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N L Harris

Publications and source records attributed to N L Harris.

At least 73 records · Page 4Linked to original sources

Myeloperoxidase detection by three-color flow cytometry and by enzyme cytochemistry in the classification of acute leukemia.

In the classification of acute leukemia, the presence of myeloperoxidase (MPO) within the leukemic blasts indicates myeloid leukemia. Previous studies compared enzyme cytochemistry (EC) or flow cytometry (FC) with immunocytochemistry, in detecting MPO. Our study is the first direct comparison of EC with 3-color FC in a large group of acute leukemias. We studied 26 cases of acute myeloid leukemia (AML) and 4 cases of B-precursor acute lymphoblastic leukemia (B-ALL). Classification was according to the French-American-British criteria. The cells were analyzed for MPO expression by 3-color FC after cell permeabilization followed by staining with anti-MPO antibody. For FC, the blasts were defined by a combination of light scatter characteristics and dim CD45 expression. Concordance between EC and FC was seen in 27 of 30 cases (23/26 AML and all B-ALL), including all AML cases of M1, M2, M3, and M4 subtypes. In 1 of 4 AML-MO and 2 of 5 AML-M5a cases, FC demonstrated the presence of MPO in 8%, 86%, and 94% blasts; EC detected none. Three-color FC may be more sensitive than routine EC in demonstrating the presence of MPO in AML cases and may offer the advantage of multiparametric analysis.

Acute Disease↗

World Health Organization Classification of lymphomas: a work in progress.

The World Health Organization (WHO) publishes classification handbooks for all neoplastic diseases. The last WHO Classification of leukemias and lymphomas was published in 1976. Since that time, through cytogenetics and molecular biology, it has been shown that many hematopoietic neoplasms are associated with a unique genetic profile. Similarly, the development of widely available and routinely applied monoclonal antibodies has allowed the identification of a unique immunophenotypic profile for most leukemias and lymphomas. These techniques have permitted the recognition of a number of distinct disease entities, and also enhance both diagnostic accuracy and reproducibility. The 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 covering T-cell and B-cell lymphomas and leukemias, myeloid and histiocytic tumors. The committees were asked to develop a list of diseases within their topic area, and to establish definitions of each disease according to established criteria. The WHO Classification uses the principles of the R.E.A.L. Classification, which defines each disease according to its morphology, immunophenotype, genetic features, postulated normal counterpart, and clinical features. Morphologic and clinical variants of individual diseases are discussed in the text, and their use is optional. The proposed classification was presented at the USCAP meeting in 1997, the site of the first joint meeting of the EAHP and SH. The presentation was followed by an open forum attended by EAHP and SH members. 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 R.E.A.L. Classification for lymphomas, with minor modifications and reassessment of provisional categories based on new data since 1994.

B-Lymphocytes↗

Workshop report on Hodgkin's disease and related diseases ('grey zone' lymphoma).

Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare cases. Lack of clear-cut diagnostic criteria represents a problem for both the pathologist and the clinician. To delineate this 'grey zone' between classical Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) and to develop criteria for classification of such cases, 12 expert hematopathologists each submitted one to five borderline cases to a workshop. Cases were reviewed and classified at a multiheaded microscope and criteria were established for the diagnosis of questionable cases. Well established entities such as classical Hodgkin's lymphoma, anaplastic large-cell lymphoma and TCRBCL were defined more strictly and cases with unusual morphology or antigen expression could be identified. A distinctive subset of cases representing mediastinal large B-cell lymphomas with features of Hodgkin's lymphoma was identified.

Diagnosis, Differential↗

The many faces of Hodgkin's disease around the world: what have we learned from its pathology?

In the past decade there have been many advances in our understanding of Hodgkin's disease. Among the most important is the discovery that the Reed-Sternberg cell is a lymphoid cell, in most cases a B cell, and that it is clonal, and thus a true lymphoma, deserving of a name change, to 'Hodgkin's lymphoma' (HL). Based on a combination of immunophenotype and morphology, the R.E.A.L. Classification recognizes two main types of HL: classical types (nodular sclerosis, mixed cellularity, lymphocyte-rich classical HL, and lymphocyte depletion) and nodular lymphocyte predominance type (NLPHL), which probably represent distinct biological entities. The immunophenotype and genetic features of both classical HL and NLPHL have been defined. These are useful in the subclassification of HL and in distinguishing HL from two recently-described, aggressive lymphomas that were in the past often diagnosed as HL: anaplastic large-cell lymphoma, T-cell type (ALCL), and T-cell/histiocyte-rich large B-cell lymphoma (T/HRBCL). Epstein-Barr virus has been detected in approximately 40% of the cases of classical HL, and is clonal, suggesting that this virus may play a role in the pathogenesis of at least some types of HL. The frequency of HL varies in different populations, and the frequency of EBV-positive HL appears to be inversely related to the overall frequency of HL in a given population. Thus, it is possible that its presence may simply reflect the prevalence of EBV-infected B cells in the individual. Despite the advances of the past ten years, many questions remain to be answered, and these will provide the challenges of the next decade.

B-Lymphocytes↗

Precursor B-Lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma: a report of four cases and review of the literature.

Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy.

Adult↗

Absence of cyclin D1 protein expression in splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a recently recognized primary splenic lymphoma. SMZL can be associated with peripheral lymphocytosis, in which some cells have a villous morphology (splenic lymphoma with villous lymphocytes [SLVL]). Several recent studies suggested involvement of the bcl-1 locus and/or the cyclin D1 gene, located on chromosome 11q, in SMZL/SLVL. Translocation t (11;14) is associated with rearrangement of the bcl-1 locus and overexpression of the cyclin D1 gene. Both the translocation and cyclin D1 protein expression are characteristic of mantle cell lymphoma (MCL) and are rare in other lymphoid neoplasms; thus, their detection is useful in the diagnosis of MCL. Because the differential diagnosis of low-grade lymphoma in the spleen can be difficult, it is important to assess the frequency of cyclin D1 expression in SMZL to determine its usefulness in differential diagnosis from MCL. We analyzed the expression of cyclin D1 nuclear protein in paraffin sections using an immunoperoxidase technique in 17 cases diagnosed as SMZL. In eight cases, the presence of cyclin D1 mRNA was also assessed by Northern blot analysis. None of the 17 cases of typical SMZL showed expression of cyclin D1 mRNA or protein. In contrast, four cases used as controls showed either expression of cyclin D1 protein or mRNA or both. We conclude that assessment of cyclin D1 protein expression can be useful in distinguishing SMZL from MCL involving the spleen.

Aged↗

[Reproducibility and prognostic value of histopathological classifications of malignant lymphomas. Prolegomena for the 1st international classification proposed by WHO. Group of the non-Hodgkin's Malignant Lymphoma Classification Project].

Different histopathologic classifications have been used in the study of malignant lymphomas. The clinical relevance (reproducibility, prognostic value) has not been precisely studied. The "non-Hodgkin's lymphoma classification project" has been organized to study a cohort of 1,403 cases in 9 sites around the world consisting of consecutive patients seen between 1988 and 1990 in order to have a good follow-up. The reproducibility of the up-dated Kiel and the ILSG (REAL) classifications between the 5 visiting expert hematopathologists was pretty good, at least 85% for the majority of the entities. According to survival curves, the lymphomas can be stratified in 4 different groups. Comparison with the international prognostic index demonstrate that for therapeutic strategy both histopathology and index should be used. The results bring a good support to the project of the WHO to propose the first international classification of lymphomas based on both forme classifications.

Age Factors↗

Genotator: a workbench for sequence annotation.

Sequencing centers such as the Human Genome Center at LBNL are producing an ever-increasing flood of genetic data. Annotation can greatly enhance the biological value of these sequences. Useful annotations include possible gene locations, homologies to known genes, and gene signal such as promoters and splice sites. Genotator is a workbench for automated sequence annotation and annotation browsing. The back end runs a series of sequence analysis tools on a DNA sequence, handling the various input and output formats required by the tools. Genotator currently runs five different gene-finding programs, three homology searches, and searches for promoters, splice sites, and ORFs. The results of the analyses run by Genotator can be viewed with the interactive graphical browser. The browser displays color-coded sequence annotations on a canvas that can be scrolled and zoomed, allowing the annotated sequence to be explored at multiple levels of detail. The user can view the actual DNA sequence in a separate window; when a region is selected in the map display, it is highlighted automatically in the sequence display, and vice versa. By displaying the output of all of the sequence analyses, Genotator provides an intuitive way to identify the significant regions (for example, probable exons) in a sequence. Users can interactively add personal annotations to label regions of interest. Additional capabilities of Genotator include primer design and pattern searching.

Base Sequence↗

Posttransplant lymphoproliferative disorders: summary of Society for Hematopathology Workshop.

Twenty cases of posttransplant lymphoproliferative disorders arising in solid organ allograft recipients (18 patients) or bone marrow allograft recipients (2 patients: 1 autologous; 1 allogeneic) were selected for presentation at the Society for Hematopathology Workshop. In the course of the Workshop discussions, based both on the submitted cases and the combined experience of the participants, it was possible to agree on several distinctive categories of PTLD. These include (1) early lesions, (2) polymorphic posttransplant lymphoproliferative disorders (PTLDs), (3) monomorphic PTLDs (B- and T-cell lymphomas), (4) plasmacytoma-like lesions, and (5) T-cell-rich large B-cell lymphoma/Hodgkin's disease-like lesions. Monomorphic lesions should be classified according to a recognized classification of non-Hodgkin's lymphoma, although specified in the report as PTLD. Polymorphic lesions should be carefully evaluated for clonality; by immunophenotyping; and, if necessary, analysis of antigen-receptor and Epstein-Barr virus (EBV) genomes. Minimal pathological evaluation should include routine morphology, immunophenotyping on fresh tissue (flow cytometry or frozen section), and preservation of tissue for molecular genetic analysis. Analysis of the presence of EBV can be useful in establishing whether early or equivocal lesions represent PTLD (EBV+) or unrelated processes, but is not required in most cases. The pathologist can make an important contribution to the management of patients with PTLD by providing a complete diagnostic evaluation of the biopsy specimens (this is the least expensive part of the care of a transplant patients, not a place to try to cut costs) and making sure the attending physicians understand the special issues in management of PTLD.

Bone Marrow Transplantation↗

Principles of the revised European-American Lymphoma Classification (from the International Lymphoma Study Group).

The International Lymphoma Study Group has proposed a consensus classification for lymphoid neoplasms. Lymphoid neoplasms are defined as distinct biological entities, based on a combination of morphologic, immunophenotypic, genetic, and clinical features. Each distinct disease may have a range of histologic grade and clinical aggressiveness. Although many distinct diseases can now be recognized, three of them (follicular lymphoma, diffuse large B-cell lymphoma, and Hodgkin's disease) account for the majority of the cases seen in Europe and the USA. Recognition of distinct disease entities is essential in order to develop and test effective therapies.

Europe↗

BCL-1 (PRAD-1/cyclin D-1) overexpression distinguishes the blastoid variant of mantle cell lymphoma from B-lineage lymphoblastic lymphoma.

The blastoid variant of mantle cell lymphoma (MCL-BV) can occur de novo or can represent a morphologic transformation of MCL associated with aggressive clinical disease. Its cytologic appearance is very similar to that of lymphoblastic lymphoma (LBL) because of its characteristic nuclear features and high proliferative rate. To assess the usefulness of antibodies to cyclin D-1 (BCL-1/ PRAD-1), CD99 (12E7), CD34, and TdT in distinguishing between MCL-BV and LBL in formalin-fixed, paraffin-embedded tissue, we studied from the Stanford data base 10 cases originally diagnosed as B-lineage LBL, 5 MCL-BVs, 2 cases thought likely to represent MCL-BV, and 2 blastic lymphomas whose morphology and immunophenotype were indeterminate. Six (60%) of 10 LBLs stained with CD99, as opposed to none of 7 MCL-BVs. Four (40%) of 10 LBLs reacted with CD34, as compared with none of 7 MCL-BVs. Eight (89%) of nine LBLs were positive for TdT, but all of the four MCL-BVs tested were negative. In contrast, the anti-cyclin D-1 antibody stained the nuclei of all of the MCL-BVs and none of the LBLs tested. On the basis of our evaluation, the probable MCL-BV cases were considered to be definite MCL-BV. Of the indeterminate cases, one was considered to be LBL, whereas we felt that the other represented MCL-BV. We conclude that staining formalin-fixed, paraffin-embedded, high-grade lymphomas with anti-cyclin D-1 antibody is useful in confirming the diagnosis of MCL-BV, whereas positive reactions with CD99, CD34, and particularly TdT are more characteristic of LBL.

12E7 Antigen↗

Expression of the retinoblastoma protein in low-grade B-cell lymphoma: relationship to cyclin D1.

The product of the retinoblastoma tumor-suppressor gene (pRB), a nuclear phosphoprotein that regulates transcription factors such as E2F, is involved in cell cycle control and differentiation. Its activity is regulated by phosphorylation; the underphosphorylated form inhibits transcription whereas the highly phosphorylated form is inactive. Cyclin D1 and its associated kinase (CDK 4/6) phosphorylate pRB in vitro, and therefore are thought to contribute to the regulation of pRB function. To examine the effect of cyclin D1 overexpression on pRB in primary tumor tissue, we studied pRB expression in low-grade B-cell neoplasms, with particular regard to mantle cell lymphoma, which is characterized by cyclin D1 (bcl-1) overexpression. pRB expression was studied by immunostaining with a well-characterized anti-pRB antibody; the phosphorylation status of pRB was examined by immunoblots; and the functional binding capacity of pRB was examined by in vitro binding to adenovirus E1A protein. We studied 3 reactive lymph nodes, 28 low grade B-cell lymphomas, 4 cases of hairy cell leukemia (HCL) and 3 plasmacytomas. Reactive lymph nodes showed intense pRB staining of germinal centers, with strongest (2+) staining in the large cells (centroblasts) of the proliferating (dark) zone and weak or no staining of small lymphocytes, including those of the mantle zone. In B-chronic lymphocytic leukemia (B-CLL) (4 cases), follicular lymphoma (3 cases) and mucosa-associated (MALT) lymphoma (3 cases) strong (2+) pRB staining was limited to centroblasts in reactive and neoplastic follicles and occasional proliferation centers, with only faint staining of small lymphoid cells. In contrast, 15 of 16 cases of mantle cell lymphoma showed strong (1-2+) staining of most cells; one blastoid mantle cell lymphoma showed only faint pRB staining. All cases of (HCL) and plasmacytoma showed strong pRB staining. Although most lymphomas with strong pRB expression were cyclin D1(+), three cyclin D1(+) cases showed only weak pRB expression (1 B-CLL, 1 blastoid mantle cell, 1 unclassifiable low grade B-cell lymphoma). Conversely, of the 4 pRB(+) HCLs and 3 pRB(+) plasmacytomas, only 1 of each was cyclin D1(+). pRB appeared to exist primarily in the underphosphorylated (fastest migrating) form on Western blot, despite the fact that cyclin D1 was complexed to CDK4, a form in which it normally phosphorylates pRB. In addition, pRB appeared to be unmutated, because it bound normally to the adenovirus E1A protein and showed nuclear localization by immunostaining. We conclude that most cases of mantle cell lymphoma, HCL, and plasmacytoma show high levels of pRB in contrast to follicle center lymphoma and small lymphocytic lymphoma; however, pRB expression does not appear to be consistently related to cyclin D1 overexpression. The pRB appears to be unmutated and underphosphorylated, and therefore should be in its active form. Our data from primary lymphoma tissue suggests that overexpression of cyclin D1, whereas tumorigenic, does not lead to pRB loss or hyperphosporylation. Thus, the mechanism by which cyclin D1 contributes to tumorigenesis and the significance of the restricted expression of pRB in low-grade lymphoid neoplasms remain to be determined.

Amino Acid Sequence↗

Primary tracheal non-Hodgkin's lymphoma. A case report and review of the literature.

BACKGROUND: Primary tracheobronchial non-Hodgkin's lymphoma (NHL) is an uncommon occurrence. The authors report a patient who presented with primary tracheal NHL, the sixth such patient described in the literature. METHODS: Using a MEDLINE search, 41 additional patients presenting with symptomatic primary or secondary tracheobronchial NHL were identified. The characteristics, management, and outcome of these patients are described. RESULTS: Patients with NHL of the upper respiratory tract present with dyspnea, wheezing, and cough, and frequently are misdiagnosed as having asthma. The majority of patients have additional sites of intrathoracic disease with tracheobronchial involvement occurring in the setting of advanced or relapsed NHL. Low grade histology is seen most commonly in patients with primary tracheal NHL. Several patients demonstrate the typical histologic features of mucosa-associated lymphoid tissue. Surgery, chemotherapy, and radiation therapy have been used alone or in combination for treatment. The outcome of these patients does not appear different from that observed in patients with lymphomas of similar histology and stage that do not involve the tracheobronchial tree. CONCLUSIONS: Thoracic surgeons, pulmonologists, and oncologists should recognize that NHL can rarely be confined to the trachea or bronchi. NHL should be considered in the differential diagnosis of airway obstruction, because it represents a highly treatable malignancy.

Antineoplastic Combined Chemotherapy Protocols↗

Hodgkin's disease presenting as a solitary bone tumor. A report of four cases and review of the literature.

BACKGROUND: Hodgkin's disease (HD) rarely presents as a solitary bone tumor. Fewer than 20 such cases have been reported in the English literature; many of these were reported prior to the development of immunohistologic markers for HD and T- and B-cell lymphomas. In this report, we describe four cases of HD that presented as a localized solitary mass in bone; the diagnosis was confirmed by immunohistochemical studies in all cases. METHODS: The biopsy specimens of four cases identified in our files were studied by conventional histopathology and immunohistochemistry. Clinical data and follow-up information were obtained for all patients. RESULTS: Three cases presented as a localized, solitary mass in the ilium and one case in the vertebra (T12). Three patients were female and one male. The average age was 43 years. Three of the patients presented with lower back pain without constitutional symptoms. All had solitary osteoblastic lesions. All four cases were diagnostic problems, and the diagnosis was confirmed in each case only after finding lymph node involvement. Bone biopsies showed fibrosis and a mixed inflammatory infiltrate with rare atypical cells. All four patients were subsequently found to have nodal involvement by HD. The histology of the associated nodal disease was mixed cellularity in two cases and nodular sclerosis in two. On immunohistochemical staining, the neoplastic cells in all cases expressed CD15 and CD30 and lacked CD45 and other B- and T-cell antigens. Three patients who were treated for HD are alive and well, 1, 6, and 14 years later. CONCLUSIONS: Although rare, HD should be considered in the differential diagnosis of solitary bone lesions. Most patients who present with apparently solitary HD of bone prove to have nodal involvement. Long-term survival is possible with aggressive treatment.

Adult↗

Cell kinetic study of thymic epithelial tumors using PCNA (PC10) and Ki-67 (MIB-1) antibodies.

We performed an immunohistochemical cell kinetic study with monoclonal antibodies to proliferating cell nuclear antigen (PCNA)-PC10-and Ki-67-MIB-1-on 62 thymic epithelial tumors, to evaluate whether there is correlation between the proliferation indices of the neoplastic epithelial cells and histological subtype, stage, and risk of relapse. The 62 cases of thymic epithelial tumors were classified as medullary thymoma (4 cases), composite (mixed) thymoma (17 cases), organoid thymoma (predominantly cortical) (11 cases), cortical thymoma (10 cases), well-differentiated thymic carcinoma (18 cases), and poorly differentiated thymic carcinoma (2 cases). Labeling indices were expressed as percentage of epithelial cells with positive nuclear immunostaining by random counting of 1,000 epithelial tumor cells, using an oil immersion 100 x objective. PCNA labeling indices were consistently higher than those of Ki-67, and they correlated with each other. Well-differentiated thymic carcinoma showed higher labeling indices (3.11% +/- 3.53%) by Ki-67 antibody compared with the medullary type (0.60% +/- 0.07%) (P < .05) but there were no statistically significant differences between the other histological subtypes. Stage IV cases showed higher PCNA labeling indices (PCNA: 11.07% +/- 7.35%, Ki-67: 6.86% +/- 5.87%) than cases of the other stages (P < .05), but there were no statistically significant differences in either labeling index between the other stages. The number of patients who relapsed was too small to permit meaningful correlation between labeling indices and relapse. Our results indicate that the differences in biological behavior of the different histological subtypes of thymic epithelial tumors may be in part explained by differences in tumor growth fraction. Analysis of a larger group of patients will be required to determine whether proliferation fraction as determined by this method can be used to predict outcome in individual cases.

Adult↗

CD5+ extranodal marginal zone B-cell (MALT) lymphoma. A low grade neoplasm with a propensity for bone marrow involvement and relapse.

Three cases of extranodal marginal zone B-cell lymphoma (low grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] type) in which the neoplastic B cells expressed the CD5 antigen are reported. The patients included 2 men and 1 woman, aged 44, 62, and 77 years. In all three cases, the histologic features were typical of marginal zone/MALT lymphoma, with reactive follicles, marginal zone (centrocyte-like) cells, and plasma cells. Pseudofollicles, prolymphocytes, and paraimmunoblasts were absent. In all cases, lymphoma from one or more sites expressed monotypic immunoglobulin (2 IgM kappa, 1 IgM lambda), pan B cell antigens and CD5. Two of 3 cases expressed CD43; one case expressed CD23. No case showed overexpression of the bcl-1 protein, cyclin D1. Interphase cytogenetic analysis revealed trisomy 3 in one of two cases examined. The two male patients presented with lymphoma in the ocular adnexa. One of them had marrow involvement, cervical lymphadenopathy and peripheral blood involvement at presentation; 24 months later, he developed a relapse in subcutaneous tissue. The second patient had marrow involvement 3 years later, at the time of recurrence of his orbital disease. The third patient presented with lymphoma at the base of the tongue. She subsequently developed lymphoma involving the left upper eyelid and right lacrimal sac and duct, the marrow, and the nasopharynx between 63 and 95 months after initial presentation. All of these patients presented with disease involving sites in the head and neck and all had multiple relapses or recurrences with bone marrow involvement at the time of presentation (1 case) or at relapse (2 cases). The presence of CD5 may be a marker for cases of MALT lymphoma with a tendency for persistent or recurrent disease, for dissemination to the marrow and other extranodal sites, and for leukemic involvement of the peripheral blood.

Adult↗

Immunohistochemical detection of p53, bcl-2, and retinoblastoma proteins in follicular lymphoma.

Mutations of p53 have been suggested to be involved in the histologic transformation of follicular lymphoma, but the role of the retinoblastoma (RB) gene, another tumor suppressor gene, in lymphomagenesis has not been established. To determine the roles of these tumor suppressor genes and their relationship with the anti-apoptotic bcl-2 gene in follicle center lymphoma, the immunohistochemical expression of p53, bcl-2, and RB proteins was correlated with cytologic grade in 50 cases of follicular lymphoma, and the results were compared to 23 cases of diffuse large B-cell lymphoma. The results showed that only 2 of 25 grade 1 follicular lymphoma were p53-positive compared to 16 of 25 grade 3 cases (P <.0001). A significantly lower number (13 of 25) of grade 3 follicular lymphomas expressed bcl-2 compared to grade 1 cases (23 of 25) (P <.004). Eight of 14 bcl-2-negative follicular lymphomas expressed p53, compared with 10 of 36 bcl-2-positive cases (P = .1). Twenty-four of 25 grade 3 follicular lymphomas showed 2+ to 3+ staining for RB protein compared to 9 of 21 grade 1 cases (P <.0002). Expression of p53 protein correlates significantly with higher cytologic grade in follicular lymphoma. Similar to earlier studies of breast cancer and lymphoma, there appears to be an inverse relationship between p53 and bcl-2 expression in follicular lymphoma. Inactivation of the retinoblastoma gene does not seem to be involved in the histogenesis of follicle center lymphoma or diffuse large B-cell lymphoma.

Antibodies↗