Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and other lymphomas

Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding. Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T-cell malignant lymphomas but not with peripheral tumours, or any B-cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non-neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In patients with ATLL and other T-cell malignant lymphomas, the positivity level of HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML-1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Some of the HML-1 positive ATLL cases co-expressed CD30. Furthermore, three of six cases of Ki-1 lymphoma (large anaplastic cell lymphoma) were positive for HML-1. We conclude that expression of HML-1 in ATLL reflects an activated state of the lymphoma cells, but not the intestinal origin of ATLL cells.     

Gastric T-cell lymphoma with cytotoxic phenotype

Primary gastric lymphoma usually originates from B cells of mucosa-associated lymphoid tissue (MALT) infected with Helicobacter pylori. When T-cell lymphomas develop in the stomach, they usually occur in association with infection by human T-lymphotropic virus type 1 and gastric involvement of adult T-cell leukemia. Reported herein is a unique and informative case of gastric peripheral T-cell lymphoma with a cytotoxic phenotype that histologically mimicked, and had to be carefully distinguished from, MALT-type B-cell lymphoma. The patient, a 73-year-old woman, underwent a gastric endoscopy examination, and the histological findings suggested MALT-type gastric lymphoma. Analysis of the immunoglobulin heavy chain (IgH) gene and T cell receptor gamma (TCRgamma) gene revealed monoclonal rearrangement of the TCRgamma gene. The tumor cells exhibited mild atypia and immunoreactivity with anti-CD3, anti-CD8, anti-T-cell intracellular antigen-1, antigranzyme B and antiperforin antibodies, but not with anti-CD20, anti-CD10, and anti-CD79a antibodies. The case was finally diagnosed as gastric T-cell lymphoma with cytotoxic phenotype, and this was confirmed after surgical resection. In cases such as this, small biopsy specimens from the stomach should be examined carefully for low grade B-cell-type malignant lymphoma (MALT lymphoma), because sometimes the proliferating B cells can hide the truly malignant T cells, and rearrangement analysis is useful for diagnosing T-cell malignancy.     

Specific phenotyping of T-cell proliferations in formalin-fixed paraffin-embedded tissues. Use of antibodies to the T-cell receptor beta F1.

Antibody beta F1 to a common framework determinant of the beta subunit of the T-cell receptor (TCR) was used as a specific phenotypic marker for T-cell differentiation in malignant lymphomas. Sensitivity of immunoperoxidase staining in paraffin sections was enhanced by pronase pretreatment, overnight incubation of primary antibody in Tween 20, and use of streptavidin horseradish peroxidase complexes to amplify the reaction. All 43 cases of B-cell lymphoma were negative for TCR. Reed Sternberg (RS) cells in 3 of 20 cases of Hodgkin's disease exhibited cell membrane staining for TCR (all nodular sclerosis type), further evidence that some RS cells may be T-cell derived. Twenty-nine of 44 cases of T-cell lymphoma expressed TCR (66%). These included 11 of 12 cases of peripheral T-cell lymphoma (PTCL) of small and mixed cell type, 8 of 9 cases of lymphoepithelioid cell (Lennert's) lymphoma, and 2 of 4 cases of T-cell lymphoblastic lymphoma. Loss of immunoreactivity for TCR occurred in lymphomas of large or activated T-cell type, including 7 of 9 cases of T-cell immunoblastic lymphoma and 3 of 4 cases of large cell PTCL. Antibody beta F1 is a specific and relatively sensitive marker of T-cell phenotype in formalin-fixed paraffin sections of malignant lymphomas.     

Ki-1 lymphomas in childhood: Immunohistochemical analysis and the significance of epithelial membrane antigen (EMA) as a new marker

Summary Two cases of Ki-1 lymphomas in childhood were analyzed immunohistochemically and immunoelectron microscopically. They expressed Hodgkin's disease associated antigen, Ki-1, interleukin-2 receptor (IL2R), OKT9, and HLA-DR. Histologically, the tumour cells were large in size with abundant cytoplasm and atypical nuclei. Lymph node involvement was characterized by parafollicular and marginal sinus infiltration. These features were identical to those reported in Ki-1 lymphomas. Electron microscopically tumour cells had abundant cytoplasmic organelles with pleomorphic nuclei but had no specific granules. Some tumour cells had marked interdigitation of cell membrane. Immunoelectron microscopically Ki-1 was positive on cell membrane. Tumour cells had no T-cell or B-cell antigens except for Leu-3 (T4). Unexpectedly they expressed epithelial membrane antigen (EMA) strongly. EMA was positive on cell membrane and in the cytoplasm. EMA was detected effectively in paraffin-embedded sections. Among the malignant lymphomas in childhood tested, two cases were EMA-positive. The pattern of EMA-reactivity and the histology were very similar to Ki-1 lymphomas. These results strongly suggest that Ki-1 lymphomas in childhood may arise from non-lymphoid haematopoietic cells and that EMA can be used as a new marker to distingish certain type of Ki-1 lymphomas in childhood.     

Burkitt's-like lymphoma of T-cell type

Over an 8-yr period, we studied 29 cases of Burkitt's/Burkitt's-like lymphoma and unexpectedly found 2 Burkitt's-like cases of the T-cell type. One case presented as diffuse adenopathy in a 35-yr-old male. A second case presented as a jaw mass in a 2-yr-old girl with Down's syndrome. Histologically, each case demonstrated usual Burkitt's-like morphology (intermediate-size cells with high nuclear/cytoplasmic ratio, 1 to 3 prominent nucleoli, high mitotic rate, basophilic cytoplasm, and cytoplasmic vacuolation). Ultrastructural morphometric data corroborated the Burkitt's-like nature of these neoplasms. Immunologically, the neoplasms were of "novel" T-cell phenotype, as seen in peripheral T-cell lymphoma (PTL). The cases showed variable expression of activation antigens (e.g., Ia) and weak to moderate expression of proliferation antigens as measured by Ki-67. This modest proliferative activity (less than 25% Ki-67 expression) contrasts with Burkitt's-like lymphomas of the B-cell type which usually show greater than 80% Ki-67 expression. The jaw tumor also demonstrated positivity for human progenitor cell antigen (HPCA) as commonly found in leukemia. Both cases mimic granulocytic sarcoma by virtue of their eosinophilic/myelocytic recruitment--a phenomenon previously reported in association with PTL. The patients have survived 62 wk and 20 wk, respectively, surpassing the survival rates seen in our concurrent B-cell Burkitt's-like lymphomas (12 wk). Burkitt's-like lymphoma of the T-cell type appears to be a distinctive immunological subset of potential clinical and prognostic relevance.     

Paraffin-immunohistochemical analysis of 226 non-Hodgkin's malignant lymphomas in the endemic area of human T-cell leukemia virus type 1

A study was conducted to evaluate the usefulness of paraffin-immunohistochemistry for histopathological classification of non-Hodgkin's malignant lymphomas (NHML). the phenotypes of lymphoma cells and other cells were examined using 11 monoclonal and 3 polyclonal antibodies by the ABC method on paraffin-embedded tissue sections of 226 cases of NHML, comprising 94 B-cell lymphomas (B-ML) and 132 T-cell lymphomas (T-ML). In 219 NHML cases (96.8%), lymphoma cells reacted with more than one of these antibodies. A set of MB-1, Mx-pan B, L26, LN-1, LN-2 and anti-immunoglobulin light chain antibodies characterized each subtype of B-MLs, categorized according to the Kiel classification. Mantle-zone lymphoma (MzML) was added as one subtype. L26 stained the largest number of B-MLs (82.8%). B-cell chronic lymphocytic leukemia (B-CLL) was labeled most frequently by MB-1. MzML was characterized by reactivity of lymphoma cells with LN-2 and by the appearance of monoclonal immunoglobulin light chain along the cell membrane. Follicle center cell lymphomas were stained by LN-1 and LN-2, although a small number of proliferating cells were labeled by LN-1 in B-CLL, MzML and the immunocytoma lymphoplasmacytic/cytoid variant. MT-1 and/or UCHL-1 showed various degrees of reactivity with the cell membranes of lymphoma cells in 94.8% of T-MLs. Among the T-cell pleomorphic lymphomas of Suchi and Lennert, the adult T-cell leukemia/lymphoma type, defined by stippled heterochromatin distribution and peculiar huge cells, reacted selectively (p less than 0.05) with anti-phosphokinase C antibody. Anaplastic large cell T-ML reacted with a set of Ber H2, LN-2 and Leu M1. In T-zone lymphomas without hyperplastic follicles, angioimmunoblastic lymphadenopathy with dysproteinemia-type T-ML, lymphoepithelioid cell lymphomas and some pleomorphic lymphomas comprising clear large lymphoma cells, there were many intermingling B cells, and their constitution varied. In some lymphoblastic lymphomas of both the T cell and B-cell type, phenotypes of T cells and B cells were expressed. Consequently, it was shown that paraffin immunohistochemistry was useful for the practical histopathological diagnosis of NHML even in the area where human T-cell leukemia virus type 1 is endemic.     

Immunopathology of cutaneous T-cell lymphomas.

In this study the authors attempted to establish immunopathologic criteria for the distinction of various T-cell lymphomas affecting the skin. We studied skin specimens from 27 patients with mycosis fungoides (MF) (n = 12), the Sézary syndrome (SS) (n = 6), adult T-cell leukemia (ATL) (n = 4), and nonepidermotropic T-cell lymphoma of large cell (n = 4) and lymphoblastic (n = 1) types. Identification of tumor cells in mixed cell populations and detection of weak expression of surface antigens by tumor cells was facilitated by immunoelectron microscopy. The mature helper T-cell phenotype (T11+ T3+ T4+) was found in 14 of 18 cases of MF/SS. One case of MF had a cytotoxic/suppressor (T4- T8+ 3A1+) phenotype; one with frequent blastic cells showed only weak expression of T4 antigen; 2 cases of SS were T11-. Tumor cells infiltrating the skin expressed 3Al antigen in 44% and cellular activation antigens Ia and/or Tac in 78% of patients with MF/SS. No consistent phenotypic differences were found between ATL cells from ATLV (HTLV) antibody-positive patients and tumor cells of patients with MF/SS who lacked this antibody. In contrast, a group of nonepidermotropic T-cell lymphomas showed phenotypic differences from MF/SS and ATL in all but 1 case. These cases were distinguished by the frequent absence of T3, T4, and Leu 1 antigens in 3 large-cell lymphomas; frequent expression of Ki-1 antigen, a Hodgkin's disease-associated antigen, in 2 cases with RS-like cells; and an immature thymocyte phenotype in lymphoblastic lymphoma. These findings demonstrate that tumor-cell phenotypes can be useful in distinguishing different histologic types of cutaneous T-cell lymphoma.     

Rearrangement of the T-cell receptor delta chain gene in T-cell lymphomas with a mature phenotype.

The configuration of the T-cell receptor (TCR) delta chain gene was assessed using restriction fragment analysis and the Southern blot technique in 39 T-cell lymphomas with a mature immunophenotype. The TCR delta gene was rearranged in four lymphomas although the gamma/delta TCR was not expressed in two cases studied. The TCR delta gene was the only TCR gene rearranged in two cases. Each lymphoma with TCR delta gene rearrangement had an aberrant T-cell immunophenotype and three cases were of the large cell anaplastic type. The TCR delta gene was deleted in 22 cases and was in the germline configuration in 13 lymphomas. Deletion of the TCR delta gene was characteristic of mycosis fungoides, adult T-cell leukemia/lymphoma (human T cell leukemia-lymphoma virus positive), and Lennert's lymphoma, and was not identified in angiocentric lymphomas. In eight cases with TCR delta deletion, however, a large number of polyclonal (presumably reactive) T cells were present and, in these lymphomas, the authors could not determine if TCR delta gene deletion occurred in the polyclonal T cells, the neoplastic cells, or both cell populations. The authors conclude that the TCR delta gene is usually deleted in mature T-cell lymphomas, as would be expected in alpha/beta TCR T cells. However, TCR delta gene rearrangement is detectable in approximately 10% of cases. Analysis of this locus may be useful diagnostically, as it occasionally may be the only molecular marker of clonality in mature T-cell lymphomas T-cell receptor delta chain gene rearrangement also is found most often in lymphomas of the large cell anaplastic type.     

肠道T细胞淋巴瘤中的EB病毒感染和T细胞内抗原1的表达

目的 探讨ＥＢ病毒感染在肠道Ｔ细胞淋巴瘤发病中的意义。方法 用ＥＢＥＲ１／２原位杂交及三步ＡＢＣ法免疫组织化学染色技术,观察２４例肠道Ｔ淋巴瘤患者中ＥＢ病毒感染及Ｑ细胞内抗原（ＴＩＡ－１）抗原表达情况,选用的抗体有ＴＬＡ－１,ＬＭＰ－１,ＣＤ３,ＣＤ２０,ＣＤ３０和ＣＤ４５ＲＯ等。     

Usefulness of follicular dendritic cell pattern in classification of peripheral T-cell lymphomas

Classification of peripheral T-cell lymphomas based on morphological criteria can present problems due to overlap in histological features amongst the subtypes. An immunohistochemical study was designed to study the follicular dendritic cell patterns in 21 cases of peripheral T-cell lymphoma which had been classified using the updated Kiel classification. Three patterns of distribution were observed: 1 follicular dendritic cells not detected (3 cases); 2 follicular dendritic cells restricted to remnant follicle centres (7); 3 follicular dendritic cells present as an expanded network of cells exceeding the confines of germinal centres (11). Ten out of 11 angioimmunoblastic lymphomas showed an expanded network of follicular dendritic cells. The only negative case showed features which, on review, were in keeping with a pleomorphic, medium and large cell lymphoma showing an unusual proliferation of small venules. Other than angioimmunoblastic lymphomas, only one other case showed follicular dendritic cell hyperplasia. This was an unclassified peripheral T-cell lymphoma. We conclude that follicular dendritic cell hyperplasia may be used an an aid to diagnosis of the angioimmunoblastic type of peripheral T-cell lymphoma, and we recommend the routine staining of these cells in typing of T-cell lymphomas to facilitate comparison between centres.     

Morphological characteristics of malignant T-cell lymphomas in baboons

Fifteen cases of generalized peripheral T-cell non-Hodgkin's lymphoma in baboons were phenotyped immunologically and morphologically. Using the updated Kiel classification the cases included low-grade and high-grade lymphomas and low-grade lymphomas that had transformed into high-grade lymphomas. In the low-grade group there were seven cases of lymphocytic type, partly corresponding to chronic lymphocytic leukaemia of T type and to T-zone lymphoma in man. In addition there were four cases of prolymphocytic-lymphocytic type, which show large nodules (proliferation centres) and which have no equivalent in the Kiel classification. In four cases there was a progression to an immunoblastic lymphoma and in one case to a large cell anaplastic lymphoma. In addition, three cases of large cell anaplastic lymphoma without a low-grade component were found. Both the immunoblastic lymphomas and the large cell anaplastic lymphomas corresponded well with the same types in the Kiel classification. The cases of large cell anaplastic lymphoma were also CD30 positive. Most of these lymphomas were CD4 positive, but there were rare cases that were either CD8 positive, showed both CD4 and CD8 positivity or had lost both antigens. Antigens associated with cell activation were often revealed. All but one baboon had antibodies in the blood against the retrovirus STLV-1 (simian T-cell leukaemia virus 1), which is very similar to human T-cell leukaemia virus 1 (HTLV-1) in man. Despite this virological resemblance, the morphology of these T-cell lymphomas does not resemble that of the HTLV-1-positive Japanese T-cell lymphomas but is like that of the HTLV-1-negative European cases.     

Production of transforming growth factor-beta activity by Ki-1 positive lymphoma cells and analysis of its role in the regulation of Ki-1 positive lymphoma growth.

The growth of activated human T lymphocytes in response to interleukin-2 (IL-2) is suppressed by transforming growth factor-beta (TGF-beta). This study presents data that show a diminished response of two human lymphoma cell lines to physiologic regulation by TGF-beta. Cell line L-428 was derived from the malignant pleural effusion of a patient with far advanced nodular sclerosing Hodgkin's disease and has been shown to have clonal gene rearrangements characteristic of both B and T lymphocytes. Cell line Mac-1 was derived from the blood of a patient with clinically indolent cutaneous T-cell lymphoma. Both cell lines express the Hodgkin's disease associated antigen, Ki-1. These Ki-1 positive lymphomas are shown to secrete TGF-beta into serum-free culture media. The addition of picogram quantities of exogenous TGF-beta to cell cultures of indolent Ki-1 lymphoma (Mac-1) suppresses IL-2-dependent mitosis; however, the suppression is less than 45%. This suppression correlates with a decrease in the number of IL-2 receptors. No inhibition of Ki-1 positive Hodgkin's cells (L-428) was observed, and proliferation dependent on polyclonal IL-2 was either not affected or was slightly potentiated by TGF-beta. Receptor analysis indicates the absence of IL-2 and TGF-beta receptors on L-428 cells. Thus, these Ki-1 lymphomas derived from activated lymphocytes appear to secrete TGF-beta activity but continue to proliferate because of defective suppression of IL-2 (and related lymphokine)-dependent DNA synthesis.     

Leu-M1 antigen expression in acute leukaemias

Leu-M1 is a differentiation antigen present in human myelomonocytic cells. Seventy-seven acute leukaemias were retrospectively stained with anti-Leu-M1 using the immunoperoxidase technique on Bouin-fixed paraffin-embedded sections. The subjects were 44 acute lymphoblastic leukaemias (ALL) and 33 acute myeloid leukaemias (AML) previously characterized by cytochemical and immunologic (cell suspension) methods. Leu-M1 was positive in all the AML and in half of the ALL cases. These results suggest that Leu-M1 does not allow differentiation between AML and ALL. For the ALL cases Leu-M1 was positive in 15/28 B-cell types, 4/12 T-cell type and 3/4 'null'-cell type cases. Thus, this antibody is of no assistance in defining types B, T, or 'null' in ALL. Leu-M1 was also studied on paraffin sections of 34 high grade malignant lymphomas. The antibody was negative in all 13 B-cell lymphomas (lymphoblastic: 6; immunoblastic: 7) and in all 4 'null' cell lymphomas. It was positive in 4/9 peripheral T-cell type, the other T-cell lymphomas (lymphoblastic: 5; immunoblastic: 3) remaining negative. Thus, Leu-M1 may be positive in T-cell lymphomas but it is negative in B-cell lymphomas and is always negative in B or T lymphoblastic types. It seems that lymphoblasts are Leu-M1 negative in non-Hodgkin's lymphoma and may be Leu-M1 positive in leukaemias.     

Expression of cyclin-dependent kinase 6 (cdk6) and frequent loss of CD44 in nasal-nasopharyngeal NK/T-cell lymphomas: comparison with CD56-negative peripheral T-cell lymphomas

Lymphomas involving the nasal and nasopharyngeal region mainly include CD56-positive natural killer (NK)/T-cell lymphomas, CD56-negative peripheral T-cell lymphomas (PTL), and B-cell lymphomas. Among these, the CD56-positive lymphoma, presumably of an NK/T-cell nature, is frequently seen in Asian, Mexican, and South American patients. NK cells are proposed to be closer developmentally to T cells than to other lymphoid cells, because bipotential common progenitor cells of NK/T-cell lineage have been isolated. In this study, we collected 47 cases of nasal lymphoma and investigated the phenotypic difference between NK/T-cell lymphoma and PTL by examining the pattern of the developmentally differentially expressed molecules cdk6 (cyclin-dependent kinase 6), CD44, CD117, and by examining the rearrangement of the T-cell receptor gene (TcR-GR). cdk6, an essential regulator of the cell cycle in G1 progression, was over-expressed in a subset of cortical thymocytes, but absent in mature thymocytes. In contrast, CD44, a glycosylated adhesion molecule, was absent in cortical thymocytes, but present in mature thymocytes and peripheral activated T cells. We found both over-expression of nuclear cdk6 (n-cdk6) and frequent absence of CD44 in nasal CD56-positive NK/T-cell lymphomas, in contrast to most nasal CD56-negative PTL, which were CD44-immunoreactive with weak or no expression of n-cdk6. Almost all tested cases of NK/T-cell lymphoma displayed a germ-line configuration of TcR, without evidence of gene rearrangement. Thus, there seems to be a useful distinction between the classical NK/T type of nasal lymphoma (CD56+/n-cdk6+/CD44-/TcR-GR-) and PTL (CD56-/n-cdk6-/CD44+/TcR-GR+) involving the nasal region. The presence of Epstein-Barr virus does not seem to be a good marker for distinguishing between NK/T lymphoma and PTL involving the nasal region.     

Paraffin-immunohistochemical Analysis of 26 Non-Hodgkin's Malignant Lymphomas n the Endemic Area of Human T-cell Leukemia Virus Type 1

A study was conducted to evaluate the usefulness of paraffin immunohistochemistry for histopathological classification of non Hodgkin's malignant lymphomas (NHML). The phenotypes of lymphoma cells and other cells were examined using 11 monoclonal and 3 polyclonal antibodies by the ABC method on paraffin-embedded tissue sections of 226 cases of NHML, comprising 94 B cell lymphomas (B ML) and 132 T cell lymphomas (T-ML). In 219 NHML cases (96.8%), lymphoma cells reacted with more than one of these antibodies. A set of MB 1, Mx pan B, L26, LN 1, LN 2 and antiimmunoglobulin light chain antibodies characterized each subtype of B MLs, categorized according to the Kiel classification. Mantle-zone lymphoma (MzML) was added as one subtype. L26 stained the largest number of B MLs (82.8%). B cell chronic lymphocytic leukemia (B CLL) was labeled most frequently by MB 1. MzML was characterized by reactivity of lymphoma cells with LN 2 and by the appearance of monoclonal immunoglobulin light chain along the cell membrane. Follicle center cell lymphomas were stained by LN 1 and LN 2, although a small number of proliferating cells were labeled by LN 1 in B CLL, MzML and the im-munocytoma lymphoplasmacytic/cytoid variant. MT 1 and/or UCHL-1 showed various degrees of reactivity with the cell membranes of lymphoma cells in 94.8% of T-MLs. Among the T cell pleomorphic lymphomas of Suchi and Lennert, the adult T cell leukemia/lymphoma type, defined by stippled heterochromatin distribution and peculiar huge cells, reacted selectively (p<0.05) with anti phospho-kinase C antibody. Anaplastic large cell T-ML reacted with a set of Ber H2, LN 2 and Leu Ml. In T zone lymphomas without hyperplastic follicles, angioimmuno-blastic lymphadenopathy with dysproteinemia type T-ML, lymphoepithelioid cell lymphomas and some pleomorphic lymphomas comprising clear large lymphoma cells, there were many intermingling B cells, and their constitution varied. In some lymphoblastic lymphomas of both the T cell and B cell type, phenotypes of T cells and B cells were expressed. Consequently, it was shown that paraffin immunohistochemistry was useful for the practical histopathological diagnosis of NHML even in the area where human T cell leukemia virus type 1 is endemic.     

Histological and immunohistochemical studies on primary gastrointestinal lymphomas.

To study the characteristics and histogenesis of the malignant lymphomas derived from the gastrointestinal mucosa, histologic and immunohistochemical analyses were performed on a series of 28 malignant lymphomas of the gastrointestinal tract. By cytomorphologic classification, there were two small lymphocytic lymphomas, one small cleaved cell lymphoma, two mixed small cleaved and large cell lymphomas, 17 large cell lymphomas, one small noncleaved cell lymphoma, three immunoblastic lymphomas, and two lymphoblastic lymphomas. This distribution of histologic types was compatible with that of nodal lymphoma. The lymphomas with poor prognostic histology (23 cases) outnumbered those with favorable prognosis (five cases). Three of 28 cases (one in the stomach and two in the small intestine) had cytologic features consistent with centrocytoid cell lymphoma of the mucosa associated lymphoid tissue and were large cell lymphomas. Immunophenotypically, 23 cases expressed B-cell markers (82.1%) and three cases reacted with T-cell markers. Two cases did not react with either T-cell or B-cell markers. True histiocytic lymphomas were not identified. Gastric lymphomas (nine cases) and colorectal lymphomas (three cases) were of B-lymphocyte origin whereas T-cell lymphomas were noted in the small intestine (two cases) and ileocecal region (one case). Three cases of centrocytoid lymphoma were of B-lymphocyte origin. Histologically B-cell lineage lymphomas were evenly distributed on various histologic subtypes but all T-lineage lymphomas belonged to the large cell type. The two cases with undetermined phenotype were lymphoblastic lymphomas histologically. This study showed that the primary GIT lymphomas, mostly of B-cell lineage, were not cytomorphologically distinctive from the nodal lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of T-cell antigens on Reed-Sternberg cells in a subset of patients with nodular sclerosing and mixed cellularity Hodgkin's disease

Expression of T-cell antigens by Reed-Sternberg (RS) cells has not been detected in most studies of Hodgkin's disease (HD). The authors employed an improved method of fixation (paraformaldehyde-lysine-periodate), which sharply defined cell borders and revealed T-cell antigens on RS cells in 8 of 30 (27%) cases of HD. Antigen-specific staining was confirmed by immunoelectron microscopy. RS cells expressed T11 (8/8 cases), Leu-3 or T4 (4/8 cases), Leu-4 or T3 (3/8 cases), but not other T-cell specific antigens (Leu-1, T8, T6, 3A1). RS cells were negative for leukocyte common antigen (LCA/T200), in contrast to positive LCA/T200 staining of RS-like cells in T-cell lymphomas. RS cells in all HD cases were positive for Ki-1 and/or Leu-M1 antigens. The percentage of RS cells expressing T-cell antigens was less than 20% (2 cases), 20-50% (3 cases), or greater than 50% (3 cases). This percentage and the specific T-cell antigens expressed varied in tissues from different sites in each of 2 cases. Expression of T-cell antigens by RS cells was found in nodular sclerosis (6 of 20 cases) and mixed cellularity (2 of 5 cases) but not in lymphocyte predominance (2 cases), lymphocyte depletion (1 case), or unclassified types (2 cases). Two cases of nodular sclerosis contained areas of necrosis surrounded by sheets of lacunar cells (syncytial variant of NSHD). Two other cases were associated with cutaneous lymphoma. One of these cases was mixed cellularity HD, which appeared to be confined to the skin. In a second case, tumor cells of similar phenotype (T4+, Ki-1+) were found in skin and lymph nodes of a patient with coexistent mycosis fungoides and HD. These results are consistent with an origin of RS cells from T cells in some cases of nodular sclerosing and mixed cellularity HD. They also suggest that the same cell type, an activated helper T-cell, is involved in the pathogenesis of both skin lesions and lymphadenopathy of some patients with coexistent mycosis fungoides and HD.     

Coexpression of epithelial membrane antigen (EMA), Ki-1, and interleukin-2 receptor by anaplastic large cell lymphomas. Diagnostic value in so-called malignant histiocytosis

A group of 63 cases of anaplastic large cell lymphomas (variants of diffuse large cell lymphomas often diagnosed as "malignant histiocytosis") was characterized on both morphologic criteria and expression of epithelial membrane antigen (EMA) and Ki-1 antigen (CD30). On the basis of the reactivity of these tumors with anti-EMA and anti-Ki-1 antibodies, four subtypes could be distinguished. In the majority of cases (n = 49), neoplastic cells coexpressed EMA and Ki-1 antigens. Nineteen of these cases were tested for IL-2R, and all were positive (Type I, EMA+, Ki-1+, IL-2R+). In the second group (n = 5), the neoplastic cells expressed EMA but not the Ki-1 antigen. These cases were not tested for the presence of IL-2R (Type II, EMA+, Ki-1-, IL-2R?). There were tumors with similar morphology expressing only Ki-1 antigen (Type III, EMA-, Ki-1+, IL-2R-) or negative for both EMA and Ki-1 antigens (Type IV, EMA-, Ki-1-, IL-2R-). EMA appeared to occur predominantly on activated cells, as has been previously shown for Ki-1 antigen. Analysis using monoclonal antibodies to T-cell, B-cell, or macrophage-associated differentiation antigens showed that these tumors were heterogeneous in terms of cell lineage. Tumors coexpressing EMA, Ki-1, and IL-2R (Type I), were most commonly of T-cell origin (n = 12); the remainder in this type expressed B-cell markers (n = 4), a mixed B/T phenotype (n = 2), or no clear phenotype (n = 9). By contrast, tumors of Types II, III, and IV were mainly from B-cell origin (n = 6) or showed a mixed B/T phenotype (n = 1). Despite the fact that a significant proportion of these cases were initially classified morphologically as "malignant histiocytosis," only 3 of the 63 cases were possibly of histiocytic origin. These results confirm that true malignant histiocytosis is rare and that most tumors with histologic features currently regarded as being consistent with this diagnosis are lymphocytic in origin and express activation antigens such as EMA, Ki-1 antigen, and IL-2R.     

Heterogeneity of CD3 antigen expression in T-cell lymphoma

CD 3 antigen expression was studied in a series of 98 T-cell lymphomas, using polyclonal antibodies which recognize this molecule in routinely processed, paraffin-embedded, tissue. We identified 40 cases in which CD3 was present on only a proportion of the neoplastic cells. This phenomenon of heterogeneous CD3 expression was commonest in pleomorphic T-cell lymphomas (22/42 cases) and in CD30 (Ki-1)-positive lymphomas (5/11 cases), and was less frequently observed in mycosis fungoides (4/18 cases) and not seen in T-cell lymphoblastic lymphoma (0/9 cases). CD3 expression was often related to cell morphology, with CD3 antigen being present on the smaller neoplastic cells but absent from the larger ones. The diagnostic significance of these observations is that, on occasion, it may be possible to diagnose a lymphoma as being of T-cell origin in paraffin sections by demonstrating a minor subpopulation of CD3-positive neoplastic cells.     

Two color flow cytometry of lymphocytes from patients with adult T-cell leukemia

Lymphocytes from eight patients with adult T-cell leukemia were analyzed by two color flow cytometry. Monoclonal antibodies (Leu 3 a, Leu 8, Leu 2 a and Leu 15) labelled with fluorescein isothiocyanate or phycoerythrin were used. The purpose was to identify the subsets of the lymphocytes as helper, suppressor/inducer, suppressor or cytotoxic by the surface marker of the cells. All eight patients had antibodies for ATLA. Proviral DNA in the lymphocytes was found in six patients. Summarising the results, OKT4-positive ATL cells were all of the helper T-cell subset, not the inducer subset. OKT8-positive ATL cells were also positive for OKT4 and were all of the cytotoxic T cell subset, not the suppressor subset. In two patients, some ATL cells had both OKT4 and OKT8 on the same cells, especially in the lymph nodes. In our study, ATL cells from eight cases of ATL had all of the helper T subset. These results suggest that the target cells of the human T cell leukemia/lymphoma virus type will be helper T cells.