lewis-x-antigen and Lymphoma--Large-B-Cell--Diffuse

To profile the clinicopathologic features of a series of grey zone lymphoma (GZL) cases with hybrid features of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL), with a purpose to gain an in-depth understanding of the borderline B-cell neoplasm.. The clinical, morphologic and immunophenotyical characteristics of 16 cases were retrospectively analyzed.. The patients were mostly male adults, with a male to female ratio of 1.7: 1.0 and a mean age of 40.2 years. Eight patients presented with peripheral nodal lesions and five cases with mediastinal involvement. Histologically and immunophenotypically, the 16 cases were classified into three sub-categories. In 4 cases, the morphologic features resembled CHL more closely, but the neoplastic cells showed uniform and intense positive staining of CD20 (pattern 1). Although the initial impression of the other 8 cases was that of DLBCL, the expression levels of CD20 and PAX5 were variable, and CD30 or CD15 was positive (pattern 2). A characteristic feature of pattern 3, observed in the remaining 4 cases, demonstrated a broad spectrum of morphology with hybrid features of both CHL and DLBCL. The neoplastic cells in pattern 3 were positive for CD20, CD30 and CD15. EBV-LMP1 was detected in 6 of the 11 tested cases. Clinically, most patients with GZL seemed insensitive to immuno-chemotherapy of the R-CHOP regimen.. The diagnostic criteria for GZL with features intermediate between DLBCL and CHL is proposed by the three histologic patterns commonly seen in these lesions. Cases presented with peripheral lesions might differ from those with mediastinal presentation pathologically. At current time, there is no effective treatment for these borderline B-cell lymphomas and the prognosis is poor.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Female; Hodgkin Disease; Humans; Ki-1 Antigen; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; PAX5 Transcription Factor; Prednisone; Prognosis; Retrospective Studies; Rituximab; Vincristine; Viral Matrix Proteins; Young Adult

Epstein-Barr virus (EBV) can be associated with both classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma of the B-cell type, particularly in immunodeficient patients or elderly individuals. While polymorphic variants of EBV-positive large B-cell lymphoma (EBV+ DLBCL) frequently resemble cHL in morphology, and thereby may cause diagnostic difficulty, a true gray zone lymphoma with overlapping morphological and immunophenotypical features of EBV+ DLBCL and EBV+ cHL has not been reported in the literature. We describe a unique case of an EBV+ malignant lymphoma of B-cell origin with hybrid features of EBV+ DLBCL and EBV+ cHL in a 67-year-old female without an identifiable etiology for immunodeficiency. The biopsy of an enlarged lymph node showed a polymorphic infiltrate containing Reed-Sternberg-like pleomorphic large cells, which were positive for CD30 and CD15. Although CD20 was negative and PAX5 and CD45 were down-regulated, the pleomorphic large cells expressed multiple other B-cell antigens which are characteristically absent in cHL. EBV-encoded RNA hybridization (EBER) studies demonstrated nuclear reactivity in the large cells as well as in the smaller bystander cells. A clonal rearrangement of the immunoglobulin heavy chain gene was also detected by PCR. Although the results of the EBV and genotypic studies suggest this case may be an example of EBV+ DLBCL of the elderly instead of EBV+ cHL, the immunophenotype is strikingly ambiguous. Thus, this case may represent an interface between EBV+ DLBCL and EBV+ cHL.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Epstein-Barr Virus Infections; Etoposide; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Herpesvirus 4, Human; Hodgkin Disease; Humans; Immunophenotyping; Ki-1 Antigen; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Prednisone; Procarbazine; Reed-Sternberg Cells; Remission Induction; Vincristine

Topics: Adult; Diagnosis, Differential; Female; Granulomatous Disease, Chronic; Hodgkin Disease; Humans; Ki-1 Antigen; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Young Adult

Topics: Aged; B-Lymphocytes; Diagnosis, Differential; Female; Hodgkin Disease; Humans; Immunohistochemistry; Ki-1 Antigen; Lewis X Antigen; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous entity. The pattern of CD15, CD30 and Bcl-2 expression is not well documented, especially in local population. We investigated 67 consecutive cases of DLBCL by immunohistochemistry on paraffin-embedded tissue. The male to female ratio was 1.2:1 with median age of 55 years, and more common nodal than extranodal in presentation. Only 3 of 67 cases expressed CD15. In addition, three cases showed weak membrane staining for CD30. Only one of these three cases was noted to have co-expression of CD15 and with occasional tumour cells showing weak CD30 expression. Bcl-2 protein was expressed in 43 of 67 (64%), more frequently in nodal than in extranodal tumours. In conclusion, CD15 and CD30 expressions are infrequent in DLBCL, and co-expression is rare. Bcl-2 protein expression is common in DLBCL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; bcl-2-Associated X Protein; Biomarkers, Tumor; Child; Female; Genes, bcl-2; Humans; Immunohistochemistry; Ki-1 Antigen; Lewis X Antigen; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prospective Studies

The purpose of this study was to evaluate fluorescence in situ hybridization abnormalities of the 2p23 anaplastic lymphoma kinase (ALK) gene loci in lymphomas with anaplastic morphology. We studied 24 anaplastic large cell lymphomas (ALCL) classified by World Health Organization criteria [17 primary nodal/systemic (10 ALK+, 7 ALK-), seven primary cutaneous], and 17 additional non-Hodgkin's lymphomas [one ALK+ B-lineage lymphoma, 14 ALK- diffuse large B-cell lymphomas (seven anaplastic variants, five nonanaplastic, two secondary CD30+), two follicular lymphomas]. ALK- lymphomas with anaplastic morphology showed extra nonrearranged anaplastic lymphoma kinase gene loci (P=0.004) due to trisomy 2 irrespective of the following factors: B or T/null phenotype (P=0.315), diagnostic categories of systemic or cutaneous ALCL or the above-mentioned B-cell lymphomas (P=0.131), and CD30 positivity by immunohistochemistry (P=1.000). Trisomy 2 was absent in all ALK+ lymphomas (P=0.009), which showed rearranged ALK gene loci (P<0.001). Whether trisomy 2 is a primary or secondary event that leads to ALK- lymphomas cannot be determined from this study. Its presence in secondary B-cell lymphomas suggests that trisomy 2 may be a secondary cytogenetic aberration in lymphomas in general. Further investigation of this finding is necessary to further our understanding of the heterogeneous group of ALK- lymphomas.

Topics: Adult; Anaplastic Lymphoma Kinase; Child; Chromosome Aberrations; Chromosomes, Human, Pair 2; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Ki-1 Antigen; Lewis X Antigen; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Mucin-1; Protein-Tyrosine Kinases; Receptor Protein-Tyrosine Kinases; Statistics as Topic

Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology.. Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed-Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein-Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL.. MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.

Topics: Aged; Aged, 80 and over; Antigens, CD; Antigens, CD20; B-Lymphocytes; Bronchi; CD79 Antigens; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 18; Female; Hodgkin Disease; Humans; Immunohistochemistry; Ki-1 Antigen; Lewis X Antigen; Lymph Nodes; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Receptors, Antigen, B-Cell; Stomach; Thyroid Gland; Translocation, Genetic; Tumor Suppressor Protein p53

To explore the prognostic factors of primary nodal diffuse large B-cell lymphomas (N-DLBCL).. According to the 2001 WHO classification of tumors of hematopoietic and lymphoid tissue, 51 cases of primary N-DLBCL were collected for clinical data analysis and immunohistochemical assay. Antibodies used for study were anti-CD20, CD79alpha, CD45RO, CD3, Bcl-2, Ki-67, CD30, CD15, kappa, lambda, Cyclin D1, TdT, GFAP, CK, MPO. The survival data was analyzed.. Of the 51 cases of N-DLBCLs, 40 were reclassified as centroblastic, 3 B-immunoblastic, 1 T-cell/histiocytes rich, 2 B-cell anaplastic large cell, 1 plasmablastic, and 4 unclassified. Expression of Bcl-2 oncoprotein was observed in 24 cases (47.1%). The median Ki-67 index was 50.0% and the index more than 40% was found in 35 cases (68.6%). Survival analysis of 35 cases had follow up data showed that the 2 year and 5-year overall survival (OS) rates were 48.54% and 35.30%, respectively. The 5-year OS rates patients with International Prognosis Index (IPI) >/= 3 was lower than that with IPI < 3 (P < 0.01). The 5-year OS rates for patients with B symptoms was lower than that without B symptoms (P < 0.05). The 5-year OS rates for patients with Ki-67 index more than 40% was lower than that with less than 40% (P < 0.05). The expression of Bcl-2 oncoprotein was uncorrelated to prognosis (P > 0.05).. IPI, B symptoms and Ki-67 index are the prognostic factors for patients with N-DLBCL.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD20; Child; Child, Preschool; Cyclin D1; Female; Follow-Up Studies; Humans; Immunohistochemistry; Ki-1 Antigen; Ki-67 Antigen; Leukocyte Common Antigens; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prognosis; Survival Analysis; Young Adult

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD; Antigens, CD20; Antineoplastic Agents; CD79 Antigens; Cell Differentiation; Chromosome Deletion; Chromosomes, Human, Pair 6; Epstein-Barr Virus Infections; fas Receptor; Hodgkin Disease; Humans; Immunohistochemistry; Ki-1 Antigen; Kidney Transplantation; Leukocyte Common Antigens; Lewis X Antigen; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoproliferative Disorders; Male; Postoperative Complications; Receptors, Antigen, B-Cell; Rituximab; Treatment Outcome

The characteristic histologic features and immunophenotype are usually diagnostic and allow distinguishing CD30 positive T-cell lymphoma (including anaplastic large cell lymphoma) from classical Hodgkin's lymphoma. The latter differs by expression of CD15 and lack of CD45, pan-T antigens and ALK expression. We report nine cases of large cell hematopoietic neoplasms in which the neoplastic cells co-expressed CD30 and CD15, and had immunophenotypic and morphologic features of T-cell lymphoproliferative process. The average age of the CD15-positive group was 61.9 years; 6 cases occurred in men and 3 in women. The tumors were located in lymph nodes in 8 cases, and in liver in 1 case. Two cases expressed ALK protein. There were no statistically significant differences in phenotypic parameters between the CD15-positive and CD15-negative neoplasms (p>0.05). However, the CD15-positive group appeared to show a minor trend toward less positivity for EMA (44% versus 72%), ALK protein (22% versus 51%), and CD45RO (33.3% versus 83.3%, p=0.07), when compared to the typical CD15-negative neoplasms. In summary, although the co-expression of CD30 and CD15 is typical for classical HL, it may be also present in a subset of peripheral T-cell neoplasms including ALK-positive anaplastic large cell lymphoma. Combined and sensible use of morphology and a broad immunophenotypic panel in cases with limited material and/or those with overlapping histologic patterns will best discriminate between HL and ALCL. It is incumbent upon the pathologist to distinguish between these two clinicopathologic entities, since treatment options and clinical outcomes differ.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antigens, CD; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Female; Hodgkin Disease; Humans; Immunophenotyping; Ki-1 Antigen; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Male; Middle Aged; Mucin-1; Neoplasm Proteins; Retrospective Studies

We report a rare case of primary pulmonary Hodgkin's lymphoma associated with Epstein-Barr virus (EBV) and cytomegaly virus (CMV) infections as demonstrated by in situ hybridisation method. Reed-Sternberg cells were CD30 positive. Numerous CD15+ cells were noticed, some of them with concomitant CMV infection.

Topics: Cytomegalovirus; Cytomegalovirus Infections; Diagnosis, Differential; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Hodgkin Disease; Humans; Immunohistochemistry; In Situ Hybridization; Ki-1 Antigen; Lewis X Antigen; Lung Neoplasms; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Middle Aged; Reed-Sternberg Cells; Tomography, X-Ray Computed

Large cell lymphomas and Hodgkin disease may develop during the course of chronic lymphocytic leukemia (CLL). In some cases the transformed cells are Epstein-Barr virus (EBV)-positive and not clonally related to the CLL cells. In other cases the transformed cells have the same clonal rearrangements as the CLL cells. Here we describe a composite lymphoma in a patient with CLL that exhibits a combination of CLL/small lymphocytic lymphoma, large cell lymphoma with anaplastic morphology, and Hodgkin lymphoma (HL). Although the large cell lymphoma cells are CD45R0 and TIA-1-positive, suggesting a T- or 0-cell anaplastic large cell lymphoma (ALCL), the genetic analysis demonstrates immunoglobulin heavy chain (IgH) gene rearrangements for both alleles, carrying the same somatic mutations as observed in the CLL component. The Reed-Sternberg (R-S) cells in the Hodgkin component also strongly express TIA-1 but differ from the anaplastic large cells by the expression of CD15 and TARC and the presence of a prominent lymphocytic infiltrate. The ALCL and HL components both are EBV negative. Analysis of the IgH gene rearrangements in micromanipulated R-S cells revealed identical Ig gene rearrangements carrying the same somatic mutations as the CLL and the large cell components. The findings indicate transformation of the CLL cells into a large cell lymphoma with anaplastic morphology and a Hodgkin component.

Topics: Aged; Base Sequence; Cell Transformation, Neoplastic; Chemokine CCL17; Chemokines, CC; Clone Cells; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Herpesvirus 4, Human; Hodgkin Disease; Humans; Immunoglobulin Heavy Chains; Immunophenotyping; Leukemia, Lymphocytic, Chronic, B-Cell; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Male; Membrane Proteins; Molecular Sequence Data; Mutation; Poly(A)-Binding Proteins; Proteins; Reed-Sternberg Cells; RNA-Binding Proteins; T-Cell Intracellular Antigen-1

The clinicopathological features of histiocyte-rich, T-cell-rich B-cell lymphoma (HRTR-BCL) were first recognized in 1992. In this study, 60 cases of HRTR-BCL were analysed in order to provide a detailed morphological and immunophenotypical profile of the disorder.. HRTR-BCL is easily distinguished from other B-cell lymphomas rich in stromal T-cells by (i) a diffuse or vaguely nodular growth pattern, (ii) the presence of a minority population of CD15-, CD20+ large neoplastic B-cells, (iii) a prominent stromal component composed of both T-cells and non-epithelioid histiocytes, and (iv) the scarcity of small reactive B-cells. These criteria also enable a reliable distinction from lymphocyte-rich classical Hodgkin's lymphoma (CHL), from lymphocyte-predominant Hodgkin's lymphoma (LPHL), paragranuloma type and from peripheral T-cell lymphoma. Based on the morphology of the neoplastic cells and on their frequent bcl-6 immunoreactivity, we speculate that HRTR-BCL may be derived from a progenitor cell of germinal centre origin.. HRTR-BCL presents characteristic clinical features, affecting predominantly middle-aged men who present with advanced stage disease and are at high risk of treatment failure. Considering these distinctive clinicopathological features, recognizing HRTR-BCL as a lymphoma entity may be justified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD20; Biomarkers, Tumor; Cyclin D1; Diagnosis, Differential; Female; Histiocytes; Humans; Immunoenzyme Techniques; Immunophenotyping; Lewis X Antigen; Lymph Nodes; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Spleen; T-Lymphocytes

Large B-cell lymphoma manifesting in the mediastinum shows distinctive clinical and immunophenotypic features and is recognized as a unique type of large B-cell lymphoma in the Revised European-American Lymphoma classification. Fifty-one cases of primary mediastinal large B-cell lymphoma were retrieved from the immunodiagnosis laboratory database files and were stained with anti-CD30 (Ber-H2). Of the 51 cases, 35 (69%) stained for CD30. This staining ranged from strong membrane staining of all or almost all of the neoplastic cells to positivity of rare individual cells. Eleven cases (22%) were negative; 4 (8%) were equivocal. Only 1 case was uninterpretable owing to B-5 fixation and lack of a positive internal control. Thus, the majority of mediastinal large B-cell lymphomas express the Hodgkin marker CD30. This finding may result in misdiagnosis of large cell lymphoma as Hodgkin disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Diagnosis, Differential; Female; Hodgkin Disease; Humans; Immunoenzyme Techniques; Ki-1 Antigen; Leukocyte Common Antigens; Lewis X Antigen; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Middle Aged

The expression of sialosylated Lewis chi (SLEX), a ligand for endothelial leukocyte adhesion molecule 1 in malignant lymphomas, was immunohistochemically examined, using the monoclonal antibody, CSLEX1, which specifically reacts with SLEX. It was expressed in 6 out of 64 non-Hodgkin's lymphomas, which consisted of 1 nasal large-cell lymphoma and 5 of 8 (62%) Ki-1-positive anaplastic large-cell lymphomas (ALCL). One nasal lymphoma positive for SLEX co-expressed a T cell marker, cluster of differentiation (CD) 5, and natural killer (NK) cell markers such as CD56 and CD16, indicating that SLEX+ nasal lymphoma cells are possibly malignant counterparts of SLEX+ NK cells. SLEX did not react with 30 B cell lymphomas or most Hodgkin's disease lymphomas, though it did with one lymphocyte predominance type. Although SLEX+ ALCL exhibit T cell markers in some cases, some ALCL expressing SLEX may represent histiocytic differentiation of the neoplastic cells. The lymphoma cells of ALCL were preferentially positive for SLEX, in contrast to Hodgkin's disease cells, and thus CSLEX1 in conjunction with CD30 and CD15 should be of use for analyzing and making differential diagnoses of routine paraffin-embedded sections of ALCL.

Topics: Antigens, CD; Antigens, Neoplasm; Female; Humans; Ki-1 Antigen; Killer Cells, Natural; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Male

We report the immunohistochemical and clinical features of two cases of morphologically typical anaplastic large-cell lymphoma. One patient had lymph node and focal visceral involvement, and the other patient had multiple-organ involvement by lymphoma. In both cases, the lymphoma cells were CD30 (Ber-H2) and CD15 (Leu-M1) positive and CD45 (common leukocyte antigen) negative--a phenotype that is commonly seen in Hodgkin's disease. This unusual phenotype in large-cell anaplastic lymphoma led to an initial misinterpretation in one of the cases. Large-cell anaplastic lymphomas are highly variable, both in immunophenotype and clinical presentation. Because of this variability, a broad immunophenotypic panel, in conjunction with morphological features, should be used to establish the correct diagnosis.

Topics: Adult; Antigens, CD; Antigens, Neoplasm; Diagnosis, Differential; Hodgkin Disease; Humans; Immunophenotyping; Ki-1 Antigen; Leukocyte Common Antigens; Lewis X Antigen; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged

Composite lymphomas have rarely been reported in Hodgkin's disease (HD), except in the lymphocyte predominance sub-type, and immunohistochemical investigations have been performed in only few cases. We describe the histological and immunophenotypical findings in a case of composite nodular sclerosing HD and high-grade, large cell non-Hodgkin's lymphoma (NHL). In our case HD and NHL cells displayed striking morphological and immunophenotypical divergence, suggesting a lack of correlation between the two neoplasms.

Topics: Adult; Antigens, CD; Antigens, CD20; Antigens, Differentiation, B-Lymphocyte; Antineoplastic Agents; beta-D-Galactoside alpha 2-6-Sialyltransferase; Histocompatibility Antigens Class II; HLA-DR Antigens; Hodgkin Disease; Humans; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Membrane Glycoproteins; Mucin-1; Neoplasms, Multiple Primary; Phenotype; Sialyltransferases