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E S Jaffe

Publications and source records attributed to E S Jaffe.

At least 73 records · Page 4Linked to original sources
PubMed1999

World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.

PURPOSE: The European Association of Hematopathologists and the Society for Hematopathology have developed a new World Health Organization (WHO) classification of hematologic malignancies, including lymphoid, myeloid, histiocytic, and mast cell neoplasms. DESIGN: Ten committees of pathologists developed lists and definitions of disease entities. A clinical advisory committee (CAC) of international hematologists and oncologists was formed to ensure that the classification would be useful to clinicians. The CAC met in November 1997 to discuss clinical issues related to the classification. RESULTS: The WHO uses the Revised European-American Lymphoma (REAL) classification, published in 1994 by the International Lymphoma Study Group, to categorize lymphoid neoplasms. The REAL classification is based on the principle that a classification is a list of "real" disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one gold standard. The WHO Neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. At the CAC meeting, which was organized around a series of clinical questions, participants reached a consensus on most of the questions posed. They concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors, such as the International Prognostic Index. CONCLUSION: The WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.

Hematologic Neoplasms↗
PubMed1999

CNS involvement in primary mediastinal large B-cell lymphoma.

PURPOSE: The risk of CNS involvement by non-Hodgkin's Lymphoma (NHL) has been associated with bone marrow and/or testicular involvement; however, it was recently reported that the number of extranodal sites is a more reliable predictor of CNS disease. Because primary mediastinal thymic large B-cell lymphoma (PMLCL) has a high propensity for involving extranodal sites, we investigated the frequency and pattern of CNS involvement in PMLCL. PATIENTS AND METHODS: The medical records of 219 patients with aggressive NHL, consecutively entered onto protocols at the National Cancer Institute between 1987 and 1998, were retrospectively reviewed. RESULTS: Twenty-three patients (11%) had clinical and pathologic features of PMLCL. These patients were young (median age, 29 years), female (61%), and presented with massive mediastinal adenopathy (70%). Extranodal disease occurred at presentation in 70% and at relapse in 93% of patients and involved contiguous intrathoracic structures and/or distant sites, including the lungs, kidneys, liver, adrenals, ovaries, pancreas, and bone. Six patients (26%) developed CNS involvement, two (9%) at presentation and four (27%) at relapse. All had extranodal disease, but only one had bone marrow involvement. Parenchymal and leptomeningeal CNS disease occurred in four and three patients, respectively. CONCLUSION: CNS involvement in PMLCL is associated with extranodal involvement other than bone marrow and may reflect the unique biology of this disease. The propensity to involve the CNS parenchyma raises the concern that intrathecal prophylaxis may not be effective and suggests that CNS imaging should be considered in patients with extranodal disease.

Adult↗
PubMed1999

Low-grade monoclonal Epstein-Barr virus-associated lymphoproliferative disorder of the brain presenting as human immunodeficiency virus-associated encephalopathy in a child with acquired immunodeficiency syndrome.

The association of the Epstein-Barr virus with human immunodeficiency virus-associated primary central nervous system lymphomas is well known. We describe a pediatric patient infected with human immunodeficiency virus who developed a lesion in the central nervous system that appeared to be histologically reactive and that proved to be an Epstein-Barr virus-associated monoclonal B-cell lymphoproliferative disorder by molecular analysis. An 8-year-old girl was diagnosed with vertically transmitted human immunodeficiency virus infection at age 5, for which she was treated empirically with a combination of zidovudine and didanosine. At the age of 7 years, during evaluation for entry into an antiretroviral protocol, a single hypodense frontal lobe lesion was identified by computed tomography. After unsuccessful treatment for presumed toxoplasmosis and progressive neurologic deterioration, a stereotactic brain biopsy was performed. Although the biopsy contained a polymorphic lymphoid infiltrate that appeared to be cytologically reactive, polymerase chain reaction and in situ hybridization studies revealed a monoclonal Epstein-Barr virus-associated B-cell lymphoproliferative disorder, which was reminiscent of polymorphic B-cell hyperplasia observed in the setting of immunosuppression following organ transplantation. Postoperative therapy included steroids and antiretroviral therapy. The lesion decreased slightly in size, and the child's neurologic status was relatively unremarkable for 5 months. Subsequently, she developed cytomegalovirus retinitis, progressive encephalopathy, and died with pancytopenia. This case represents a newly described manifestation of Epstein-Barr virus-associated lymphoproliferative disorder, a diagnosis that should be considered in patients with neurologic symptoms and immunodeficiency. In addition, this case exhibited histologic features reminiscent of posttransplant lymphoproliferative disease, a histologic pattern that to our knowledge has not previously been reported in the setting of acquired immunodeficiency syndrome.

AIDS Dementia Complex↗
PubMed1999

Hematopathology: integration of morphologic features and biologic markers for diagnosis.

The Revised European-American Classification of Lymphoid Neoplasms (REAL) represented a new paradigm for the classification of lymphomas. Although earlier classification schemes relied strictly on morphologic features or immunophenotype for the definition of diagnostic categories, the REAL classification emphasized that each disease was a distinct entity, defined by a constellation of clinical and laboratory features, i.e., morphologic and genetic features, immunophenotype, clinical presentation, and course. It also noted that the site(s) of presentation were often a signpost for important underlying biologic distinctions. The inclusion of clinical criteria for the definition of disease entities was one of the more novel aspects of the REAL classification. These principles of classification of lymphomas and leukemias also have an impact on diagnostic hematopathology. The REAL classification stresses that diagnoses are based on a multiparameter approach. Although morphologic features alone might suffice for some diagnoses, diagnostic accuracy and reproducibility are enhanced when immunophenotypic and genetic studies are also used. In addition, adequate clinical information is essential for some diagnoses, in particular the mature T-cell lymphomas and leukemias. The proposed World Health Organization classification of lymphoid and hematopoietic neoplasms incorporates these principles of classification and diagnosis.

Antigens, Neoplasm↗
PubMed1999

Mantle-cell lymphoma.

Mantle-cell lymphoma (MCL) is a lymphoproliferative disorder derived from a subset of naive pregerminal center cells characterized by a nodular or diffuse proliferation of atypical lymphoid cells with a monoclonal B-cell phenotype and coexpression of CD5. Two cytologic variants have been identified, typical and blastic. Typical cases show a proliferation of small to intermediately sized lymphoid cells with irregular nuclei and scarce cytoplasm. Blastic variants include a spectrum of intermediate to large cells with round or irregular nuclei and finely dispersed chromatin. These cases have a higher proliferative activity and a more aggressive clinical evolution. MCL is genetically characterized by 11q13 translocations and bcl-1 rearrangement. This alteration leads to a constant overexpression of cyclin D1, which plays an important pathogenetic role, probably deregulating cell-cycle control by overcoming the suppressor effect of retinoblastoma protein (Rb) and p27Kip1. Detection of cyclin D1 may be used as a highly specific marker of MCL because it is expressed in virtually all of these tumors, but in only a few reported cases of aggressive variants of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and a small percentage of cases of multiple myeloma. Aggressive variants have additional genetic alterations, including inactivation of p53 and p16INK4a tumor-suppressor genes. Clinically, MCL presents in elderly males with advanced disease and frequent extranodal involvement, particularly with involvement of bone marrow, gastrointestinal tract, and spleen. The clinical evolution is relatively aggressive, with poor response to conventional therapeutic regimens and a median survival duration of 3 to 4 years. Further studies are needed to define better new therapeutic strategies for the management of these patients.

Chromosomes, Human, Pair 11↗
PubMed1999

MIP-1alpha expression in tissues from patients with hemophagocytic syndrome.

Hemophagocytic syndrome (HPS) is a clinicopathologic syndrome that can be precipitated by a variety of causes and is characterized by a systemic activation of macrophages, which are induced to undergo phagocytosis. Chemokines play an important role in the inflammatory cell recruitment into tissues. We examined the expression of chemokines and cytokines in tissues exhibiting histologic evidence of HPS in a variety of settings: peripheral T-cell lymphoma, three patients; nasal T/NK cell lymphoma, one patient; subcutaneous panniculitis-like T-cell lymphoma, one patient; and chronic EBV infection, one patient. Compared with control tissues, we found elevated macrophage inflammatory protein-1alpha (MIP-1alpha) and interferon-gamma (IFN-gamma) expression, but not macrophage-derived chemotactic factor (MDC) or TNF-alpha, in tissues of patients with HPS irrespective of the cause or setting. MIP-1alpha can promote macrophage chemotaxis and IFN-gamma promotes macrophage activation. Elevated expression of IP-10 and monokine induced by IFN-gamma (Mig) was also detected in tissues exhibiting features of HPS, providing an explanation for the occurrence of chemoattraction of T-cells and NK cells. Immunohistochemical analysis of tissues with evidence of phagocytic activity in that site showed MIP-1alpha characteristically localized to endothelial cells of blood vessels and splenic sinuses, lymphocytes, and macrophages. These results provide evidence for MIP-1alpha chemokine expression in tissues from patients with HPS and suggest that MIP-1alpha may play an important role in the pathogenesis of the hemophagocytic syndrome.

Adolescent↗
PubMed1999

World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. A progress report.

The World Health Organization (WHO) classification has been developed under the joint auspices of the European Association for Hematopathology (EAHP) and the Society for Hematopathology (SH). First organized in 1995, the Steering Committee appointed 10 committees for T-cell and B-cell lymphomas and leukemias and myeloid and histiocytic tumors to develop a relevant list of diseases and establish definitions of each disease according to established criteria. The WHO classification uses the principles of the Revised European American Classification of Lymphoid Neoplasms (REAL), which defines each disease according to its morphologic features, immunophenotype, genetic features, postulated normal counterpart, and clinical features. The proposed classification was presented at the United States-Canadian Academy of Pathology meeting in 1997. The Steering Committee also appointed a Clinical Advisory Committee to ensure that the classification meets clinical needs and to resolve questions of clinical significance. The proposed WHO classification for lymphomas is similar to the REAL classification for lymphomas, with minor modifications and reassessment of provisional categories based on new data since 1994.

Hematologic Neoplasms↗
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

PTEN gene alterations in lymphoid neoplasms.

Recently, a novel phosphatase designated PTEN/MMAC1/TEP1 and located on chromosome 10q23.3 has been implicated as a new tumor suppressor gene in human cancer. Allelic loss and mutation of this gene has been reported in epithelial derived tumors, including breast cancer and prostate cancer, and in glioblastoma multiforme. The present study was designed to evaluate the potential involvement of PTEN in the pathogenesis of lymphoid neoplasms. We analyzed 27 hematopoietic cell lines (representing a variety of lymphoid lineages), 65 primary lymphoid tumors (including 24 lymphoblastic leukemia/lymphoma [LBL], 30 large B-cell lymphoma [LBCL], 7 Burkitt's lymphoma [BL], and 4 anaplastic large cell lymphoma [ALCL]), and 25 nonmalignant lymph node controls. Gene deletion and gross rearrangement were evaluated using Southern blot analysis, and mutations were studied by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) (PCR-SSCP) and sequencing. Six of 27 cell lines (22.2%) and 3 of 65 primary lymphomas (4.6%) contained alterations of this gene. A large homozygous deletion spanning exons 2 through 5 was detected in one LBL cell line, and two insertions potentially resulting in premature termination, were detected in a second LBL cell line. Nonconservative nucleotide variations were found in two other cell lines (one LBCL and one BL) and in one primary case of LBCL. In addition, two other cell lines (one BL and one myeloma) and two primary lymphomas, both LBCL, contained small deletions within intron 7. These deletions mapped to a poly-T-rich tract just 5' to the intron 7/exon 8 spice site. Their significance is unclear, as they may represent polymorphisms. Overall, our results suggest that abnormalities of the PTEN gene can contribute to pathogenesis in a small percentage of malignant lymphomas.

Cell Transformation, Neoplastic↗
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

Epstein-Barr virus in nasal lymphomas contains multiple ongoing mutations in the EBNA-1 gene.

We have described 5 major subtypes of Epstein-Barr virus (EBV) based on variations in EBNA-1 sequences. These include P-ala (identical to the prototype B95.8 virus), P-thr, V-pro, V-leu, and V-val. Normal individuals often carry multiple EBV subtypes, the most common being P-ala, whereas EBV-associated tumors examined to date always contain a single subtype, which only on rare occasion is P-ala. The primary hypotheses that these observations generate are as follows: (1) Each of these EBV subtypes are naturally occurring, and in normal individuals the multiplicity of subtypes results from multiple infections. (2) EBV subtypes in normal individuals are generated in vivo from a single infecting virus subtype by mutations in EBNA-1. The second hypothesis essentially excludes the possibilities that the nonrandom association of certain subtypes with lymphomas is secondary to the geographic distribution of EBV subtypes and, if proven correct, could provide strong support for a direct role of EBV in tumorigenesis. In this report, we provide evidence for the latter hypothesis. We show that the P-ala EBV subtype present in most nasal lymphomas undergoes and accumulates multiple mutations consistent with the generation of variant species of EBNA-1 in vivo. This phenomenon is similar to the generation of quasispecies in RNA viruses and is the first description of in vivo generation of subtypes in DNA viruses. In RNA-based viruses, including human immunodeficiency virus and hepatitis C virus, the emergence of quasispecies is linked to replication infidelity and significantly influences disease processes through its effect on viral tropism, the emergence of viruses resistant to the host defenses or to therapy, and pathogenicity. The present data thus raise important questions relating to the mechanisms whereby these mutations are generated in EBV and their relevance to the pathogenicity of EBV-associated lymphomas.

Genes, Viral↗
PubMed1998

Spectrum of AIDS-associated malignant disorders.

BACKGROUND: To clarify which types of cancer result from AIDS, we compared the cancer experiences of people with AIDS with those of the general population by matching population-based cancer and AIDS registries in the USA and Puerto Rico. METHODS: We used a probabilistic matching algorithm to compare names, birth dates, and, where available, social-security numbers of 98,336 people with AIDS and 1,125,098 people with cancer aged less than 70 years. We defined AIDS-related cancers as those with both significantly raised incidence post-AIDS and increasing prevalence from 5 years pre-AIDS to 2 years post-AIDS. FINDINGS: Among people with AIDS, we found 7028 cases of Kaposi's sarcoma (KS), 1793 of non-Hodgkin lymphoma (NHL), and 712 other cases of histologically defined cancer. Incidence rates among people with AIDS were increased 310-fold for KS, 113-fold for NHL, and 1.9-fold (95% CI 1.5-2.3) for other cancers. Of 38 malignant disorders other than KS and NHL, only angiosarcoma (36.7-fold), Hodgkin's disease (7.6-fold), multiple myeloma (4.5-fold), brain cancer (3.5-fold), and seminoma (2.9-fold) were raised and increasing significantly (p<0.02) from the pre-AIDS to the post-AIDS period. INTERPRETATION: Interpretation is complicated by screening and shared risk factors, such as sexual behaviour and cigarette smoking. However, our data indicate that AIDS leads to a significantly increased risk of Hodgkin's disease, multiple myeloma, brain cancer, and seminoma. Immunological failure to control herpes or other viral infections may contribute to these malignant diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Homozygous deletions at chromosome 9p21 involving p16 and p15 are associated with histologic progression in follicle center lymphoma.

Low-grade follicle center lymphoma (LGFCL) is characterized genetically by the t(14;18) translocation and an indolent clinical course. Histologic progression from LGFCL to an aggressive diffuse large B-cell lymphoma (DLCL) occurs in 60% to 80% of cases, and this transformation is associated with the accumulation of secondary genetic alterations. Using 10 polymorphic microsatellite markers spanning the chromosome 9p21 region harboring the p15 (p15(INK4B)/MTS-2/CDKN2B) and p16 (p16(INK4A)/MTS-1/CDKN2) tumor-suppressor gene loci, we analyzed 11 matched pairs of LGFCL and their corresponding progressed DLCL biopsies for loss of heterozygosity and homozygous deletions at 9p21. A comparative multiplex polymerase chain reaction assay was also used for the detection of homozygous deletions. Deletions were identified in 8 of the 11 cases studied (73%): 6 homozygous (54%) and 2 hemizygous (18%). The deletions were identified exclusively in the progressed DLCL biopsies. Immunohistochemical studies showed an excellent correlation with the results from the genetic analyses. Of the 9 matched pairs of LGFCL and progressed DLCL with interpretable immunohistochemical staining, 9 of 9 (100%) of the LGFCL showed diffuse reactivity for p16. Four of the 9 (44%) immunohistochemically evaluable cases of progressed DLCL showed loss of or, in 1 case, markedly diminished p16 expression. All 4 of these cases correspondingly showed homozygous deletions at 9p21. Five of the 9 progressed DLCL cases showed p16 expression and demonstrated retention of one or both 9p21 alleles by genetic analysis. This is the first longitudinal series examining sequential biopsy specimens of low-grade and progressed FCL for genetic loss at 9p21 encompassing the p16 and p15 loci. The high frequency and exclusive occurrence of deletions involving p16 in the progressed DLCLs suggests that genetic loss at 9p21 targeting p16 and/or p15 is an important secondary genetic event in the histologic progression of FCL.

Carrier Proteins↗
PubMed1998

Response during radiotherapy may be associated with outcome in mediastinal Hodgkin's disease.

A relationship between the rate of regression of lymphomas treated with chemotherapy and long-term outcome has been observed. This study was undertaken to determine if the rate of tumor regression during radiotherapy for mediastinal Hodgkin's disease is a predictor of in-field recurrence. Twenty-nine patients with early-stage Hodgkin's disease treated with radiotherapy alone as part of an NCI randomized trial had both a non-massive mediastinal component of disease and all requisite simulation and port films available for analysis. The histology was nodular sclerosis in all patients. Stage distribution was as follows: IA-1; IIA-17; IIB-8; IIIA1-3. The median age was 27 years and the median radiation dose was 4470 cGy. A mediastinal mass ratio was calculated from each patient's simulation and weekly port films by dividing the width of the mediastinal mass by the intrathoracic diameter at the level of the carina. Histopathologic correlation was also done to quantify the degree of tumor vs. sclerosis in the specimens. Univariate analysis and Cox proportional hazards analysis were used to study the association between several covariates (stage, sex, symptoms, extra-lymphatic disease, initial mediastinal mass ratio, age, dose, percent tumor in the specimen, and cumulative percentage of tumor regression) and time to in-field recurrence, as well as probability of any failure. Univariate analysis indicates that lower dose, higher percent tumor in the specimen, and lower cumulative percent regression are statistically significant predictors for in-field recurrence, as well as for any failure. By Cox regression analysis, cumulative percent regression is the sole factor independently associated with in-field recurrence (two-tailed P=0.04). The percent tumor in the specimen is the only factor similarly identified for time to any failure (two-tailed P=0.02). Histopathologic correlation suggests that patients with early stage mediastinal Hodgkin's disease who demonstrate a high percent tumor in the specimen may be at increased risk of failure. Patients with a low cumulative percent regression during radiotherapy appear to be at an increased risk of in-field recurrence.

Adolescent↗