pathologists was better than that in Asian study.Conclusion:The interobserver variation on the evaluation of the nuclear features of NIFTP is probably due to the education level, working experience, personal understanding of the diagnostic criteria, the regional difference, and some uncertain reasons. There is overall a weak consistency in the interpretation of NIFTP by Chinese pathologists, and it is necessary to popularize the diagnostic criteria and specify the criteria in detail. It is important to exclude high-risk genetic mutation using immunohistochemical staining or molecular examination on those patients with morphology of NIFTP.

Microcystic stromal tumor (MCST) is a rare subtype of sex cord-stromal neoplasm. Tumors from all 31 previously reported cases were located in the ovary. Herein, we present a unique case of a right-side testicular tumor in a 33-year-old Chinese male. The tumor is composed of predominantly lobulated cellular nodules separated by hyalinized fibrous stroma and they expressed CD10, β-catenin (nuclear), and cyclin D1. Molecular analysis identified a point mutation (c.110C>G) in exon 3 of CTNNB1. The histopathological features, immunohistochemistry profiles, and molecular analysis of this tumor were consistent with MCST of the ovary. Therefore, a diagnosis of MCST of the right testicle was determined. To the best of our knowledge, this is the first case of MCST occurring in the testicles. The study may provide new insights to the tumor biology of MCST and a better understanding of this rare entity.
Adult ; Asian Continental Ancestry Group ; Biology ; Cyclin D1 ; Diagnosis ; Exons ; Female ; Humans ; Hyalin ; Immunohistochemistry ; Male ; Ovary ; Point Mutation ; Testis*

Objective: To investigate the clinicopathological features, morphological characteristics, immunophenotypes of littoral cell angioma (LCA) in spleen, and to provide new evidence for making diagnosis and avoiding misdiagnosis.Methods: Clinicopathological data, histological characteristics of 13 cases of LCA were retrospectively studied and immunohistochemical staining was imposed on the paraffi-nembedded specimens, and 5 cases of cavernous hemangioma, 4 cases of normal littoral cells of spleens were used as control groups, simultaneously.Results: All the 13 LCA patients included 7 males and 6 females, aged from 39 to 70 years with an average of 54.2 years and a median age of 55 years.Among these tumor patients, 6 cases were accompanied by malignances, benign tumors or inflammation states at abdominal cavities, and 7 cases were accidentally discovered by physical examinations.Grossly, spleens contained solitary or multiple gray red nodules ,which ranged from 0.5 to 6.2 cm in diameter.Histologically, tumors were composed by anastomosing vascular spaces which were lining by plump, rounded to cuboidal littoral cells that extended into vascular lumens.Usually, papillary frameworks that were covered by these cells were also seen extending into the lumens in some areas.Other types of histiocytoid cells were identified in lumens and the sizes were larger than the littoral cells.Both types of cells absented cytologic atypia.Immunohistochemical study demonstrated that the littoral cells in all cases were positive for vascular endothelial and histiocyte markers, such as CD21, CD31, CD68, polyclone FⅧRAg and ERG, while these cells were negative for CD8, CD34, and WT-1.These findings manifested that immunophenotype of littoral cell in LCA distinctive from that in controls.Conclusion: LCA is a benign lesion, which frequently occurs in the elderly.Its etiology remains confusion, however, immune dysregulation may associate with it because of the concomitance with other tumor or inflammation in some cases.The littoral cells in LCA show a hybrid endothelial-histiocytic phenotype on immunohistochemistry, therefore these cells may have features that intermediate between those of endotheliocytes and histiocytes.Emphasizing the histological findings and immunophenotypes is significant for diagnosis and differential diagnosis.

With the development of imaging technology,the detection rate of gallbladder benign lesions has increased year by year.And part of the diseases may evolve into gallbladder cancer through a series of pathophysiologic processes.There are some misunderstandings in the understanding of gallbladder benign lesions for surgeons,so it is difficult for the clinical decision-making.The relationship between gallbladder benign lesions and gallbladder cancer should be correctly understood.Surgeons can neither exaggerate the risk of gallbladder cancer nor miss optimal timing of operation.The key point of the diagnosis and treatment of gallbladder benign lesions should be based on making full use of imaging data and strictly grasp pre-and intraoperative indications,and it is important to identify the malignant transformation of gallbladder benign lesions as soon as possible and carry out standardized treatment.

Purpose To investigate the clinicopathological features, histogenesis, morphological characteristics, immunophenotypes and differential diagnosis of primary extragonadal yolk sac tumor ( eYST) . Methods Clinicopathological data, morphological charac-teristics and immunophenotypes results of 40 cases of eYST were retrospectively studied and the relevant literatures were reviewed. Re-sults All 40 patients, which included 24 male and 16 female, aged from 6 months to 42 years with a 12 years average age and 17 (42.5%) cases were over 12 years old. Mediastinum, sacrococcygeal, retroperitoneal, pineal gland and vagina were involved in 16 (40.0%), 12(30.0%), 5(12.5%), 4(10.0%) and 3(7.5%), respectively. All 40 cases included 32(80.0%) cases pure YSTs, while other 8(20.0%) cases contained other one or two types of germ cell tumor (GCT) components. Conclusions Primary eYST is rare, mediastinum and sacrococcygeal are the most common anatomic sites for eYST, and these mediastinal tumor patients are overwhelmingly confined to adult males, whose average age are significantly older than that in sacrococcygeal, retroperitoneal, pineal gland and vaginal tumor patients (P<0.05), while other sites eYST are restricted to prepubertal children. Adult eYST contain other types of GCT components in some cases, and children's counterparts are always pure YST. Extragonadal eYST manifestate pleomorphic histological features, which combine with immunohistochemical markers is definite value for diagnosis, differential diagnosis.

This study examined the effect of astilbin on the proliferation of rat aortic smooth muscle cells (RASMCs) induced by angiotensin Ⅱ (Ang Ⅱ) and explored the possible mechanisms.Cell proliferation model of RASMCs was induced by treatmente with Ang Ⅱ.Cells were randomly divided to 8 groups.Normally cultured VSMCs serves as blank control group; in Ang Ⅱ model group,cells were treated with AngⅡ at 10-7 mol/L; in three astilbin groups,cells were treated with 10,15,30 mg/L of astilbin; in three Ang Ⅱ +astilbin groups,cells were treated with Ang Ⅱ (at 1 0-7 mol/L) and astilbin at 10,15,30 mg/L.Cell proliferation ability was detected by MTT method and the cell cycles and proliferation index were flow cytometrically determined.The expression of c-myc mRNA was assessed by using reverse transcription polymerase chain reaction (RT-PCR),and the expression of NF-κB in RASMCs was immunocytochemically observed.Our results showed that MTT metabolism in RASMCs in the basic and Angll stimulated situation was inhibited by astilbin,and the cells numbers of G0/G1 phase were increased and that of G2/S phase were decreased markedly.Not only highly expression of c-myc gene stimulated by Ang Ⅱ could be inhibited by Astilbin significantly,but also the expression of NF-κB protein can be down regulated by Astilbin.We are led to conclude that astilbin astilbin can inhibit the Ang Ⅱ -mediated proliferation of RASMCs by blocking the transition of RASMCs from Go/G1 phase to S phase and by down-regulating the expression of NF-κB,c-mvc gene.