To study the characteristics and histogenesis of the malignant lymphomas derived from the gastrointestinal mucosa, histologic and immunohistochemical analyses were performed on a series of 28 malignant lymphomas of the gastrointestinal tract. By cytomorphologic classification, there were two small lymphocytic lymphomas, one small cleaved cell lymphoma, two mixed small cleaved and large cell lymphomas, 17 large cell lymphomas, one small noncleaved cell lymphoma, three immunoblastic lymphomas, and two lymphoblastic lymphomas. This distribution of histologic types was compatible with that of nodal lymphoma. The lymphomas with poor prognostic histology (23 cases) outnumbered those with favorable prognosis (five cases). Three of 28 cases (one in the stomach and two in the small intestine) had cytologic features consistent with centrocytoid cell lymphoma of the mucosa associated lymphoid tissue and were large cell lymphomas. Immunophenotypically, 23 cases expressed B-cell markers (82.1%) and three cases reacted with T-cell markers. Two cases did not react with either T-cell or B-cell markers. True histiocytic lymphomas were not identified. Gastric lymphomas (nine cases) and colorectal lymphomas (three cases) were of B-lymphocyte origin whereas T-cell lymphomas were noted in the small intestine (two cases) and ileocecal region (one case). Three cases of centrocytoid lymphoma were of B-lymphocyte origin. Histologically B-cell lineage lymphomas were evenly distributed on various histologic subtypes but all T-lineage lymphomas belonged to the large cell type. The two cases with undetermined phenotype were lymphoblastic lymphomas histologically. This study showed that the primary GIT lymphomas, mostly of B-cell lineage, were not cytomorphologically distinctive from the nodal lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Gastrointestinal Neoplasms/classification/immunology/*pathology ; Humans ; Immunohistochemistry ; Lymphoma/classification/immunology/*pathology ; Male ; Middle Aged

OBJECTIVETo describe the relative frequency, morphologic features, immunophenotype and clinical data of different types of B-cell non-Hodgkin lymphoma (B-NHL) and to evaluate the practical application of the 2001 World Health Organization (WHO) classification of lymphoid neoplasms.

METHODS369 documented cases of B-NHL were further subtyped according to the 2001 WHO classification of lymphoid neoplasms, on the basis of hematoxylin and eosin staining, immunohistochemistry and in-situ hybridization techniques.

RESULTSAmongst the 369 cases of B-NHL studied, 353 cases could be further classified into 11 subtypes. Diffuse large B-cell lymphoma, extranodal marginal zone lymphoma and follicular lymphoma were the commonest subtypes, accounting for 51.2% (189 cases), 14.9% (55 cases) and 10.6% (39 cases) of all cases respectively. Tumors in lymph nodes were seen in 158 cases (42.8%) and in extra node in 211 cases (57.2%). B-cell prolymphocytic leukemia and hairy cell leukemia were not identified. When comparing the diagnosis based on morphologic examination alone with the diagnosis based on both morphology and immunophenotype, there was a 80% concordance rate. Immunohistochemical study was helpful in reaching the correct diagnosis in many cases and could improve the overall diagnostic accuracy by about 20%.

CONCLUSIONSAmongst cases of B-NHL, diffuse large B-cell lymphoma is the commonest subtype, followed by MALToma and follicular lymphoma. While morphologic examination forms the basis for lymphoma diagnosis, immunohistochemical study also plays an important role in further subtyping. A combination of both modalities are sufficient for arriving at an accurate diagnosis in most cases of B-NHL, in keeping with the recommendation of the 2001 WHO classification of lymphoid neoplasms.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; CD79 Antigens ; metabolism ; Child ; Female ; Humans ; Immunohistochemistry ; Leukosialin ; metabolism ; Lymphoma, B-Cell ; immunology ; pathology ; Lymphoma, B-Cell, Marginal Zone ; immunology ; pathology ; Lymphoma, Follicular ; immunology ; pathology ; Lymphoma, Large B-Cell, Diffuse ; immunology ; pathology ; Lymphoma, Non-Hodgkin ; classification ; immunology ; pathology ; Male ; Middle Aged ; World Health Organization

Antigens, CD ; metabolism ; Diagnosis, Differential ; Epstein-Barr Virus Infections ; Herpesviridae Infections ; Humans ; Immunohistochemistry ; Lymphoma ; classification ; immunology ; pathology ; virology

This study sponsored by the Lymphoreticular Study Group of the Korean Society of Pathologists was carried out to provide nationwide data about the histopathologic-immunophenotypic features of malignant lymphomas in Korea. Two hundred and ninety Non-Hodgkin's lymphoma (NHL) among 312 malignant lymphomas collected from three representative areas in Korea were histologically reclassified. Two hundred and fifty three cases were immunohistochemically studied. T-cell lymphoma comprised 35.2% of NHL in this study and showed a quite comparable incidence to that of Japan and China, but it was much higher than in Western countries. A very low prevalence rate of the follicular variety (4.0%) and a higher propensity of primary extranodal involvement (60%) are additional characteristics of NHL in Korea. The most common histologic subtype of B cell lymphoma was diffuse large cell type, whereas the most common subtype of T cell lymphoma was diffuse mixed small and large cell type.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Immunophenotyping ; Korea ; Lymphoma, Non-Hodgkin/classification/*immunology/*pathology ; Male ; Middle Aged

OBJECTIVETo investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors.

METHODSA total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CD8, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis.

RESULTSSignificant differences in 11 factors (age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8+ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum β2-microglobulin) were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index (IPI), revised IPI, and NCCN-IPI models] (P < 0.05). Concordance rates were high (81.4%-100.0%) when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data.

CONCLUSIONWe developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed.

Adult ; Biomarkers, Tumor ; Gene Expression Regulation, Neoplastic ; immunology ; Humans ; Lymphoma, B-Cell ; classification ; pathology ; Prognosis ; Retrospective Studies ; Survival Analysis

Recently immunophenotyping has become a valuable tool in the diagnostic workup of malignant lymphoma. We classified 79 consecutive cases of non-Hodgkin's lymphoma experienced at our hospital during the last two years according to the Working Formulation and immunologically using MT1, UCHL1 and MB2 monoclonal antibodies. The results of this study are as follows: 1) four cases (5.1%) were low grade, 54 cases (68.4%) were intermediate grade, and 21 cases (23.3%) were high grade. The most common subtype was 'diffuse, mixed' type, 2) fifty cases (63.3%) showed T-cell phenotype and 14 cases (17.7%) showed B-cell phenotype. Immunophenotyping was impossible in 15 cases due to either double staining or negative staining. 3) the incidence of extranodal presentation was high (65.8%) and the most common extranodal site was the upper aerodigestive tract (29.1%) followed by the gastrointestinal tract (16.4%), and 4) MT1, UCHL1 and MB2 monoclonal antibodies are valuable markers of T- and B-cells in paraffin embedded tissue, enabling retrospective study. However, because these antibodies are not lineage specific, the results of immunostaining should be interpreted with caution.
Adult ; Aged ; Aged, 80 and over ; Female ; Human ; Immunohistochemistry ; Immunophenotyping ; Lymphoma, Non-Hodgkin/classification/immunology/*pathology ; Male ; Retrospective Studies ; Support, Non-U.S. Gov't ; T-Lymphocytes

To evaluate the significance of FCM in minimal residual disease (MRD) detection, the immunophenotyping and leukemia-associated immunophenotypes (LAIP) of leukemia cells from 273 adult and 142 childhood patients with B lineage acute lymphoblastic leukemia (B-ALL) were detected by four to six antibody combinations of 4-color CD45/SSC gating multiparametric flow cytometry (FCM). The results showed that the B-ALL patients could be classified into 4 subtypes based on different expression CD34 and CD10: subtype I (CD34(+)/CD10(-)), subtype II (CD34(+)/CD10(+)), subtype III (CD34(-)/CD10(+)), subtype IV (CD34(-)/CD10(-)). The LAIP was observed in 100% and 92% patients of subtype I and subtype II, respectively, whereas only 79.2% in subtype III. The incidence of LAIP in total B-ALL cases was 90% by using the antibodies detected in this investigation. There was no significantce different for incidence of LAIP between adult and pediatric patients. LAIP was observed in 77.6% of patients by labeling only CD34/CD10/CD19/CD45 4-color antibody combination. It is concluded that in 90% of childhood and adult B-ALL patients LAIP can be found, which suits MRD detection by multiparameter flow cytometry.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; analysis ; B-Lymphocytes ; immunology ; Burkitt Lymphoma ; classification ; immunology ; pathology ; Cell Lineage ; Female ; Flow Cytometry ; methods ; Humans ; Immunophenotyping ; Male ; Middle Aged ; Neoplasm, Residual ; diagnosis ; Neprilysin ; analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; classification ; immunology ; pathology

OBJECTIVETo assess the value of histologic examination, immunohistochemistry and gene rearrangement studies in the diagnosis and subtyping of lymphoma with bone marrow involvement (BMI).

METHODSSixty-two formalin fixed, paraffin embedded bone marrow biopsy specimens were studied. Immunohistochemical and immunoglobulin heavy chain (IgH) and T-cell receptor gene rearrangement studies were performed in each case.

RESULTSChronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) demonstrated mainly and interstitial infiltration by dysplastic lymphocytes, with intertrabecular nodular arrangement or in dispersion. Sometimes, pseudofollicles may be noted. A predominantly para- or intertrabecular infiltration by nodules of lymphoma cells was characteristic of follicle center cell lymphoma (FCL) cases. In most lymphoplasmacytoid lymphoma (LPL) cases, there was infiltration by small lymphocytes and plasma cells between bony trabeculae. In marginal zone cell lymphoma (MZL), vague inter- or para-trabecular nodules of polymorphic lymphoma cells with clear cytoplasm might be noted. Small to medium-sized dysplastic lymphocytes, with absence of paraimmunoblasts or pseudofollicles, were the most frequent findings in mantle cell lymphoma (MCL). Hairy cell leukemia (HCL) might be identified by the presence of distinct cell membrane and abundant clear cytoplasm, resulting in a "fried-egg" appearance. Tumor cells with large nuclei and eosinophilic nucleoli were characteristically seen in lymphomatosis diffusa (Hodgkin's disease, HD). In T-cell non-Hodgkin lymphoma with BMI, dispersed or clusters of intertrabecular neoplastic lymphoid cells with clear cytoplasm and gyriform nuclei were often observed. In diffuse large B-cell lymphoma (DLBL), the tumor cells were large and isolated or arranged in diffuse pattern. Immunohistochemically, a panel of markers, including CD3 CD20, and CD79 are valuable for the differential diagnosis of T- and B-cell lymphomas. The neoplastic cells in MCL were cyclin D1- and CD5-positive, while BCL2- and CD10-positivity was characteristic for FCL. CLL/SLL cells might be stained with CD5 and CD23, in addition to CD20 and CD79. CD25 expression might be noted in HCL: the positivity for CD15, CD30 and fascin suggests HD. There was a higher positivity rate for IgH gene rearrangement in CLL/SLL, LPL MZL and DLBL (80%, 60%, 66.7%, 70% respectively) and for T- cell receptor gamma gene rearrangement in T-cell lymphoma (66.7%).

CONCLUSIONA combination of histopathology, immunohistochemistry and IgH / T-cell receptor gamma gene rearrangement studies may be of aid to the diagnosis and subtyping of lymphoma with BMI, especially if there is only a small number of tumor cells present in the specimen.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; chemistry ; pathology ; Diagnosis, Differential ; Female ; Gene Rearrangement ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; pathology ; Lymphoma ; classification ; immunology ; pathology ; Lymphoma, Follicular ; pathology ; Male ; Middle Aged

OBJECTIVEGene expression profiling of diffuse large B-cell lymphoma (DLBCL) of different immunophenotypes.

METHODSThe 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.

RESULTSThe 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.

CONCLUSIONSGene 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.

Aged ; Cluster Analysis ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Immunophenotyping ; methods ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; classification ; genetics ; immunology ; pathology ; Middle Aged ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Young Adult

OBJECTIVETo categorize diffuse large B-cell lymphoma (DLBCL) into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subgroups by immunohistochemistry; and to investigate the underlying prognostic significance.

METHODSImmunohistochemical study for CD10, bcl-6 and MUM1 was performed on 133 cases of DLBCL. The cases were then categorized into GCB and non-GCB subgroups. The 5-year overall survival and 5-year progression-free survival rates were compared between the GCB and non-GCB groups, and among the cases with different immunohistochemical expression or with different IPI.

RESULTSAmongst the 133 case studied, CD10 was expressed in 33.1%, while bcl-6 was positive in 34.6% and MUM1 in 45.1%. CD10 expression had a favorable impact on 5-year overall survival (P=0.041) and 5-year progression-free survival (P=0.031). On the other hand, bcl-6 expression had a favor able impact on 5-year progression-free survival (P=0.044). Expression of MUM1 carried an adverse effect on 5-year overall survival (P=0.031) and 5-year progression-free survival (P=0.028). GCB immunophenotype was demonstrated in 40.6% of the cases, while 59.4% showed a non-GCB profile. GCB DLBCL had a significantly longer 5-year overall survival (P=0.004) and 5-year progression-free survival (P=0.003), as compared with the non-GCB group. When dividing the cases into two groups according to their IPI score (IPI=0 to 1 and IPI=2 to 5), it turned out that the 5-year overall and progression-free survival rates of the GCB group were significantly higher than those of the non-GCB group (P=0.019 and 0.014 respectively in cases with IPI of 0 to 1 and P=0.006 and 0.009 respectively in cases with IPI of 2 to 5). The non-GCB cases with a IPI of 2 to 5 had the poorest prognosis.

CONCLUSIONDLBCL subgrouping by immunohistochemistry and analysis of the subgrouping with IPI is feasible and useful in predicting clinical outcome.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; B-Lymphocytes ; pathology ; Child ; Child, Preschool ; DNA-Binding Proteins ; metabolism ; Disease-Free Survival ; Female ; Follow-Up Studies ; Germinal Center ; pathology ; Humans ; Immunohistochemistry ; Interferon Regulatory Factors ; metabolism ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse ; classification ; immunology ; pathology ; Male ; Middle Aged ; Neprilysin ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; Survival Rate ; Young Adult