[B-cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations].

OBJECTIVE: To identify and investigate clinicopathological features of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations ("double-hit" lymphoma). METHODS: 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. RESULTS: 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. CONCLUSIONS: "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.

[Neuroendocrine neoplasm of digestive system with different grades: a clinicopathologic and prognostic study].

OBJECTIVE: To study the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. METHODS: The clinicopathologic features of 139 cases of neuroendocrine neoplasm occurring in digestive system were retrospectively reviewed and graded according to the 2010 World Health Organization classification of tumours of the digestive system. Immunohistochemical study for synaptophysin, chromogranin A and Ki-67 was carried out. The follow-up and survival data were analysed using Kaplan-Meier method. Prognostic factors were tested by Log-rank testing and independent risk factors were analysed using Cox regression model. RESULTS: Amongst the 139 cases studied, there were 88 cases (63.3%) of grade 1 tumors, 9 cases (6.5%) of grade 2 tumors and 42 cases (30.2%) of grade 3 tumors. There was diffusely positive staining for synaptophysin and chromogranin A in most of the grade 1 and grade 2 tumors. The staining in grade 3 tumors however was focal (P < 0.05). The differences in tumor size, depth of invasion, presence of tumor emboli, perineural permeation, nodal involvement, distant metastasis and survival rate amongst the three groups was statistically significant (P < 0.05). CONCLUSIONS: There is significant difference in the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. It is considered as an independent prognostic factor and represents a useful tool for prognostic evaluation of such tumors, both in clinical practice and research.

[Immunophenotypes and prognosis of diffuse large B-cell lymphoma: a study of 500 cases].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Association of HER2 protein expression with clinicopathologic features and prognosis in Chinese patients with gastric carcinoma].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Clinicopathological features of Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly].

OBJECTIVE: To investigate the clinicopathological features of EB virus positive diffuse large B-cell lymphomas (EBV + DLBCL) of the elderly. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Efficacy of intraoperative GeneSearch Breast Lymph Node (BLN) Assay for breast cancer metastasis detection in sentinel lymph node in Chinese patients.

UNLABELLED: Although intraoperative assessment of the sentinel lymph node (SLN) is useful, it has not gained popularity in China as it involves a heavy workload for pathologists. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay performed in 158 SLNs from 97 patients by comparison with postoperative permanent section histopathology, to validate its potential usefulness in China. Every SLN was cut into alternating 1.5 to 3.0 mm slabs. The BLN assay processed 50% of the fresh alternating slabs to detect the presence of cytokeratin 19 and mammaglobin mRNA. Assay results were compared with those for permanent section histopathology and intraoperative imprint cytology. Slides for imprint cytology were prepared from the BLN assay node tissue before it was processed. Full axillary lymph node (ALN) dissections were performed on some patients after a SLN biopsy. The BLN assay was successfully performed on 158 SLNs from 97 patients. Overall performance of the BLN assay compared with permanent section histopathology was sensitivity 83.9% (26/31), specificity 95.5% (63/66), positive predictive value 89.7% (26/29), negative predictive value 92.6% (63/68), and overall agreement 91.8% (89/97). The BLN assay detected about 25% more metastases than imprint cytology. Moreover, the BLN assay correctly identified most of the additional non-sentinel ALNs metastases (P = 0.005). Our results from a large series of Chinese patients with breast cancer indicate that the BLN assay may be a viable alternative for the standard intraoperative procedures used for metastases detection, especially in early stage breast cancer patients. Name of the trial register: GeneSearch Breast Lymph Node (BLN) Assay China Registration Study. CLINICAL TRIAL REGISTRATION NUMBER: NCT00869674.

[Extranodal nasal type NK/T-cell lymphoma: clinicopathologic and prognostic study of 55 cases].

OBJECTIVE: To study the clinicopathologic features and prognostic factors of extranodal nasal type NK/T-cell lymphoma (EN-NK/TCL) in Chinese patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Significance of high-risk human papillomavirus DNA in atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion].

OBJECTIVE: To explore significance of high-risk human papillomavirus (HR-HPV) testing in atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H). METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

[Analysis of diagnosis accuracy of frozen sections in 73 cases of borderline tumor of ovary].

OBJECTIVE: To assess the sensitivity and positive predictive value (PPV) of intraoperative frozen section diagnosis of the borderline tumor of ovary (BTO). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Role of AIB1 gene in development of esophageal squamous cell carcinoma and its clinicopathologic significance].

OBJECTIVE: To investigate the role of AIB1 gene in the development of esophageal squamous cell carcinoma (ESCC) and its clinicopathologic significance. METHODS: Two tissue microarrays, including 203 cases of ESCC, were prepared. Fluorescence in-situ hybridization (FISH) and immunohistochemistry were performed to detect the amplification of AIB1 gene and expression of its encoded protein in ESCC. The results were correlated with various clinicopathologic parameters. RESULTS: In the 203 cases of ESCC studied, FISH was successful in 115 cases. Amongst those, amplification/gain of AIB1 gene was observed in 15 cases, including high-level amplification in 5 cases (4.3%) and low-level gain in 10 cases (8.7%). As for immunohistochemical study, AIB1 protein was overexpressed in 94 cases of ESCC. There was a significant association of AIB1 overexpression and tumor staging. AIB1 was overexpressed in 66 of the 123 cases in advanced T stages (T3 to 4), compared with 25 of the 80 cases in early T stages (P = 0.008). Those cases with high-level amplification of AIB1 also showed overexpression of its encoded protein. On the other hand, 8 of the 10 cases with low-level gain of AIB1 showed protein overexpression. The remaining 41 of the 100 cases which did not have AIB1 gene amplification/gain demonstrated overexpression of AIB1 protein. CONCLUSION: Overexpression of AIB1 protein caused by gene amplification/gain or other molecular mechanisms may play an important role in the development and/or progression of a subset of ESCC.

[Clinicopathologic significance of bcl-6 gene rearrangement and expression in three molecular subgroups of diffuse large B-cell lymphoma].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Clinicopathologic study of pulmonary adenocarcinoma with features of bronchioloalveolar carcinoma].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Correction: MYC Expression in Concert With BCL2 and BCL6 Expression Predicts Outcome in Chinese Patients With Diffuse Large B-Cell Lymphoma, Not Otherwise Specified.

[This corrects the article DOI: 10.1371/journal.pone.0104068.].

[Tumors showing perivascular epithelioid cell differentiation: a clinicopathologic study of 39 cases].

OBJECTIVE: To investigate the clinicopathologic features of tumors showing perivascular epithelioid cell differentiation (PEComas). METHODS: The clinicopathologic data of 39 cases pf angiomyolipoma (AML), 17 males and 22 females, with the primary focus in the kidney on 30 cases, in the liver in 4 cases, in the lung, uterus and broad ligament, abdominal wall, retroperitoneum, and nasal cavity in 1 case respectively, were analyzed. Immunohistochemistry (HIC) was used to detect the expression of pan-cytokeratin (CK), S-100 protein, smooth muscle actin (SMA), desmin, vimentin, HMB45, Melan-A, microphthalmia transcription factor (MiTF), CD117, and CD34 in the specimens of the tumors obtained during operation. Twenty patients were followed up. RESULTS: Pathological examination showed branched capillaries or arterioles, often thick-walled similar to those in the renal cell carcinoma, and the cancerous cells consisting of the mixture of epithelial cells and spindle cells. HIC showed that the expression rates of Melan-A, HMB45, MITF, SMA, desmin, S-100 protein, vimentin, CD117, CK, and CD34 were 95% (37/39), 72% (32/39), 46% (18/39), 82% (32/39), 27% (10/39), 15% (6/39), 82% (32/39), 10% (4/39), 0, and 0 respectively. Clinical follow-up showed 1 patient alive with tumor, and 19 alive free from disease. CONCLUSION: PEComas have distinctive morphological and immunohistochemical features.

[Gene expression profiling of diffuse large B-cell lymphoma in China].

OBJECTIVE: Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) of different immunophenotypes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Diagnostic value of p16INK4a in squamous intraepithelial lesion in gynecologic cytology].

OBJECTIVE: To study the diagnostic value of p16(INK4a) in squamous intraepithelial lesion in gynecologic cytology and its relationship with types of human papillomavirus (HPV). METHODS: 88 liquid-based gynecologic cytology cases with histologic correlation, including 20 cases of cervicitis, 18 cases of low-grade squamous intraepithelial lesion (LSIL), 34 cases of high-grade squamous intraepithelial lesion (HSIL) and 16 cases of squamous cell carcinoma (SCC), were enrolled into the study. Immunocytochemistry for p16(INK4a) protein and polymerase chain reaction-based HPV DNA testing (for HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68, as well as HPV types 6, 11, 42, 43 and 44) were performed. RESULTS: The rate of expression of p16(INK4a) protein was 0, 27.8%, 100% and 100% in the cervicitis group, LSIL group, HSIL group and SCC group, respectively. The expression was significantly higher in the latter 3 groups than that in the cervicitis group (P < 0.01). Besides, the expression was significantly higher in cases associated with high-risk HPV genotypes (96.4%) than in cases associated with low-risk HPV genotypes (7.7%). CONCLUSION: p16(INK4a) is a valuable biomarker for detection of HPV-related dysplastic squamous cells, with high sensitivity and specificity.

[Differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma].

OBJECTIVE: To study the differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and T-cell/histiocyte-rich B-cell lymphoma (TCRBCL). METHODS: 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. RESULTS: 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. CONCLUSION: 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.