Non-Hodgkin's Lymphoma with Histological Features of Neoplastic Angioendotheliosis

Three cases of non-Hodgkin's lymphoma, B-cell type, identical histologically to so called neoplastic angioendotheliosis (NAE), are reported. All showed a rapidly progressive clinical course and were not properly diagnosed before death. The lymphoma cells were distributed in many vessels of systemic organs with a tendency to form aggregates. The primary sites in the three cases were probably the adrenal gland, lymph node, and spleen, respectively. In particular, in one case it was suggested that the lymphoma cells had spread from the adrenal tumor to other organs, showing the histological features of NAE. In the literature, the primary sites of NAE have been scarcely mentioned. However, gross tumors were present in some cases. In such cases, it is possible that the tumors could be the primary sites of NAE. We conclude that some non Hodg-kin's lymphomas can exhibit the features of NAE during their course, particularly in the terminal stages. Acta Pathol Jpn 42: 272-278, 1992.     

Expression of Functional Molecules in Non-Hodgkin's Lymphoma

It is well known that non Hodgkin's lymphoma (NHL) cells express various antigens which are normally involved in a variety of functions. In addition, NHL is diverse in its proliferative capacity. To investigate the relation between these factors and the clinical picture, 45 cases of NHL were studied by immunohistochemistry using snap-frozen materials obtained before therapy. Reactivities with 27 monoclonal antibodies were examined and the results were correlated with clinical findings. The expression of surface μ and CAM-1 in B-NHLs and CD25 in T-NHLs were significantly associated with bone marrow involvement. B-NHLs without expression of CD21(B2) and T-NHLs with CD25 were seen more frequently in cases with a LDH value of over 500 units/ml. The positivity rate of Ki-67 on B-NHLs was correlated with serum LDH value, NHL histologic classification, and overall survival. These data indicate that immunophenotyping and determination of the proliferative capacity of NHL are of value not only for confirmation of the histopathologic classification of the tumor but also for assessment of clinical behavior.     

B-cell Lymphoma with Vimentin-positive Cytoplasmic Inclusions

A 60-year-old woman complaining of cervical lymph-adenopathy was admitted to Keiyu General Hospital, Yokohama. Malignant lymphoma involving systemic lymph nodes and the bilateral tonsils was suspected by computed tomography. The biopsy diagnosis of the cervical lymph nodes was B-cell lymphoma, diffuse medium-sized cell type. The cleaved centrocytic lymphoma cells were immunoreactive for CD20 and CD22 but negative for immunoglobulins. Characteristically, a considerable number of neoplastic lymphocytes possessed eosinophilic round inclusions in the cytoplasm. The inclusions were green in color by Papanicolaou staining, whereas they appeared vacuole like in Giemsa-stained preparations. Ultrastructural study confirmed the presence of aggregates of intermediate-sized filamentous structures mainly in the perinuclear area. The rough endoplasmic reticulum and Golgi apparatus were poorly developed. Immunocyto-chemical staining using cytologic specimens and fresh-frozen sections disclosed that the inclusions were composed of vimentin filaments. Morphologic similarities to signet ring cell lymphoma are discussed. Acta Pathol Jpn 41: 473 479, 1991.     

Non-Hodgkin's lymphoma in the first two decades

Summary The histopathologic and anatomoclinical features of 211 cases of non-Hodgkin's lymphoma (NHL) were reviewed and each case reclassified according to Lukes-Collins, Kiel and Rappaport criteria. Immunologic determination of cell phenotype in 63 cases as well as assessments of immunoglobulin and lysozyme by immunoperoxidase in 48 cases, permitted a precise definition of cell lineage on a functional basis and showed a high degree of predictability of immunologic phenotype of lymphoma cells by conventional morphology. The results of immunologic cell typing and immunoperoxidase studies were consistent with functional schema of Lukes-Collins and Kiel. True histiocytic proliferations, (9 cases) showed biologically different behavior from malignant lymphoma (ML), by a high incidence of extralymphatic (skin and soft tissue) presentation, rapid course, and frequent conversion to histiocytic leukemia. Fifty-two percent of studied ML cases were categorized morphologically as B-cell line proliferations, 36.7% as T-cell line and 6.9% as undefined group (ML U type). The ratio of T-cell to B-cell malignancies was 11.4. The convoluted type lymphoma was characterized by a high incidence (70%) of anterior mediastinal presentation, high incidence (over 60%) of hematologic and CNS involvement, and a high probability of testicular relapse, especially late. In contrast to malignancies of the T-cell line, B-cell proliferations tended to be localized below the diaphragm, and the most common anatomic location of lymphoma growth appeared to be the gastrointestinal tract, where small and large noncleaved follicular center cell types predominated. The nodular lymphoid hyperplasia in the vicinity of intestinal lymphoma and lack of secretory component within enterocytes were other substantial findings in abdominal B-cell malignancies. Among immunoblastic proliferations, the B-cell type was found to predominate over T-cell and was characterized as highly aggressive disease with a relatively common marrow infiltration. A low anatomic stage of disease and a favorable outcome were closely related to small cleaved type of follicular center cell lymphoma, which comprised only 1.5% of the patients studied. The less defined and morphologically heterogeneous group formed ML U, which in over 95% of patients converted to acute lymphocytic leukemia. This joint analysis of primary leukemic and non-leukemic NHL patients disclosed striking differences in anatomic presentation and natural history of disease between T, B and null cell proliferations versus related cytologic types.Supported by Cancer Center Support (CORE) Grant CA 21765 from the National Cancer Institute, Grant IN 99-E from the American Cancer Society and by ALSAC     

R-CHOP方案治疗B细胞非霍奇金淋巴瘤与CHOP方案对比的Meta分析

目的 以Meta分析的方法来评价利妥昔单抗联合CHOP方案治疗B细胞性非霍奇金淋巴瘤的疗效。方法 计算机检索维普数据库、中国知网、万方数据库、pubmed数据库等,检索利妥昔单抗联合化疗治疗B细胞性非霍奇金淋巴瘤的随机对照试验,并手工检索相关会议记录及纸质文献,应用国际Cochrane协作网的系统评价方法对所得数据进行质量评分,进行资料提取后,采用RevMan5.3软件进行Meta分析。结果 共检索到14个随机对照试验,共包括2433例患者,异质性检验P＞0.1,基线具有可比性,选择固定效应模型分析所得结果显示R-CHOP方案化疗组的完全缓解率高于单纯CHOP化疗组（RR=1.3,95%CI为1.3~1.41),差异有统计学意义（P＜0.05）;R-CHOP方案总有效率高于CHOP组（RR=1.32,95%CI为1.22~1.42）,差异有统计学意义（P＜0.05）;其不良反应与对照组比较,差异无统计学意义（P＞0.05）。结论 R-CHOP方案相对CHOP方案治疗B细胞性非霍奇金淋巴瘤来说具有更高的完全缓解率和总有效率,进一步证明其治疗效果需开展更多的随机对照试验。     

Paraffin section immunohistochemistry. I. Non-Hodgkin''s lymphoma

Reagents that recognize antigens on lymphoid cells in fixed and wax-embedded sections have been applied to a series of cases of non-Hodgkin's lymphomas. The panel consisted of MB1, 4KB5 (CD45r), LN1, L26 and MB2 which recognize antigens expressed predominantly on B-lymphocytes; UCHL1 and MT1 which recognize antigens expressed on T-lymphocytes and myeloid cells; antibodies recognizing the non-lineage antigens LeuM1 (CD15), BerH2 (CD30), anti-EMA; anti-lysozyme and MAC 387 which detect antigens present on some macrophages; and finally TAL1B5 (class II MHC), CAM 5.2 (low molecular weight cytokeratin) and PD7/26 + 2B11(CD45). Two hundred and four cases of non-Hodgkin's lymphoma have been studied, of which 158 had been fully characterized on frozen sections. The series was biased towards high-grade (n = 108) and T-cell (n = 44) tumours and these were largely prospectively accrued. It was found that discrimination between B-cell and T-cell lymphomas can be reliably achieved using these reagents and that a small panel (CD45, L26, MB2, MT1, UCHL1) is adequate for this purpose. Using the full range of reagents it is not possible to subdivide cases into groups that correspond with morphological subtypes of lymphoma. Although paraffin section immunohistochemistry is of value, the diagnosis of lymphoproliferative disorders must still be based upon the assessment of well fixed, carefully prepared tissue sections using conventional tinctorial methods.     

Case 8: T-Cell Lymphoma with Large Multilobated Nuclei

The vestibular nerve of patients with Meniere's disease and vascular cross-compression syndrome of the root entry zone due to the antero-inferior cerebellar artery was studied. All patients underwent vestibular neurectomy using the retrosig-moid approach, which permits the removal of a long nerve segment. CA were found in the cytoplasm of astrocytes that had not shown signs of degeneration at the central portion of the vestibular root entry zone. No membrane intervened between CA and the surrounding cytoplasm, which was rich in filaments, in particular near the CA, and poorly equipped with other organelles. CA were round or oval inclusions measuring 10–12 μm in diameter. The matrix of the CA was composed of low-density amorphous material, with irregular masses displaying a medium density. A network of randomly oriented filaments and bilaminar, osmiophilic lipid fragments with the same structure and thickness of myelin layers were embedded in the matrix. The CA rich in bilaminar fragments were recognizable also at low magnification for their high electron density. In the astrocytic cytoplasm, near the CA, round or oval-shaped, electron-dense bodies with a multilamellar structure were often visible. These results confirm the hypothesis that CA may contain degenerating myelin embedded in a microen-vironment rich in glucose polymers and that CA could be an indicator of neurodegeneration.     

18例鼻咽恶性淋巴瘤临床病理分析

报告18例鼻咽部非何杰金恶性淋巴瘤,大多属中、高度恶性,预后较差。80%患者血清中EB病毒-VcA-IgA阴性,与鼻咽癌有明显差异。     

Paraffin-immunohistochemical Analysis of 26 Non-Hodgkin's Malignant Lymphomas n the Endemic Area of Human T-cell Leukemia Virus Type 1

A study was conducted to evaluate the usefulness of paraffin immunohistochemistry for histopathological classification of non Hodgkin's malignant lymphomas (NHML). The phenotypes of lymphoma cells and other cells were examined using 11 monoclonal and 3 polyclonal antibodies by the ABC method on paraffin-embedded tissue sections of 226 cases of NHML, comprising 94 B cell lymphomas (B ML) and 132 T cell lymphomas (T-ML). In 219 NHML cases (96.8%), lymphoma cells reacted with more than one of these antibodies. A set of MB 1, Mx pan B, L26, LN 1, LN 2 and antiimmunoglobulin light chain antibodies characterized each subtype of B MLs, categorized according to the Kiel classification. Mantle-zone lymphoma (MzML) was added as one subtype. L26 stained the largest number of B MLs (82.8%). B cell chronic lymphocytic leukemia (B CLL) was labeled most frequently by MB 1. MzML was characterized by reactivity of lymphoma cells with LN 2 and by the appearance of monoclonal immunoglobulin light chain along the cell membrane. Follicle center cell lymphomas were stained by LN 1 and LN 2, although a small number of proliferating cells were labeled by LN 1 in B CLL, MzML and the im-munocytoma lymphoplasmacytic/cytoid variant. MT 1 and/or UCHL-1 showed various degrees of reactivity with the cell membranes of lymphoma cells in 94.8% of T-MLs. Among the T cell pleomorphic lymphomas of Suchi and Lennert, the adult T cell leukemia/lymphoma type, defined by stippled heterochromatin distribution and peculiar huge cells, reacted selectively (p<0.05) with anti phospho-kinase C antibody. Anaplastic large cell T-ML reacted with a set of Ber H2, LN 2 and Leu Ml. In T zone lymphomas without hyperplastic follicles, angioimmuno-blastic lymphadenopathy with dysproteinemia type T-ML, lymphoepithelioid cell lymphomas and some pleomorphic lymphomas comprising clear large lymphoma cells, there were many intermingling B cells, and their constitution varied. In some lymphoblastic lymphomas of both the T cell and B cell type, phenotypes of T cells and B cells were expressed. Consequently, it was shown that paraffin immunohistochemistry was useful for the practical histopathological diagnosis of NHML even in the area where human T cell leukemia virus type 1 is endemic.     

Expression of Histone Deacetylases in Diffuse Large B-cell Lymphoma and Its Clinical Significance

Background: Histone deacetylase inhibitors are a new class of drugs used in treatment of malignant tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, and it accounts for more than 40% of all B-cell lymphomas. In this study, we aimed to determine the expression patterns of histone deacetylases (HDACs) in DLBCL, to examine whether HDAC expression patterns differ among cases, and to assess whether these findings have clinical significance.Materials and methods: We selected 91 cases of DLBCL diagnosed at St. Vincent Hospital, The Catholic University of Korea, from 2001-2012. We performed a pathology slide review and collected clinical data including age, sex, tumor site, survival time, and mortality. Immunohistochemical analysis was performed using primary antibodies for HDACs, including HDAC1 and 2 of class I, HDAC4 and 5 of class IIa, and HDAC6 of class IIb. Expression site was determined to be nuclear, cytoplasmic, or both. Staining intensities were graded as low and high. We assessed correlations between HDAC expression levels and clinical data and survival analysis.Results: Of the 91 cases examined, 46 (50.5%) were men and 45 (49.5%) were women. Most of the patients were elderly, and 74 (81.3%) cases were older than 46 y. Forty-six (50.5%) cases showed lymph node involvement, and 45 (49.5%) cases showed lymphoma at extranodal sites. In nodal lymphoma, staining was strongly positive for HDAC2, whereas staining was weak or negative for HDAC4; however, there was no significant correlation with survival. But nodal lymphoma cases with high nuclear expression of HDAC2 and nodal lymphoma cases with high nuclear expression of HDAC2 and low nuclear expression of HDAC4 showed significantly shorter survival times compared with other cases.Conclusions: High nuclear expression of HDAC2 may play an important role in survival of DLBCL patients, especially in those with nodal lymphoma, which is associated with a shorter survival time. Our results may have important implications for treatment of DLBCL by epigenetic regulation.     

Image Analysis in Non-Hodgkin's Lymphoma

Abstract

Morphometry allows an objective method of assessing various cell features that are relevant in the subtyping of non Hodgkin's lymphoma (NHL). A wide variety of morphometric parameters that quantify features such as nuclear size and shape can be obtained with fully automated or interactive computerized image analysis. Most of these parameters rely on simple measures of area and perimeter, whereas others, especially those describing shape, use complicated mathematical formulas. Certain parameters have been found to be useful in specific situations; for example, the identification of cells of mycosis fungoides and Sézary syndrome is aided by the nuclear contor index. The application of morphometry in the subtyping of NHL is reviewed. Examples of cytologic preparations are given to illustrate theuse of nuclear size parameters to distinguish small, mixed, and large cell subtypes of follicular NHL. Large cell lymphoma and irnrnunoblastic sarcoma are categorized by nuclear area and shape, nucleolar area, and the standard deviation of nuclear-cytoplasmic ratio. Morphometric analysis is a useful method to subtype difficult cases of malignant lymphoma, particularly in identifying the controversial category of mixed cell lymphoma. (The J Histotechnol 15:263-276, 1992)     

Flow Cytometry in the Diagnosis of Non-Hodgkin's Lymphoma (NHL)

Abstract

In recent years, flow cytometry has become an important adjunct to light microscopy in the diagnosis of malignant lymphoma. Flow cytometric techniques are useful in distinguishing benign from malignant lesions and in determining the lineage and stage of differentiation of a neoplastic infiltrate. Certain immunophenotypic antigen profiles are characteristic of specific neoplasms, whereas other profiles are useful as prognostic indicators of outcome. In this review, we present details of the flow cytometric analyses that we perform on suspected lymphoid malignancies, including methods of gating, criteria that we have found useful in distinguishing benign from malignant processes, details of antibody panel selection for two color studies, and common pitfalls in the use of flow cytometry in the clinical laboratory. Highlights of new areas of investigation in the study of malignant lymphomas are presented. By utilizing flow cytometric techniques, these recent scientific advances can be rapidly integrated into routine patient care. As with any specialized diagnostic technique, flow cytometric data must always be integrated with the morphologic and clinical features of each case. (The J Histotechno 1 15:219-227, 1992)     

Development of angioimmunoblastic T-cell lymphoma after treatment of diffuse large B-cell lymphoma: a case report and review of literature

Cases of diffuse large B-cell lymphoma (DLBCL) arising after the initial diagnosis of angioimmunoblastic T-cell lymphoma (AITL) and DLBCL synchronous with AITL have been reported. To date, there is no report on the subsequent development of AITL in patients with DLBCL. Here we presented a rare case of AITL developing six months after the initial diagnosis of DLBCL. In order to investigate the clinical and molecular features of patients with AITL and DLBCL, we also reviewed the literature on AITL patients developing DLBCL, and patients with composite AITL and DLBCL.     

Expression of cytotoxic molecules in intestinal T-cell lymphomas

Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from αβ intraepithelial T-lymphocytes. Since these lymphocytes may contain cytotoxic molecules, the question of whether this also holds true for ITCL arises. Twenty ITCL cases were examined for the presence of granzyme B, perforin, and T-cell-restricted intracellular antigen (TIA-1)/granule membrane protein of 17 kD (GMP-17). Two molecules with restricted expression in cytotoxic cells, granzyme B and perforin, were detected by immunocytochemistry and by in situ hybridization with an isotopically labelled RNA probe, respectively. Immunocytochemistry was also performed with the antibody 2G9, which recognizes two molecules, one expressed by cytotoxic cells (TIA-1) and the other found in granulocytes and cytotoxic cells (GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neoplastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectively, of ITCL, but not in the tumour cells of the control group, which consisted of intestinal B-cell lymphomas (five cases) and CD8-negative peripheral nodal T-cell lymphomas (six cases). At least one of these molecules was expressed in the tumour cells of all ITCL cases. 2G9 proved to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cases, but also found in high numbers of neoplastic cells in positive cases. In conclusion, ITCL appears to show cytotoxic differentiation in all cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithelial αβ cytotoxic T-lymphocytes. © 1997 John Wiley & Sons, Ltd.     

The demonstration of B-cell, T-cell and myeloid antigens in paraffin sections

The monoclonal antibodies MB1 and MT1, which detect B cells and T cells respectively, have been applied to human lymphoid tissues. The distribution of staining within paraffin sections was compared with that observed using frozen sections and was found to be identical. The antibodies were then applied to paraffin sections of 19 B-cell lymphomas and 10 T-cell lesions in which full immunophenotyping had been performed. The B lymphomas all consisted of a large majority of MB1 positive cells with a variable infiltrate of small MT1 positive lymphocytes. The T cell lesions consisted of MT1 positive cells with few MB1 positive cells except in residual B cell areas of lymph nodes. In paraffin sections from cases of Hodgkin's disease anti-Leu M1 identified Reed-Sternberg cells and their variants and MB1 and MT1 showed a similar distribution of B cells and T cells to that demonstrated in previous studies using frozen sections. The results show that MB1 and MT1 are useful markers for B and T cells in routinely fixed paraffin embedded tissue. In conjunction with anti-Leu M1 they provide a valuable panel of antisera for the examination of lymph nodes and other biopsies when frozen tissue is not available.     

Electron Microscopic Analysis of Lymphocyte Nuclei in Non-Hodgkin's Lymphoma

Ultrastructural studies of normal and neoplastic lymphocytes are presented that qualitatively and quantitatively assess the central cell organelle currently used by surgical pathologists in the classification of non-Hodgkin's lymphoma, the nucleus. Events occurring during normal lymphocyte transformation can be used to appreciate essential mechanisms involved in producing the appearance of the nucleus as seen by microscopy. Quantitation of nuclear subcompartments by morphometric image analysis reveals that determination of nuclear size is primarily due to the ribonucleoprotein materials distributed between condensed chromatin masses, the interchromatinic (euchromatin or nuclear matrix) region. Furthermore, such investigations show that amounts and distribution of condensed chromatin in lymphocyte nuclei cannot be adequately assessed from routine histologic sections. Ultrastructural morphometric analysis of representative cases of the principal subtypes of NHL indicates that the atypical morphologic appearance of neoplastic lymphocytes results from a complex interplay between total amounts of condensed chromatin in nuclei and the size of individual aggregates of condensed chromatin, one or both of which may be abnormal in NHL. Abnormalities of interchromatinic materials are also likely involved in ordering the gross appearance of the nucleus. Understanding of both the dynamic capabilities of the nucleus, and the organization of and interplay between the various subcompartments of this organelle will be helpful in improving the classification of NHL by surgical pathologists.