Diagnosis, Differential ; Gene Rearrangement ; Hodgkin Disease ; genetics ; metabolism ; pathology ; Humans ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Mediastinal Neoplasms ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism

Burkitt Lymphoma ; metabolism ; pathology ; Cell Nucleus ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Lymphoma, B-Cell ; classification ; metabolism ; pathology ; Lymphoma, Follicular ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Mantle-Cell ; metabolism ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; SOXC Transcription Factors ; genetics ; metabolism

The metastasis-suppressing role of the nm23 gene in the metastatic spread of malignant tumor is still debated. We examined the nm23-H1 protein expression and gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic parameters. The expression of nm23-H1 protein was immunohistochemically examined in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DL-BCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25 peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1 protein was associated with the high IPI score (p=0.019) and the low survival rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in 10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon 1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the mutational change of gene may operate in the lymphomagenesis.
Tissue Array Analysis ; Survival Analysis ; Prognosis ; Polymorphism, Single-Stranded Conformational ; Nucleoside-Diphosphate Kinase/*genetics/metabolism ; Mutation/*genetics ; Middle Aged ; Male ; Lymphoma, T-Cell/genetics/metabolism/pathology ; Lymphoma, Non-Hodgkin/genetics/metabolism/*pathology ; Lymphoma, Mantle-Cell/genetics/metabolism/pathology ; Lymphoma, Large-Cell, Diffuse/genetics/metabolism/pathology ; Lymphoma, B-Cell/genetics/metabolism/pathology ; Immunohistochemistry ; Humans ; Female ; DNA Mutational Analysis ; Base Sequence

OBJECTIVETo investigate bcl-6 protein expression and gene rearrangement patterns in diffuse large B-cell lymphoma (DLBCL) and their clinicopathologic significance.

METHODSImmunohistochemical studies for bcl-6 and CD10 proteins were performed on 51 cases of DLBCL paraffin-embedded tissues (including 22 nodal samples and 29 extranodal samples) and 10 cases of reactive lymphoid hyperplasia (RLH) paraffin-embedded tissues. Interphase fluorescence in-situ hybridization (FISH) with dual color breakapart probe was also used to identify rearrangement of bcl-6 gene in 32 cases of nodal DLBCL tissues (including 22 paraffin-embedded samples and 10 fresh samples) and 5 cases of RLH paraffin-embedded tissues.

RESULTS(1) The rates of bcl-6 protein expression in nodal DLBCL, extranodal DLBCL and RLH were 72.7% (16/22), 75.9% (22/29) and 100.0% (10/10) respectively. The rates of CD10 expression were 40.9% (9/22), 41.4% (12/29) and 100.0% (10/10) respectively. All lymphoma samples which expressed CD10 also showed co-expression of bcl-6 protein. (2) The co-expression of bcl-6 and CD10 was observed in 40.9% (9/22) nodal DLBCL and 41.4% (12/29) extranodal DLBCL. Low clinical stage (stage I and II) was more frequently observed in cases with co-expression of bcl-6 and CD10 (P < 0.05). (3) The rates of bcl-6 gene rearrangement in nodal DLBCL was 28.1% (9/32), with 27.3% (6/22) in paraffin-embedded tissues and 30.0% (3/10) in fresh tissues. There was no statistically significant difference found between the two groups (P > 0.05). Bcl-6 gene rearrangement was not found in all the 5 cases of RLH, and there was a significant difference between RLH and DLBCL (P < 0.05).

CONCLUSIONSThe rate of bcl-6 protein expression is high in DLBCL cases, and the detection of bcl-6 and CD10 protein co-expression may help in the diagnosis and differential diagnosis of DLBCL. Those DLBCL cases with co-expression of bcl-6 and CD10 may also have a better prognostic implication. On the other hand, bcl-6 gene rearrangement can be identified by interphase FISH with dual color breakapart probe in both paraffin-embedded and fresh lymphoma tissues.

Diagnosis, Differential ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; genetics ; metabolism ; Pseudolymphoma ; genetics

Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 18 ; Dendritic Cells, Follicular ; metabolism ; pathology ; Humans ; Lymphoma, Follicular ; genetics ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Translocation, Genetic

OBJECTIVETo investigate clinicopathologic features of solitary plasmacytoma of bone (SPB) and the role of immuno-phenotype and immunoglobulin gene rearrangement detection in the diagnosis and differential diagnosis of SPB.

METHODSA total of 21 cases of SPB were selected during a period from 1990 to 2008. A retrospective clinicopathologic study and immunohistochemistry (EnVision or EliVision methods) of 17 antigens were performed. In addition, universal IgH (FR3A/LJH/VLJH) primers and BIOMED-2 PCR multiplex tubes were used for IgK and IgL rearrangement analysis.

RESULTSThe age of patients ranged from 36 to 72 years with a media of 50 years. Axial skeleton was the most common site of involvement, accounting for 66.7% of the cases (14 of 21), followed by the extremities of 33.3% (7 cases). Low serum level of M-components was found in 5 cases, including two of IgG type (21.4 g/L) and three of IgA type. Clinical manifestations were closely related to the anatomic sites involved, such as pain due to bone destruction, symptoms and signs caused by compression of spinal cord or nerve root, and pathological fracture. All cases presented as a solitary osteolytic lesion. According to the histological grading criteria, grade I tumor was seen in 12 of 21 cases (57.1%). The remaining were grade II (5 cases, 23.8%) and grade III (4 cases, 19.0%). Immunohistochemically, the neoplastic cells expressed two or more plasma cell antigens, including CD138, CD38 and PC, but no CD19 and CD20. CD79a expression detected in 23.8%(5/21) of the cases. Expression of CD56, CD27 and CD44v6 were 57.1% (12/21), 15.0% (3/20) and 23.8% (5/21), respectively. Follow-up data were available in 12 of the 21 patients (57.1%). Five patients were alive and 7 died. Three patients developed multiple myeloma (MM) and died of the tumor.

CONCLUSIONSSPB is a rare tumor with bone pain as the most common presenting symptom due to bone destruction. The diagnosis of EMP can only be established after exclusion of an extramedullay invasion by MM. Immunophenotype and IgH gene rearrangement analysis play important roles in the diagnosis of SPB.

ADP-ribosyl Cyclase 1 ; metabolism ; Adult ; Aged ; Bone Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Humans ; Immunophenotyping ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Male ; Melanoma ; metabolism ; pathology ; Middle Aged ; Multiple Myeloma ; pathology ; Plasmacytoma ; genetics ; metabolism ; pathology ; surgery ; Retrospective Studies ; Survival Rate ; Syndecan-1 ; metabolism

OBJECTIVETo study the clinicopathologic features, immunohistochemical findings, EBV and c-myc gene status of intra-abdominal non-Hodgkin B-cell lymphoma occurring in children.

METHODSSeventy-four cases of pediatric intra-abdominal non-Hodgkin B-cell lymphoma were retrieved from the archival file. The cases were classified according to the 2008 WHO classification. Tissue microarray including tumor tissues from all the 74 cases was produced. Immunohistochemical study (SP method) for CD20, CD3, CD79a, CD10, bcl-6, MUM1, bcl-2, CD43, CD38 and Ki-67 was performed. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) and fluorescence in-situ hybridization for c-myc gene were also carried out.

RESULTSAmongst the 74 cases studied, 65 of them (87.8%) were Burkitt lymphoma (BL), 4 cases (5.4%) were diffuse large B-cell lymphoma (DLBCL) and the remaining 5 cases (6.8%) showed features in-between DLBCL and BL (DLBCL/BL). The patients often presented with abdominal pain, abdominal masses, ileus and intussusception. The ileocecal bowel wall and mesenteric lymph nodes were commonly involved. The lymphoma cells were of high histologic grade and suggested an aggressive clinical behavior. The staining for CD20 and CD79a were positive in all of the cases, while CD3 was negative. The positive rates of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER in BL were 96.9% (63 cases), 95.4% (62 cases), 0 (0 case), 23.1% (15 cases), 70.8% (46 cases), 96.9% (63 cases) and 41.5% (27 cases), respectively. Fifty-four cases carried translocation of c-myc gene. As for DLBCL, the positive cases of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER were 3 cases, 2 cases, 3 cases, 2 cases, 2 cases, 2 cases and 0 case, respectively. One of these cases showed c-myc gene translocation. Amongst the 4 cases of DLBCL, 2 of them belonged to germinal center B-cell-like subtype, while the remaining 2 cases were of non-germinal center B-cell-like subtype. The expression rates of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER in DLBCL/BL were 5/5, 4/5, 0, 3/5, 5/5, 3/5 and 0, respectively. Three of the cases were positive for c-myc gene translocation.

CONCLUSIONSThe majority of pediatric intra-abdominal non-Hodgkin B-cell lymphoma belonged to BL. They have characteristic clinical presentation and sites of predilection and are often associated with an aggressive clinical behavior. Thorough morphologic assessment, immunohistochemistry and in-situ hybridization play an important role in subtyping this group of lymphoid malignancy.

Antigens, CD20 ; metabolism ; Burkitt Lymphoma ; genetics ; metabolism ; pathology ; CD79 Antigens ; metabolism ; Child ; Child, Preschool ; Female ; Genes, myc ; Humans ; Intestinal Neoplasms ; genetics ; metabolism ; pathology ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Male ; Neprilysin ; metabolism ; RNA, Viral ; metabolism ; Translocation, Genetic

OBJECTIVETo evaluate the efficiency of the BIOMED-2 PCR assay and its implication in the diagnosis of mature B-cell non-Hodgkin's lymphomas.

METHODSClinical, morphological and immunohistochemical features of 72 cases of non-Hodgkin's lymphomas were studied, including 25 reactive lymphoid hyperplasia, 37 diffuse large B cell lymphomas (DLBCL) and 35 extranodal marginal zone lymphomas of mucosa associated lymphoid tissues (MALT lymphoma and in addition, 25 cases of reactive lymphoid hyperplasia were used as the controls). DNA was exacted from the paraffin embedded formalin fixed tissue blocks and the quality of DNA was assessed using the BIOMED-2 specimen control reaction. Adequate samples were then analyzed by BIOMED-2 for immunoglobulin heavy and kappa light chain rearrangements.

RESULTSAdequate DNA was obtained in 83 of 97 samples, including 60 mature B cell lymphomas and 23 reactive lymphoid hyperplasia. Clonal B-cell gene rearrangements were detected in 57 of 60 (95%) lymphomas. In contrast, clonal Ig gene rearrangements were not detected in any of the 23 cases of reactive lymphoid hyperplasia.

CONCLUSIONBIOMED-2 assay is highly sensitive and specific for the detection of clonal B cell gene rearrangement using routine paraffin embedded formalin fixed specimens.

Antigens, CD20 ; metabolism ; CD79 Antigens ; metabolism ; DNA, Neoplasm ; genetics ; Gene Rearrangement, B-Lymphocyte ; genetics ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; genetics ; Gene Rearrangement, B-Lymphocyte, Light Chain ; genetics ; Genes, Immunoglobulin ; Humans ; Immunophenotyping ; Lymphoma, B-Cell ; genetics ; immunology ; pathology ; Lymphoma, B-Cell, Marginal Zone ; genetics ; immunology ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; immunology ; pathology ; Paraffin Embedding ; Pseudolymphoma ; genetics ; immunology ; pathology ; Sensitivity and Specificity

Adult ; Aged ; Antigens, CD20 ; metabolism ; Diagnosis, Differential ; Female ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Humans ; Immunohistochemistry ; Leukocyte Common Antigens ; metabolism ; Lymphoma, B-Cell ; genetics ; metabolism ; pathology ; surgery ; Lymphoma, Extranodal NK-T-Cell ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Tonsillar Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Tonsillectomy ; Tonsillitis ; pathology ; Young Adult

OBJECTIVETo study clinicopathologic and genetic features of anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL).

METHODSLight microscopy, EliVision immunohistocheimical method and fluorescence in-situ hybridization were used to evaluate three ALK + LBCL cases recently diagnosed accompanied with a literature review.

RESULTSAll three cases were male adult patients (mean age = 36.3 years) with nodal involvement by lymphoma. Histologic evaluation revealed a diffuse effacement of the nodal architecture by the infiltration of tumor cells. Sinusoidal infiltration was seen. The neoplastic cells were large and exhibited the immunoblastic/plasmablastic morphology. By immunohistochemistry, all the cases showed a cytoplasmic granular staining of ALK. They were positive for CD45, CD138, and epithelial membrane antigen (EMA), but were negative for CD3, CD20, CD79a and CD30. Fluorescence in situ hybridization (FISH) demonstrated the presence of ALK gene translocation in all of the cases.

CONCLUSIONSALK + LBCL represents a distinct variant of diffuse large B-cell lymphoma, usually involving lymph node of middle-aged men. The tumor has a immunoblastic/plasmablastic morphology along with a distinct immunophenotypic profile and ALK gene rearrangement.

ADP-ribosyl Cyclase 1 ; metabolism ; Adult ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Leukocyte Common Antigens ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Male ; Mucin-1 ; metabolism ; Multiple Myeloma ; metabolism ; pathology ; Receptor Protein-Tyrosine Kinases ; genetics ; metabolism ; Translocation, Genetic