Small Cleaved Cell Lymphoma Research Articles

Common Acute Lymphoblastic Leukemia‐associated Antigen (CALLA)‐positive B cell lymphoma

We analyzed the expression of common acute lymphoblastic leukemia-associated antigen (CALLA) in 134 cases of non-Hodgkin's lymphoma of the B cell type using an immunohistochemical method. The incidence of CALLA expression in B cell lymphomas was higher in follicular lymphomas (29%) than in diffuse lymphomas (15%). Malignant lymphoma (ML), follicular small cleaved cell (FSC) according to the histologic type, showed a considerably high incidence of CALLA (43%), whereas ML, diffuse small cleaved cell (DSC) displayed a very low incidence (5%). These findings suggest the possibility that these two morphologically similar lymphomas may be derived from distinct populations of B cells [CALLA+-germinal center (GC) cells, CALLA- -germinal center (GC) cells or mantle zone (MZ) cells]. In addition, one case of DSC expressed surface immunoglobulin D (SIgD) and alkaline phosphatase (ALPase) as well as CALLA. This indicates that CALLA-positive small cleaved cell lymphoma expressing SIgD or ALPase may represent neoplastic proliferation of CALLA-positive MZ cells of secondary follicles in lymph nodes.

Multiple lymphomatous polyposis of the gastrointestinal tract. A clinicopathologically distinctive form of non-Hodgkin's lymphoma of B-cell centrocytic type.

Multiple lymphomatous polyposis of the gastrointestinal tract was initially described as mucosal lymphomatous involvement by any of a variety of Hodgkin's or non-Hodgkin's lymphomas that produced a polypoid appearance over long segments of the gastrointestinal tract. We studied four patients in whom histology revealed diffuse small cleaved cell lymphoma (one case), or intermediate lymphocytic lymphoma of diffuse type (one case), or mantle zone pattern (two cases). All four cases are classifiable as centrocytic lymphoma. Cell suspension and immunocytochemical studies demonstrated B-cells of IgMD or M type with light chain restriction (two kappa, two lambda) showing a B1+ HLA Dr+ LN2+ CD5+ CD10+. Although all four patients had a partial response to combination chemotherapy, three of them died within 3 years. Analysis of 24 cases reported since 1971 (including the present cases) suggests that MLP is a distinct clinicopathological entity that results from gastrointestinal involvement by a B-cell centrocytic lymphoma. It is distinct from the recently described clinicopathological forms of centrocytic lymphoma and intermediate lymphocytic lymphoma, which both show extensive peripheral lymphadenopathy and splenomegaly, but it is probably closely related to them. The differences are probably attributable to distinct cell tropism or homing properties rather than to cellular histogenesis or degree of maturation.

Hypocellular paratrabecular foci of treated small cleaved cell lymphoma in bone marrow biopsies.

Because of the new drug combinations being used to treat follicular lymphomas, the small cleaved cell lymphomatous foci in bone marrow biopsies appear to be altered. They become progressively hypocellular and contain a few and sometimes no small cleaved cells within oligocellular paratrabecular fibrous foci. These hypocellular paratrabecular foci (HPF) (a) are a clue that deeper sectioning is necessary to determine whether there are diagnostic foci of residual involvement by small cleaved cell lymphoma, (b) may indicate that other portions of the patient's bone marrow still contain viable foci of small cleaved cell lymphoma, and further, (c) should alert the clinician to the possibility of recurrence of small cleaved cell lymphoma in subsequent bone marrow biopsies. A comparison of patients who developed HPF in one or more of their bone marrow biopsy specimens with those who did not indicates that the changes are related to combinations of chemotherapy other than CHOP-Bleo (cyclophosphamide, adriamycin, vincristine, prednisone, bleomycin). Eighty-one percent of patients who developed HPF had received additional chemotherapeutic regimens, whereas 75% of patients whose bone marrows did not contain HPF had received only CHOP-B. The older age of the HPF-negative patients (median age 64 versus median age 43 for HPF-positive cases) may reflect more aggressive chemotherapy in the younger age group. While HPF appear to reflect some increased chemotherapeutic cytotoxicity affecting the lymphomatous foci in bone marrow, they do not appear to predict for a longer survival or cure.

Philadelphia chromosome without breakpoint cluster region rearrangement in a case of Lennert's lymphoma of suppressor phenotype

A 60-year-old woman presented with diffuse lymphadenopathy. Diagnostic and staging work-up showed that the patient had diffuse small cleaved cell lymphoma (diffuse poorly differentiated lymphocytic lymphoma) with associated histiocytes (lymphoepithelioid cell lymphoma) by the Kiel classification system. Immunohistologic staining showed a T suppressor cell tumour phenotype. Cytogenetic studies revealed the Philadelphia chromosome (Ph1). On DNA studies, the breakpoint cluster region (BCR) gene was not rearranged suggesting that the Ph1 involvement was not identical to that seen in chronic myelogenous leukemia (CML). This case is presented because of the rarity of Ph1 in lymphoid malignancies, particularly in those of T-cell origin, and because of its potentially adverse implications.

High activity of mitoxantrone in previously untreated low-grade lymphomas.

A consecutive series of 21 previously untreated patients with low-grade non-Hodgkin lymphomas were treated with mitoxantrone 5 mg/m2 daily for 3 days every 3 weeks. The cumulative dose did not exceed 165 mg/m2 in any patient. In this group, 7 patients had small lymphocytic lymphomas, 10 patients had follicular small cleaved cell lymphomas, and 4 patients had follicular mixed small- and large-cell lymphomas. Of the 21 patients, 20 obtained remission (complete in 6, partial in 14), and 15 of these are still in remission. Relapse-free survival is 68% at 2 years. None of the patients has died. Nonhematologic toxicity was modest. No severe alopecia was seen, and only 6 patients had nausea and vomiting (WHO grade 1-3). No cardiac toxicity was seen. In conclusion, mitoxantrone is a highly active and well-tolerated drug in this subset of patients. Hematologic toxicity, especially leukopenia, was dose limiting, and a reduction of the dose was necessary in 15 out of the 21 patients.

Significance of Extra 18q- Chromosome in Japanese t(14;18)-Positive Lymphoma

Karyotype evolution of t(14;18)-positive lymphoma was studied in 13 Japanese patients. The extra 18q- chromosome, found in six of ten patients with complex karyotypes, was the most common change subsequent to a t(14;18)(q32;q21) chromosome translocation. The additional change was interpreted as being a duplication of an 18q- derived from a t(14;18). The six patients had transformed histology of follicular small cleaved cell lymphoma or diffuse large cell lymphoma, and five of them had extranodal expansion associated with a poor prognosis. These findings indicate that the extra 18q-, together with other chromosome abnormalities, is closely associated with the advanced grade disease of t(14;18)-positive lymphoma, and the extra chromosome is evolutionally comparable with the second Philadelphia (Ph1) chromosome often found in the blastic phase of chronic myelocytic leukemia carrying a t(9;22)(q34;q11). In addition, since the extra 18q- is rarely found in American patients with t(14;18)-positive lymphoma, there appears to be a difference in the karyotype evolution between Japanese and American patients.

Significance of extra 18q- chromosome in Japanese t(14;18)-positive lymphoma

Karyotype evolution of t(14;18)-positive lymphoma was studied in 13 Japanese patients. The extra 18q- chromosome, found in six of ten patients with complex karyotypes, was the most common change subsequent to a t(14;18)(q32;q21) chromosome translocation. The additional change was interpreted as being a duplication of an 18q- derived from a t(14;18). The six patients had transformed histology of follicular small cleaved cell lymphoma or diffuse large cell lymphoma, and five of them had extranodal expansion associated with a poor prognosis. These findings indicate that the extra 18q-, together with other chromosome abnormalities, is closely associated with the advanced grade disease of t(14;18)-positive lymphoma, and the extra chromosome is evolutionally comparable with the second Philadelphia (Ph1) chromosome often found in the blastic phase of chronic myelocytic leukemia carrying a t(9;22)(q34;q11). In addition, since the extra 18q- is rarely found in American patients with t(14;18)-positive lymphoma, there appears to be a difference in the karyotype evolution between Japanese and American patients.

Transferrin receptor expression by non-Hodgkin's lymphomas. Correlation with morphologic grade and survival.

The monoclonal antibody OKT9 was applied to cryostat sections of 267 non-Hodgkin's lymphomas and related neoplasms. It was found that the transferrin receptor is expressed by a wide variety of B- and T-lineage non-Hodgkin's lymphomas. The OKT9 staining also was loosely correlated with the three morphologic grades of non-Hodgkin's lymphomas identified by the International Working Formulation. In general, higher grade lymphomas more often and more intensely expressed the T9 antigen. However, transferrin receptor expression by certain histologic subtypes of lymphoma did not correlate with their morphologic grade: low-grade follicular lymphomas expressed the T9 antigen more frequently than diffuse low-grade lymphomas; diffuse small cleaved cell lymphomas were stained by OKT9 less often than other histologic subtypes of intermediate-grade lymphomas; and diffuse immunoblastic lymphomas expressed transferrin receptors less often than the other high-grade histologic subtypes of non-Hodgkin's lymphoma. Intermediate lymphocytic lymphomas, not recognized in the International Working Formulation, were infrequently and weakly stained by OKT9 in a manner similar to diffuse low-grade lymphomas. We obtained clinical follow-up data on 43 individuals with chronic lymphocytic leukemia/small lymphocytic lymphoma and 64 individuals with diffuse large cell and immunoblastic lymphoma. Transferrin receptor expression in these two groups did not correlate significantly with survival.

Image analysis applied to proliferating cells in malignant lymphoma.

This study describes a method for obtaining the distribution of a given cell type in histological sections, as revealed by a specific immunological marker. Two hundred fifty-six contiguous microscopic fields were analysed, and a cellular map was automatically constructed. The resulting images were stored on magnetic media for subsequent quantification and statistical tests. The method was applied to the analysis of 20 small cleaved-cell lymphomas in which the monoclonal antibody Ki-67 was used to mark proliferating cells. Clusters of proliferative cells were observed in both diffuse and nodular lymphomas. Cellularity and the percentage of marked cells were not significantly different in the two types of tumors.

Lymphoma cell line (FL-18) and Epstein-Barr virus-carrying cell line (FL-18-EB) obtained from a patient with follicular lymphoma: monoclonal derivation and different properties

A novel cell line, FL-18, was established from the pleural effusion of a patient with follicular small cleaved cell lymphoma. At the same time, an Epstein-Barr virus (EBV) nuclear antigen (EBNA)-positive cell line, FL-18-EB, was established from the EBV-infected culture of the same pleural effusion cells. Both cell lines had the same monoclonal surface immunoglobulin (IgG kappa), and they had the same karyotype as that of the fresh pleural effusion cells in which a reciprocal translocation between the long arm of chromosomes 14 and 18 [t(14;18)(q32;q21)] was detected. Gene rearrangement analysis of immunoglobulin heavy-chain gene (JH) and kappa light-chain gene (J kappa) showed the same rearranged configuration in the two cell lines; however, some morphological and phenotypic differences were found. The FL-18-EB cells, which were morphologically similar to common EBNA- positive lymphoblastoid cell lines of normal B cell origin at the initial phase of culture, were larger than the FL-18 cells and contained multinucleated giant cells. The FL-18 cells lacked cytoplasmic immunoglobulin and were positive for common acute lymphoblastic leukemia antigen (CALLA), whereas the FL-18-EB cells had cytoplasmic immunoglobulin and were negative for CALLA. Thus, the phenotype of FL-18-EB seems to be a result of a shift by EBV infection to a more mature stage in the B cell differentiation pathway than that of FL-18. The paired availability of EBV-free and EBV-infected cell lines of a neoplastic clone is unique and valuable in considering EBV infectibility of neoplastic B cells and resultant phenotypic changes.

Lymphoma Cell Line (FL-18) and Epstein-Barr Virus–Carrying Cell Line (FL-18-EB) Obtained From a Patient With Follicular Lymphoma: Monoclonal Derivation and Different Properties

A novel cell line, FL-18, was established from the pleural effusion of a patient with follicular small cleaved cell lymphoma. At the same time, an Epstein-Barr virus (EBV) nuclear antigen (EBNA)-positive cell line, FL-18-EB, was established from the EBV-infected culture of the same pleural effusion cells. Both cell lines had the same monoclonal surface immunoglobulin (IgG kappa), and they had the same karyotype as that of the fresh pleural effusion cells in which a reciprocal translocation between the long arm of chromosomes 14 and 18 [t(14;18)(q32;q21)] was detected. Gene rearrangement analysis of immunoglobulin heavy-chain gene (JH) and kappa light-chain gene (J kappa) showed the same rearranged configuration in the two cell lines; however, some morphological and phenotypic differences were found. The FL-18-EB cells, which were morphologically similar to common EBNA-positive lymphoblastoid cell lines of normal B cell origin at the initial phase of culture, were larger than the FL-18 cells and contained multinucleated giant cells. The FL-18 cells lacked cytoplasmic immunoglobulin and were positive for common acute lymphoblastic leukemia antigen (CALLA), whereas the FL-18-EB cells had cytoplasmic immunoglobulin and were negative for CALLA. Thus, the phenotype of FL-18-EB seems to be a result of a shift by EBV infection to a more mature stage in the B cell differentiation pathway than that of FL-18. The paired availability of EBV-free and EBV-infected cell lines of a neoplastic clone is unique and valuable in considering EBV infectibility of neoplastic B cells and resultant phenotypic changes.

Chromosomal abnormalities in indolent lymphoma

Cytogenetic studies were performed on lymph node biopsies from 60 patients with indolent (low grade) non-Hodgkin's lymphoma. Thirty-two of the 39 successfully cultured biopsies had abnormal clones. The 32 abnormal clones represented the following histologies: seven small lymphocytic lymphoma (SL), eight follicular small cleaved cell lymphoma (FSC), 14 follicular mixed, small cleaved, and large cell lymphoma (FM), and three composite lymphomas. One of the composite lymphomas had FSC/DSC (diffuse small cleaved cell) and the other two FM/DM (diffuse mixed, small cleaved and large cell). Twenty-seven of the 32 biopsies were immunologically typed, and all were B cell. The clones all exhibited more structural than numerical abnormalities, and there was no difference in the modal chromosome number of the abnormal clones found in each histology. Biopsies with no normal cells were more frequently found in the SL histology (71%) than in the two follicular lymphoma groups (54%–55%). A translocation of the 14q32 segment was the most common abnormality found in all three histologies. In the follicular lymphomas a t(14;18)(q32;q21) was seen in 52% (13 of 25) of these patients, this translocation was not observed in the SL patients. Overall 84% (21 of 25) of the follicular lymphoma patients had abnormalities of 14q32 and/or 18q21. Other specific abnormalities included anomalies of chromosome #3 in FM, an abnormal 10q in FSC and FM lymphoma, and a high incidence of +18 and chromosome #1 abnormalities in patients with t(14;18). The presence of specific chromosome abnormalities in the indolent lymphoma patients suggests a relationship between certain karyotypic features and histology.

Malignant lymphoma of the skin in children.

The clinical and histopathologic findings in eight cases of malignant lymphoma of the skin in children are presented. All patients had skin lesions as a primary manifestation of the disorder. Three patients had simultaneous regional lymph node involvement documented by the findings of subsequent biopsies. The majority (five patients) had solitary nodules involving the skin of the head and neck region. Three of the skin biopsy specimens were classified as lymphoblastic lymphoma, two large cell lymphoma, two mixed small and large cell lymphoma, and one small cleaved cell lymphoma. Disseminated disease subsequently developed in four patients in an interval that ranged from 4 to 30 months after diagnosis. The follow-up period ranged from 8 to 56 months, and median survival was 56 months. A literature review of 33 previously reported patients and our eight patients indicate that: skin of the head and the neck region is the most common site of involvement (56%); the majority of lymphomas are diffuse (93%); lymphoblastic lymphoma is the predominant type (53%), with a high proportion showing a non-T-cell phenotype; Burkitt's lymphoma and Hodgkin's disease of the skin are extremely rare; and most patients presented in an early clinical stage (Stage IE 56%, Stage IIE 21%), and prolonged disease-free survival was seen mostly in Stage I patients. The cumulative probability of survival for Stage I patients at 24 months was 0.71; while for Stages II to IV patients combined, it was 0.33 at 26 months.

Multiple recurrent genomic defects in follicular lymphoma. A possible model for cancer.

Several steps in the clinical evolution of human neoplasia are associated with a variety of recurrent chromosomal defects that could prove essential to the understanding of cancer. We found 15 types of nonrandom chromosomal abnormalities in a study of 71 patients with follicular lymphoma; 10 of the types appeared to influence the histopathological findings, clinical course, or response to treatment. A translocation, t(14;18), observed in 85 percent of all patients appeared to be the main determinant of a follicular pattern. Ten patients with a t(14;18) as a single defect had the histologic features of follicular small cleaved-cell lymphoma. Most did not require treatment for one to four years, because their tumors had an initial indolent course. In contrast, patients with follicular small cleaved-cell lymphoma with t(14;18) and deletion 13q32 acquired the hematologic features of leukemia and had an acceleration of the disease. A deletion 6q together with a complete or partial trisomy 7 or trisomy 12 (or both) was associated with the clinically more aggressive follicular mixed small- and large-cell or large-cell histologic type, which often evolves from follicular small-cell lymphoma. A complete or partial trisomy 3, 18, or 21 correlated almost exclusively with follicular large-cell lymphoma. In all follicular stages, a trisomy 2 or duplication 2p often accompanied an accelerated clinical course and a poor response to treatment. This study suggests that several discrete genomic defects may govern the evolution of a patient's malignant disease.

Follicular mantle zone cell subpopulations detected by monoclonal antibody SN3.

A monoclonal antibody, SN3, has been prepared against a cell membrane fraction of the pre-B leukemic cell line NALM-1. By radioimmunoassay, SN3 reacted with four of four non-T/non-B, two of two pre-B and one of three leukemic B cell lines. The reagent was unreactive, however, with established leukemic T and myelomonocytic cell lines or normal B cell lines. On immunohistochemical assays on frozen sections of nine reactive lymph nodes and three spleens, SN3 showed a preferential binding to 50-95 per cent mantle zone (MZ) cells and 5-20 per cent interfollicular or red pulp B-lymphocytes. This was uninhibited by pre-incubation with heterologous anti-HLA-DR or anti-delta reagents. SN3 was unreactive with normal germinal centre (GC), epidermal or Langerhans cells but did react with less than 1 per cent thymic B-lymphocytes. In eight follicular small cleaved cell lymphomas tested SN3 exhibited three patterns of reactivity: peripheral follicular, combined peripheral and central follicular, and combined follicular and interfollicular. Three follicular lymphomas were essentially SN3-. In three diffuse small lymphocytic lymphomas, SN3 showed patchy areas of reactivity unassociated with proliferation centres. In four diffuse B-cell lymphomas (one mixed small and large cell, two large non-cleaved cell, and one small non-cleaved (Burkitt) cell), SN3 reactivity was uniformly distributed in the majority (60-90 per cent) of the cells. SN3 was unreactive with one diffuse B-large cell lymphoma, three nodal T-cell lymphomas and three cases of mycosis fungoides. The findings indicate that SN3 detects an antigen that is present in subpopulations of normal MZ cells, the antigen is also detected in GC cells undergoing lymphomatous transformation but is not readily detected in normal GC cells, and the antigen is also expressed in subpopulations of diffuse B- but not T-cell lymphomas.

Liver biopsy immunotyping to characterize lymphoid malignancies.

To determine the feasibility of liver biopsy immunotyping to characterize hepatic lymphoid malignancies, we employed a panel of monoclonal antibodies on snap-frozen hepatic tissue from 18 patients. Six patients proved to have a histologic diagnosis of lymphoid malignancy. By using free avidin and biotin-blocking reagents to block endogenous biotin, followed by standard immunochemistry, immunotyping was successful in all six cases. Serial section typing allowed delineation of complex B cell phenotypes. Furthermore, architecture was preserved allowing discernment of disease patterns (e.g., sinusoidal, hairy cell leukemia vs. portal, follicular small-cleaved cell lymphoma. Unexpectedly, we found striking expression of common ALL antigen in normal bile canaliculi, which may prove of diagnostic or therapeutic relevance. This study establishes the utility of immunohistochemical techniques applied to hepatic biopsies as a valuable adjunct to histologic diagnosis as well as a tool in revealing the immunobiology of the liver.

Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow

To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases. In addition to the identification of straightforward monoclonal surface immunoglobulin expression in small cleaved cell lymphomas (four cases), the battery approach added immunologic certainty in malignancies with unusual or difficult phenotypes: peripheral T-cell lymphomas with idiosyncratic antigen expression, and chronic lymphocytic leukemias and small cell lymphomas with faint surface immunoglobulin expression (four cases). For the chronic lymphocytic leukemias and the small cell lymphomas, the combined IgD+, B2+, B1+, Ia+, Leu-1+ phenotype taken as a whole had greater utility than any isolated marker. The acute lymphocytic leukemias and the myelomas studied demonstrate the wide range of B-cell antigens that must be detected to account for the variety of B-cell neoplasms encountered. Additionally, the previously undescribed phenotypic subset of CALLA+ myelomas, which is of prognostic relevance, was identified. Marrow frozen section immunotyping is a major asset in the evaluation of patients with lymphoma, leukemia, and myeloma when special care is accorded to tissue handling and to treatment of endogenous peroxidase/pseudoperoxidase and interstitial immunoglobulin.

Histiocytic lymphoma cell lines: Immunologic and cytogenetic studies

Cell lines were established from 15 patients with diffuse histiocytic lymphoma (DHL) of the intermediate grade, diffuse large cell (class G), and high-grade, large cell immunoblastic (class H) types. Immunologic studies indicated that 11 of the 15 DHL cell lines were B cell in origin, 2 were histiocytic, and 2 were null cell. Cytogenetic studies revealed 1 hypodiploid, 11 hyperdiploid, and 3 near-tetraploid cell lines. Chromosome #7 was trisomic in 3 lines, chromosomes #12 in 4 lines, and chromosome #13 in 3 lines. Chromosome #2 was monosomic in 3 lines, chromosome #8 was monosomic in 5 lines, chromosome #14 in 4 lines, and chromosome #22 in 6 cell lines. This is of special interest, as chromosomes #2, #8, #14, and #22 are clearly concerned with rearrangements in Burkitt's lymphoma and immunoglobulin expression. The most common rearrangement in the DHL cell lines involved chromosome #14 at band 14q32. However, in contrast to Burkitt's lymphoma, the pattern of translocation in DHL is between chromosome #14 and usually chromosome #11 or chromosome #18. The 14;18 translocation is not restricted to patients with low-grade follicular, small cleaved cell lymphomas, as has been reported. The 14q+ chromosome is characteristic of lymphoid malignancies in general. It is due, invariably, to a translocation with the breakpoint in band 14q32, which is the locus of the immunoglobulin heavy chain genes. We propose that in each translocation, for example, chromosomes #11 or #18, an oncogene may be transposed onto chromosome #14, and that each 14q+ translocation in DHL represents an event that transposes an oncogene from another chromosome to chromosome #14.

Lymphocytic infiltrates of the conjunctiva and orbit: immunohistochemical staining of 16 cases.

The authors have performed frozen section immunologic stains on 16 cases of ocular lymphocytic infiltrates and correlated the results with clinical and histologic findings. Their cases included inflammatory pseudotumor (3), reactive lymphoid hyperplasia (3), atypical lymphocytic infiltrate (9), and small cleaved cell lymphoma (1). Seven of the nine cases with an atypical lymphocytic infiltrate expressed one immunoglobulin light chain, while only one of six considered reactive on histologic evaluation had immunologic results suggestive of a neoplastic B cell proliferation. The case of follicular small cleaved cell lymphoma expressed B lineage antigens but did not express immunoglobulin; this patient died of disseminated lymphoma two years after conjunctival involvement. Percentages and subset ratios of T lymphocytes were quantitated and showed similar results in reactive and neoplastic lesions. There is no apparent difference in clinical presentation or follow-up information between patients with reactive lesions and those having an atypical lymphocytic infiltrate with monotypic immunoglobulin.

Non-hodgkin's lymphoma phenotyping: Problems in the use of heterologous and monoclonal antibodies

Cell suspensions or frozen sections of lymph node biopsies from 32 patients with non-Hodgkin's lymphoma (NHL) were studied for sheep erythrocyte (E)-binding under three conditions (E standard, E AET, E gravity), F c and C receptors, immunoglobulin (Ig) heavy and light chain class and reactivity with heterologous antisera to T cells (T-LCL), HLA-D (Ia-like) and common acute lymphocytic leukemia (c-ALL) antigens. Selected B and T cell lymphomas were also tested for reactivity with the monoclonal antibodies OKT 3, OKT 4, OKT 6, OKT 8, OKT 11A, Leu-1, leu-2a, Leu-3a, Leu-4 and Leu-7. There were 26 B and 6 T lymphomas. Most B lymphomas were μ+ (81%), χ+ (77%) and 31% were μ+ δ+. One of the T lymphomas arose in a patient with antecedent follicular small-cleaved (B) cell lymphoma. The most accurate marker for characterizing the immunologic phenotype in NHL was the clonal excess of χ+ or λ+ cells. Neither E standard, E AET, E gravity or T-LCL were consistently reliable as sole reagents in identifying T-cell lymphomas, their individual scores often being lower than those of monoclonal pan-T cell reagents. HLA-D (Ia-like) antigen was noted in 89% of B and 50% of T lymphomas. The corresponding values for c-ALL antigen were 12 and 33%, respectively. The comparative scores in T-lymphomas between OKT 4 and Leu-3a for “helper-inducer” (HE) cells and OKT 8 and Leu-2a for “suppressor-cytotoxic” (SU) cells were not uniformly consistent. Four T lymphomas had a mixed HE/SU cell phenotype, one was HE, and another SU. Anti-T reactivity was detected in the neoplastic follicles of six of seven follicular lymphomas. The percentage of anti-T reactive cells within positive neoplastic follicles was usually small (5–15%) and of the same order as that noted within reactive lymphoid follicles (5–30%). High numbers (50–100%) of cells from five small lymphocytic B, three diffuse small cleaved cell B and six T cell lymphomas were also positive with one or more anti-T reagents, suggesting the presence of cross-reactive antigens that make phenotyping of lymphomas with monoclonal antibodies problematic. Reactivity with the monoclonal antibody Leu-7 (HNK-1), a putative NK-specific reagent, was seen in one of five B and three of five T lymphomas.