Histologic subtypes and survival of Chinese patients with non-Hodgkin's lymphomas

The histologic subtypes and survival of 840 Chinese patients with non-Hodgkin's lymphoma (NHL) were reviewed. All cases were classified according to the Rappaport and Kiel systems and the Working Formulation (WF). A low incidence of nodular/follicular lymphomas (12%) was observed. The most common histologic subtypes were diffuse histiocytic, diffuse centroblastic, and diffuse large cell lymphomas, according to Rappaport, Kiel, and the WF, respectively. A high proportion (24%) of the cases were unclassifiable, according to Kiel, because of the precise terms of the classification. The "favorable"-prognosis NHL, according to Rappaport, or the low-grade NHL, according to Kiel and the WF, had a more indolent clinical course. However, except for the nodular mixed (Rappaport) or follicular mixed (WF) lymphomas which appeared to behave like the more aggressive NHL, a plateau was not seen in the survival curves of our patients with other kinds of favorable-prognosis or low-grade NHL, indicating the lack of curative potential of these tumors. The lymphoplasmacytoid lymphoma, according to Kiel, also appeared to have a more aggressive clinical course. A plateau was seen in most of the other survival curves of patients with the more aggressive tumors, indicating the prospect of cure. However, the prognosis of the very aggressive tumors such as the diffuse lymphoblastic and diffuse small noncleaved cell lymphomas, according to the WF, remains very poor with a median survival of less than 10 months.     

Comparison of the working formulation of non-Hodgkin's lymphoma with the Rappaport, Kiel, and Lukes & Collins classifications. Translational value and prognostic significance based on review of 658 patients treated at a single institution

Six hundred fifty-eight cases of previously untreated non-Hodgkin's lymphoma seen between 1970 and 1979 at the Medical Department, the Finsen Institute, were the basis for a comparative study of the prognostic value of the Rappaport, Kiel, and Lukes & Collins classifications and the new translation system, the Working Formulation of Non-Hodgkin's Lymphoma. Each histopathologic system proved equally effective in separating patients into subgroups with a spectrum of prognoses ranging from a median survival of less than 1 year to greater than 7 years. The established classifications were compared with the Working Formulation in order to evaluate its translational value. The Working Formulation was more similar to the Rappaport and the Lukes & Collins systems than to the Kiel system, since 82%, 89%, and 75% of the cases, respectively, were translatable following the guidelines outlined in the National Cancer Institute (NCI)-sponsored study. Similarities among the four systems were demonstrated in lymphomas with follicular growth pattern, and in diffuse lymphomas composed of small mature appearing lymphocytes or small cleaved lymphocytes. Incongruity among the systems was more marked in lymphomas composed of large lymphoid cells or in lymphomas of mixed cellular composition. A comparison was performed for each classification against the Working Formulation. All such subdivided subsets were tested for prognostic heterogeneity and the following conclusions were reached: the diffuse poorly differentiated lymphocytic category of Rappaport was separated into two subgroups (malignant lymphoma [ML] small cleaved cell and ML lymphoblastic) with different prognoses (P = 0.01); the diffuse "histiocytic" lymphomas were prognostically homogeneous, since none of the newer systems were able to identify subpopulations with significantly different prognoses; the subtypes of the Kiel classification were prognostically homogeneous; the only weakness of the Lukes & Collins classification was the undefined cell subtype, encompassing two populations with different prognoses; and (5) the importance of follicular growth pattern was confirmed for small cleaved cell and mixed cell cytology, whereas large cell cytology implied a poor prognosis regardless of pattern. By the use of the Cox regression model it could be demonstrated that the Working Formulation can substitute any of the established classifications in terms of prognostic value.     

Surface phenotyping, histology and the nature of non-Hodgkin lymphoma in 157 patients.

In a study of 157 patients with lymphoid malignancy, the phenotype of the tumour cells was correlated with the histological classification of the tumour using the Rappaport and the Kiel classifications. The markers used included E, Fc gamma, Fc micron (IgM) and C3d rosetting, estimation of SIg and CyIg, and tests for the expression of HTLA, Ia and ALL. Repeat biopsy specimens were studied in 23 of these patients. The phenotypic features of lymphoblastic malignancy indicated B-cell, T-cell and ALL-positive null-cell tumours in this group. Immunoblastic lymphomas were predominantly of non-capping B-cell type, but T-cell immunoblastic lymphoma occurred in 2 patients. Immunoblastic lymphomas of receptor-silent cells occur, and are ALL- and HTLA-negative. In the category of diffuse, poorly differentiated lymphocytic lymphomas, most cases are of centroblastic and centrocytic tumour of diffuse type, but pure centrocytic tumours and centroblastic tumours occur. The dominant phenotype in this group is of B cells expressing C3d receptors. Nodular poorly differentiated lymphocytic lymphomas (Rappaport) are classified as centroblastic and centrocytic follicular (Kiel) and most express SIg+ C3d+ phenotype. The frequency of this phenotype appeared the same in both diffuse and nodular poorly differentiated lymphocytic neoplasms. The Rappaport group of diffuse well-differentiated lymphocytic lymphoma includes 2 Kiel categories, malignant lymphoma lymphocytic, and malignant lymphoma lymphoplasmacytoid. Cells of the former tumour were considered to be immature B cells resembling those seen in CLL, and characteristically expressing SIg weakly, with a high frequency of single kappa light chain. Cells of the latter tumour are by contrast mature, and are related to the centroblastic and centrocytic follicular tumour by their histogenesis and phenotypic features. Repeat biopsy examinations indicate that T-cell predominance occurs in the prodromal phase of B-cell-predominant tumours of SIg+ C3d+ phenotype. It is concluded that non-Hodgkin lymphoma can be divided into 2 categories: (1) tumours of immature immunologically incompetent cells of lymphoblastic histology and with phenotypic features akin to T, B and Null-cell ALL, and (2) tumours of differentiated lymphocytes expressing the phenotypic features of B lymphocytes, with maturation arrested at one of several stages of an antigen-dependent immune response.     

Non-Hodgkin's lymphomas: a simplified classification scheme

1,292 cases of malignant Non-Hodgkin's lymphomas were classified according to the Rappaport and Kiel classifications and to the New Working Formulation for Clinical Usage (NWF). Subsequently, all lymphoma entities were grouped together following the simple criteria of cell size and growth pattern (small cell, large cell, and mixed cellularity; nodular and diffuse growth). Supplementing these morphological criteria, were data from immunological and cytochemical cell marker studies. The accumulated information was correlated to clinical-prognostic parameters. The results show that using above simplified criteria, all Non-Hodgkin's lymphomas can be classified according to a simple scheme which is of clinical relevance. It can further be deduced from all currently used lymphoma classifications, avoids confusion, and offers abbreviated data useful for computer storage.     

Antibodies to epstein-barr virus-specific antigens in patients with hairy-cell leukemia

Antibody titers to Epstein-Barr virus (EBV)-specific antigens of 19 patients with hairy-cell leukemia (HCL) were markedly elevated. All patients showed high titers of IgG anti-viral capsid antigen (VCA) reactivity equal to or greater than 320 (reciprocal titer). The anti-VCA reciprocal geometric mean titer (GTM) was 1106 in contrast to a GMT of 80 for healthy controls (p < 0.001). No IgM anti-VCA antibody was detected, but three patients had IgA anti-VCA antibodies. Fourteen patients had elevated anti-early antigen (EA) titers (GMT = 177) which were indicative of active infections with EBV. Seven of the 14 patients demonstrated the diffuse component antibody of the early antigen (EA) complex at a GMT of 98. Anti-Epstein-Barr virus nuclear antigen (EBNA) was detected in sera of 16 patients (GMT = 64, controls GMT = 79). It is noteworthy that three patients with anti-VCA titers lacked anti-EBNA titers. These antibody responses suggest that immunodeficiency secondary to HCL allowed reactivation of the virus.     

A new working formulation of non-Hodgkin's lymphomas. A retrospective study of the new NCI classification proposal in comparison to the Rappaport and Kiel classifications

Two hundred thirty cases of malignant non-Hodgkin's lymphomas were reclassified in a retrospective study according to the New Working Formulation for Clinical Usage of the NCI as compared to the Rappaport and Kiel classifications. The reproducibility for the individual schemes this study was 81% (Rappaport), 79% (Kiel), and 85% (New Working Formulation). In keeping with the results of the NCI international study, all lymphomas were subdivided into 3 prognostic groups: (1) low-grade malignancy (6.0 years median survival); (2) intermediate-grade malignancy (3.5 years median survival); and (3) high-grade malignancy (1.4 years median survival). The NCI-proposed New Working Formulation for Clinical Usage is thus recommended as practical and unprejudicing classification scheme for general application; however, its usefulness as tool for translating one classification scheme into another appears limited.     

Surface markers and functional properties of non-Hodgkin's lymphoma cells in relation to histology.

Cells from 32 adult patients with non-Hodgkin's lymphoma were studied with respect to surface markers and functional properties in short-term culture. Twenty-six lymphomas were of B-cell origin, including all nodular and diffuse lymphocytic lymphomas. Three tumors were of T-cell origin (one histiocytic lymphoma and two undifferentiated lymphomas). In the remaining three cases (histiocytic lymphomas) the immunological nature of the tumor cells could not be determined. All reactivity to mitogenic stimuli of cells from B-cell lymphomas was due to residual normal T cells. In follicular lymphocytic lymphomas more reactive T cells prevailed among the malignant B cells than in diffuse lymphocytic lymphomas. Heterogeneity among B-cell lymphomas was indicated by differences in intensity of fluorescence with anti-Ig reagents and in stimulatory capacity in mixed lymphocyte culture. T-cell lymphomas were characterized by high percentages of T cells together with impaired responses to stimuli. The results of immunological studies correlated well with the histological classifications of Rappaport, Lukes and Lennert.     

Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin's disease

Epstein-Barr virus (EBV) is detected in Hodgkin and Reed-Sternberg (HRS) cells in up to 50% of patients with Hodgkin's disease (HD). HD patients have been reported to express high serum titers against EBV antigens, even prior to the diagnosis of HD. Patients with high serum titers have a poorer prognosis. The aim of this study was to examine the relationship between the presence of EBV in HRS cells and the antibody titers reactive with different EBV antigens. Frozen serum and histopathological tissues were available from 107 untreated HD patients diagnosed between 1979 and 1991. The presence of EBV in the HRS cells was evaluated with immunohistochemistry directed against the LMP-1 antigen and/or with in situ hybridization of EBER-1. Analyses were performed of serum titers against early antigen (EA), diffuse (IgA and IgG) and restricted (IgG), virus-capsid antigen (VCA) (IgA and IgG), and EBV-encoded nuclear antigens (EBNA, EBNA 1, EBNA 2A, EBNA 2B, EBNA 6). EBV was detected in 27/107 (25%) tumor specimens, with a higher proportion in the MC group 8/13 (62%) (p < 0.01). IgG VCA and EBNA were detected in 99/107 (93%), evidence of a previous EBV infection. There were no significant relationships between antibody titers reactive with different EBV antigens and detectable EBV in HRS cells. Furthermore, there did not appear to be any relationship between EBV serology or the presence of EBV in HRS cells and clinical outcome. The role of EBV in the development of HD, especially its relationship to the immunological response, remains unclear. Int. J. Cancer 72:394–397, 1997. © 1997 Wiley-Liss, Inc.     

Primary gastrointestinal lymphoma. A clinicopathologic study of 102 patients

Clinicopathologic findings in 102 patients with primary gastrointestinal lymphomas were reviewed. Abdominal pain was the common presenting symptom. The primary sites of the tumors were: 67 in the stomach, 24 in the small intestine, 7 in the ileocecal region, 3 in the large intestine, and 1 in the esophagus. The disease more frequently affected males than females and showed peak incidence in the 5th decade of life. Gastric lymphomas usually presented with a single lesion, but multiple lesions were frequent in the small intestine. The body and/or antrum of the stomach were the commonest sites of the lymphomas. Gastric lymphomas were diagnosed at an earlier stage than intestinal lymphomas. There was 1 case with Hodgkin's disease. The remaining 101 patients with non-Hodgkin's lymphomas were classified according to the Rappaport and the Kiel classifications. The proportion of nodular lymphomas in the present series was 7%. The frequencies of diffuse histiocytic type ard germinal center cell tumors were 62 and 74%, respectively. Cox's multivariate analysis for prognostic factors revealed that the stage of the tumor, sex, and age were prognostically significant.     

Relationship between clinical stage, histopathology and antibody titers against the second Epstein-Barr virus nuclear antigen (EBNA-2) in non-Hodgkin's lymphoma patients

Non-Hodgkin lymphoma (NHL) patients with centroblastic (Cb) or centroblastic-centrocytic (Cb/Cc)-diffuse lymphomas, immunocytoma (IC) and chronic lymphocytic leukemia (CLL) in clinical stages III-IV and with active disease (highly malignant group) were compared to NHL patients with CLL, IC, and centrocytic (Cc) or centroblastic-centrocytic (Cb-Cc)-diffuse/follicular lymphomas, in clinical stages I-II and with inactive disease (low malignant group) based on the presence of antibodies to Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) and 2 (EBNA-2). In the highly malignant group, anti-EBNA-1 geometric mean titers (GMT) were 13.2 (range less than 2-80) and anti-EBNA-2 60.6 (range: 20-320). The ratio between the logarithms of anti-EBNA-1 and anti-EBNA-2 antibody titers was less than 1.0 (mean: 0.32) in all the patients examined. In 6 out of 8 patients of the low malignant group, anti-EBNA-1 titers were higher (mean: 30.1; range 10-160) than anti-EBNA-2 titers (mean: 4.3; range less than 2-80) and the EBNA 1/2 ratio was greater than 1.0. In healthy EBV-seropositive individuals, anti-EBNA-1 GMT were 49 (range: 10-320) and only 5 out of 17 individuals had detectable anti-EBNA-2 titers (GMT: 3; range less than 5-20). The EBNA-1/2 ratio was in all cases greater than 1. Among patients of the highly and low malignant groups, patients with follicular-cell-derived lymphomas had elevated antibody titers against the restricted component of early antigens (EA-R), whereas all patients with IC and 2 out of 4 CLL patients had elevated antibody titers against the diffuse component of early antigens (EA-D). The results indicate that the ratio between anti-EBNA-1 and anti-EBNA-2 antibody titers may be of diagnostic importance in patients with immunodeficiencies.     

Clinico-pathological features of malignant lymphomas in 294 Hong Kong Chinese patients, retrospective study covering an eight-year period

The clinical records and histological material from 294 adult Chinese patients with malignant lymphoma were examined. These patients were first seen at the Queen Mary Hospital, Hong Kong, during the 8-year period 1975-82. There were 27 patients (9.2%) with Hodgkin's disease (HD) and 267 with non-Hodgkin's lymphoma (NHL). The median age at presentation was younger for HD (45 years) and the male: female ratio was higher (2:1) than the corresponding figures for NHL of 51 years and 1.4:1. In 76 patients (28.5% of NHL), the disease was thought to have originated in an extra-nodal site, 48 of these cases being gastrointestinal lymphomas. It was possible to reclassify 234 NHL according to the Rappaport and Kiel classifications, and the Working Formulation (WF) proposed by the US National Cancer Institute Study; for HD, the Rye classification was used in 26 cases where suitable material was available. Nodular/follicular lymphomas made up 17.1% of nodal NHL and 5.3% of extra-nodal NHL. The "histiocytic" (Rappaport) or large-cell (WF) subtype was the commonest amongst diffuse NHL. There were only four cases of Burkitt's lymphoma. For HD, the nodular sclerosing subtype was commonest in females (5 out of 8 cases) and for males, the commonest was mixed cellularity (10 out of 18 cases). Of patients with nodal NHL 64.7%, presented with Stage IV disease. For HD, there were about equal numbers of patients presenting with Stage II and Stage IV disease (10 and 9 respectively). The low incidence of Hodgkin's disease and of follicular lymphomas is comparable to figures from other "oriental" countries such as Japan.     

Primary pulmonary lymphomas. A clinicopathologic analysis of 36 cases

The clinical and pathologic findings in 36 patients with primary pulmonary non-Hodgkin's lymphoma were retrospectively evaluated. Each lymphoma was classified according to the Rappaport, Lukes-Collins, Working Formulation, and Kiel criteria. Twenty-one (58%) of the 36 patients had lymphomas classified as lymphoplasmacytic/lymphoplasmacytoid type or LP immunocytoma (LPI) according to the Kiel classification. The remainder of the patients (42%) had lymphomas distributed among the follicular center cell (FCC) types and immunoblastic sarcoma in the Lukes-Collins classification. Survival of patients with LPI was significantly longer than that of patients with other types of lymphoma (88% versus 47% 5-year actuarial survival estimate), and the LPIs were more often confined to the lung without hilar or mediastinal lymph node involvement. Seven (33%) of the 21 LPI eventually recurred after a mean follow-up of 69 months, and 4 of these 7 developed serum paraproteins. Most of the patients with lymphomas other than LPI had persistent disease or an early recurrence. LPI, as described by Lennert, seems prone to arise in extranodal sites and to recur late. Measurement of serum immunoglobulins may be helpful in detecting recurrences of LPI.     

Reduced phagocytosis of apoptotic cells in malignant lymphoma

Efficient removal of lymphocytes undergoing programmed cell death (apoptosis) by macrophages plays an important role for the proper function of normal immune system. Furthermore, in malignant lymphoma, elimination of apoptotic tumor cells by phagocytes contributes to the anti-tumor immune response. It is unknown, however, whether macrophages in normal and malignant lymphoid tissues differ in their ability to recognize and remove apoptotic cells. Our present results demonstrate that normal and malignant lymphoid tissues differ according to the extent of the infiltration by macrophages. The highest densities of macrophages (p < 0.0001) were detected in diffuse large B-cell lymphoma, centroblastic (DLBCL-CB) and immunoblastic variants and Burkitt's lymphoma. The grade of the macrophage infiltration correlated with the proliferation rates of the tumors (p < 0.0001). Compared with normal lymphoid organs, malignant lymphoma contained lower percentages of apoptotic cells phagocytosed by tissue macrophages (p < 0.001). Of all lymphomas tested, mantle cell lymphoma and DLBCL-CB expressed the lowest percentages of phagocytosed apoptotic cells (p < 0.0001). Int. J. Cancer 75:675–679, 1998.© 1998 Wiley-Liss, Inc.     

Report on the EORTC lymphoma trial 20751

The preliminary survival data are reported for the second non-Hodgkin lymphoma trial (LR-11, 20751) of the EORTC (European Organization for Research and Treatment on Cancer). A total of 576 patients were collected. Pathology was reviewed for $\text{2}\text{3}$ of the patients according to the Rappaport, the Lukes-Collins and the Kiel classification. Survival is correlated to pathology, stage and treatment.     

CORRELATION OF IMMUNOLOGICAL SURFACE ANTIGENS WITH SURVIVAL IN DIFFUSE LARGE CELL LYMPHOMA

The prognostic value of immunophenotyping lymphomas with a panel of monoclonal antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry after labelling by indirect immunofluorescence. Thirty-eight cases were demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis demonstrated that survival was significantly longer in patients expressing higher levels of HLA-DR (p=0·01) and normal levels of CD8 (p=0·04) but was not significantly associated with any of the other antigens. Our results support the possible value of HLA-DR in determining the prognosis of patients with diffuse large cell lymphoma.     

The relation between Epstein-Barr virus antibodies and clinical symptomatology and immunodeficiency in patients with Hodgkin's disease.

Anti-Epstein-Barr virus (EBV) titers were measured in the sera of 37 patients with Hodgkin's disease and in 40 normal controls. The patients were grouped according to histologic type, clinical symptomatology (relapse or remission), and their immune state (immunodeficient or non-immunodeficient). Anti-Epstein-Barr nuclear antigens (EBNA) and antiviral capside antigens (VCA) titers were higher in patients with Hodgkin's disease than in the controls. Anti-EBNA titers were significantly higher in patients with lymphocyte predominance, and anti-VCA titers were significantly higher in patients with mixed cellularity. Patients in clinical relapse had higher anti-EBV antibody titers than patients in remission or those in the control group. Immunodeficent pateints had significantly higher anti-VCA titers than either the non-immuno-deficient or the control cases. We believe high anti-EBV titers are related to immunodeficiencies. The relationship between Hodgkin's disease and EBV is discussed.     

Comparison of S-phase fraction, working formulation, and Kiel classification in non-Hodgkin's lymphoma

The prognostic value of S-phase fraction (SPF), determined by flow cytometric study from paraffin-embedded tissue, and grading by Working Formulation (WF) and Kiel classification were compared among 245 patients with non-Hodgkin's lymphoma followed for the median of 89 months or until death. Histologic reclassification and SPF determinations were done without knowledge on clinical data. SPF (P equals 0.0001), WF (P equals 0.0003), and Kiel classification (P equals 0.0008) were associated with mortality in lymphoma in a univariate analysis, and WF and SPF were independent prognostic factors in Cox's multivariate analysis. Although SPF correlated strongly both with WF and Kiel grades (P less than 0.0001), low-grade and high-grade malignant lymphomas according to Kiel classification, and high-grade lymphomas according to WF could be divided into groups with significantly different outcome by SPF. The results suggests a role for SPF in therapeutic decision-making.     

CD26 expression in mature B‐cell neoplasia: its possible role as a new prognostic marker in B‐CLL

CD26 (dipeptidyl peptidase IV, DPP IV) is widely expressed by T and natural killer (NK) cells, epithelial and endothelial cells of different tissues, and it is strongly upregulated in activated B‐cells; moreover it plays a regulatory role in the neoplastic transformation and progression of various types of tumours. CD26 expression was evaluated by means of flow cytometry in various peripheral B‐cell lymphoid tumours: 12 follicular and 12 mantle cell lymphomas, 20 multiple myelomas (MMs), 12 hairy cell leukaemias (HCLs), 112 chronic lymphocytic leukaemias (CLLs), 20 CD5^negative B‐cell chronic lymphoproliferative diseases (CD5^neg B‐CLPDs) and 12 diffuse large cell lymphomas (DLCLs). CD26 expression was absent or barely detectable in follicular and mantle cell lymphomas, high in MMs and HCLs, and variable in CLLs, in CD5^neg B‐CLPDs and in DLCLs. CD26 significantly correlated with CD49d and CD38 expressions (p < 0.0001) in B‐CLLs, and there was a significant correlation between CD26 and ZAP‐70 expressions or IgVH mutational status (p < 0.0001). After a median follow‐up of 36 months, 65 B‐CLL patients were treated; taking 10% as the best CD26 cut‐off value, Kaplan–Meier curves revealed a significantly shorter time to treatment in the CD26‐positive cases (p < 0.0001). Overall, our data indicate that CD26 expression may identify subsets of B‐CLL patients with an unfavourable clinical outcome in terms of therapeutic need, thus suggesting its potential role as a marker (together with CD38 and CD49d) in a future routine cytofluorimetric panel to be validated for the prognostic stratification of B‐CLLs. Copyright © 2009 John Wiley & Sons, Ltd.     

Prognosis in low grade non-Hodgkin's lymphoma: relevance of the number of sites involved,absolute lymphocyte count and serum immunoglobulin level

Eighty-eight patients with low grade non-Hodgkin's lymphoma were followed for a median period of 63 months. Sixty-eight per cent of the group were centrocytic/centroblastic B cell lymphomas by the updated Kiel classification. Fifty-one (58 per cent) of the patients were stage IV by the Ann Arbor classification. In 18 of these patients the bone marrow was the only site of extranodal involvement. Univariate survival analysis showed that the sum of involved sites was more discriminatory than Ann Arbor stage. Analysis by site of involvement showed that the liver and other intraabdominal sites were associated with worse survival than involvement of peripheral lymph nodes. Bone marrow and spleen involvement were not significantly associated with short survival. Increasing age at presentation was strongly associated with shorter survival and was also inversely correlated with serum albumin. Both low absolute lymphocyte count (<1.0 × 10 ⁹/1), low serum IgG level (<10 g/1) and low total immunoglobulins on presentation were significantly associated with short survival. Multivariate analysis showed that age, serum albumin and number of involved sites gave the best survival prediction. The sum of involved sites, immunoglobulin level and absolute lymphocyte count may be useful objective markers of prognosis in low-grade non-Hodgkin's lymphoma.     

Lymphocyte populations and TAC-antigen in diffuse B-cell lymphomas

Immune cell populations in 8 diffuse histology B-cell lymphomas were analysed in frozen tissue sections by indirect immunofluorescence to gain insight into their possible modulating influence in these tumors. Use of monoclonal antibodies to identify cellular and extracellular antigens combined with nuclear counterstaining allowed precise quantitation, localization and comparison of T- and B-lymphocyte populations. T lymphocytes clustered in non-random fashion. Areas of high T-lymphocyte density manifested higher T4:T8 ratios than locales with fewer T lymphocytes (p less than 0.05). Few cells had surface antigens (Leu 7, 73.1, OKM1) associated with natural killing. Cells strongly reactive with anti-TAC (Interleukin-2 receptor, associated with T-lymphocyte activation) were also T11 reactive and were usually helper (Leu 3) phenotype. In addition, B-lineage lymphoma cells in some tissues reacted with anti-TAC. The pattern of tumor cell reactivity with anti-TAC correlated with Rappaport histologic classification. These findings suggest that non-malignant T lymphocytes modulate B-lymphoma cell growth in situ, and that in some lymphomas the T-cell product IL-2 may be an important local growth factor.