Centrocytic Lymphoma Research Articles

Immunophenotyping of cutaneous germinal center cell-derived lymphomas

Monoclonal antibodies were used to label cutaneous germinal center cell-derived lymphomas (CGCCL) obtained from 10 patients. According to the Kiel classification, they were classified into 2 types. Eight patients had centroblastic/centrocytic (CB/CC) lymphomas while 2 patients and centrocytic (CC) lymphomas. After monoclonal antibody labelling, the results were consistent with those of the clinical and morphologic analyses. Of the 10 cases, 9 were B1 positive, 6 were K positive, and 4 were λ positive. In 8 cases labeled with immunoglobulin, 6 were IgGFab positive, 2 were IgM positive and 8 were IgA negative. Five cases (CB/CC 3, CC 2) were both B1, K and IgG positive (γ K). Four cases CB/CC were both B1 and λ positive. Only one case (CB/CC) was both K and IgM positive (μ K). Two cases (CB/CC) were both λ and IgG positive (γ λ). The results indicate that B1, K and λ are the most important markers to phenotype cutaneous B-cell lymphomas. Our findings also show a higher percentage of γ K types in CGCCL as compared with Western countries.

Immunoglobulin and T Cell Receptor Gene Rearrangements in Lymphoproliferative Disorders

Thirty-one samples representing Hodgkin's and non-Hodgkin's lymphomas, angioimmunoblastic lymphadenopathy (AILD), and benign follicular hyperplasia in HIV infections were examined for rearrangements of the immunoglobulin (Ig) and T cell receptor (TcR) beta-chain gene loci. In 11 of 12 non-Hodgkin's lymphomas (classified as Burkitt lymphoma (2), centrocytic lymphoma (1), centrocytic-centroblastic lymphoma (5), centroblastic lymphoma (3], only rearranged Ig genes could be detected. The exceptional case was an unclassified high-grade lymphoma, which represented a rearrangement of the TcR beta-chain. We also examined DNA from lymphoid neoplasms in which the lineage of the malignant cell was still controversial. Rearrangement of the TcR could exclusively be demonstrated in all 3 cases of AILD. One Ig gene rearrangement and 4 TcR beta-chain rearrangements were found in 13 samples of Hodgkin's lymphomas (11 lymph nodes, 1 pleura effusion and 1 bone biopsy with proven infiltration). Examination of 3 cases of benign follicular hyperplasia in HIV infection represented one Ig rearrangement.

Triggering of neoplastic B cells via surface IgM and the cell surface antigens CD20 and CDw40. Responses differ from normal blood B cells and are restricted to certain morphologic subsets

By raising monoclonal antibodies (MAbs) against B cells, a number of cell surface molecules have recently been identified which after binding by their specific antibody can trigger B cells, either alone or in co-operation with antibodies to surface immunoglobulin (sIg). The anti-CD20 (Bp35) MAb IF5 can deliver a strong activation signal to resting normal B cells, and the anti-CDw40 (Bp50) MAb G28-5 can promote activated G1 B cells to enter S phase. These antibodies were tested for their functional effects in vitro on suspended cells from 17 follicle-center-cell (FCC) lymphomas, 5 cases of chronic lymphatic B-cell leukemia (B-CLL) and 8 cases of various histological types. Changes in cellular volume, RNA and DNA synthesis were compared with the results obtained with a polyclonal anti-mu [F(ab')2] antiserum, a MAb to surface IgM (AF6), 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and B-cell growth factor (low-molecular-weight BCGF). Our data reveal differences in the requirements for triggering of various B-cell subsets: cells from CLL responded strongly to TPA but not to anti-mu, which is a potent stimulator not only of normal B cells but also of cells from individual cases of FCC lymphomas. Our observations suggest that the differentiation stage of B-CLL cells is distinct from that of small resting B cells from peripheral blood. Centrocytic lymphomas could not be activated by any of the reagents. CD20-mediated triggering was seen in neoplastic B cells from only 4 of 30 cases, indicating that most B-cell neoplasias were not responsive to this activation pathway. In contrast, the anti-CDw40 MAb consistently stimulated DNA synthesis together with anti-mu or TPA in cells from FCC lymphomas, but not from CLL. Together, these results suggest that activation in different neoplastic B-cell subsets depends on distinct signal transduction mechanisms.

Primary malignant lymphoma of the colon and rectum. A histopathological and immunohistochemical analysis of 45 cases with clinicopathological correlations

Primary colorectal lymphoma accounts for only about 0.2% of large intestinal malignancies. Management difficulties are compounded by a lack of consistent pathological reporting and by the use of numerous different classifications. Forty-five cases of primary colorectal lymphoma are included in this study. The presenting features are indistinguishable from those of colorectal cancer. Seven patients had a history of chronic ulcerative colitis but no other predisposing factors were identified. Immunohistochemical studies showed that all tumours were of B-cell phenotype. Most tumours were difficult to characterize using standard pathological classifications such as Kiel, except for the 11 cases of malignant (multiple) lymphomatous polyposis, which were morphologically diffuse centrocytic lymphomas. Twenty-nine lymphomas showed the morphological and immunohistochemical features associated with tumours arising in mucosa-associated lymphoid tissue. These tumours showed variable but often marked polymorphism and we have used the term polymorphic B-cell lymphoma to describe them. Consistency was achieved between three observers as to whether these tumours were low or high grade, and grade was found to be prognostically important. A modified Dukes staging system was adopted and there was a trend for early stage to give prognostic advantage. This study supports the view that surgery should be the primary treatment for localized lymphoma of the gastrointestinal tract with radiotherapy and/or chemotherapy for advanced cases and for malignant lymphomatous polyposis.

Defective expression of MHC class I antigens is frequent in B-cell lymphomas of high-grade malignancy.

An unselected series of 66 immunohistologically proven B-cell lymphomas was examined for the expression of MHC class I antigens with monoclonal antibodies directed against non-polymorphic determinants of HLA-A,B,C heavy chain and beta 2-microglobulin. The tumors were classified according to the Kiel classification. No significant differences were observed in the reaction for HLA-A,B,C and beta 2m which may be indicative of a coordinate expression in our lymphoma series. In 37 cases (56%), all tumor cells exhibited strong staining for class I antigens as observed in normal B cells. The remaining 29 cases (44%) showed abnormally low or undetectable class I expression in varying tumor cell subsets; 13 cases were completely devoid of HLA-A,B,C. Twenty-two out of 30 lymphomas of high-grade malignancy but only 7/36 lymphomas of low-grade malignancy presented defective class I expression. This difference in proportion is highly significant (p less than 0.00002). Eleven of the 13 class I-negative lymphomas belonged to the group of high-grade malignancy. Centrocytic lymphoma, which has the poorest prognosis among the B-cell lymphomas of low-grade malignancy, was defective in 40% of the cases examined. The lymphoblastic type represented an exception within the lymphomas of high-grade malignancy as no defective expression was observed. In addition to the correlation between the high-grade malignancy and defective class I expression, defects occurred more frequently in lymphomas with an extra-nodal primary manifestation (p less than 0.05). The grade of malignancy, however, was not correlated with the primary site of the lymphoma.

Mitoses in Non-Hodgkin's Lymphomas: Frequency and prognostic relevance

The frequency of mitoses was investigated in 279 lymph node biopsies from untreated patients with non-Hodgkin's lymphomas. The data were correlated with histological subtypes and survival time. It could be shown that the frequency of mitoses increases parallel to the amount of large tumor cells, except for lymphoblastic varieties. The proliferative activity was not influenced by a plasmacytoid differentiation. The nodules of follicular centroblastic centrocytic lymphomas revealed more mitoses than did the diffuse lymphomas of a similar grade of malignancy which shows that the growth pattern must be considered when the frequency of mitoses is interpreted. Immuno- and centroblastic lymphomas exhibited no marked differences with regard to mitotic activity. If all lymphomas are subdivided into three groups according to the mitotic grade alone, three survival curves are obtained that differ significantly from each other. It is concluded, therefore, that the mitotic activity of malignant lymphomas is a useful prognostic parameter that, until now, has received unduly limited attention.

Immunologic cell markers of peripheral blood and lymph node lymphocytes in chronic lymphocytic leukemia

The immunologic phenotype of the lymphocytes of 100 patients with chronic lymphocytic leukaemia (CLL) was investigated. Peripheral blood lymphocytes (PBL) were examined in all cases; in 46 patients with lymphadenopathy, a lymph node was biopsied and the histologic and immunologic patterns were assessed: 24 had a lymphocytic-lymphoplasmocytoid histology and 22 the follicular variant of lymphocytic lymphoma (mantle zone lymphoma, MZL). For comparison, lymph node suspensions from 19 patients with non-leukemic centrocytic lymphoma (CCL) were also studied. Significant differences in the PBL immunologic features were found between stage 0 and stage I patients. The phenotype of the lymphocytes of patients with lymphocytic histology was similar to that of stage 0 CLL patients, whereas major differences were found between these patients and those with mantle zone histology. This enables these patients to be recognized easily on immunologic grounds.

Purine degradative enzymes in circulating malignant cells of patients with chronic B cell neoplasia.

Previous reports have shown that the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and ecto-5'-nucleotidase (5'NT), play an important role in the normal development of lymphocytes and that investigations of these enzymes are of value in defining subsets of lymphoid malignancies of T-cell origin. Pharmacological inhibition of one of these enzymes has been found to be an effective treatment for a few lymphatic neoplasia. We have studied the activities of the above enzymes in the circulating malignant cells of 25 patients with B-chronic lymphatic leukemia (B-CLL), four patients with B prolymphocytic leukemia (PLL), seven patients with leukemic centrocytic lymphoma (CC), 18 patients with hairy cell leukemia (HCL) and 16 patients with immunocytoma (IC). For comparison, the blasts of nine patients with 'common' acute lymphatic leukemia (cALL) and normal T (n = 12) and B (n = 8) cells were simultaneously investigated. Despite morphologic similarity, the leukemic cells of the chronic B cell malignancies demonstrate different enzyme patterns. B-CLL is characterized by very low activities of all the enzymes ADA, PNP and 5'NT. In the cells of HCL the highest values of PNP are found. The leukemic cells of IC are characterized by low levels of ADA but moderate levels of PNP and high levels of 5'NT. Thus some of the entities of B malignancies show typical enzyme patterns which might be of importance in defining maturation stages of the disease. The differences in these enzyme patterns can also be made use of in therapy with enzyme inhibitors such as deoxycoformycin.

Immunoelectron microscopic localization of immunoglobulin in B-cell lymphomas.

Subcellular localization of immunoglobulin (Ig) by immunoelectron microscopy was performed on 20 B-cell lymphomas of low- and high-grade malignancy. The efficiency in demonstrating Ig by pre-embedding technique depends on the antibodies used. F(ab')2 fragments of antibodies were more sensitive than both intact polyclonal and monoclonal antibodies in detecting cytoplasmic Ig. With immunoelectron microscopy Ig could be demonstrated in all cell types of B-CLL and LP-immunocytoma, even in some of the small lymphocytes in B-CLL. Thus, the presence of intracytoplasmic Ig has no diagnostic relevance in differentiating B-CLL from LP-immunocytoma. However, the amount of Ig in the tumor cells of LP-immunocytoma seemed to be greater than in B-CLL. Centrocytic lymphoma and centroblastic/centrocytic lymphoma could be differentiated by their different localization of Ig. In centrocytic lymphoma Ig was localized mainly on the surface membrane, whereas in centroblastic/centrocytic lymphoma moderate amounts of Ig could be detected in the rough endoplasmic reticulum and perinuclear space of the centroblasts and in roughly one third of the centrocytes. In malignant lymphomas of high-grade malignancy (ML centroblastic, ML immunoblastic, and ML lymphoblastic) Ig was localized mainly in the rough endoplasmic reticulum and sometimes in the perinuclear space.

Cluster differentiation antigen expression, proliferative activity and clinical stage in centroblastic centrocytic lymphomas.

Using a panel of B-cell antibodies recognizing clusters of leucocyte differentiation antigens, immunostaining patterns of eight reactive lymph nodes and 28 centroblastic/centrocytic and centrocytic lymphomas have been studied. Centroblastic/centrocytic and centrocytic lymphomas retained many of the B-cell differentiation antigens and neoplastic follicles partially recapitulated the staining patterns observed in reactive follicles. Centrocytic lymphomas usually expressed a heavy chain mantle zone-like phenotype. Nearly one-half of follicular lymphomas showed extension of neoplastic cells into interfollicular areas as evidenced by positivity for CD10 (common acute lymphoblastic leukaemia) and/or CD9 (immature B-cell) and CD23 (B-blast cell) antigens. Cases showing interfollicular involvement also manifested considerable phenotypic heterogeneity. Light chain restriction could not be used to determine interfollicular involvement because of the presence of many non-neoplastic cells. Most follicular lymphomas retained a polyclonal mantle around at least some neoplastic follicles and in no case was a monoclonal mantle seen. Most lymphomas (16/21) were diploid when examined by flow cytometry. Diploid tumours exhibiting interfollicular lymphomatous involvement had high proliferation (S + G2) fractions and these lymph nodes were usually derived from patients with widespread disease. Tumours containing a high percentage of cells in the G0/G1 phases displayed fewer B-cell differentiation antigens than tumours with low G0/G1 fractions.

Expression of the T1 (CD5, p67) surface antigen in B‐CLL and B‐NHL and its correlation with other B‐cell differentiation markers

The T1 surface antigen (CD5,p67) expression on blood lymphocytes (PBL) and lymphoid cells from lymph node biopsies (LN) from 31 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 79 with B non-Hodgkin lymphoma (B-NHL), was detected in 25 B-CLL (80 per cent) and in 11 B-NHL (13 per cent) belonging to the following histologic subtypes: lymphocytic of CLL type (DLWD) one case, lymphoplasmacytoid (DLWD) four cases, centrocytic (DLPD) five cases, immunoblastic (DH) one case. All B-CLL and the T1 + B-NHL were also tested with monoclonal antibodies against the Common Acute Lymphoblastic Leukemia Antigen, B cells (FMC7, FMC8, BA1, Y29-55), T cells (OKT11a), HLA-DR and HLA-DQ monomorphic determinants. All the B-CLL and the T1+ B-NHL were CALLA-, BA1+, Y29.55+. FMC7+ cells were detected in large numbers six B-CLL (three T1+ and three T1-) and in four centrocytic lymphomas. FMC8 reacted with 70 per cent of leukemias (where it stained 30 per cent of neoplastic cells) and with 8/9 T+ B-NHL. HLA-DR and HLA-DQ molecules were detected in 100 per cent and 90 per cent of cases respectively. In vitro treatment of HLA-DQ- or T1- B-CLL with phorbol ester TPA led to the expression of these antigens as well as of the receptors for Interleukin 2 and MLR3 activation antigen. Surface membrane Ig (SIg) was detected in 79 per cent of cases, its density measured by FACS analysis varied, even markedly, from case to case. Among the B-CLL, cells with high SIg content were either T1+ or T1- and more likely FMC7+. The SIg- cases were seven B-CLL (five T1+ and two T1-) and two B-NHL, in which, however, cytoplasmic IgM was detected. This study reveals the existence of four major B-CLL subgroups: T1- SIg-, T1+ SIg+, T1+ SIg+, T1- SIg+. It also indicates that the T1 antigen may be transitionally present during B-cell differentiation and that its expression may precede that of SIg as supported by the in vitro studies. In addition, the finding that some B-NHL are T1+ suggests that they derive similarly to the B-CLL from a common progenitor.

Alkaline phosphatase and gamma glutamyltranspeptidase in human lymphomas.

Alkaline phosphatase (AP) and gamma glutamyltranspeptidase (GGT) were studied in normal lymphoid cells and in 28 cases of human lymphomas (23 of non-Hodgkin's and 5 of Hodgkin's disease). The expression of AP was enhanced in several samples with a high proportion of mature B cells, particularly in centroblastic-centrocytic lymphoma, whereas tissues mainly composed of T cells always showed low levels of this enzyme. GGT levels were high in thymus, as well as in centroblastic-centrocytic lymphoma and other NHL, thus demonstrating no restriction to a particular cell lineage. Some B-cell neoplasms with cellular origin different from that of centroblastic-centrocytic lymphoma, such as chronic lymphocytic leukemia and centrocytic lymphoma, had low levels of both enzymes. The role of investigation with specific antibodies against these two enzymatic activities in the physiology of lymphoma cell membrane is discussed.

Mantle-zone lymphoma

We analyzed the distribution and immunologic phenotype of the neoplastic cells in eight cases of mantle-zone lymphoma. Although in all the cases the follicle centers appeared reactive on routine histologic examination, polyclonal staining for immunoglobulin was found in the follicle centers in only five of the eight cases; in the other three cases the follicle centers were monoclonal. In three cases, the immunologic phenotype was that of centrocytic (diffuse small cleaved cell) lymphoma: IgM+IgD+B1+B2+Ia+Tl+. In one case the phenotype was that of a follicular (centroblastic/centrocytic) lymphoma: IgG+B1+B2+Ia+CALLA+. In the other four cases, the phenotype was IgM+B1+B2+ or B2-Ia+; this phenotype can be seen in diverse B cell lymphomas. The phenotype of normal mantle-zone cells (IgM+IgD+B1+B2+Ia+) was not reproduced by any of the lymphomas. A mantle-zone pattern may be produced by either follicular or diffuse lymphomas of predominantly small cleaved cell type, and does not indicate an origin from the cells of the normal mantle zone.

Progress in the management of high risk non-Hodgkin's lymphomas. 10 years of experience of the 3rd Medical Department of Hanusch Hospital, Vienna.

An analysis of 173 cases of non-Hodgkin's lymphoma (NHL) admitted to our hospital from January 1973 to January 1983 is presented. Of the 173 cases, 124 patients suffered from NHL of high grade malignancy according to the Kiel classification (37 centroblastic lymphoma (CB), 30 immunoblastic lymphoma (IB), 43 lymphoblastic lymphoma (LB), 14 NHL high grade malignancy unclassifiable). In addition, 26 patients with secondary high grade malignant NHL were included in the analysis (14 secondary CB, 10 secondary IB, 2 secondary LB). Also investigated were 23 patients with anaplastic centrocytic lymphoma (CC) (20 primary CC, 3 secondary CC), an entity originally classified as low grade malignant lymphoma, but showing a poor outcome and need for aggressive therapy. Symptoms at presentation of all patients are described. Of the 173 patients, 71% had an advanced stage of the disease at the time of diagnosis (Ann Arbor stage III or IV). B-symptoms were observed in 81%. Extranodal involvement, (exceptive bone marrow involvement), determined by clinical examination was seen in 55%. Survival of patients changed significantly after replacing initial radiotherapy with aggressive chemotherapy (P less than 0.001). Improvement of survival statistics was due to the better outcome of patients with localized stages (Ann Arbor stages I and II) as compared to those with generalized disease (P less than 0.002). Prognostic factors influencing survival were elevation of lactic dehydrogenase (P less than 0.0001) and response to therapy (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Human B cell development. II. Subpopulations in the human fetus.

In man, during fetal development the B cell populations show distinct phenotypes at different tissue sites. The pre-B and B lymphocytes of the fetal liver and bone marrow express IgM and B cell markers, B1 (CD20) and BA-1 (CD24). These "early" cells are negative with a number of other reagents, anti-IgD, RFB4 (CD22), RFB6 (CD21), and RFA-2, which on the other hand recognize peripheral B cells. These peripheral B lymphocytes in the developing fetus are heterogeneous. The diffusely distributed B cells in the earliest lymph node samples, 16 to 17 wk of gestational age, and from 16 to 21 wk in the spleen, are strongly IgM+ (IgD+,RFB4+,RFB6+, and RFA-2+) but lack T cell-associated markers such as T1 (CD5, p 67,000 dalton equivalent of murine Ly-1) and Tü-33. In fetal lymph nodes, primary nodules develop around the follicular dendritic (FD) cells from 17 wk onward, and contain a virtually pure population of B cells; B1+,BA1+,RFB4+,RFB6+,RFA-2+, which simultaneously express IgM,IgD together with T1 (CD5), a T cell-associated antigen. A sizeable subpopulation of these IgM+,T1+ cells are also positive for Tü-33, another T cell-associated marker. In the spleen, the B cells of the IgM+,IgD+,T1+ type appear in smaller numbers and only relatively late around wk 22. These cells are diffusely distributed at first, and start accumulating around the small FD cell clusters as soon as these emerge about the 23rd gestational wk. At that time, the IgM+,T1+B cells can also be washed out from the peritoneal and pleural cavities. The T1+,IgM+B cells may represent the normal equivalent cells of B chronic lymphoid leukemia and centrocytic lymphoma, and appear to be the counterpart of Ly-1+,IgM+B cells in the mouse.

Prognostic information from cytogenetic analysis in chronic B- lymphocytic leukemia and leukemic immunocytoma

Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic lymphocytic leukemia (CLL), 29 had immunocytoma (IC), two had prolymphocytic leukemia, and one had centrocytic lymphoma; one was not subclassified. Cytogenetic studies after B cell mitogen stimulation showed that six patients had an extra chromosome 12 as the sole abnormality. Another ten patients had an extra chromosome 12 together with other abnormalities. One patient had dup(12). Fifteen patients showed clonal aberrations without +12. Eleven patients showed only normal metaphases, and 12 patients were not evaluated cytogenetically. The cytogenetic subgroup pattern did not distinguish between CLL and IC patients. There was no significant difference between the CLL and IC groups as regards clinical findings and prognosis. However, the cytogenetic typing proved to be of prognostic significance. Increasing numbers of chromosomal aberrations within the cell clone were significantly associated with a poorer prognosis, ie, with impairment of survival (P = .04) and therapy-free survival (P less than 10(-4]. Patients with complex karyotypes (at least clonal aberrations) showed the poorest survival (P = .007). Patients with +12 required treatment earlier than patients with a normal karyotype (P = .01) and patients with karyotypic changes other than +12 (P = .006). These latter differences were even more pronounced when only IC patients were considered (P = .005 and P = .002, respectively). A multivariate analysis revealed that +12 was as strong an indicator of poor survival as advanced Rai or Binet stages and a stronger predictor of therapy-demanding disease.

Prognostic Information From Cytogenetic Analysis in Chronic B-Lymphocytic Leukemia and Leukemic Immunocytoma

Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic lymphocytic leukemia (CLL), 29 had immunocytoma (IC), two had prolymphocytic leukemia, and one had centrocytic lymphoma; one was not subclassified. Cytogenetic studies after B cell mitogen stimulation showed that six patients had an extra chromosome 12 as the sole abnormality. Another ten patients had an extra chromosome 12 together with other abnormalities. One patient had dup(12). Fifteen patients showed clonal aberrations without +12. Eleven patients showed only normal metaphases, and 12 patients were not evaluated cytogenetically. The cytogenetic subgroup pattern did not distinguish between CLL and IC patients. There was no significant difference between the CLL and IC groups as regards clinical findings and prognosis. However, the cytogenetic typing proved to be of prognostic significance. Increasing numbers of chromosomal aberrations within the cell clone were significantly associated with a poorer prognosis, ie, with impairment of survival (P = .04) and therapy-free survival (P less than 10(-4]. Patients with complex karyotypes (at least clonal aberrations) showed the poorest survival (P = .007). Patients with +12 required treatment earlier than patients with a normal karyotype (P = .01) and patients with karyotypic changes other than +12 (P = .006). These latter differences were even more pronounced when only IC patients were considered (P = .005 and P = .002, respectively). A multivariate analysis revealed that +12 was as strong an indicator of poor survival as advanced Rai or Binet stages and a stronger predictor of therapy-demanding disease.

Metalophil histiocytes in non-Hodgkin's lymphomas particularly in malignant proliferations of B-lymphocytes.

The metalophil method for the demonstration of histiocytes was applied to 108 non-Hodgkin lymphomas diagnosed according to the Kiel classification. In 41 lymphomas the presence of histiocytes was assessed with the aid of the non-specific esterase reaction. The same procedures were performed on 12 lymph nodes with follicular hyperplasia and/or sinus histiocytosis. The number of histiocytes was estimated and graded from 0 to 3. A good correlation between the two methods was found. Dendritic histiocytes were typically absent in lymphocytic lymphomas (CLL type). The follicles were clearly delineated by the distribution of dendritic histiocytes in follicular centroblastic/centrocytic lymphomas. In diffuse centrocytic lymphomas a small to moderate number of slender dendritic histiocytes was seen (grades 1-2). In lymphoplasmacytic/lymphoplasmacytoid lymphomas and in diffuse centroblastic/centrocytic malignant lymphoma the majority showed a great number of pleomorphic dendritic histiocytes (grade 3). In high-grade malignant lymphomas (centroblastic, immunoblastic and lymphoblastic categories) either a high to moderate number of pleomorphic dendritic histiocytes was found or they were totally absent. The lack of histiocytes in centroblastic lymphomas was especially noteworthy. It is proposed that dendritic histiocytes proliferate or are attracted in malignant lymphomas by the presence of centrocytes, especially in combination with centroblasts and by the presence of plasmacytoid cells or their precursors. The frequent absence of dendritic histiocytes in high-grade malignant lymphomas may alternatively be explained by the loss of physiological properties in less differentiated cells.

Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas results of a prospective multicenter study by the Kiel Lymphoma Study Group.

Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas (NHL) was investigated in 1127 patients entering a prospective multicenter observation study. Survival of the 782 (69.4 per cent) patients with low-grade malignant NHL (lymphocytic lymphomas, predominantly B-CLL, LP immunocytoma, centrocytic lymphoma, centroblastic-centrocytic lymphoma) exceeded that of the 341 patients (30.2 per cent) with high-grade malignant NHL (centroblastic, immunoblastic, lymphoblastic lymphomas). Prognosis was best in centroblastic-centrocytic lymphoma and in B-CLL and least favorable in immunoblastic and lymphoblastic lymphomas. Survival of LP immunocytoma and centrocytic lymphoma patients was intermediate after 2 to 2.5 years of follow-up. Corresponding to histopathology, pattern of survival curves of low-grade malignant NHL (slow decline, no plateauing) differed from that of high-grade malignant NHL (rapid decline, subsequent plateauing). Prognosis of B-CLL was superior to that of LP immunocytoma. Stages I and II were more frequent in centroblastic-centrocytic lymphoma (21 per cent) than in LP immunocytoma (2.5 per cent) and centrocytic lymphoma (11 per cent). Ability of radiotherapy to induce stable complete remissions in stage III of centroblastic-centrocytic lymphoma indicates prolonged restriction of lymphoma to the lymphatic system. In immunoblastic and centroblastic lymphomas, stages I and II were diagnosed in 34 and 38 per cent of cases, respectively, but only in stage I/IE of centroblastic lymphoma prolonged remissions were achieved by radiotherapy. In advanced high-grade malignant NHL marked improvement of prognosis was solely possible by induction of complete remissions whereas in corresponding low-grade malignant lymphomas also partial remissions were prognostically relevant.

Cytophotometric Measurements of the DNA in Hodgkin Lymphomas and Non-Hodgkin Lymphomas

In smear preparation of lymph nodes excised from 36 patients with a malignant lymphoma the DNA content was estimated in different tumor cells following Feulgen staining by means of quantitative cytophotometric measurements. The tumors investigated included 11 Hodgkin lymphomas and various types of Non-Hodgkin lymphomas (altogether 25). Whereas the small lymphoid cells found in Hodgkin lymphomas show a diploid DNA content with a wide scattering, in the large mononuclear reticular cells (Hodgkin cells) as well as in Sternberg's giant cells only aneuploid DNA values are seen lying in the hyperdiploid, hypertetraploid and hyperoctoploid regions. DNA stemlines are found in the aneuploid regions, but in some cases they are missing. This indicates that we are dealing with malignant tumor cells. In Non-Hodgkin lymphomas with a low grade of malignancy (centrocytic-centroblastic lymphoma, centrocytic lymphoma, CLL) an aneuploid DNA content is found particularly in the large cells (centroblasts, lymphoblasts) with or without a DNA stemline. These cells must be considered as primary malignant tumor cells. In the immunoblastic lymphoma of high malignancy only aneuploid tumor cells are present showing a particularly intense DNA content in the large immunoblasts, whereas a DNA stemline is usually missing. The range of aneuploid values, the number of polyploid tumor cells and the presence or absence of a DNA stemline are important criterions in determining the degree of malignancy. By means of cytophotometric measurements of the DNA content in the tumor cells of malignant lymphomas it is possible to assertain the degree of malignancy and to establish an objective prognosis.