Small Noncleaved Cell Lymphoma Research Articles

Small noncleaved cell lymphoma in adults: superior results for stages I-III disease.

Small noncleaved cell lymphoma (SNCCL), a rare lymphoma in adults, is associated with not only a rapid complete response (CR) to chemotherapy but also with the potential to rapidly relapse both systemically and in the CNS. We treated 44 assessable adults with two similar protocols, consisting of three sequential chemotherapy combinations and intrathecal prophylaxis with methotrexate and cytarabine. The overall CR rate was 80%; it was 100% in patients with Ann Arbor (AA) stages I-III disease and 57% in those with stage IV disease. The overall survival (OS) rate at 5 years was 52%. The overall 5-year freedom from tumor mortality (FTM) rate was 63%; it was 95% for patients with AA stages I-III disease, and 29% for those with stage IV disease. Stepwise multivariate analysis of factors associated with remission duration and survival indicated that advanced-disease stage and age of 40 years or over were predictors of poor prognosis. Twelve patients with positive human immunodeficiency virus (HIV) serology were also included in this series. They had an 83% CR rate and an 83% 5-year FTM, but only a 36% 5-year OS; most deaths were secondary to opportunistic infection. Histologic subtype (Burkitt's lymphoma [BL] or non-Burkitt's lymphoma [NBL]) did not correlate with patient age, site of tumor presentation, response to therapy, or survival. Both protocols achieved comparable results. The approach used in these protocols is highly effective for patients with early staged disease, regardless of their HIV status; however, better therapy is necessary for those with SNCCL presenting in an advanced stage.

Imprint cytology of non-Hodgkin's lymphomas based on a study of 212 immunologically characterized cases: Correlation of touch imprints with tissue sections

The classification of non-Hodgkin's lymphomas (NHLs) has been traditionally based on analysis of histologic sections and has been supplemented more recently by immunologic marker studies. It was the purpose of the present study to illustrate, side-by-side, sections and Romanowsky-stained imprints from the same surgical specimen from practically all categories of immunophenotyped NHLs, including rare and atypical variants that were difficult to classify from the histologic sections alone. Our results indicate that imprint cytology may reveal nuclear and cytoplasmic details not discernible in even the best tissue sections and that it may be selectively helpful in contributing to the classification of NHLs. Our results also show that the relative value of imprint cytology in the classification of malignant lymphomas varies greatly among categories. Specifically, we have found that imprints assist in three ways: the recognition of plasmacytoid features in small cell lymphocytic lymphomas, the recognition of plasmacytoid immunoblastic lymphoma, and the differentiation between NHLs which may be difficult to distinguish histologically. These include (1) small lymphocytic lymphoma versus lymphocytic lymphoma of intermediate differentiation, (2) true histiocytic malignancies versus large cell malignant lymphomas with abundant cytoplasm and/or phagocytosis, (3) anaplastic myeloma versus plasmacytoid immunoblastic lymphoma, (4) large noncleaved versus plasmacytoid immunoblastic lymphoma, (5) lymphoblastic lymphoma versus diffuse small cleaved cell lymphoma, and (6) lymphoblastic lymphoma versus small non-cleaved cell lymphoma. Lymph node imprints are easy to prepare and readily interpretable by those experienced in the study of abnormal blood and bone marrow films. Their value as an ancillary methodology aimed at optimal accuracy in the classification of NHLs should be recognized.

Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma.

We report a case of untreated non-Hodgkin's lymphoma with histologic progression over 1 yr from a low-grade, small cleaved follicular center cell lymphoma to a high-grade, small noncleaved follicular center cell lymphoma. Both lymphomas had identical immunoglobulin (Ig) heavy-chain joining gene (JH), kappa light-chain joining gene, and bcl-2 gene rearrangements, indicating the clonal identity of the two tumors. The Ig heavy chain locus on one chromosome 14 was involved in an initial t(14; 18) translocation as shown by comigrating JH and bcl-2 rearrangements. However, the oncogene c-myc was in the germline configuration in the initial lymphoma but had one allele rearranged near the 3' end of exon I in the high-grade tumor; DNA sequence analysis was consistent with a chromosomal breakpoint at that site. The presence of the c-myc rearrangement in the high-grade tumor suggest a role for c-myc in the clonal evolution of the low-grade tumor into a more aggressive lymphoma. The coexistence of both bcl-2 gene and c-myc oncogene rearrangements in the same tumor is unusual, with only a few cases reported. Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.

Involvement of c-myc oncogene in lymphoma cell lines with no detectable chromosome rearrangement of band 8q24

Two lymphoma cell lines of B-cell type were established from Japanese patients with diffuse small noncleaved cell lymphoma. Cytogenetic analysis revealed a 14q+ marker chromosome in both cell lines, and a t(8;14)(q24.1;q32.3) seemed most likely to have occurred. The chromosome 8 pair, however, had no abnormalities. Molecular analysis demonstrated c-myc amplification lacking gross rearrangement in one cell line and genetic rearrangement of c-myc at the first intron as well as aberrant sizes of c-myc mRNA in the other cell line. In the latter case, it is possible that a t(8;14)(q24.1;q32.3) was buried in an unrecognized complex translocation. A combination of cytogenetic and molecular studies to determine the precise nature of the 14q32 translocation is discussed.

Oral lymphomas in HIV-infected patients: Association with Epstein-Barr virus DNA

Nine instances of oral non-Hodgkin's lymphoma occurring in homosexual male patients infected with the human immunodeficiency virus were evaluated for clinical features, histopathologic features, lymphocyte phenotypic markers, and Epstein-Barr virus (EBV) DNA. Histologically, the tumors represented immunoblastic sarcoma and small noncleaved cell lymphomas, some manifesting Burkitt-like features. Five cases exhibited positive staining with monoclonal antibody L26, a B-cell marker; none of the tumors showed evidence of a T-cell lineage with the use of monoclonal antibody UCHL 1. DNA in situ hybridization studies disclosed the presence of EBV DNA sequences in seven instances. These findings indicate that most oral lymphomas among patients with AIDS, similar to extraoral lymphomas in this population, are of B-cell lineage and harbor EBV DNA.

Primary extranodal non‐Hodgkin's lymphoma of the oral region

Seventy cases (47M, 23F) of primary extranodal non-Hodgkin's lymphoma of the oral region were studied to determine tumor characteristics. The most frequent disease sites were the palate (21 cases), gingiva (17 cases) and parotid gland (13 cases). Each lymphoma was classified according to the criteria of the Working Formulation for Clinical Usage. Only 5.7% of cases were follicular lymphomas while diffuse lymphomas had a high incidence. Histologic subtypes included small lymphocytic (1%), small cleaved cell (7%), mixed small and large cell (20%), large cell (43%), large cell, immunoblastic (17%), lymphoblastic (9%) and small non-cleaved cell lymphoma (3%). Immunologic study utilizing the avidin-biotinylated horseradish peroxidase complex (ABC) technique demonstrated the presence of intracytoplasmic monoclonal immunoglobulin in 24 (34%) of the suggested B-cell lymphoma cases; 20 tumors (28%) were classified as T-cell lymphoma based on a positive reaction for mouse monoclonal antibody (UCHL-1) to T-cell related membrane antigen; 11 tumors (16%) contained intracytoplasmic alpha 1-antitrypsin, suggesting true histiocytic lymphoma; 15 tumors (22%) did not contain immunoglobulin, UCHL-1 or alpha 1-antitrypsin positive cells and showed no definite characteristics.

Non-Hodgkin's lymphoma in children younger than 3 years.

The distribution of histologic subtypes of non-Hodgkin's lymphoma (NHL) in children is known to differ from that in adults, but the histologic characteristics of NHL in very young children have seldom been investigated. The authors retrospectively studied 331 patients with NHL, of whom 16 were younger than 3 years old and found that the distribution of histologic subtypes in the very young patients was similar to that in older children. Six patients had small noncleaved cell lymphomas, five diffuse large cell immunoblastic, four lymphoblastic, and one had a diffuse large noncleaved cell lymphoma. The complete remission rate was 62.5% and six (37.5%) patients are long-term disease-free survivors, although remissions in the six children with large cell lymphomas were relatively brief, lasting no more than 7 months. These cases illustrate that NHL should be included in the differential diagnosis of tumors in infants and young children and that the distribution of histologic subtypes is similar to that in older children.

Non-Hodgkin's lymphoma in bone. Pathologic and radiologic features with clinical correlates.

Thirty-seven lymphomas of bone were studied, including 33 diffuse large cell lymphomas, three undifferentiated (small noncleaved cell) lymphomas, and one well-differentiated (small) lymphocytic lymphoma. The large cell lymphomas were subclassified as large cleaved, large noncleaved, multilobated cell, and immunoblastic sarcoma (large cell lymphoma, immunoblastic type). Eleven of 26 large cell lymphoma patients with adequate follow-up were long-term survivors (free of disease for more than 5 years). Nineteen of the 33 large cell lymphomas were localized to one bone. The stage and histologic pattern significantly correlated with long-term survival among large cell lymphomas. Seventy-three percent of patients with localized lymphoma were long-term survivors, in contrast to 9% of those with disseminated disease. Sixty-seven percent of patients with large cleaved and multilobated cell lymphoma were long-term survivors, but only 21% of those with large noncleaved cell and immunoblastic sarcoma were. The tumors had a blastic, lytic, or mixed radiographic appearance and had either sclerotic, lytic, or permeative borders; none of the radiologic findings were diagnostically useful.

Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia- lymphoma. Fifth International Workshop on Chromosomes in Leukemia- Lymphoma

To correlate cytogenetic findings with histology and immunophenotype, 260 newly diagnosed patients with non-Hodgkin's lymphoma (NHL) and 31 with adult T cell leukemia/lymphoma (ATL) were studied at the Fifth International Workshop on Chromosomes in Leukemia-Lymphoma. Clonal chromosome abnormalities were found in 85% of cases of NHL and in all cases of ATL. The most significant associations of histology with cytogenetics involved the 8q24 and 14;18 translocations. Of 23 NHL patients with an 8q24 translocation, 20 (87%) had small noncleaved cell (SNC) lymphoma. Of 57 NHL patients with a t(14;18)(q32;q21), 37 (65%) had a follicular lymphoma, and at least 13 others (23%) had a diffuse lymphoma of follicular center cell origin. Five others including two who also had an 8q24 translocation had SNC lymphoma; tumors in these patients lacked the monomorphic features seen in those with only an 8q24 translocation. The most striking associations of immunology with cytogenetics involved rearrangements of 14q11-13, abnormalities of 1p, trisomy 3, and trisomy 12. Abnormalities of 14q11-13 were correlated with T cell disease. Among 138 NHL and 24 ATL cases that lacked involvement of 8q24, t(14;18), or rearrangements of 14q11-13, abnormalities of 1p and trisomy 3 were significantly associated with the T cell phenotype (P less than .01) and trisomy 12 with the B cell phenotype (P less than .01). No karyotype difference was found between Japanese ATL and non-Japanese T cell lymphomas except that +3 occurred more often in the former (P = .06). Although the 8q24 translocations in 23 patients were distributed relatively equally among geographic regions (United States, ten; Europe, ten; Japan, three), the t(14;18) in 57 patients was much less frequently seen in Japan than in the other parts of the world (United States, 31; Europe, 21; Australia, four; Japan, one). Thirty-nine chromosome bands had breaks in five or more cases; a number of protooncogenes and genes related to lymphocyte function located in these bands are likely to be involved in the development of lymphoma. Thus, besides confirming the close association of particular chromosome abnormalities with histology, we have identified a number of new associations that merit molecular analysis.

Correlation of Chromosome Abnormalities With Histologic and Immunologic Characteristics in Non-Hodgkin's Lymphoma and Adult T Cell Leukemia-Lymphoma

Abstract To correlate cytogenetic findings with histology and immunophenotype, 260 newly diagnosed patients with non-Hodgkin's lymphoma (NHL) and 31 with adult T cell leukemia/lymphoma (ATL) were studied at the Fifth International Workshop on Chromosomes in Leukemia-Lymphoma. Clonal chromosome abnormalities were found in 85% of cases of NHL and in all cases of ATL. The most significant associations of histology with cytogenetics involved the 8q24 and 14;18 translocations. Of 23 NHL patients with an 8q24 translocation, 20 (87%) had small noncleaved cell (SNC) lymphoma. Of 57 NHL patients with a t(14;18)(q32;q21), 37 (65%) had a follicular lymphoma, and at least 13 others (23%) had a diffuse lymphoma of follicular center cell origin. Five others including two who also had an 8q24 translocation had SNC lymphoma; tumors in these patients lacked the monomorphic features seen in those with only an 8q24 translocation. The most striking associations of immunology with cytogenetics involved rearrangements of 14q11–13, abnormalities of 1p, trisomy 3, and trisomy 12. Abnormalities of 14q11–13 were correlated with T cell disease. Among 138 NHL and 24 ATL cases that lacked involvement of 8q24, t(14;18), or rearrangements of 14q11–13, abnormalities of 1p and trisomy 3 were significantly associated with the T cell phenotype (P less than .01) and trisomy 12 with the B cell phenotype (P less than .01). No karyotype difference was found between Japanese ATL and non-Japanese T cell lymphomas except that +3 occurred more often in the former (P = .06). Although the 8q24 translocations in 23 patients were distributed relatively equally among geographic regions (United States, ten; Europe, ten; Japan, three), the t(14;18) in 57 patients was much less frequently seen in Japan than in the other parts of the world (United States, 31; Europe, 21; Australia, four; Japan, one). Thirty-nine chromosome bands had breaks in five or more cases; a number of protooncogenes and genes related to lymphocyte function located in these bands are likely to be involved in the development of lymphoma. Thus, besides confirming the close association of particular chromosome abnormalities with histology, we have identified a number of new associations that merit molecular analysis.

The non-Hodgkin's lymphomas: Pathology, staging, treatment

The non-Hodgkin's lymphomas include a broad range of neoplasms derived from the T cells and B cells and their precursors in the lymphoid system. Although they are not among the most common cancers, the lymphomas have engendered a great deal of interest among researchers because of their interesting biology and responsiveness to therapy. The non-Hodgkin's lymphomas include at least ten major subtypes of diseases with different morphologic characteristics and clinical behavior. Based upon survival characteristics, it is convenient to divide the lymphomas into three broad categories, low grade, intermediate grade, and high grade. The low grade lymphomas usually arise in middle age or older individuals (median age, 55 years). They are derived from B cells and often have a folicular architectural pattern. They usually present with advanced stages of disease, often by virtue of bone marrow involvement. Nevertheless, patients are usually asymptomatic and may even have spontaneous regressions of disease. These lymphomas are responsive to a broad range of therapies including irradiation, single agent or multiagent chemotherapy, or combined modality therapy. They also are affected by treatment with biologicals such as alpha interferon and monoclonal antibodies. Unfortunately, response to any of these therapies is often transient and relapse is common. The intermediate grade lymphomas include the common large cell lymphomas (follicular or diffuse) and diffuse mixed cell lymphoma. These lymphomas, together with the high grade immunoblastic lymphoma, are often grouped together for the development of management strategies. These lymphomas may be derived from B cells or T cells. They occur over a broader age range than the low grade lymphomas and they are much more aggressive in their natural behavior. Effective treatment programs have been developed for both limited and advanced clinical stages of disease. In limited disease, moderately intensive chemotherapy is often combined with involved field irradiation. In advanced stage disease, more aggressive combination chemotherapy programs are usually employed. From 40% to 80% of patients may be cured with these approaches, depending upon the initial extent of disease. Two types of high grade lymphoma-lymphoblastic and small noncleaved cell are particularly aggressive in their behavior. Lymphoblastic lymphoma is a T cell lymphoma that often arises in adolescent males and presents with a large mediastinal mass, marrow, and CNS involvement. It closely resembles acute lymphoblastic leukemia (ALL) and similarly intensive chemotherapy programs as are utilized in ALL may be successful in its management. Small noncleaved cell lymphoma is a B cell lymphoma that commonly presents with bulky disease, often involving intra-abdorninal sites such as the mesentery and gastrointestinal tract. This lymphoma has a short cell cycle time and rapid tumor doubling time and prompt initiation of treatment is indicated, in view of the poor prognosis for patients who present with either of these high grade lymphomas in the presence of adverse prognostic factors such as an elevated lactic dehydrogenase (LDH) or bone marrow involvement, investigational programs such as intensive systemic therapy combined with whole body irradiation, and bone marrow transplantation are being explored.

Proliferative rates of non-Hodgkin's lymphomas as assessed by Ki-67 antibody

The Ki-67 antibody, a monoclonal antibody that reacts with nuclei in actively proliferating cells, was used in an immunohistochemical study to assess the growth fractions of non-Hodgkin's lymphomas and related disorders. The lowest proliferative indices were found in small lymphocytic lymphoma/chronic lymphocytic leukemia and intermediate lymphocytic/mantle zone lymphoma. An intermediate proliferative index was seen in the follicular lymphomas and diffuse small cleaved cell and diffuse mixed cell lymphomas. A high index was seen in the diffuse large cell lymphoma and lymphoblastic lymphoma. The highest and most consistent proliferative index was seen in small noncleaved cell lymphoma. Cases of reactive follicular hyperplasia had a significantly higher proliferative index than those of follicular lymphoma. We conclude that the Ki-67 antibody has great utility in providing an estimate of the proliferative rate of non-Hodgkin's lymphomas. Prospective studies may show this information to have prognostic value independent of histologic classification.

Expression of the Leu-8 Antigen by B-Cell Lymphomas

The Leu-8 antigen is found on the surface of many hematologic cells, including many T- and B-lymphocytes. With the use of a frozen-section immunoperoxidase technic, 152 B-cell non-Hodgkin's lymphomas were examined for Leu-8 expression. Of these lymphomas, 53% expressed Leu-8. Subclassification of the lymphomas with the use of the International Working Formulation showed that most small lymphocytic, intermediate lymphocytic, and diffuse large cell lymphomas and about half of diffuse small cleaved, diffuse mixed, and follicular lymphomas expressed Leu-8. In contrast, all 17 cases of small noncleaved cell (Burkitt's) lymphoma and 9 of 10 cases of multiple myeloma/plasmacytoma were Leu-8 negative. These results indicate that Leu-8 is expressed on a wide variety of B-cell lymphomas and that differences in Leu-8 expression may be useful in the diagnostic separation of small lymphocytic lymphoma with plasmacytoid features from multiple myeloma/plasmacytoma, and diffuse large cell lymphoma from Burkitt's lymphoma.

The gene located at chromosome 18 band q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas

The karyotypic abnormality t(14;18)(q32;q21) is reported to occur in 75% of follicular lymphomas. This translocation results in the rearrangement of a putative oncogene bcl-2, which resides at chromosome 18 band q21 (the 18q21 gene). Using two human genomic DNA fragments cloned from the chromosome 18 band q21 as probes, we analyzed 65 uncultured human lymphoma samples by the Southern blot technique. The 18q21 gene was rearranged in 18 of 26 (69%) follicular lymphomas, 3 of 5 (60%) follicular lymphomas transformed to large cell lymphomas, 8 of 20 (40%) diffuse large cell lymphomas (DLCLs), and 2 of 7 (29%) small noncleaved cell lymphomas (SNCs). Our analysis detected rearrangement of the 18q21 gene in 10 of 13 (77%) cases in which the t(14;18)(q32;q21) translocation was found by cytogenetic techniques. Our analysis also proved helpful in difficult karyotyping situations: (a) identifying the donor chromosome fragment as chromosome 18 band q21 in 4 of 9 (44%) cases that cytogenetically displayed a 14q+ chromosome of unknown origin, and (b) identifying a rearrangement of chromosome 18 band q21 in 12 of 18 (67%) cases that cytogenetically yielded no cells in metaphase. We also demonstrated three cases of submicroscopic rearrangement of the 18q21 gene. In our studies, patients with DLCLs and rearrangement of the 18q21 gene had a significantly higher incidence of extranodal involvement when compared with patients with DLCLs and no 18q21 gene rearrangement (P = 0.03).

The Gene Located at Chromosome 18 Band q21 Is Rearranged in Uncultured Diffuse Lymphomas as Well as Follicular Lymphomas

The karyotypic abnormality t(14;18)(q32;q21) is reported to occur in 75% of follicular lymphomas. This translocation results in the rearrangement of a putative oncogene bcl-2, which resides at chromosome 18 band q21 (the 18q21 gene). Using two human genomic DNA fragments cloned from the chromosome 18 band q21 as probes, we analyzed 65 uncultured human lymphoma samples by the Southern blot technique. The 18q21 gene was rearranged in 18 of 26 (69%) follicular lymphomas, 3 of 5 (60%) follicular lymphomas transformed to large cell lymphomas, 8 of 20 (40%) diffuse large cell lymphomas (DLCLs), and 2 of 7 (29%) small noncleaved cell lymphomas (SNCs). Our analysis detected rearrangement of the 18q21 gene in 10 of 13 (77%) cases in which the t(14;18)(q32;q21) translocation was found by cytogenetic techniques. Our analysis also proved helpful in difficult karyotyping situations: (a) identifying the donor chromosome fragment as chromosome 18 band q21 in 4 of 9 (44%) cases that cytogenetically displayed a 14q+ chromosome of unknown origin, and (b) identifying a rearrangement of chromosome 18 band q21 in 12 of 18 (67%) cases that cytogenetically yielded no cells in metaphase. We also demonstrated three cases of submicroscopic rearrangement of the 18q21 gene. In our studies, patients with DLCLs and rearrangement of the 18q21 gene had a significantly higher incidence of extranodal involvement when compared with patients with DLCLs and no 18q21 gene rearrangement (P = 0.03).

Small noncleaved follicular center cell lymphoma: Burkitt's and non-Burkitt's variants in the US II. Pathologic and immunologic features

The morphologic criteria for the two variants of small noncleaved follicular center cell (SNC FCC) lymphoma in the Lukes-Collins classification, Burkitt's (BL) and non-Burkitt's variants (NBL), were evaluated and related to the results of multiparameter laboratory and clinical studies. Forty-two patients were studied: 25 cases were classified as BL according to World Health Organization (WHO) criteria. Seventeen cases were classified as NBL on the basis of greater variability in nuclear size and shape, more prominent nucleoli, and greater variation in the amount of cytoplasm. Neoplastic follicles were present in three cases of BL and two of NBL, indicating an FCC origin for this lymphoma. Electron microscopic examination confirmed the light microscopic features. Immunoglobulin (Ig) monoclonality, as demonstrated by immunofluorescence (surface Ig) and/or immunoperoxidase staining for cytoplasmic immunoglobulin (CIg), was demonstrated in 21 of 24 (87.5%) of BL and 13 of 16 (71%) of NBL. Clinically, BL presented more frequently in extranodal sites and with gastrointestinal involvement than NBL. Bone marrow involvement was more common in NBL patients. Both groups had advanced stage disease at diagnosis. The median survival was 10.5 months in BL and 7.7 months in NBL. The results of this study indicate that BL and NBL are biologically related variants of SNC FCC lymphoma but have different presentations, which may be clinically significant.

Small non-cleaved follicular center cell lymphoma in Turkey. Burkitt's and non-Burkitt's types. A retrospective clinicopathologic analysis of 53 cases in the pediatric age group.

Fifty-three patients in the pediatric age group diagnosed as having small non-cleaved follicular center cell (FCC) lymphoma (40 Burkitt's and 13 non-Burkitt's type) have been re-evaluated. Although the histopathologic distinction between the two subgroups is fairly easy to determine there is a considerable degree of clinical overlap in regard to age, sex, anatomic presentation of the disease, the incidence of bone marrow and central nervous system involvement, and the survival. The most important determinant of survival in both subgroups is the stage of the disease.

The non-hodgkin's lymphomas: pathology, staging, treatment

The non-Hodgkin's lymphomas include a broad range of neoplasms derived from the T cells and B cells and their precursors in the lymphoid system. Although they are not among the most common cancers, the lymphomas have engendered a great deal of interest among researchers because of their interesting biology and responsiveness to therapy. The non-Hodgkin's lymphomas include at least ten major subtypes of diseases with different morphologic characteristics and clinical behavior. Based upon survival characteristics, it is convenient to divide the lymphomas into three broad categories, low grade, intermediate grade, and high grade. The low grade lymphomas usually arise in middle age or older individuals (median age, 55 years). They are derived from B cells and often have a folicular architectural pattern. They usually present with advanced stages of disease, often by virtue of bone marrow involvement. Nevertheless, patients are usually asymptomatic and may even have spontaneous regressions of disease. These lymphomas are responsive to a broad range of therapies including irradiation, single agent or multiagent chemotherapy, or combined modality therapy. They also are affected by treatment with biologicals such as alpha interferon and monoclonal antibodies. Unfortunately, response to any of these therapies is often transient and relapse is common. The intermediate grade lymphomas include the common large cell lymphomas (follicular or diffuse) and diffuse mixed cell lymphoma. These lymphomas, together with the high grade immunoblastic lymphoma, are often grouped together for the development of management strategies. These lymphomas may be derived from B cells or T cells. They occur over a broader age range than the low grade lymphomas and they are much more aggressive in their natural behavior. Effective treatment programs have been developed for both limited and advanced clinical stages of disease. In limited disease, moderately intensive chemotherapy is often combined with involved field irradiation. In advanced stage disease, more aggressive combination chemotherapy programs are usually employed. From 40% to 80% of patients may be cured with these approaches, depending upon the initial extent of disease. Two types of high grade lymphoma-lymphoblastic and small noncleaved cell are particularly aggressive in their behavior. Lymphoblastic lymphoma is a T cell lymphoma that often arises in adolescent males and presents with a large mediastinal mass, marrow, and CNS involvement. It closely resembles acute lymphoblastic leukemia (ALL) and similarly intensive chemotherapy programs as are utilized in ALL may be successful in its management. Small noncleaved cell lymphoma is a B cell lymphoma that commonly presents with bulky disease, often involving intra-abdorninal sites such as the mesentery and gastrointestinal tract. This lymphoma has a short cell cycle time and rapid tumor doubling time and prompt initiation of treatment is indicated, in view of the poor prognosis for patients who present with either of these high grade lymphomas in the presence of adverse prognostic factors such as an elevated lactic dehydrogenase (LDH) or bone marrow involvement, investigational programs such as intensive systemic therapy combined with whole body irradiation, and bone marrow transplantation are being explored.

Combined modality therapy for adults with small noncleaved cell lymphoma (Burkitt's and non-Burkitt's types).

Between June 1979 and June 1984 18 adult patients with small noncleaved cell lymphoma (SNCL) (diffuse undifferentiated lymphoma, Burkitt's and non-Burkitt's types of the Rappaport classification) were treated with high-dose cyclophosphamide, doxorubicin, vincristine, prednisone, midcycle high-dose methotrexate, and intrathecal methotrexate. Early in the course of treatment, hyperfractionated radiotherapy (125 cGy, every two days, for 1,500 to 2,250 centigray [cGy]) was administered to unresected masses greater than 10 cm in their greatest dimension. Chemotherapy was administered every 21 days for six to ten cycles. Treatment was generally well tolerated; however, one patient died of probable tumor lysis syndrome. With a median follow-up of 1.2 years, actuarial survival was 66.8% and relapse-free survival (RFS) was 71.3% for the entire group. All treatment failures and deaths occurred in patients with stage D disease. RFS projected at 2 years was 100% for stages A and AR and 60.6% for stage B, C, and D (P = .13 Gehan). Two-year RFS for patients with stage A, AR, B, or C disease was 100 v 41% for those with stage D disease. Patients with adverse prognostic features (n = 7)--unresected bulk measuring greater than 10 cm, pretreatment serum lactate dehydrogenase (LDH) 500 IU/L (normal, 200) or involvement of CNS or bone marrow--had a projected RFS of 28.6% compared with 100% for those patients without these features (P = .002 Gehan). Too few patients received induction radiotherapy to assert its role in therapy. By using aggressive multiagent therapy, cure can be expected in a high percentage of adults with SNCL. In the subset with adverse prognostic features, more effective therapy is necessary.

Small noncleaved cell lymphoma: An immunophenotypic study of 18 cases and comparison with large cell lymphoma

Eighteen cases of small noncleaved cell lymphoma (SNCL) were studied with a large panel of monoclonal antibodies applied to tissue frozen sections and compared with 18 cases of immunoglobulin-expressing diffuse large cell lymphoma (DLCL). Immunoglobulin expression was seen in all cases of SNCL, with a predominance of cases showing lambda light chain restriction. Expression of mu and delta heavy chains was common, but gamma and alpha chain expression was uncommon. In the cases of SNCL T015, B1, B2, 41H, BA-1, BA-2, Ia, CALLA, and OKT10 were generally expressed, and a large percentage of cells expressed Ki-67. Only rare expression of T05, Leu-8, and Leu-9 was seen, and in no case was reactivity with anti-Tac antibodies observed. In contrast, the immunoglobulin-expressing DLCLs showed the typical predominance of cases of kappa light chain restriction, a lower proportion of cases with mu or delta expression, and a higher proportion of cases with gamma expression. A lower incidence of Leu-8, T05, and Tac expression and a higher incidence of BA-1, CALLA, Ki-67 and OKT10 were seen in the SNCLs as compared with the DLCLs. It is concluded that immunologic studies may be of considerable aid in the differential diagnosis of SNCL and DLCL.