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Steven H Swerdlow

Publications and source records attributed to Steven H Swerdlow.

31 records · Page 2Linked to original sources
PubMed2003

T(14;18)(q32;q21) involving MALT1 and IGH genes in an extranodal diffuse large B-cell lymphoma.

Two translocations involving the MALT1 gene have been described in extranodal marginal zone B-cell lymphomas of MALT type. A t(11;18)(q21;q21) involving API2 and MALT1 occurs in a subset of MALT lymphomas but with only rare exception is absent in diffuse large B-cell lymphomas (DLBCL), even at MALT sites. More recently, a t(14;18)(q32;q21) involving IGH and MALT1 has been described in nongastric extranodal MALT lymphomas. This translocation is indistinguishable from the IGH-BCL2 translocation by using classical cytogenetics. We report the IGH-MALT1 translocation in a cutaneous DLBCL as shown by classical cytogenetics and molecular cytogenetic analysis. This is the first report of an IGH-MALT1 translocation in DLBCL. These findings indicate that MALT1 translocations are not restricted to indolent-appearing lymphomas, provide further evidence that API2-MALT1 and IGH-MALT1 translocations exhibit biologic differences, have implications regarding the pathogenesis of some extranodal DLBCL, and emphasize that a t(14;18)(q32;q21) cannot be assumed to reflect a BCL2 translocation.

Aged↗
PubMed2003

Nodal marginal zone B-cell lymphoma with a novel t(X;5)(q28;q22): conventional and molecular cytogenetic analysis.

Cytogenetic studies provide important information for the diagnosis and classification of malignant lymphomas that in some cases also has prognostic significance. Furthermore, the investigation of isolated novel cytogenetic findings in malignant lymphoma has led to the discovery of many important oncogenes and tumor suppressor genes. For this reason, a case of nodal marginal zone B-cell lymphoma in a 72-year-old woman is described in which analysis by conventional and molecular cytogenetic techniques demonstrated the presence of a t(X:5)(q28;q22) as the sole chromosomal abnormality. This translocation has not been previously reported in the literature.

Aged↗
PubMed2003

Indolent mantle cell lymphoma with nodal involvement and mutated immunoglobulin heavy chain genes.

Mantle cell lymphoma (MCL) is typically considered an aggressive but incurable neoplasm composed of cyclin D1+ monoclonal B-cells with a t(11;14)(q13;q32) and usually unmutated immunoglobulin (Ig) genes. Although it has been suggested that a more indolent leukemic disorder exists with the same phenotype and genotype but with mutated Ig genes, others have considered these cases to be variants of chronic lymphocytic leukemia. We present a case of an indolent MCL that was documented with cyclin D1 expression in a lymph node biopsy performed more than 12 years ago. The patient has peripheral blood involvement with a lymphocyte count in the reference range, variable thrombocytopenia, and minimal adenopathy but is otherwise well, never having received any antineoplastic therapy. Study of peripheral blood samples from 2002 revealed a CD5-variable B-cell monoclonal proliferation with a t(11;14)(q13;q32) plus other karyotypic abnormalities, positive fluorescence in situ hybridization studies for the CCND1/IgH translocation, and clonal Ig gene rearrangement with mutated Ig genes (95.7% homology to VH 4-31). The subtle but diagnostic lymph node biopsy in this case helps to further support that an indolent t(11;14) monoclonal lymphocytosis with mutated Ig genes can represent an MCL variant rather than chronic lymphocytic leukemia.

Adult↗
PubMed2003

Lymph node grading for staging of mycosis fungoides may benefit from examination of multiple excised lymph nodes.

BACKGROUND: Lymph node (LN) histopathologic class has been shown to be a significant determinant of survival in patients with mycosis fungoides. Often, histopathologic evaluation of just 1 node is used in staging patients with cutaneous T-cell lymphoma. OBJECTIVE: We examined whether sampling multiple nodes alters the staging and prognostic group placement of patients with mycosis fungoides as compared with sampling just 1 node. METHODS: Multiple LNs were obtained from a single, local region for histopathologic evaluation and grading in 8 patients with mycosis fungoides. RESULTS: Differences in histopathologic grading using multiple nodes were found in 5 of 8 patients. There was a potential upstaging of the assigned disease stage, compared with the stage that might have been assigned had just 1 node been sampled, in 3 patients. The differences in LN grading also potentially led to differences in prognostic group placement in 4 patients. CONCLUSION: Determining histopathologic grades from multiple LNs may allow a more accurate stage and prognosis to be assigned to patients.

Adult↗
PubMed2003

Primary and secondary cutaneous diffuse large B-cell lymphomas: a multiparameter analysis of 25 cases including fluorescence in situ hybridization for t(14;18) translocation.

Although primary cutaneous diffuse large B-cell lymphomas (DLBCLs) except for those of the leg are grouped together with primary cutaneous follicle center cell lymphoma in the European Organization for Research and Treatment of Cancer classification of primary cutaneous lymphomas, they typically lack the usual phenotypic profile of follicular lymphoma. Whether they are truly of follicular center cell origin, have a molecular pathogenesis similar to nodal follicular lymphoma, or have any biologic features that distinguish them from secondary DLBCL involving skin remains uncertain. To address these issues, a retrospective multiparameter study of 25 patients including clinical, histologic, immunophenotypic, and cytogenetic analyses was performed. A classic CD10+, bcl-6+ follicular center cell profile was found in 10 (40%) cutaneous DLBCL (2 of 11 primary, 5 of 8 secondary, 3 of 6 unclassified) with bcl-2 expression seen only in the nonprimary cases. Of the remaining cases, 14 cases (56%) were CD10-, bcl-6+, bcl-2+/- (9 primary) and one case (4%) was CD10-, bcl-6-, bcl-2+ (0 primary). Fluorescence in situ hybridization analysis showed a t(14;18) in 0 of 9 primary and 3 of 5 secondary cases. Primary cases were frequently found in the head/neck region, whereas secondary cases were more common on the trunk and extremities. Patients with primary disease were all alive, usually having received only local therapy, at a median follow-up of 19 months. Most secondary cases were treated with chemotherapy with only one untreated patient dead of disease at a median follow-up of 5 months. Primary cutaneous DLBCLs therefore appear to be distinctive as they have fewer features of follicular lymphoma than do secondary cases. Nevertheless, some appear to be of follicular center cell origin, even though they probably have a different molecular pathogenesis than most nodal follicular lymphomas.

Adult↗
PubMed2003

Cell cycle alterations in the blastoid variant of mantle cell lymphoma (MCL-BV) as detected by gene expression profiling of mantle cell lymphoma (MCL) and MCL-BV.

Overexpression of cyclin D1 is necessary but by itself insufficient for the development of mantle cell lymphoma (MCL). To identify pathways in the pathogenesis of MCL and the blastoid variant (MLC-BV), we compared the gene-expression profiles of microdissected normal mantle cells, MCL, and MCL-BV by oligonucleotide microarrays and quantitative reverse transcriptase PCR (QRT-PCR). We identified and confirmed the overexpression of several genes in MCL-BV that are involved in the cell cycle control at the G1/S and G2/M checkpoints or inhibit apoptotic cell death. The highly expressed cyclin dependent kinase 4 (CDK4) is a cell cycle kinase that associates with cyclin D1 for the progression through the G1/S checkpoint, whereas overexpression of cdc28 protein kinase 1 (CKS1) blocks the inhibition of the cyclin D1/CDK4 complex by the CDK inhibitor p27/Kip1. Other highly expressed genes in MCL-BV that promote the cells through the G1/S-checkpoint include the oncogenes B-Myb, PIM1, and PIM2, and passage through the G2/M-checkpoint is enhanced by high levels of cdc25B. Furthermore, two highly expressed genes that inhibit apoptosis are defender against cell death (DAD1) and RSK1. In summary, our microarray and QRT-PCR analyses identified several candidate genes whose expression increased when comparing normal follicular mantles with MCL and MCLBV, suggesting a potential pathogenic role in the evolution of MCL-BV.

Cell Cycle↗
PubMed2003

Benign CD10-positive T cells in reactive lymphoid proliferations and B-cell lymphomas.

Recent reports have indicated that the neoplastic T cells of angioimmunoblastic T-cell lymphoma express CD10. It has been suggested that the demonstration of a CD10+ T-cell population may assist in establishing a diagnosis of angioimmunoblastic T-cell lymphoma and in distinguishing angioimmunoblastic T-cell lymphoma from other peripheral T-cell lymphomas. It has been unclear, however, whether this phenotypically unusual T-cell population might be present in other settings as well. In this report, we have retrospectively examined 64 cases of lymph node and solid tissue biopsies for the presence of CD10+ T cells using multicolor flow cytometry. Discrete populations of CD10+ T cells were found in 5 of 28 cases (18%) of reactive lymphoid hyperplasia, 4 of 17 cases (23%) of follicular lymphoma, and 9 of 19 cases (47%) of marginal zone B-cell lymphomas. The CD10+ T cells constituted 1-6% of total cells analyzed and </=14% of the total T-cell population. Using two-color immunohistochemical stains, many of the CD10+ PAX5-negative presumptive T cells were found to be located within germinal centers. These findings indicate that a normal small subset of CD10+ peripheral T cells exists and, at least when present in small numbers, should not be considered an indication of a T-cell neoplasm.

Biomarkers, Tumor↗
PubMed2003

bcl-2 expression by multicolor flow cytometric analysis assists in the diagnosis of follicular lymphoma in lymph node and bone marrow.

The expression of bcl-2, CD10, and CD20 was examined by multicolor flow cytometry in 78 samples including lymph node or other tissue biopsy specimens containing follicular lymphoma (FL; n = 17), reactive hyperplasia (RH; n = 28), or other malignant lymphomas (n = 20), as well as bone marrow aspirates (n = 13). The presence of CD10+ cells with high bcl-2 expression predicted the presence of FL rather than RH with a positive predictive value of 100% and negative predictive value of 96%. CD10+ cells with high bcl-2 expression also were found in a subset of diffuse large B-cell lymphomas and were otherwise rare in other types of malignant lymphoma. In contrast with immunohistochemical studies, a reduced but apparently measurable level of bcl-2 was present in benign follicular center cells. Hematogones showed lower bcl-2 levels than did FL cells in the bone marrow, and neutrophils were bcl-2-. Measurement of bcl-2 expression levels by multiparameter flow cytometry offers a rapid, quantitative assessment that may assist in the diagnosis of FL in lymph nodes or bone marrow, even when other CD10+ cells or admixed normal B cells are present.

Bone Marrow↗
PubMed2002

Splenic marginal zone lymphomas appear to originate from different B cell types.

Splenic marginal zone lymphomas (SMZLs) have been proposed to originate from postgerminal center memory B cells that usually have mutated immunoglobulin heavy-chain variable (VH) genes. However, the majority of SMZLs are thought to express both IgD and IgM, which is more typical of naïve B cells that have unmutated VH genes. To better define the SMZL cell of origin and pathogenesis, we studied the histological and immunophenotypic features of eight cases and also sequenced their rearranged VH genes. Half of the cases had unmutated VH genes consistent with a naïve B-cell origin and half had mutated VH genes consistent with a memory B-cell origin. Most of the unmutated cases (three of four) were positive for IgD, which further supports a naïve B-cell origin, whereas the others were negative. In addition, VH gene segment use seems to be nonrandom because seven of eight cases used genes from the VH1 or VH4 families and repetitive use of the V1-2, V1-69, and V4-34 gene segments was observed. Our results suggest there are two types of SMZLs, one that originates from naïve marginal zone B cells in addition to one that originates from memory marginal zone B cells, and that antigen selection may be occurring during lymphomagenesis.

Aged↗
PubMed2002

From centrocytic to mantle cell lymphoma: a clinicopathologic and molecular review of 3 decades.

Mantle cell lymphoma (MCL), described almost 3 decades ago as centrocytic lymphoma and by a variety of other names, was initially recognized morphologically. MCL is a classic illustration of how the field of hematopathology and our basic understanding of neoplasia have evolved. The advent of immunophenotypic and increasingly sophisticated genotypic and cytogenetic studies, together with clinical investigations, have led to a better practical and biologic understanding of MCL and have broader implications as well. MCL is now recognized as an aggressive, difficult to treat, B-cell lymphoma with a broader morphologic spectrum than was initially appreciated and a characteristic phenotype (CD5+, CD10-, CD23-, FMC7+). Virtually all MCLs carry the translocation t(11;14)(q13;q32) with overexpression of the involved CCND1 (cyclin D1) gene. Additional cytogenetic and molecular abnormalities have been identified, including some that are early events (such as ATM gene deletion and mutation) and others that appear to be late events (such as deletions and mutations in the negative cell cycle regulatory elements p53, p16, and p18). The latter are often associated with a blastoid morphology and more aggressive clinical course. Ongoing clinical and basic investigations including microarray analysis will undoubtedly provide additional insights into MCL and perhaps more effective and specific therapeutic modalities.

Chromosomes, Human, Pair 11↗
PubMedDate not supplied

MALT Lymphoma in Children: Case Report and Review of the Literature.

Mucosa-associated lymphoid tissue (MALT) lymphoma predominantly occurs in adults, and is rare in children. We report a case of MALT lymphoma involving minor salivary gland of the lip in an otherwise healthy 12-year-old boy. This is the second case report of MALT lymphoma of minor salivary gland in an immunocompetent child. Of 24 cases of MALT lymphomas in children reported in the English literature, parotid MALT lymphomas in human immunodeficiency virus (HIV) patients and H. pylori infection-associated gastric MALT lymphomas are the most common. As in adult cases, most MALT lymphomas in the pediatric age group are localized and follow an indolent clinical course, respond well to therapy, and have an excellent outcome.

Antigens, CD↗