Introduction on the update of the 5th edition WHO classifications of B-cell neoplasms / 中华病理学杂志

The 5th edition WHO classification of B-cell tumors is a systematic update to the fourth revised version of the classification. The changes include updated names of entities, sharpened diagnostic criteria, and upgrades from provisional to definite entities. This review focuses on the changes in the content of each chapter of B-cell tumors, facilitating domestic colleagues engaged in the diagnosis and treatment of lymphohematopoietic tumors to understand the latest progress and guide daily work.

Animal Model Analysis of Multiple Sclerosis Based on Clinical Characteristics of Traditional Chinese and Western Medicine / 中国实验方剂学杂志

Based on the clinical characteristics of multiple sclerosis （MS） in traditional Chinese medicine （TCM） and western medicine and literature analysis， this paper aims to formulate the diagnostic criteria of TCM and western medicine for MS. Moreover， the modeling methods of experimental autoimmune encephalomyelitis （EAE）， animals for the modeling， and characteristics of the models were analyzed and summarized， and the consistency between the EAE models and the diagnostic criteria of TCM and western medicine was evaluated. The results showed that animal models had low consistency with the clinical characteristics in TCM （highest consistency 68%） and western medicine （highest consistency 60%）. Pathological models account for the majority of animal models for MS research， but there is a lack of intuitive performance indicators. Thus， it is difficult to comprehensively evaluate the models. The mental state， limb numbness， lack of strength， loss of muscle tone， tremor， and balance disorders of the mice are among the diagnostic criteria in western medicine. In TCM diagnostic criteria， the major symptoms which are reflected in animal behavior， such as physical fatigue， lack of strength， mental fatigue， distinclination to talk， and weak heavy numb limbs， are consistent with the western diagnostic criteria. The minor symptoms， including mental decline， bitter taste in mouth， frequent and urgent urination， fecal incontinence， and aggravated fever， are not well reflected in the models. According to TCM， MS is caused by deficiency of kidney essence and external contraction of pathogen， but no index is available for evaluating the external contraction of pathogen in existing animal models. The key to experimental research on MS is to establish an appropriate animal model based on the clinical pathogenesis and characteristics. However， there is a lack of MS animal model with TCM characteristics for syndrome classification. Therefore， renewed efforts should be made to prepare animal models with both TCM and western medicine characteristics that can be used in both basic experiments and clinical research.

Clinicopathological features of T-lymphoblastic lymphoma with Langerhans cell histiocytosis in the same lymph node / 中华病理学杂志

To investigate the clinicopathological features, immunophenotypes, genetics and prognosis of T-lymphocyte lymphoma/myeloid sarcoma combined with Langerhans cell histiocytyosis (coexistence of T-LBL/MS and LCH). Clinical and pathological data of the 6 patients with coexistence of T-LBL/MS and LCH were analyzed, who were diagnosed at the Foshan Hospital of Sun Yat-sen University and the Friendship Hospital of Capital Medical University, from December 2013 to April 2019. The hematoxylin and eosin stain, immunohitochemistry (EnVision) and in situ hybridization were used. Related literatures were reviewed. Four patients were T-LBL combined with LCH, 1 was T-LBL/MS combined with LCH, and 1 was MS combined with LCH. There were 2 male and 4 female patients, with age ranged from 5 to 77 years old (median, 59 years old). Three patients represented with only multiple lymph node swelling. The other 3 displayed both multiple lymph node swelling, and skin/liver or spleen lesions. Lymph node structure was destroyed in 5 cases, while 3 cases had several residual atrophic follicles. Histologically, there were two types of tumor cells: one type of the abnormal lymphoid-cells exhibited small to medium-sized blast cells, typically showing a nested distribution, and these cells were mainly identified in residual follicles and paracortical areas; the other type of histiocytoid cells had a large cell size and abundant pale or dichromatic cytoplasm. Their nuclei were irregularly shaped, showing folded appearance and nuclear grooves. These cells were mainly present in marginal sinus, medullary sinus and interstitial area between follicles. Eosinophil infiltration in the background was not evident in any of the cases. The lymphoid-cells of medium size showed TdT+/CD99+/CD7+, with variable expression of CD34/MPO/CD2/CD3. Ki-67 index was mostly 30%-50%. However, the histiocytoid cells showed phenotype of CD1a+/S-100+/Langerin+/-, while CD163/CD68 were positive in some degree. These cells did not express any T or B cell markers. The Ki-67 index mostly ranged between 10%-20%. None of the cases had Epstin-Barr viral infection. Among the 6 patients, 4 patients were followed up (6-63 months, median time, 18.5 months), of whom 1 patient died of the disease and 3 patients were alive at the end of follow-up. T-LBL/MS combined with LCH is a rare mixed type of immature hematopoietic disease, and mainly occurs in lymph node and skin. The clinical course is overall aggressive. Therefore, it is helpful to recognize and identify the two pathologic components in the same tissue for accurate diagnosis and proper treatment.

Relationship between the status of BRAF V600 and EGFR gene mutation and clinicopathological features in patients with non-small cell lung cancer / 临床与实验病理学杂志

Purpose To study the status of BRAF V600 and EGFR mutations in patients with non-small cell lung cancer (NSCLC) and to examine the relations between them.Methods BRAF V600 and EGFR mutations were detected with DNA sequencing.The relationship between BRAF V600,EGFR mutations and the clinicopathological features were analyzed.Results BRAF V600 mutations were detected in 11 (7.5％) of the 146 specimens.BRAF V600 mutations were found morelfrequently in non-smokers (P =0.045).There were no significant differences in age,gender,histological subtype and differentiation between patients with and without BRAF V600 mutations (P ＞ 0.05).EGFR mutations were detected in 68 (46.6％) of the 146 specimens.EGFR mutations were found more frequently in women,non-smokers and adenocarcinoma (P ＜ 0.05).Four tumors with BRAF V600 mutations (three V600 and one V600D) showed concomitant EGFR mutations (two DEL and two L858R).Conclusion BRAF V600 mutations in patients with NSCLC are found more frequently in non-smokers.There are no significant differences in age,gender,histological subtype and differentiation between patients with and without BRAF mutations.

EGFR gene mutation status, ERCC1 and Ki-67 protein expression in non-small cell lung cancer and relationship with clinicopathologic features / 临床与实验病理学杂志

Purpose To study the status of EGFR mutations and the expression of excision repair cross-complementation group 1 ( ER-CC1) and Ki-67 protein in patients with non-small cell lung cancer (NSCLC) and to examine the relationship between their expression and clinicopathologic features. Methods EGFR mutations were analyzed with DNA sequencing, and the expression of ERCC1 and Ki-67 protein was examined by immunohistochemistry EnVision. The relationship of EGFR mutations with the expression of ERCC1and Ki-67 and the clinicopathological features were analyzed. Results EGFR mutations were detected in 143 (143/291, 49. 1%) of the 291 specimens. EGFR mutations were found more frequently in women, non-smokers and adenocarcinoma. The difference of EGFR muta-tion rate between the histological subtypes according to the IASLC/ATS/ERS classification of lung adenocarcinoma was significantly ( P=0. 008). The mean tumor diameter was smaller in patients with EGFR mutations than in those with wild-type EGFR (P=0. 020). EGFR mutations were not related to age, lymph node metastasis. However, EGFR mutations were not related to the expression of ER-CC1 and Ki-67 protein (P>0. 050). Conclusions EGFR mutation is closely linked to several clinicopathological factors, such as gender, differentiation, and histological subtype. There is heterogeneity of EGFR mutation in patients with NSCLC. EGFR mutations were not related to the expression of ERCC1 and Ki-67 protein.

Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy: risk factors and survival / 癌症

<p><b>INTRODUCTION</b>Hepatitis B virus (HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B (hepatitis B surface antigen [HBsAg]-negative and hepatitis B core antibody [HBcAb]-positive). This study aimed to assess HBV reactivation and hepatitis occurrence in diffuse large B-cell lymphoma (DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reactivation and hepatitis occurrence and to analyze whether HBV reactivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.</p><p><b>METHODS</b>We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center, China. Predictive factors for HBV reactivation, hepatitis development, and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression model.</p><p><b>RESULTS</b>Among the 278 patients, 165 were HBsAg-negative. Among these 165 patients, 6 (10.9%) of 55 HBcAb-positive (resolved HBV infection) patients experienced HBV reactivation compared with none (0%) of 110 HBcAb-negative patients (P = 0.001). Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients (21.8% vs. 8.2%, P = 0.013). HBcAb positivity and elevated baseline alanine aminotransferase (ALT) levels were independent risk factors for hepatitis. Among the 55 patients with resolved hepatitis B, patients with elevated baseline serum ALT or aspartate aminotransferase (AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels (P = 0.037, P = 0.005, respectively). An elevated baseline AST level was an independent risk factor for hepatitis in these patients. Six patients with HBV reactivation recovered after immediate antiviral therapy, and chemotherapy was continued. HBcAb positivity, HBV reactivation, or hepatitis did not negatively affect the survival of DLBCL patients.</p><p><b>CONCLUSIONS</b>DLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reactivation and hepatitis than HBsAg-negative/HBcAb-negative patients. Close monitoring and prompt antiviral therapy are required in these patients.</p>

Hepatitis B surface antigen affects the expression of lipid metabolism-related genes in HepG2 cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the influence of hepatitis B virus (HBV)-encoded small surface protein (SHBs) on hepatic cell expression of host genes related to lipid metabolism.</p><p><b>METHODS</b>The full-length SHBs gene was amplified from HBV genotype C by polymerase chain reaction (PCR) and cloned into the pcDNA3.1(+) expression vector for stable transfection into HepG2 cells (selected by G418 screening); cells transfected with empty vector served as control. The SHBs mRNA and protein levels were detected by reverse transcription-PCR and enzyme-linked immunosorbent assay. SHBs effects on expression of genes and proteins related to lipid metabolism were detected by real-time quantitative (q)PCR and western blotting, respectively.</p><p><b>RESULTS</b>The stably transfected cell line HepG2-pn3.1-SHBs was established successfully. qPCR showed that the HepG2-pn3.1-SHBs cells had significantly down-regulated transcription of the ECHS1, APOA1 and LPL genes (0.161+/-0.043 vs. control cells: 0.210+/-0.022, t = 2.479; 0.031+/-0.007 vs. 0.094+/-0.055, t = 2.752; 0.770+/-0.036 vs. 0.982+/-0.031, t = 10.914), but significantly up-regulated ACC and SREBP-1c genes (0.113+/-0.027 vs. 0.059+/-0.022, t = -3.757; 0.019+/-0.002 vs. 0.015+/-0.001, t = -4.330). The CPT1a and PPARa genes' expression was slightly, but not significantly, down-regulated in the HepG2-pn3.1-SHBs cells (0.028+/-0.005 vs. 0.030+/-0.004, t = 1.022; 0.014+/-0.004 vs. 0.015+/-0.002, t = 0.758). Western blotting showed similar expression trends for the corresponding proteins.</p><p><b>CONCLUSION</b>SHBs alters the expression of some host genes with known functions in fatty acid synthesis and decomposition; however, it remains unclear whether the hepatitis B surface antigen can directly contribute to development of hepatic steatosis.</p>

Clinicopathologic study of 963 cases of mature T-cell and natural killer/T-cell lymphoma with respect to 2008 WHO classification of lymphoid neoplasms / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of various types of mature T-cell and natural killer (NK)/T-cell lymphoma in Guangdong, China, with respect to the 2008 WHO classification of lymphoid neoplasms.</p><p><b>METHODS</b>Eleven hundred and thirty-seven (1137) cases of mature T-cell or NK/T-cell lymphoma diagnosed during the period from 2002 to 2006 in Guangzhou area were retrieved. The clinical data, histologic features and immunohistochemical findings were reviewed by a panel of experienced hematopathologists. Additional immunostaining was performed if indicated. The cases were re-classified according to the 2008 WHO classification of lymphoid neoplasms.</p><p><b>RESULTS</b>Nine hundred and sixty-three (963) cases fulfilled the diagnostic criteria of mature T-cell or NK/T-cell lymphoma and accounted for 20.1% of all cases of lymphoma encountered during the same period (963/4801). A predominance of extranodal involvement was noted in 644 cases (66.9%), while 319 cases (33.1%) showed mainly nodal disease. The prevalence of various lymphoma subtypes was as follows: peripheral T-cell lymphoma, unspecified (PTCL, NOS) 293 cases (30.4%), extranodal NK/T-cell lymphoma, nasal type 281 cases (29.2%), anaplastic large cell lymphoma (ALCL) 198 cases (20.6%), and angioimmunoblastic T-cell lymphoma (AILT) 46 cases (4.8%). The male-to-female ratio was 1.99. The median age of the patients was 44 years, with the peak age of PTCL, NOS, extranodal NK/T-cell lymphoma, nasal type and AILT being 55 to 64 years, 25 to 54 years and 65 to 74 years, respectively. ALK-positive ALCL occurred more frequently in young age, while the ALK-negative ALCL cases occurred mainly in the elderly.</p><p><b>CONCLUSIONS</b>Extranodal lesions predominate in mature T-cell and NK/T-cell lymphomas occurring in Guangzhou area. There is a male predominance and the overall incidence shows no increasing trend with age of the patient. The peak age of various subtypes however varies. The most common subtype was PTCL, NOS, followed by extranodal NK/T-cell lymphoma, nasal type, ALCL and AILT. The relatively frequent occurrence of extranodal NK/T-cell lymphoma, nasal type in Guangdong area is likely associated with the high incidence of Epstein-Barr virus infection there.</p>

Follicular dendritic cell sarcoma: a clinicopathologic analysis of ten cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of follicular dendritic cell sarcoma (FDCS) and its differential diagnosis.</p><p><b>METHODS</b>Ten cases of FDCS were studied by light microscopy, immunohistochemistry and in-situ hybridization. The clinical features and follow-up information were analyzed.</p><p><b>RESULTS</b>Amongst the 10 cases of FDCS studied, the male-to-female ratio was 1:1. The mean age of the patients was 42 years. Six of them were located in cervical and peritoneal lymph nodes and four in extranodal sites (including tonsil, pelvic cavity, tail of pancreas and spleen). Histologically, the tumor cells had whorled, storiform or diffuse growth patterns. They were spindle in shape and contained syncytial eosinophilic cytoplasm, with round or oval nuclei, vesicular chromatin, distinct nucleoli and a variable number of mitotic figures. Multinucleated tumor giant cells and intranuclear pseudoinclusions were occasionally seen. There was a sprinkling of small lymphocytes and neutrophils within the tumor as well as in the perivascular region. Immunohistochemical study showed that the tumor cells were diffusely or focally positive for CD21, CD23, CD35 and D2-40, but negative for LCA, CD20, CD3, CD1a, HMB45 and CK. Some of them showed EMA, CD68 and S-100 reactivity. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed positive signals in only one case (which was diagnosed as inflammatory pseudotumor-like FDCS). Of the 7 patients with follow-up information available (duration: 2 months to 39 months; mean: 14 months), 2 cases with paraneoplastic pemphigus died of pulmonary infection at 5 and 7 months respectively. The remaining 5 patients were alive and disease-free after surgical excision (+/- chemotherapy and radiotherapy).</p><p><b>CONCLUSIONS</b>FDCS is a rare low to intermediate-grade malignant tumor. Appropriate application of FDC markers, such as CD21, CD35 and D2-40, would be helpful for arriving at a correct diagnosis. Most cases are associated with good prognosis after surgical treatment, with or without chemotherapy and radiotherapy. Patients with paraneoplastic pemphigus carry a less favorable prognosis.</p>

The role of Skp2 in extranodal NK/T-cell lymphoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Expression of Skp2 was related with the prognosis of several tumors. However, there was no intensive study on the relationship between Skp2 and extranodal NK/T cell lymphoma. This study was to explore the role of Skp2 in extranodal NK/T cell lymphoma.</p><p><b>METHODS</b>The clinicopathological data of 39 patients with extranodal NK/T cell lymphoma were analyzed. The expression of Skp2 was examined by immunohistochemistry on formalin fixed, paraffin embedded tissue sections.</p><p><b>RESULTS</b>Among the patients with high expression of Skp2, complete remission (CR) rate was only 14.3% (2/14). However, CR rate among the patients with low expression of Skp2 was 68.0% (17/25). Significant difference was shown between these two groups (P < 0.001). In the group of low expression, the median overall survival (OS) was 85.59 months (95% CI: 35.83 135.34 months), the 1 and 2 year OS rates were 81% and 71%, respectively. However, in the group of high expression, the median OS was only 9.73 months (95% CI: 2.05-17.40 months), the 1 and 2 year OS rates were 42% and 14%, respectively. There was statistical difference between these two groups (P < 0.001). Multivariate analysis showed that Skp2 expression (P <0.001), LDH (P = 0.026) and ECOG PS (P = 0.003) were dependent prognostic factors of extranodal NK/T cell lymphoma.</p><p><b>CONCLUSION</b>High expression of Skp2 is an independent unfavorite adverse prognostic factor of extranodal NK/T cell lymphoma.</p>

Significance of expression of THY1 protein in epithelial ovarian cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this study was to investigate the clinical significance of THY1 protein expression in epithelial ovarian cancer.</p><p><b>METHODS</b>Immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining were used to detect the protein expression of THY1, Ki67 and cell apoptosis in 76 epithelial ovarian cancers by tissue microarray. The correlation between THY1 expression and patients' clinical features was analyzed.</p><p><b>RESULTS</b>Of the 76 epithelial ovarian cancer samples, 64 were informative for IHC and TUNEL assays and 42 (65.6%) among them showed down-regulated/loss expression of THY1 protein. A significant positive correlation of THY1 protein expression with clinical stage and distant metastasis was observed in this ovarian cancer cohort (P < 0.05). The more advanced the tumor stage, the more frequency of loss expression of THY1 protein. In addition, the mean positive rate of Ki67 staining in tumors with down-regulated/loss expression of THY1 was 33.7% +/- 3.5%, significantly higher than that in the tumors with normal expression of THY1 (17.3% +/- 6.1%, P = 0.0027). However, no significant correlation was observed between THY1 protein expression and tumor cell apoptosis as well as patients' survival in this series (P > 0.05).</p><p><b>CONCLUSION</b>Down-regulated/loss expression of THY1 protein in epithelial ovarian cancer is significantly correlated with cancer cell proliferation and metastasis in the epithelial ovarian cancer, and it may be used as one of the new molecular biomarkers to predict the disease progression in patients.</p>

Effect of p53 expression in the primary lesion and the surgical margin on the postoperative radiotherapy for laryngeal squamous carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the correlation between prognosis and p53 expression in primary lesion and the surgical margin of laryngeal squamous cell carcinoma (SCC) as an indication of postoperative radiotherapy.</p><p><b>METHODS</b>Sixty-seven laryngeal SCC with pathological negative margin were analyzed retrospectively. Immunohistochemical method was used to detect the expression of p53.</p><p><b>RESULTS</b>The p53 positive rates in the primary tumor and the surgical margin were 19.4% (13/67) and 50.7% (34/67). In p53 positive primary tumor group, the survival rate was higher in patients who received postoperative radiotherapy than those without (60.6% vs 20.0%, P = 0.000 5) and the recurrent rate was just the reverse (42.1% vs 93.3%, P = 0.002), though these differences were not significant in p53 negative primary tumor group (87.5% vs 94.1%, P = 0.409 6; 25.0% vs 5.9%, P = 0.175). The recurrent rate and survival rate between patients with and without postoperative radiotherapy did not show any significant difference either in p53 positive surgical margin group (47.4% vs 20.0%, P = 0.378 1; 62.5% vs 80.0%, P = 1.0) or p53 negative ones (84.9% vs 66.6%, P = 0.074 3; 20.6% vs 40.7%, P = 0.248).</p><p><b>CONCLUSION</b>Postoperative radiotherapy should be given to patients with p53 positive primary laryngeal cancer. But those who are pathologically margin negative but p53 positive should not be taken, at least for the present, as candidates for postoperative radiotherapy.</p>