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L Krenacs

Publications and source records attributed to L Krenacs.

15 recordsLinked to original sources
PubMed2001

Follicular dendritic cells in reactive and neoplastic lymphoid tissues: a reevaluation of staining patterns of CD21, CD23, and CD35 antibodies in paraffin sections after wet heat-induced epitope retrieval.

Structural alterations in the meshwork of follicular dendritic cells (FDCs) are frequently found in malignant lymphomas. Formaldehyde fixation and paraffin embedding, however, have long prevented consistent detection of FDCs. Wet heat-induced epitope retrieval in Dako Target Retrieval Solution (TRS) (pH 6.0) enabled the reliable detection of FDCs through CD21, CD23, and CD35 antigens in routinely processed tissues from 11 reactive and 69 neoplastic lymphoproliferations, thus allowing the distribution of the FDCs to be reevaluated. Germinal center FDCs in lymphoid hyperplasias and expanded FDC meshworks in the 8 mantle cell lymphomas, 7 low-grade MALT lymphomas, and 6 low-grade follicular lymphomas were intensely stained with all these markers. In 6 cases of B cell chronic lymphocytic leukemia, tumor cells were CD23+. In four cases of nodular lymphocyte predominance Hodgkin's disease (HD), expanded FDC meshwork's sharply delineating negative tumor cells and their rosetting T cell, were revealed mainly with the CD21 and CD35 antibodies. Follicular dendritic cells were also demonstrated in 11 cases of grade I nodular sclerosing HD, including follicular HD. Striking dendritic cell clusters were revealed with all 3 antibodies in 9 angioimmunoblastic T cell lymphomas. Sparse or no FDC meshworks were detected in the 4 cases of grade II nodular sclerosing HD, 5 follicular lymphomas with high-grade transformation, and 5 T cell-rich B cell lymphomas. CD35 immunostaining showed the most consistent labeling in the four FDC sarcomas studied in the current article. Reproducible demonstration of FDCs in routinely processed paraffin sections with CD21, CD23, and CD35 antibodies, as presented here, provides invaluable pieces of information in the diagnosis of lymphoproliferative disorders.

Antigens, CD↗
PubMed1999

Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru: high prevalence of p53 overexpression.

Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus (EBV). These lymphomas are rare in Western populations and much more prevalent in some Asian and Latin American countries. Although there are several sizable studies from Asian countries, the same is not true from South America. The aim of this study was to analyze a series of 32 cases of nasal T-cell lymphoma from Peru and to further extend the characterization of this disease. Immunohistochemistry was performed on paraffin sections using the following antibodies: CD20 (L26), CD45RO, CD3, Ki67, CD57, CD56, TIA-1, bcl-2, and p53. The presence of EBV was investigated with immunohistochemical analysis for latent membrane protein (LMP)-1 and in situ hybridization using an antisense riboprobe to EBER 1. The 32 patients included 18 men and 14 women (M:F ratio, 1.2:1), with a median age of 43 years (11 to 72). Three categories were identified: (1) Nasal NK/T cell lymphomas (28 cases): The morphology ranged from small or medium-sized cells to large transformed cells. Necrosis was present in 86% of the cases, and angioinvasion was seen in 36% of the cases. All cases were positive for CD45RO, CD3, and for TIA-1. CD56 was positive in 21 of 27 cases (78%), and CD57 was negative in all cases. EBER 1 positivity was identified in most of the tumor cells in 27 of 28 cases (96%), including the six cases in which CD56 was negative. Overexpression of p53 was detected in 24 cases (86%). (2) Blastic NK cell lymphoma (1 case): The neoplastic cells resembled those of lymphoblastic lymphoma. CD56 and CD45RO were positive; TIA-1, TdT, and EBER-1 were negative. (3) Peripheral T-cell lymphoma (PTCL) unspecified (3 cases): CD56, TIA-1, and EBER-1 were negative. Nasal lymphomas from Peru with a T cell phenotype are predominantly EBV-associated NK/T cell lymphomas, similar to those described in Asian countries. The expression of CD56, TIA-1, and EBER-1, in combination, are very useful markers for the diagnosis of nasal NK/T cell lymphoma in paraffin-embedded tissue. The differential diagnosis of T-cell lymphomas in the nasal region should include rare cases of PTCL unspecified and the blastic variant of NK cell lymphoma. P53 is overexpressed in 86% of the cases. The significance of this finding with regard to clinical behavior and prognosis remains to be determined.

Adolescent↗
PubMed1999

Primary nodal marginal zone lymphomas of splenic and MALT type.

The existence of primary nodal marginal zone lymphomas (MZL) is controversial, as is their relationship to putative extranodal counterparts. Most nodal lymphomas with monocytoid B cell/marginal zone differentiation exhibit the morphologic and immunophenotypical characteristics of extranodal MALT-lymphomas. Splenic marginal zone lymphoma (SMZL) is also of putative marginal zone derivation, but it differs immunophenotypically from MALT lymphoma. To clarify the relationship between nodal and extranodal MZLs and to investigate the possible existence of a nodal variant of SMZL, 36 MZL initially considered to be primary nodal neoplasms were examined. Other low-grade lymphomas with marginal zone differentiation were excluded (small lymphocytic lymphoma/chronic lymphocytic leukemia [SLL/CLL], follicular lymphoma, and mantle cell lymphoma). Six nodal MZLs showed morphologic and phenotypic characteristics similar to those of SMZL, whereas 30 tumors were more similar to MALT-type lymphomas. The six tumors with SMZL features showed a polymorphic infiltrate surrounding residual germinal centers with absent or very attenuated mantle cuffs. These lymphomas were IgD positive (6/6) but cyclin D1 (0/5), CD5 (0/6), and CD23 (0/6) negative. Five of these patients came for treatment in stage I or II. No patient manifested splenomegaly, peripheral blood, and/or bone marrow infiltration either at diagnosis or during follow-up. Lymph nodes from 30 patients with MALT-type features showed a perisinusoidal and perivascular infiltration of monocytoid/centrocytoid cells and residual germinal centers with a relatively well-preserved mantle cuff. The neoplastic cells were negative for IgD (0/17), cyclin D1 (0/8), and CD5 (0/12). Seven of 16 (44%) patients with a detailed history and clinical follow-up had evidence of extranodal lymphoma. These observations suggest that most nodal B cell lymphomas with marginal zone differentiation are of the MALT type and that they are frequently associated with an extranodal component. In addition, a primary nodal counterpart of splenic MZL also exists, and may occur in the absence of splenomegaly.

Adult↗
PubMed1999

Extranodal peripheral T-cell and NK-cell neoplasms.

Mature or peripheral T-cell lymphomas are uncommon, accounting for only 10% to 15% of all non-Hodgkin lymphomas, and their classification has been controversial. In contrast to B-cell lymphomas, cytologic features have not been useful in defining disease entities, and cytologic grade has not been useful in predicting the clinical course. Similarly, many entities of T-cell or NK-cell derivation do not have a specific immunophenotype. Clinical features are of major importance, sometimes more important than the precise cell of orgin, in defining T-cell and NK-cell neoplasms. Most extranodal T-cell/NK-cell lymphomas have a cytotoxic phenotpye. The expression of cytotoxic molecules may predispose to apoptosis by tumor cells and normal bystander cells. Three major categories of extranodal T/NK cell tumors are nasal, intestinal, and subcutaneous panniculitis-like. Hepatosplenic gamma delta T-cell lymphoma is a more systemic disease derived from functionally immature cytotoxic cells. Many extranodal T-cell and NK-cell neoplasms are associated with Epstein-Barr virus (EBV); the association seems site dependent and shows some geographic variation. Tumors resembling any of the 3 prototypes may occur in a variety of extranodal sites. Extranodal T/NK cell lymphomas occur with increased frequency in the setting of immune suppression, especially after organ transplantation.

Humans↗
PubMed1998

Transcription factor B-cell-specific activator protein (BSAP) is differentially expressed in B cells and in subsets of B-cell lymphomas.

The paired box containing gene PAX-5 encodes the transcription factor BSAP (B-cell-specific activator protein), which plays a key role in B-lymphocyte development. Despite its known involvement in a rare subtype of non-Hodgkin's lymphoma (NHL), a detailed examination of BSAP expression in NHL has not been previously reported. In this study, we analyzed normal and malignant lymphoid tissues and cell lines, including 102 cases of B-cell NHL, 23 cases of T- and null-cell NHL, and 18 cases of Hodgkin's disease. Normal lymphoid tissues showed strong nuclear BSAP expression in mantle zone B cells, less intense reactivity in follicular center B cells, and no expression in cells of the T-cell-rich zones. Monocytoid B cells showed weak expression, whereas plasma cells and extrafollicular large transformed B cells were negative. Of the 102 B-cell NHLs, 83 (81%) demonstrated BSAP expression. All of the 13 (100%) B-cell chronic lymphocytic leukemias (B-CLLs), 21 of (100%) mantle cells (MCLs), and 20 of 21 (95%) follicular lymphomas (FLs) were positive. Moderate staining intensities were found in most B-CLL and FL cases, whereas most MCLs showed strong reactions, paralleling the strong reactivity of nonmalignant mantle cells. Eight of 12 (67%) marginal zone lymphoma cases showed negative or low BSAP levels, and 17 of 24 (71%) large B-cell lymphomas displayed moderate to strong expression. None of the 23 T- and null-cell lymphomas reacted with the BSAP antisera, whereas in Hodgkin's disease, 2 of 4 (50%) nodular lymphocytic predominance and 5 of 14 (36%) classical cases showed weak nuclear or nucleolar BSAP reactions in a fraction of the tumor cells. Western blot analysis showed a 52-kD BSAP band in B-cell lines, but not in non-B-cell or plasma cell lines. We conclude that BSAP expression is largely restricted to lymphomas of B-cell lineage and that BSAP expression varies in B-cell subsets and subtypes of B-cell NHL. The high levels of BSAP, especially those found in large-cell lymphomas and in some follicular lymphomas, may be a consequence of deregulated gene expression and suggest a possible involvement of PAX-5 in certain B-cell malignancies. This is a US government work. There are no restrictions on its use.

Antigens, CD20↗
PubMed1998

Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes.

Subcutaneous panniculitic T cell lymphoma (SCPTCL) is characterized by primary involvement of the subcutaneous fat in a manner mimicking panniculitis. We studied 16 cases of this lymphoma to define its immunophenotypical profile as well as cellular origin. Involvement of the subcutaneous fat in a lacelike pattern with neoplastic cells rimming individual fat spaces was present in all cases. All 16 cases were of T cell phenotype. Thirteen of the 16 cases were CD8+, whereas three were negative for both CD4 and CD8. Twelve cases were stained for betaF1; of these, eight were betaF1+ and four were betaF1-. Focal staining for CD56 and CD30 was seen in 2 of 13 and two of eight cases, respectively. Intense diffuse positivity for the cytotoxic granular proteins T cell intracellular antigen-1 (TIA-1) and perforin was present in all cases, indicating an origin from cytotoxic T lymphocytes. Ten cases studied for Epstein-Barr viral sequences were negative. Eight of 9 cases with amplifiable DNA showed a clonal TCR gamma gene rearrangement by polymerase chain reaction. Controls included seven cases of benign panniculitis and seven other peripheral T cell lymphomas involving the skin and subcutaneous tissues: two peripheral T cell lymphomas, not otherwise specified (PTL,NOS), four anaplastic large cell lymphomas (ALCL), one T/NK cell lymphoma. The seven cases of panniculitis lacked cytological atypia and were characterized by an admixture of CD4+ and CD8+ cells with interspersed aggregates of L26+ B cells. Only infrequent cells showed staining for TIA-1 and perforin. In the control cases of T cell lymphoma, the infiltrate had a tendency for dermal and sometimes even epidermal involvement, with sheeting out of malignant cells, in contrast to the characteristic subcutaneous localization and rimming of fat spaces noted in SCPTCL. The two PTL, NOS were CD4+ and negative for both TIA-1 and perforin. Although the remaining controls expressed TIA-1 and perforin, in keeping with their cytotoxic T or natural killer (NK) cell origin, histological and other immunophenotypical features allowed distinction from SCPTCL. Five cases of SCPTCL were also stained for apoptosis using a tdt-mediated end labeling kit. All cases showed numerous positive apoptotic bodies, suggesting apoptosis as the mechanism of cell death in these tumors. Our study indicates that SCPTCL constitutes a distinctive clinicopathological entity derived from cytotoxic T lymphocytes and should be differentiated from other benign and malignant lymphoid infiltrates involving the subcutis. The apoptosis seen in these tumors may be mediated by release of cytotoxic granular proteins.

Adult↗
PubMed1998

Cytotoxic granular protein expression, Epstein-Barr virus strain type, and latent membrane protein-1 oncogene deletions in nasal T-lymphocyte/natural killer cell lymphomas from Mexico.

Nasal T-lymphocyte/natural killer cell lymphomas (nT/NKLs) are a distinct group of neoplasms highly associated with Epstein-Barr virus (EBV), with a high prevalence in Asia but rare in Western countries. Recent studies indicate that these neoplasms are of cytotoxic T- or NK-cell derivation. Previous studies identifying a characteristic 30-base pair deletion within the 3' end of latent membrane protein-1 (del-LMP-1) in other EBV-associated lymphomas suggested a pathogenetic role for del-LMP-1 in those neoplasms. We examined 23 cases of nT/NKL from Mexico for expression of the cytolytic granular proteins TIA-1 and perforin (PRF), and for the presence of EBV by in situ hybridization (ISH). Polymerase chain reaction was performed to identify the EBV (EBNA-2) strain type and the status of the LMP-1 gene (del-LMP-1). Controls consisted of 11 sinonasal B-cell lymphomas (nBLs) and 30 reactive tonsils (RTs) from healthy Mexican individuals. The nT/NKLs expressed TIA-1 in 21 (91%) of 23 cases and PRF in 15 (65%) of 23 cases. In contrast, all of the nBLs were negative for TIA-1 and PRF. Twenty-two (96%) of 23 nT/NKLs were positive for EBV by ISH. In contrast, only 2 (18%) of 11 nBLs were positive for EBV by ISH. EBV strain Type A was identified in 21 (91%) of 23 cases, whereas strain Type B was present in 2 (9%) of the 23 nT/NKLs. A similar percentage (80%) of Type A was noted in 12 of the 15 RTs. del-LMP-1 was detected in 6 (26%) of 23 nT/NKLs, comprising 4 cases of Type A and 2 of Type B. del-LMP-1 was detected in 9 (45%) of 20 RTs. Our results indicated that TIA-1 and PRF were sensitive markers of nT/NKL. The presence of del-LMP-1 in comparable frequencies in the RTs and nT/NKLs suggested to us that this genotype was common in the Mexican population and argued against a definite pathogenetic role for del-LMP-1 in nT/NKL.

Adolescent↗
PubMed1997

Cytotoxic cell antigen expression in anaplastic large cell lymphomas of T- and null-cell type and Hodgkin's disease: evidence for distinct cellular origin.

Anaplastic large cell lymphoma (ALCL) is composed of large, frequently bizarre, cells of T- or null-cell phenotype that show a preferential sinusoidal growth pattern and consistent CD30 positivity. Whether these tumors represent a single entity or several, and what the exact cell origin, is controversial. Recently, granzyme B, a cytotoxic granule component, was reported in a small percentage of ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To further investigate this possibility, we performed an immunohistochemical study of 33 ALCLs of T- and null-cell type, using monoclonal antibodies to cytotoxic cell-associated antigens, including CD8, CD56, CD57, and the cytotoxic granular proteins perforin and TIA-1. In addition, CD4 expression was also evaluated. ALCL cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC) forms, and 3 acquired immunodeficiency syndrome-associated forms. Cytotoxic antigen expression was also studied in 51 cases of Hodgkin's disease (HD) and 17 large B-cell lymphomas (LBCLs) with anaplastic cytomorphology and/ or CD30 positivity. We found that 76% of ALCLs, representing all subtypes except the PC forms, expressed either TIA-1, perforin, or both proteins. Expression of TIA-1 and perforin were highly correlated (P < .001). On the basis of their immunophenotypic profiles, several subtypes of cytotoxic antigen positive and negative ALCL could be recognized. Fifty-five percent of ALCLs (18 of 33) displayed an immunophenotypic profile consistent with cytotoxic T cells. Six cases expressed cytotoxic granular proteins in the absence of lineage specific markers, and one case expressed both T-cell- and natural killer cell-like markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic lymphocytes of unspecified subtype. Twenty-four percent (8 cases) of ALCLs were cytotoxic granule protein negative. All but one of these displayed a T-cell phenotype. Cytotoxic granule protein expression did not correlate with the presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD cases were found to be TIA-1+, and none expressed perforin. Cytotoxic antigen expression was absent in LBCL. The expression of cytotoxic granule proteins in the majority of ALCL implies a cytotoxic lymphocyte phenotype and suggests that most cases originate from lymphocytes with cytotoxic potential. Furthermore, the demonstration of cytotoxic cell related proteins may be a useful addition to the current panel of antibodies used to distinguish ALCL, HD, and anaplastic LBCL.

Adolescent↗
PubMed1997

Localization of the cell proliferation and apoptosis-associated CAS protein in lymphoid neoplasms.

We have evaluated the expression and distribution of the cellular apoptosis susceptibility (CAS) protein in normal lymphoid tissue and malignant lymphomas. CAS protein, the product of the CAS gene, is associated with microtubules and the mitotic spindle. Immunohistochemistry with an antibody to CAS shows many CAS-positive cells in normal tonsils. The majority of strongly CAS-positive cells were localized to the dark zone of the follicles, whereas the mantle zone and interfollicular areas were essentially negative. Double staining for CAS and Ki-67 revealed co-expression of the two proliferation markers in approximately 85 to 90% of the CAS-positive cells. Different subtypes of lymphomas exhibited varying patterns of CAS expression. Low-grade non-Hodgkin's lymphoma generally revealed weak staining with CAS, with 10 to 60% of all cells being positive. In contrast, highly malignant non-Hodgkin's lymphoma and malignant cells of Hodgkin's disease displayed very strong CAS positivity, with staining of up to 80% of the atypical cells. Overall, the staining pattern of CAS and Ki-67 was superimposable within a particular lymphoma subtype. However, in all lymphomas we observed a significant fraction of CAS-positive normal and malignant lymphocytes that were Ki-67 negative, probably because they were momentarily noncycling cells. We conclude that a high expression of CAS correlates with proliferation of normal and malignant lymphoid cells. The fact that detection of CAS protein identifies a higher portion of proliferating and malignant cells than Ki-67 warrants further evaluation of CAS protein as a marker with a diagnostic potential.

Apoptosis↗
PubMed1997

Classification of T-cell and NK-cell neoplasms based on the REAL classification.

Mature or peripheral T-cell lymphomas are uncommon, accounting for only 10%-15% of all non-Hodgkin's lymphomas. The classification of these neoplasms has been controversial. In contrast to B-cell lymphomas, cytologic grade has not been very useful in predicting the clinical course. This finding may result from the generally aggressive clinical course associated with T-cell lymphomas. Prior studies have suggested that stage of disease may be more important than cytologic subtype. Clinical presentation is very important in the classification of T-cell malignancies. For T-cell lymphomas, cytologic features alone are not sufficient to distinguish among disease entities. For example, adult T-cell leukemia/lymphoma (ATLL) often cannot be distinguished morphologically from HTLV-1-negative T-cell lymphomas. Most extranodal T-cell lymphomas appear to be derived from cytotoxic T cells, which express perforin, TIA-1, and granzyme B. Three broad groups of T-cell malignancies can be identified: (1) leukemic or systemic disease; (2) nodal disease; (3) extranodal disease. Anaplastic large-cell lymphoma (ALCL) is probably the single most common subtype of T-cell lymphoma. Classical ALCL should be distinguished from primary cutaneous ALCL (CD30+ lymphoproliferative disease of the skin), which is a distinct disease entity.

Humans↗
PubMed1996

Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin.

We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T-cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation.

Adolescent↗
PubMed1996

bc1-1 rearrangement and cyclin D1 protein expression in multiple lymphomatous polyposis.

Multiple lymphomatous polyposis (MLP), characterized by multiple polyps involving long segments of the gastrointestinal (GI) tract, is believed to represent GI involvement by mantle cell lymphoma (MCL), primarily based on its histologic and immunophenotypic similarities with MCL. However, rearrangement of the bcl-1 locus, the molecular lesion characteristic of MCL, has not been investigated in this group of patients. The authors evaluated the morphologic, immunophenotypic, and molecular features of 18 cases of MLP and 8 B-cell lymphomas involving the GI tract (including 6 MALT lymphomas). All MLP cases presented with GI disease, and were histologically similar to MCL. DNA extracted from formalin-fixed, paraffin-embedded tissue was analyzed for evidence of bcl-1 rearrangement by PCR, using chromosome 11 specific and consensus JH primers. Amplifiable DNA was obtained in 24 of 26 cases (16 of 18 MLP cases and 8 of 8 controls). bcl-1 rearrangement was detected in 6 of 16 cases (38%), subsequently confirmed by sequencing of the breakpoint region, and in 0 of 8 controls. Immunostaining for cyclin D1 was positive in 14 of 18 MLPs, including the 6 bcl-1 rearranged cases and negative in 6 of 6 evaluable controls. The detection of bcl-1 rearrangement and cyclin D1 expression in cases of MLP supports the view that MLP represents primary MCL, of the GI tract. These techniques may also be helpful in differentiating MLP from other GI lymphomas, particularly low grade lymphomas of MALT, when only small routinely fixed endoscopic biopsies are available.

Adult↗