Morphological and immunohistochemical investigation of non-Hodgkin's lymphoma combined with Hodgkin's disease

Twenty cases with a morphological picture highly suspicious for a combination of non-Hodgkin's lymphoma and Hodgkin's disease were investigated. The infiltrates of Hodgkin's disease differed from those of non-Hodgkin's lymphoma in their cellular component of Hodgkin and Sternberg-Reed cells and the irregularity in the fibre pattern. Based upon histological and immunohistochemical criteria the 20 cases were divided into three groups. Group 1 (n = 10) contained seven chronic lymphocytic leukaemias of B type, one lymphoplasmacytoid immunocytoma, and two centroblastic/centrocytic lymphomas. The non-Hodgkin's lymphoma components showed a monotypic immunoglobulin distribution pattern and/or leukaemic blood picture. Adjacent to the non-Hodgkin's lymphoma was typical Hodgkin's disease in which Hodgkin and Sternberg-Reed cells were positive for both immunoglobulin light chains and IgG and reacted with anti-CD15. Group 2 (n = 5) consisted exclusively of centroblastic/centrocytic lymphoma in combination with Hodgkin's disease in which the few Hodgkin and Sternberg-Reed cells were negative with anti-CD15 monoclonal antibody. Group 3 (n = 5) consisted of four chronic lymphocytic leukaemias of B type and one lymphoplasmacytoid immunocytoma. In these cases no combination with Hodgkin's disease could be diagnosed apart from the presence of partially CD15 positive Hodgkin and Sternberg-Reed cells. The following conclusions were drawn: anti-CD15 (LeuM1 and 3C4/C3D-1) can neither confirm nor exclude Hodgkin's disease since, while they do not detect Hodgkin and Sternberg-Reed cells in all cases of Hodgkin's disease, they do recognize Hodgkin and Sternberg-Reed cells in some B-cell lymphomas; anti-CD30 (Ber-H2) reacted with Hodgkin and Sternberg-Reed cells in all cases of Hodgkin's disease and also detected these cells in cases of non-Hodgkin's lymphoma.     

Diagnostic value of biochemical analysis of pleural effusions. Carcinoembryonic antigen and beta 2 microglobulin.

Pleural effusions from 105 patients with malignant and nonmalignant diseases were examined for tumor cells, content of CEA, beta2 microglobulin, ceruloplasmin, alpha2 macroglobulin, orosomucoid, lysozyme, and hexosaminidase. Only CEA and beta2 microglobulin determinations were of diagnostic value. CEA concentrations greater than 11 ng/ml were found only in malignant effusions. Beta 2 microglobulin values were increased in pleural effusions due to lymphoma or immune diseases. Measurement of CEA and beta2 microglobulin in addition to the cytologic examination could increase the diagnostic significance of the analysis of pleural effusions.     

Primary gastric malignant lymphoma. A morphological and immunohistochemical study of 38 cases

Thirty-eight cases of primary gastric malignant lymphoma were studied morphologically and immunohistochemically. The Working Formulation was used for classification of non-Hodgkin's lymphoma (1). The results indicated that 37 cases were non-Hodgkin's lymphoma while the remaining case was Hodgkin's disease. Thirty-three cases (89%) of non-Hodgkin's lymphoma were considered to be of B cell origin and 2 cases (5%) of histiocytic origin. No case was considered to be of T cell origin. We suggest that the majority of primary gastric malignant lymphomas are derived from follicular center cells, and that gastric plasmacytoma is not as rare as previously described.     

HLA-DR expression in B-cell non-Hodgkin's malignant lymphomas: a multiparameter flow cytometry study

Ten cases of reactive follicular hyperplasia and 31 cases of B-cell non-Hodgkin's malignant lymphoma were studied using multiparameter flow cytometry. A bimodal distribution for HLA-DR expression, but not for surface immunoglobulin or B cell-specific antigens CD19 and CD20, was observed commonly in mixed cell type and infrequently in non-mixed cell type B-cell malignant lymphomas. On the basis of HLA-DR distribution alone, 31 cases of B-cell malignant lymphomas of low, intermediate, and high grades could be separated into mixed and non-mixed cell types, with only two misclassifications (P = 0.0001). Exceptionally, one case of malignant lymphoma, follicular and diffuse, mixed-cell type had a unimodal HLA-DR distribution, and one case of malignant lymphoma, diffuse, large noncleaved cell type had a bimodal HLA-DR distribution. In all cases of malignant lymphoma, follicular, mixed-cell type studied, low HLA-DR was correlated with small cells, and high HLA-DR was correlated with large cells. In contrast, HLA-DR expression and cell size were not as directly correlated in cases of malignant lymphoma, diffuse, mixed-cell type. These observations suggest that most, but not all, cases of B-cell malignant lymphomas of the mixed cell type can be separated from other B-cell lymphomas on the basis of HLA-DR distribution.     

Hodgkin's disease coexistent with plasma cell dyscrasia.

We describe a case of Hodgkin's disease, mixed cellularity type, associated with nodal monotypic plasma cells and monoclonal serum gammopathy. Although plasma cells are often found in tissues involved by Hodgkin's disease and may be numerous, the occurrence of Hodgkin's disease with monotypic plasmacytosis and/or monoclonal serum gammopathy is rare. The simultaneous occurrence of Hodgkin's disease and monotypic plasma cell proliferation may represent a coincidental occurrence. However, previously we have described cases of Hodgkin's disease associated with B-cell non-Hodgkin's lymphoma, perhaps suggesting a relationship between the Reed-Sternberg and Hodgkin cells and B-lineage lymphoid cells. The case presented further extends these observations.     

Role of autologous CD4+ T cell clones in human B non-Hodgkin's lymphoma: aborted activation and G1 blockade induced by cell-cell contact.

This article describes the study of the functional relationship between auto-tumor-reactive CD4(+) T cell clones (TCC) and autologous malignant B cells. Four auto-tumor-reactive CD4(+) TCC were derived from tumor-infiltrating T lymphocytes (TIL-T) from a freshly isolated human follicular lymphoma by the following technique: total CD4(+) TIL-T were negatively purified by an immunomagnetic procedure, then CD4(+) TCC were obtained by limiting dilution in the presence of IL-2 and autologous non-irradiated follicular lymphoma cells as feeders. After expansion, these CD4(+) TCC were co-cultured with non-irradiated autologous malignant B cells. All four TCC were activated by B lymphoma cells and proliferated, as assessed by CD25 expression and cell cycle analysis. Activation and proliferation of B lymphoma cells were studied in response to activated CD4(+) T cells. Although all four TCC were able to induce B lymphoma cell activation (Ki-67 antigen induction and CD40 up-regulation), cells were subsequently blocked in G1 phase. Activation of B-NHL cells was mediated by TCR-HLA class II interaction, as shown by a blocking experiment using an anti-CD4 monoclonal antibody (mAb). Since anti-CD40 mAb with or without IL-4 did not induce proliferation of B lymphoma cells in contrast to normal B cells, we suggest that the blockade in G1 phase is due to the presence of abnormalities in B lymphoma cells. This is the first evidence that autologous reactive CD4(+) TCC can engage follicular lymphoma B cells to enter the cell cycle and induce an aborted activation stage.     

淋巴瘤血管内皮细胞人白细胞DR抗原和第Ⅷ因子相关抗原的表达

目的试图揭示人白细胞ＤＲ抗原（ＨＬＡ－ＤＲ）和第Ⅷ因子相关抗原（ＦⅧＲＡｇ）的表达规律,研究血管内皮细胞的生物学行为。方法应用ＨＬＡ－ＤＲ和ＦⅧＲＡｇ的抗血清,对３９例淋巴瘤中血管内皮细胞的功能异质性进行免疫组织化学及其形态定量研究,同时取新生儿、成人淋巴结及反应性增生淋巴结做对照。结果新生儿、成人淋巴结及反应性增生淋巴结内各类血管内皮细胞对ＨＬＡ－ＤＲ、ＦⅧＲＡｇ均呈阳性,其中高内皮后微静脉（ＨＥＶ）呈强阳性;Ｈｏｄｇｋｉｎ病和Ｔ细胞淋巴瘤中血管多数是ＨＥＶ样血管,内皮细胞均表达ＨＬＡ－ＤＲ及ＦⅧＲＡｇ;Ｂ细胞淋巴瘤中血管多数是毛细血管样血管,内皮细胞很少表达或不表达ＨＬＡ－ＤＲ,只表达ＦⅧＲＡｇ。结论说明Ｈｏｄｇｋｉｎ病和Ｔ细胞淋巴瘤中血管内皮细胞既参与免疫调节过程,又参与凝血过程;而Ｂ细胞淋巴瘤内血管内皮细胞只参与凝血过程,不参与免疫调节过程。     

抗人白细胞单克隆抗体1C34-5与正常及肿瘤组织或细胞的反应性

用免疫组化方法及EUSA测检研究抗人白细胞单克隆抗体1C34-5与正常及肿瘤细胞组织的反应性,发现1C34-5仅与正常的白细胞和淋巴造血组织来源的肿瘤细胞反应。在所观察的1例毛细胞白血病、10例恶性淋巴病,2例何杰金氏病的肿瘤组织均与1C34-5呈不同程度的阳性反应,而31例各种不同类型非淋巴造血组织来源的肿瘤均为阴性反应。浸润到肿瘤细胞间或邻近部位的淋巴样细胞也为阳性反应。此抗体在辅助鉴别形态学难以区分的小圆细胞癌和淋巴瘤的病理诊断中,将有一定意义。此外也为观察判断转移癌细胞分布及浸润程度,以及宿主抗肿瘤的免疫反应提供了一种新手段。     

Tuberculous pleural effusions: lymphocyte phenotypes in comparison with other lymphocyte-rich effusions

This study investigated whether the analysis of T cell subsets and of activation markers on T cells in pleural fluids can be helpful for diagnostic purposes in tuberculous pleurisy and other lymphocyte-rich pleural effusions. Pleural effusion fluids were obtained from 18 patients with tuberculous pleurisy (TB), 21 with effusions following radiotherapy (RT) for a malignant disease, and 11 with congestive heart failure (CHF). Lymphocyte subsets were analyzed by a battery of monoclonal antibodies using an immunoperoxidase method. The majority of the lymphocytes were CD3-positive T cells (TB, 86 +/- 7% of lymphocytes; RT, 81 +/- 8%; CHF, 84 +/- 12%). The ratios of CD4-positive helper-inducer to CD8-positive suppressor-cytotoxic T cells were higher than those reported for the peripheral blood but not significantly different between the study groups (TB, 3.3 +/- 1.9; RT, 2.8 +/- 1.4; CHF, 2.5 +/- 1.1). The activation marker studies revealed that only a few pleural T cells were positive for CD38, CD25 (interleukin-2 receptor), HLA-DR antigen, and OKT9 (transferrin receptor), the proportion of CD25-positive T cells being higher in TB and in RT than in CHF and the proportion of HLA-DR-positive T cells being higher in TB than in CHF (P less than 0.05). Significant differences were not observed relative to the natural killer-cytotoxic phenotypes staining positive for Leu-7 or for CD16. Thus, we concluded that phenotypic analysis of lymphocytes is of limited diagnostic usefulness to differentiate tuberculous from other nonmalignant effusions.     

Granulocyte and HLA-D region specific monoclonal antibodies in the diagnosis of Hodgkin''s disease.

Tissue sections embedded in paraffin and fixed in formalin from 32 patients with Hodgkin's disease, representing the major histological subtypes, were studied using two granulocyte specific monoclonal antibodies (Leu-M1 and 3C4) and an HLA-D region specific monoclonal antibody (TAL-IB5). Reed-Sternberg cells were stained with one or other of the antigranulocyte antibodies in the nodular sclerosing and lymphocyte depleted subtypes. Reed-Sternberg cells in all but three cases of mixed cellularity Hodgkin's disease were positive with both Leu-M1 and 3C4. One case stained with only Leu-M1, and two cases were consistently negative with both antibodies. HLA-DR was widely expressed in the Reed-Sternberg cells of all three subtypes. In the four cases of lymphocyte predominant Hodgkin's disease the multinucleated Reed-Sternberg cells did not stain with either antigranulocyte antibody but were strongly positive with anti-HLA-DR. Twenty five cases of non-Hodgkin's lymphoma, in which there were multinucleated giant cells resembling Reed-Sternberg cells, were studied in a similar way. These cases included pleomorphic T cell and B cell lymphomas, histiocytic lymphomas, and malignant histiocytosis of the intestine. In none of these did the multinucleated cells stain with either antigranulocyte antibody, but in most cases the multinucleated cells stained with anti-HLA-DR. In two cases of the tumour stage of mycosis fungoides dot like intracytoplasmic staining was shown in the tumour cells with both antigranulocyte markers. The monoclonal antigranulocyte antibodies Leu-M1 and 3C4 are of considerable value in both the diagnosis and the differential diagnosis of Hodgkin's disease and are particularly valuable in that they can be applied to tissue fixed in formalin and embedded in paraffin. Antibody to HLA-DR, while useful, is of less value.     

Morphologically normal, CD30-negative B-lymphocytes with chromosome aberrations in classical Hodgkin's disease: the progenitor cell of the malignant clone?

A recent study observed that numerical chromosome abnormalities in Hodgkin's disease (HD) are detected not only in morphologically abnormal Hodgkin/Reed-Sternberg cells, but also in a fraction of morphologically normal cells. However, the phenotypic constitution of these genetically abnormal, morphologically normal cells and their relationship to the malignant Hodgkin/Reed-Sternberg cells could not be established in the earlier cases studied, because of the low frequency of these cells. The present study investigated two cases of classical Hodgkin's disease containing a relatively large population of such apparently normal cells with aberrant chromosome copy numbers. The phenotype and their position within the developmental route of the malignant compartment were examined by a combined in situ hybridization and immunocytochemistry approach. Numerical abnormalities for chromosome 1 in one case and for chromosomes X, Y, and 1 in the other case were observed not only in CD30-positive Hodgkin/Reed-Sternberg cells, but also in CD30-negative, morphologically normal cells. It was shown that these genetically aberrant cells expressed the B-cell antigen CD19, thus confirming their B-cell nature. These studies indicate a relationship between the genome aberrations in these genetically abnormal, morphologically normal B-cells and the Hodgkin/Reed-Sternberg cells, suggesting that they are progenitor cells of the malignant cell fraction.     

A monoclonal antibody (OPT1) to T cells which is available for paraffin-embedded materials

A monoclonal antibody (MAb), OPT1, reactive with T cells in formalin-fixed, paraffin-embedded tissue sections, has been identified through immunization with activated T cells from peripheral blood lymphocytes (PBL). The antibody is an IgG1 antibody as demonstrated by the Ouchterlony technique. By cytofluorometric analysis, almost all CD3+ lymphocytes and only a few CD20+ lymphocytes of peripheral blood expressed the OPT1 antigen. Nonhematolymphoid cell lines were negative for OPT1 by the immunoperoxidase staining using acetone-fixed cell lines. On the contrary, peripheral T cells, cells of two T cell lines out of four and a part of the cells of one B cell line out of two were positive for OPT1. The immunoperoxidase staining of paraffin-embedded tissue sections revealed that most of lymphocytes in T cell areas of lymph nodes expressed OPT1 antigen. Some lymphocytes in both cortex and medulla of the thymus and erythroid precursors of the bone marrow were OPT1+. In the malignant lymphoma series, approximately 90% of T cell lymphomas and 6% of B cell lymphomas reacted with OPT1. None of the Reed-Sternberg cells nor Hodgkin cells in Hodgkin's disease were positive. Consequently, OPT1 may be useful for the diagnosis and study of malignant lymphomas and other related lesions.     

Monoclonal antibody L26: an antibody that is reactive with normal and neoplastic B lymphocytes in routinely fixed and paraffin wax embedded tissues.

Formalin fixed and paraffin wax embedded tissue from 85 well characterised cases of non-Hodgkin's lymphoma and Hodgkin's disease were studied using the avidin-biotin-peroxidase complex technique. Among the non-Hodgkin's lymphomas all cases of B cell lymphoma were reactive with L26, a monoclonal antibody which is as yet an unclustered pan B cell reagent, with the exception of pre-B cell acute lymphoblastic leukaemia and malignant lymphoma plasmacytic. Eighteen well characterised cases of T cell lymphoma, selected to include tumours previously shown to exhibit cross reactivity with antibodies to fixation resistant B cell related antigens, were similarly studied. Neoplastic cells in all but one case were unstained by L26. Twenty seven cases of Hodgkin's disease were also examined. In five cases all Reed-Sternberg cells and their variants were strongly stained by L26; only a proportion of Reed-Sternberg cells and their variants were recognised in a further five cases. Monoclonal antibody L26 promises to be a valuable reagent for the diagnosis of malignant lymphoma in routinely fixed and paraffin wax embedded tissues. Its advantage lies in its sensitivity and greater B cell specificity than any of the B cell related reagents currently available for the study of malignant lymphoma in fixed tissues.     

经典型霍奇金淋巴瘤组织中脆性三联组氨酸蛋白表达的意义

目的探讨脆性三联组氨酸（FHIT）蛋白在经典型霍奇金淋巴瘤（CHL）组织中的表达及其意义。方法对33例确诊的CHL组织采用免疫组织化学EnVision法检测其抑癌基因蛋白FHIT、造血系统肿瘤干细胞标记CDl33／AC133、CD34、B细胞标记CD20、T细胞标记CD3和癌基因蛋白c-erbB-2表达状况。结果90．9％（30／33）CHL组织中FHIT蛋白表达阳性,表达定位于肿瘤细胞的胞质、胞核和胞膜;对照组正常B、T淋巴细胞和B、T细胞淋巴瘤FHIT蛋白表达均为阴性;单核细胞、组织细胞以及树突状组织细胞均表达阳性。CDl33／ACl33、CD34、CD3、c-erbB-2表达均为阴性．2例CD20阳性。结论FHIT蛋白检测可作为诊断CHL的一个辅助指标。     

Expression of Fas and Fas ligand and apoptosis in tumor-associated lymphocytes and in tumor cells from malignant pleural effusions

The CD95 (APO-1/Fas)-Fas ligand (FasL) system is an important mediator of antitumor T cell cytotoxicity. The aim of the current study was to assess its significance in human cancer. Malignant effusions were selected as an environment allowing direct cell-to-cell contact in a fluid phase. Malignant pleural effusions collected from 23 patients with metastatic carcinoma of the bronchus, ovary, stomach or breast were examined by means of flow cytometry. The expression ofFas and FasL, probed with the appropriate antibodies, apoptosis of tumor cells and the characteristics of tumor-associated lymphocytes (TAL) were determined by TUNEL reaction in malignant and nonmalignant (control) effusions. All malignant cells had partially or completely lost the expression of CD95 and expressed an elevated level of FasL. In contrast, TAL obtained from malignant pleural effusions demonstrated a marked decrease in the expression of surface FasL and an increase in surface-bound Fas. The percentage of apoptotic malignant cells was significantly decreased, as compared to TAL and lymphocytes from nonmalignant pleural effusions. There were also differences in the expression of Fas and FasL among mononuclear cells from malignant and nonmalignant pleural effusions. The ability of TAL from malignant pleural effusions to induce apoptosis of K562 cells was diminished, as compared to peripheral blood lymphocytes. Taken together, these data suggest that tumor cells in the microenvironment of malignant pleural effusions can evade immune attack by downregulation of the CD95 receptor and by killing lymphocytes through the expression of FasL. These results confirm earlier reports which showed that lymphocytes from a tumor microenvironment appear to have a depressed cytotoxic action.     

B细胞特异性激活蛋白Pax-5在淋巴瘤组织中的表达

目的探讨B细胞特异性激活蛋白(BSAP)／Pax-5在淋巴瘤的表达情况及应用价值。方法按2001年WHO关于淋巴造血组织肿瘤分类标准收集102例弥漫性大B细胞淋巴瘤(DLBCL)、3例滤泡型淋巴瘤(FL)、3例黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT淋巴瘤)、1例结节性淋巴细胞为主型的霍奇金淋巴瘤(NLPHL)、10例间变性大细胞淋巴瘤(ALCL)和10例浆细胞瘤,用免疫组织化学LSAB法同步检测比较BSAP与CD20的表达情况。结果102例DLBCL全部表达CD20,100例表达BSAP,3例FL、3例MALT淋巴瘤和1例NLPHL BSAP和CD20全部阳性表达,10例ALCL、10例浆细胞瘤BSAP和CD20全部阴性表达。BSAP与CD20的表达差异无统计学意义。结论。BSAP/Pax-5是一种新的B细胞标记,阳性信号定位于细胞核,抗BSAP抗体在常规外科病理诊断工作中的应用价值有限。     

骨小细胞恶性肿瘤34例病理形态学研究

目的 研究骨小细胞恶性肿瘤(SCMT)的病理形态和免疫组化特点。方法 应用免疫组化SP法对34例SCMT进行组织学观察。结果 34例SCMT中22例为弥漫型非霍奇金恶性淋巴瘤，其中21例B细胞性，1例T细胞性；瘤组织表达CD45(LCA)、CD20(L26)或C1345RO(UCHL—1)。7例浆细胞肿瘤，其中5例为多发性骨髓瘤、2例为孤立性浆细胞瘤，表现为单一的不同分化程度的肿瘤性浆细胞；免疫组化示6例CD38( )。2例Ewing肉瘤显示排列密集、大小较一致的圆形细胞；肿瘤表达CD99和Vim。1例小细胞骨肉瘤，肿瘤由丰富密集的小细胞和网格状的骨样组织组成，瘤细胞Vim阳性。1例间叶性软骨肉瘤示富于血管的圆形或梭形细胞和透明软骨；瘤细胞表达Vim，软骨细胞表达S—100蛋白。1例小细胞癌示小细胞紧密片巢状排列，表达CK和EMA。结论 骨SCMT组织学类型各有不同的病理形态和免疫组化特征，结合临床和X线表现可作出正确的病理诊断。     

Flow cytometry as an adjunct to cytomorphologic analysis of serous effusions

The role of flow cytometry (FC) in the diagnosis of lymphoid lesions by fine-needle aspiration (FNA) is well established. However, studies evaluating the usefulness of FC in serous cavity effusions (SCE) are few. We performed a retrospective review of 115 consecutive SCE with concurrent FC analysis, comparing the provisional cytopathologic diagnosis (PCD), i.e., before the FC results were added, with final diagnoses as modified by subsequent FC immunophenotyping. The predominant clinical indication for the FC analysis was the presence of a spontaneous SCE in a patient with a history of malignant lymphoma. Three- or four-color analysis was performed using antibodies against CD45, CD71, CD33, CD22, CD19, CD20, kappa, lambda, CD5, CD3, and CD56. The PCD was benign in 47%, atypical in 16%, and malignant in 37% of cases. The latter category consisted mostly of malignant lymphoma (n = 32), but also included acute lymphoblastic leukemia (1 case), T-cell lymphoma/leukemia (2 cases), acute myelogenous leukemia (1 case), multiple myeloma (1 case), Hodgkin's lymphoma (1 case), sarcoma (1 case), and adenocarcinoma (4 cases). In 18 cases (16%), the PCD was later modified by the FC results from atypical/suspicious to benign (8) and from benign or atypical/suspicious to malignant (10 cases). The latter group included acute natural killer (NK) cell leukemia (1 case), chronic lymphocytic leukemia (1 case), mantle cell lymphoma (2 cases), follicular lymphoma (3 cases), angioimmunoblastic lymphoma (1 case), large cell lymphoma (1 case), and multiple myeloma (1 case). As expected, FC was noncontributory in cases of Hodgkin's lymphoma and nonlymphoid malignancies. In summary, immunophenotyping by FC modified the PCD significantly in 16% of SCE, permitting appropriate cancer staging and management. The above data underscore the importance of FC as an adjunct to cytomorphology in SCE.     

Hodgkin's and non-Hodgkin's lymphoma: spectrum of morphologic and immunophenotypic overlap.

Immunoperoxidase markers are useful and often essential in distinguishing among lymphocyte-predominant Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and lymphocyte-rich classic Hodgkin's lymphoma. However, it is becoming increasingly clear that these "entities" are closely related clonal B-lineage neoplasms that may intertransform and/or coexist. We hypothesized that, just as there are cases with morphologic overlap, there would also be immunophenotypic overlap that would be found when a series of such cases is studied in detail. Eight cases of lymphocyte predominant Hodgkin's lymphoma, eight cases of lymphocyte-rich classic Hodgkin's lymphoma, seven cases of T-cell-rich B-cell lymphoma, and four cases of large B-cell lymphoma with focal features of T-cell-rich B-cell lymphoma were examined by the immunoperoxidase technique for expression of CD3, CD15, CD30, CD20, CD57, epithelial membrane antigen, and Epstein-Barr virus latent membrane protein (EBV LMP). All eight of the lymphocyte-predominant Hodgkin's lymphoma cases had CD20+ lymphocytic and histiocytic cells and CD57+ rosettes; however, in two cases, occasional lymphocytic and histiocytic cells were also weakly positive for CD15, CD30, and EBV LMP. Among the eight lymphocyte-rich classic Hodgkin's lymphoma cases, CD15+ Reed-Sternberg (R-S) cells were found in seven; however, in three of these cases rare rosettes of CD57+ cells surrounded the R-S or lacunar cells. In one case of large B-cell lymphoma the malignant cells resembled R-S cells and were CD20+, EBV LMP+, CD30+, CD15-, and surrounded by rosettes of CD57+ T cells. The majority of the cases exhibited the "expected" immunophenotypic patterns; however, the exceptional cases that were found serve to confirm the interrelationship among these clonal B-lineage neoplasms.     

Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas

The purpose of the study was to determine in human malignant lymphomas the expression patterns of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), the primary, rate-limiting enzymes in the synthesis of NAD+. NAMPT is a potential biomarker for sensitivity to NAMPT inhibitors and NAPRT is a biomarker for the use of nicotinic acid as a chemoprotectant in treatment with NAMPT inhibitors. The NAMPT inhibitor, APO866, is currently in clinical phase II trials in lymphomas. The expression of NAMPT and NAPRT was investigated in 53 samples of malignant lymphomas (diffuse large B-cell lymphoma, follicular B-cell lymphoma, Hodgkin's lymphoma and peripheral T-cell lymphoma). The expression of NAMPT was generally high in the more aggressive malignant lymphomas, with >80% strong expression, whereas the expression in the more indolent follicular lymphoma (FL) was significantly lower (>75% moderate or low expression, p = 0.0002). NAMPT was very highly expressed in Hodgkin Reed-Sternberg cells in Hodgkin's lymphoma. NAPRT expression was more varied (p > 0.0001) with 30-50% low expression except for Hodgkin's lymphoma where 85% displayed low expression (p = 0.0024). In conclusion, FL are a promising target for NAMPT inhibitors whereas substantial subsets of malignant lymphomas especially in Hodgkin lymphoma may be suitable for a combination treatment with nicotinic acid and NAMPT inhibitors.