B-cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations / 中华病理学杂志

<p><b>OBJECTIVE</b>To identify and investigate clinicopathological features of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations ("double-hit" lymphoma).</p><p><b>METHODS</b>Tissue microarray was constructed from formalin-fixed and paraffin-embedded tissue samples of aggressive B cell lymphomas diagnosed between 2009 and 2012, including 129 cases of diffuse large B cell lymphoma (DLBCL), 5 cases of B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU), 7 cases of Burkitt lymphoma and 4 cases of high-grade follicular lymphoma with diffuse large B cell lymphoma component. Interphase fluorescence in-situ hybridization (FISH) was performed with a panel of probes including myc, bcl-2/IgH and bcl-6 to document related gene translocation and copy number changes. Medical record review was performed and follow-up data was recorded.</p><p><b>RESULTS</b>Among 145 cases, 5 cases (3.4%) of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 rearrangements (double-hit lymphomas) were identified, including 2 cases involving myc and bcl-2 translocations (1 DLBCL and 1 BCLU), and 3 cases involving myc and bcl-6 translocations (all DLBCLs). Three cases with concurrent bcl-2/IgH and bcl-6 translocations were found. Single gene translocations or increase of copy numbers were found in 66 cases, representing 51.2% (66/129) of all de novo DLBCLs. Ki-67 index of the 5 "double-hit" lymphomas ranged from 60% to 100%. Clinical follow-up data were available in 4 of the 5 "double-hit" lymphoma patients, three of whom died within 2 years and 1 patient was alive after 36 months of follow-up.</p><p><b>CONCLUSIONS</b>"Double-hit" B-cell lymphomas are rare and can only be identified by molecular detection. They should not be considered synonymous with BCLU morphologically, and may present entities within other morphological spectra. Most of the patients have a poor prognosis. Further in-depth studies of larger case numbers are required to determine the pathologic and genetic variables of the lesion.</p>

Accuracy of liquid-based cytology in diagnosis of high-grade squamous cervical intraepithelial neoplasia / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate factors affecting the diagnostic accuracy of cervical liquid-based cytology for high-grade squamous intraepithelial lesion (HSIL).</p><p><b>METHODS</b>A retrospective evaluation of cytological and histological slides was performed in 415 patients who had cytological HSIL between 2007 and 2010.</p><p><b>RESULTS</b>Among 42 209 cases screened by ThinPrep liquid-based cytology, 415 cases (1.0%) of HSIL were eventually identified. The mean age of HSIL patients was 41.6 years, and 30-49 years were the most common age group. Among 415 cases, 325 patients had available histological diagnosis as follows: 23 (7.1%) negative, 22 (6.8%) CIN1/HPV, 223 (68.6%) CIN2/CIN3, and 57 (17.5%) squamous cell carcinoma (SCC). The positive predictive values of HSIL to predict CIN2 (or higher grade of dysplasia) and CIN1 were 86.2% (280/325) and 92.9% (302/325), respectively. Inadequate biopsy, reactive glandular cells, islet atrophy, chemo/radiotherapy and others were responsible for the cytologically false-positive diagnosis. Fifty-seven (17.5%) cases of HSIL had a histological diagnosis of SCC. The possible causes of misdiagnosis were social factors, under-recognized cytological features of poorly-differentiated SCC and absence of typical diagnostic features in cytology slides.</p><p><b>CONCLUSIONS</b>Cytology of HSIL has a high positive predictive value for the presence of CIN2/CIN3 and SCC. Cytologists and gynecologists should be aware of the diagnostic pitfalls that may lead to the discrepancy between cytology and histology.</p>

Association of HER2 protein expression with clinicopathologic features and prognosis in Chinese patients with gastric carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the epidemiological status of HER2 protein expression in Chinese patients with gastric carcinoma, and to study its clinical and prognostic significance and the association with the clinicopathological features.</p><p><b>METHODS</b>The clinical data were reviewed in 860 patients with gastric carcinoma admitted to Guangdong General Hospital from 2003 to 2010. The HER2 status was evaluated using immunohistochemistry (IHC). The modified HercepTest scoring criterion was used to assess HER2 protein expression. The association between HER2 expression and clinicopathological features was analyzed by χ(2) test. Kaplan-Meier analysis, log-rank test and Cox regression model were used for the survival analysis.</p><p><b>RESULTS</b>The median age of the patients was 59 years, and the male-to-female ratio was 2.06:1. Positive expression of HER2 protein (3+) was found in 77 (9.0%) cases of gastric carcinoma, and in 69 (8.9%) advanced gastric cancers. There was significantly positive association between HER2 over-expression and tumor differentiation, Lauren classification and WHO classification. No significant association was observed between HER2 protein expression and patients' age, gender, tumor location and clinical stage. There was no statistically significant difference in survival rate between patients with positive HER2 expression and negative ones.</p><p><b>CONCLUSION</b>Though there was significantly positive association between HER2 expression status and tumor differentiation, histological type, it may be of limited prognostic value in gastric cancer patients.</p>

Immunophenotypes and prognosis of diffuse large B-cell lymphoma: a study of 500 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the immunophenotype and overall survival of diffuse large B-cell lymphoma (DLBCL) classified according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues.</p><p><b>METHODS</b>Five hundred cases of DLBCL were retrospectively analyzed with histologic review, immunohistochemistry, gene rearrangement study, in situ hybridization and fluorescence in situ hybridization. Follow-up data were collected. The overall survival rates of germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB) subtypes, as well as those of DLBCL, not otherwise specified (NOS) and Epstein-Barr virus (EBV)-positive DLBCL of the elderly, were compared.</p><p><b>RESULTS</b>DLBCL-NOS was the commonest subtype which accounted for 77.2% (386/500) of the cases. EBV-positive DLBCL of the elderly, primary DLBCL of central nervous system, primary mediastinal (thymic) large B-cell lymphoma and T cell/histiocyte-rich large B-cell lymphoma accounted for 9.4% (47/500), 4.4% (22/500), 2.8% (14/500) and 2.6% (13/500), respectively. 68.5% (219/320) of DLBCL-NOS belonged to non-GCB subtype. The percentage of GCB subtype and CD5-positive subtype were 28.4% (91/320) and 3.1% (10/320), respectively. Comparison of the overall survival, GCB and non-GCB immunophenotypic groups have no significant difference (P = 0.93). And the same result in which of the EBV-positive DLBCL of the elderly and DLBCL-NOS group, before and after age matched (P = 0.13 and 0.28, respectively). A double-hit lymphoma was found by FISH detection, which presenting as gray zone lymphoma in morphology.</p><p><b>CONCLUSIONS</b>By using Hans algorithm, GCB and non-GCB subtypes show no significant difference in overall survival. EBV-positive DLBCL of the elderly and DLBCL-NOS also do not have significant difference in overall survival. Fluorescence in situ hybridization technique is helpful in identification of DLBCL with rare phenotypes.</p>

Clinicopathological features of Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features of EB virus positive diffuse large B-cell lymphomas (EBV + DLBCL) of the elderly.</p><p><b>METHODS</b>Four hundred and ninety-six cases of DLBCLs were retrospectively studied by in situ hybridization (ISH) to detect the EBV in tumor cells, and by immunohistochemistry to evaluate the expression of CD10, CD20, CD30, CD79a, bcl-6, bcl-2, MUM-1, CD5, CD3, TIA-1 and Ki-67 protein. Their clinicopathological correlations were analyzed.</p><p><b>RESULTS</b>Of the 59 cases of EBV + DLBCL, 48 cases were EBV positive. The median age of these EBV + DLBCLs was 73 years with male predominance (1.4:1). There were 11 cases with nodal presentation only, 18 cases with extra-nodal presentation and 19 cases with both lymph nodal and extra-nodal involvements, whereas about one third cases with more than one extra-nodal involvement. Thirty-five patients presented with advanced disease (Ann Arbor stage III/IV). A performance status was available in 36 cases and 5 cases had performance status of more than 1. Seven of 30 patients were found with high lactate dehydrogenase value (more than twice of the normal). An IPI-score was calculated in 30 cases and 18 cases had an intermediate/high IPI-score (3-5). The median survival for these patients was 35 months. Morphologically, EBV + DLBCLs of the elderly generally showed a diffuse and polymorphic proliferation of large lymphoid cells with varying degrees of reactive components including small lymphocytes, plasma cells, histiocytes, and epithelioid cells. These tumor cells were frequently characterized by a broad range of B-cell maturation, containing centroblasts, immunoblasts, and Hodgkin- and Reed-Sternberg (HRS)-like giant cells. The study cohort was further morphologically divided into large cell lymphoma subtypes (n = 33) and polymorphic lymphoma subtypes (n = 14) and one case with mixed subtype. Immunohistochemical studies showed that tumor cells were positive for CD20 (47/48) and/or CD79a (45/45) in almost cases. Tumor cells were MUM-1-positive in the majority of the cases (44/47) and were stained for CD10 or bcl-6 in a few cases. Expression of bcl-2 and CD30 was observed in 80.0% (28/35) and 28.9% (11/38) cases, respectively, and most of the cases (33/39) had a high proliferative index (by Ki-67 with a 50% cut-off point). Compared with other EBV + DLBCLs, except the older age and low frequency of bcl-6 staining, no other significant differences were observed in EBV + DLBCLs of the elderly.</p><p><b>CONCLUSIONS</b>EBV + DLBCLs of the elderly constitute a distinct clinicopathologic subtype of DLBCL, although many clinical and histological features with EBV + lymphomas are similar with that of younger ages. Differential diagnosis from other types of lymphomas should also be considered.</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>

Extranodal nasal type NK/T-cell lymphoma: clinicopathologic and prognostic study of 55 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and prognostic factors of extranodal nasal type NK/T-cell lymphoma (EN-NK/TCL) in Chinese patients.</p><p><b>METHODS</b>Fifty-five cases of EN-NK/TCL diagnosed in Chinese patients during the period from 1998 to 2007 were studied by light microscopy, immunohistochemistry and in-situ hybridization. The follow-up information was analyzed.</p><p><b>RESULTS</b>The male-to-female ratio was 1.89:1. The median age of the patients was 38 years. The commonest sites of involvement included nasal cavity and adjoining tissue (85.5%). Histologically, EN-NK/TCL was composed of small to medium-sized lymphoid cells. Angiocentric and angiodestructive growth patterns, coagulative tumor necrosis and apoptotic bodies were frequently observed. Immunohistochemical study showed that CD20, the B-cell marker, was negative in all cases. The positivity rates for T-cell markers CD3epsilon, CD4, CD5 and CD8 were 100% (49/49), 7% (3/46), 8% (4/48) and 63% (29/46), respectively. Most cases were also positive for NK-cell marker CD56 (79% 42/53). All cases expressed cytotoxic granule-associated proteins TIA-1 and granzyme B. Only 17% (8/46) of the cases were positive for anti-apoptotic protein bcl-2. The proliferation index, as demonstrated by Ki-67 immunostain, varied: 30% (14/47) with a low Ki-67 expression level (< or = 29%), 28% (13/47) with a medium level (30%-59%) and 42% with a high level (> or = 60%). There was a significant positive correlation between the bcl-2 positive expression and a high Ki-67 expression level. In-situ hybridization for EBV-encoded RNA was positive in all cases. Amongst the 41 cases with clinical information available, 63.4% presented with Ann Arbor stage I to II. The performance status score was 1 in 87.8% cases. High lactate dehydrogenase level was demonstrated in some patients (31.8%). Amongst the 27 cases with follow-up data available, the median survival was 13 months. The overall 1-year, 2-year and 5-year survival rates were 52%, 31% and 20%, respectively. In general, cases with high proliferation index carried poor prognosis.</p><p><b>CONCLUSIONS</b>EN-NK/TCL is a mature T-cell and NK-cell neoplasm which can be accurately diagnosed by histologic examination, immunohistochemical study and in-situ hybridization. The prognosis is usually not favorable. Proliferation index of the tumor represents an independent prognostic factor.</p>

Significance of high-risk human papillomavirus DNA in atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore significance of high-risk human papillomavirus (HR-HPV) testing in atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H).</p><p><b>METHODS</b>Presence of HR-HPV DNA was examined in 45 patients with ASC-H using hybrid capture II (HC-II) test. Colposcopic examination and biopsy were taken all results were evaluated.</p><p><b>RESULTS</b>Overall, 33 of 45 (73.3%) ASC-H cases were biopsy proven cervical intraepithelial lesion (CIN). 36 of 45 ASC-H cases were HPV-DNA positive, including 19 cases of HSIL and over lesion; whereas no HSIL or over was found in 9 HR-HPV negative cases. Sensitivity and negativity predictive value of HR-HPV in ASC-H with HSIL and over lesion were both 100%.</p><p><b>CONCLUSIONS</b>ASC-H strongly predicts the presence of HSIL, HR-HPV may serve as a predict select whether a patient with ASC-H should take colposcopic examination immediately, patients with positive HR-HPV should undergo immediate colposcopic examination, while negative HR-HPV is an excellent predictor of the absence of HSIL.</p>

Analysis of diagnosis accuracy of frozen sections in 73 cases of borderline tumor of ovary / 中华病理学杂志

<p><b>OBJECTIVE</b>To assess the sensitivity and positive predictive value (PPV) of intraoperative frozen section diagnosis of the borderline tumor of ovary (BTO).</p><p><b>METHODS</b>A retrospective analysis and comparison were done respectively between the accuracies of diagnoses made by using frozen and paraffin sections from the same tissue blocks for BTO from March 1995 to May 2008 achieved in the Department of Pathology, Guangdong General Hospital. Univariate and multivariate regression models were used to assess the influence of patient and tumor characteristics on the likelihood of underdiagnosis and overdiagnosis.</p><p><b>RESULTS</b>Of the 73 patients analyzed, 39 cases (53.42%) were histologically serous tumors, 32 (43.84%) were mucinous and 2 (2.74%) were endometrioid tumors. Diagnoses identical in those made by using either frozen or routine paraffin sections were 55/73 (75.34%). The sensitivity and positive predictive value of frozen section diagnosis were 87.30% and 85.94%, respectively. Underdiagnosis of frozen section were 18/73 (24.66%). There was no overdiagnosis cases obtained. Univariate analysis showed that tumor diameter and tumor histology were the predictors of underdiagnosis in frozen section analysis. And in multivariate analysis, only tumor diameter, rather than patient age, tumor histology and stage, bilateral side tumor, serum CA-125 and concurrent presence of endometriosis was a predictor of underdiagnosis.</p><p><b>CONCLUSIONS</b>Intraoperative frozen section diagnosis of BTO has a low sensitivity and PPV. Underdiagnosis is not uncommon. Surgical management based on intraoperative frozen section diagnosis should be used with caution.</p>

Role of nerve growth factor/TrkA in perineural invasion and pain in pancreatic cancer / 中华神经医学杂志

Objective To investigate the expressions of nerve growth factor(NGF)/TrkA in pancreatic cancer and evaluate their association with perineural invasion and pain in patients with pancreatic cancer. Methods Twenty-eight patients with pancreatic cancer were divided into group A wim pain(n=14)and group B without pain(n=14),and in all the patients the expressions of NGF/TrkA in the pancreatic CanCel tissue were detected by Northern blot analysis and immunohistochemistry.The molecular findings were analyzed in relation to the perineural invasion scores and pain scores.Results Perineural invasion scores in group A were significantly higher than that in group B (P＜0.05).Northern blot analysis revealed significantly higher NGF/TrkA levels and NGF/TrkA immunoreactivity in group A than in group B (P＜0.05).Immunohistochemistry showed that NGF was strongly expressedin the cytoplasm of the pancreatic cancer cells but TrkA Was localized in the perineurinm of the pancreatic Berve.NGF and TrkA mRNA expressions in the tumors were found to positively correlate to perineural invasion of the tumors(r=622,P＜0.05,and r=0.681,P＜0.05,respectively)and the pain scores(r=0.624,P＜0.05;r=0.632,P＜0.05).The immunohistochemical scores of NGF and TrkA expressions in the tumor were also positively correlated to perineural invasion of the tunlor(r=0.602,P＜0.05;r=0.551,P＜0.05)and the pain scores(r=q).603,P＜0.01;r=0.612,P＜0.01).Conclusions The NGF/TrkA system might play important roles in nerve infiltration by the tumor cells and pain sensation in pancreatic cancer patients.

Clinicopathologic study of pulmonary adenocarcinoma with features of bronchioloalveolar carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>Further investigation on the incidence and clinicopathologic features of bronchioloalveolar carcinomas (BAC) including: (1) BAC of strictly defined, (2) adenocarcinoma with bronchioloalveolar features, (3) other different histologic subtypes of lung adenocarcinomas.</p><p><b>METHODS</b>Surgical specimens from 348 lung adenocarcinoma patients admitted in that hospital between 1998 - 2005 were included. And clinical data were collected at the same time. Patients of strictly defined BAC, BAC with focal invasion (BWFI), and adenomas with bronchioloalveolar features (AWBF) were followed-up. Data were analyzed using SPSS statistics software and Kaplan-Meier survival curves were constructed.</p><p><b>RESULTS</b>The resected lung adenocarcinomas consisted of different histologic subtypes. The most frequent one was adenocarcinoma of mixed subtypes (78.2%, 272/348), followed by the acinar type (8.1%, 28/348), the papillary type (4.0%, 14/348), the BAC (3.7%, 13/348), the mucinous (colloid) type (3.4%, 12/348) and the solid types (2.3%, 8/348). The fetal adenocarcinoma was the least component detected. There was no significant difference on the survival curves between groups BAC and BWFI. The survival rate of patients with AWBF was poorer than that of BAC and BWFI.</p><p><b>CONCLUSIONS</b>Since patients with strictly defined (simple) BAC, BWFI, and AWBF have their own distinct clinicopathologic features and prognosis respectively, they should be strictly distinguished from other types of pulmonary adenocarcinomas.</p>

Clinicopathologic significance of bcl-6 gene rearrangement and expression in three molecular subgroups of diffuse large B-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of bcl-6 gene rearrangement and bcl-6 expression in three molecular subgroups of diffuse large B-cell lymphoma (DLBCL) and its clinicopathological significance.</p><p><b>METHODS</b>Tissue microarray including 163 newly diagnosed DLBCL was constructed. Fluorescence in situ hybridization (FISH) was performed to detect the bcl-6 gene rearrangement and immunohistochemistry (EnVision method) was used to evaluate the expression of bcl-6, Ki-67, cyclin D3, Geminin and P27(Kip1) proteins in DLBCL. The association with clinicopathological features was analyzed.</p><p><b>RESULTS</b>One hundred and forty nine of 163 cases were further classified into three molecular subgroups: 40 cases of germinal center B-cell-like (GCB) type, 75 cases of activated non-germinal center B-cell-like (ABC) type, 34 cases of Type 3. Of these 149 cases, FISH for bcl-6 gene rearrangement was successful in 118 cases. bcl-6 gene rearrangement was observed in 33 of 118 (28.0%) cases. The bcl-6 gene rearrangement was more frequently seen in the ABC subgroup (22/62, 35.5%) than in GCB (6/31, 19.4%) and Type 3 subgroups (5/25, 20.0%, P=0.16). The correlation of bcl-6 gene rearrangement and expression of its encoded protein was further analyzed. Most of DLBCL (26/33, 78.8%) with bcl-6 gene rearrangement presented with overexpression of its encoded protein, which was higher than those without bcl-6 gene rearrangement (53/84, 62.4%, P=0.088). DLBCL with bcl-6 gene rearrangement (24/33, 72.7%) more frequently expressed cyclin D3, and had a higher proliferative activity than those without bcl-6 gene rearrangement (37/81, 45.7% , P=0.009). Twenty-nine of 33 (87.9%) cases of DLBCL with bcl-6 gene rearrangement presented with advanced stage (Ann Arbor stage III/IV), which was higher than those without bcl-6 gene rearrangement (65/85, 76.5% , P=0.167). Univariate Cox proportional hazards regression analysis showed that bcl-6 gene rearrangement was associated with an increased relative risk (at 1.842) of death in DLBCL cases compared with those without bcl-6 gene rearrangement.</p><p><b>CONCLUSION</b>Overexpression of bcl-6 protein caused by bcl-6 gene rearrangement may play some important roles in the development and/or progression of a subset of DLBCL.</p>

Gene expression profiling of diffuse large B-cell lymphoma in China / 中华病理学杂志

<p><b>OBJECTIVE</b>Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) of different immunophenotypes.</p><p><b>METHODS</b>The study included 156 cases of DLBCL, which were subclassified by immunohistochemistry including CD10, bcl-6 and MUM1. Affymetrix U133 plus2.0 oligonucleotide microarrays were used to obtain differential gene expression profiling of 9 DLBCL (3 representative cases from each immunophenotypical group) and 3 tonsils. Clinical stages of all 9 lymphomas were Ann Arbor stage IV.</p><p><b>RESULTS</b>The immunohistochemistry subclassified 156 cases of DLBCL into 3 groups: CD10(+) and/or bcl-6(+), MUM1(-) (group 1); CD10(+) and/or bcl-6(+), MUM1(+) (group 2); CD10(-) and bcl-6(-), MUM1(+) (group 3). By gene expression array, 9 lymphomas and 3 tonsils were clustered in an unsupervised fashion into 4 groups (A, B, C and D), which were in accordance with the immunophenotypical groups (group 1, 2, 3 and normal). A total of 81 genes were markedly decreased and 86 genes were over-expressed in all DLBCL groups. Although Group B lymphomas showed mixed immunophenotypical features of both germinal center B-cell-like DLBCL (Group A) and activated B-cell-like lymphomas (Group C), gene profile clustering showed that Group B was dissimilar to Group A or Group C, with 45 over-expressed and 27 uniquely expressed genes.</p><p><b>CONCLUSIONS</b>Gene expression profiling indicates that DLBCL can be subgrouped at the molecular level and can be identified by immunophenotyping. The gene expression profile of Group B lymphomas suggests that factors other than the cell-of-origin may contribute to the pathogenesis of DLBCL.</p>

Differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and T-cell/histiocyte-rich B-cell lymphoma (TCRBCL).</p><p><b>METHODS</b>15 cases of NLPHL and 16 cases of TCRBCL were studied on both morphology and immunophenotype according to the WHO classification of lymphoid neoplasms. SP-immunohistochemical staining were performed on paraffin sections. In situ hybridization for EBER1/2 and gene rearrangement of immunoglobulin heavy chain (IgH) were carried out in 3 cases of NLPHL and 4 cases of TCRBCL, respectively.</p><p><b>RESULTS</b>Histologically, a few atypical large cells scattered in a background of small lymphocytes with or without histiocytes were a common finding in both NLPHL and TCRBCL. Of NLPHL, nodular pathern predominated in 11 cases, diffuse patterns without nodules in 3 cases and one case showed nodular and diffuse pattern intermixed with a increased number of large cells. 14 cases of TCRBCL showed diffuse pattern. One case with micronodular pattern involving the splenic white pulp. One case showed a combination of nodules of NLPHL, diffuse areas of TCRBCL and a sheet of large cells of diffuse large B-cell lymphoma (DLBCL) within the same lymph node biopsy specimen. Immunophenotypically, the large cells showed and CD20, CD79a, bcl-6 and EMA positive, and CD15, CD30, CD3, CD45RO and LMP-1 negative. In NLPHL, small B cells and CD57 positive cells were common, whereas in TCRBCL, TIA-1 positive cytotoxic cells and histiocytes dominated, small B cells were scarce or absent. EBER1/2 were negative and gene rearrangement of IgH was found in all tested 3 cases of NLPHL and 4 cases of TCRBCL, respectively.</p><p><b>CONCLUSION</b>There are some morphologic and immunophenotypic resemblance between NLPHL and TCRBCL. A combination of the morphological characteristics and the reactivity of the background cells for CD57 and TIA-1 seem to reliably discriminate between the entities and should therefore help to increase the interobserver reproducibility of diagnosis in the gray zone around Hodgkin lymphomas.</p>

T-cell/histiocyte-rich B-cell lymphoma: histology, immunophenotype and differential diagnosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the histology, immunophenotype and differential diagnosis of T-cell/histiocyte-rich B-cell lymphoma (TCRBCL).</p><p><b>METHODS</b>A review of 245 cases of so-called Hodgkin lymphoma diagnosed during the period from 1980 to 2000 in 3 hospitals in Guangzhou, 8 cases were reclassified as TCRBCL, according to the 2001 World Health Organization classification of lymphoid neoplasms. An additional 8 cases of TCRBCL were retrieved from consultation files, as well as routine biopsy cases encountered between 2000 and 2004. Immunohistochemical studies were performed on paraffin-embedded tissue by SP technique in order to study the immunophenotype of the large neoplastic cells (CD20, CD79a, CD3, CD45RO, CD15, CD30, CD10, bcl-6 and EMA) and background non-neoplastic cells (CD3, CD8, CD20, CD45RO, CD79a, CD57, CD68, CD21, CD35, cyclin D1, TIA-1). In-situ hybridization for EBER 1/2 and immunoglobulin heavy chain gene rearrangement study were also performed in 4 and 4 cases respectively.</p><p><b>RESULTS</b>Among the TCRBCL cases studied, there were 8 males and 8 females. The age of patients ranged from 10 to 68 years old (mean = 40.3 years old). All had lymphadenopathy and hepatosplenomegaly. On presentation, 3 cases belonged to stage II, 10 cases stage III and 3 cases stage IV. Histologically, scattered atypical large neoplastic cells were seen in a background of small lymphocytes and sometimes histiocytes. The large cells exhibited CD20+, CD79a+, EMA+, CD15- and CD30- phenotype. On the other hand, the background small lymphocytes were CD3 and CD45RO-positive. Most of these background T cells expressed CD8 and TIA-1, while they were mostly CD57-negative. The histiocytic cells were CD68-positive; and CD21 and CD35-positive follicular dendritic cell meshworks were absent. In-situ hybridization for EBER 1/2 showed negative nuclear signals. Immunoglobulin heavy chain gene rearrangement study revealed clonal pattern in all the 4 cases tested.</p><p><b>CONCLUSIONS</b>TCRBCL is a rare subtype of lymphoma, with distinctive histology and immunophenotype. The above features are helpful in delineating this entity from Hodgkin lymphoma, reactive lymphoid hyperplasia and lymphomatoid granulomatosis.</p>

Diagnosis and differential diagnosis of granulocytic sarcomas / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the diagnosis and differential diagnosis of granulocytic sarcoma (GS).</p><p><b>METHODS</b>The morphological and immunological characteristics of 12 cases of GS were studied. FAB classification was made by peripheral blood, bone marrow picture and bone marrow biopsy assay.</p><p><b>RESULTS</b>All of the 12 cases presented with lymphadenopathy and soft tissue mass. Histologically, the tissue infiltration of GS was composed of blastic cells with round to oval nuclei showing an even, pale chromatin pattern. Some with cleaved or notched nuclei. There were prominent nucleoli and scant cytoplasm in the cells and mitosis was easily found. Immunohistochemically, CD(45) and lysozyme were positive in all of the cases, MPO in 11 (92%), CD(68) in 10 (83%), CD(34) in 5 (42%), and TdT in 2 cases (17%). CD(15) and Mac387 were mainly expressed in mature granulocytes. Examination of bone marrow sections and marrow aspirate smears showed that out of the 11 cases tested 8 were AML-M(2), 2 AML-M(1) and 1 AML-M(0). Only 1 case was nonleukemic, ie. solitary granulocytic sarcoma.</p><p><b>CONCLUSION</b>Granulocytic sarcomas are difficult to identify in routine paraffin-embedded tissue sections and usually misdiagnosed as non-Hodgkin's lymphomas. Immunohistochemistry study with a panel of antibodies in combination with bone marrow and peripheral blood examination are helpful in identification of granulocytic sarcoma.</p>