A phenotypic and genotypic study of three node-based, low-grade peripheral T-cell lymphomas: angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma.

Phenotypic and genotypic findings were correlated and compared for 35 specimens taken from 34 patients with three specific types of low-grade peripheral T-cell lymphoma: lymphoepithelioid (LeL), angioimmunoblastic (AILD), and T-zone (TzL) lymphoma. Frozen sections were stained by the double immunoenzymatic method using a combination of the monoclonal antibody Ki-67 for proliferating nuclei and those against lymphocyte surface antigens. Data were correlated by observing clonal rearrangements in the genes of the T-cell receptor beta chain (TCR beta). Of the 35 specimens studied, 32 (91%) were of predominantly CD4+ helper cell proliferation, and 21 (60%) showed the TCR beta gene rearrangement. There were 15 cases of AILD and TzL with predominantly helper cell proliferation, which contained a minimum of 21% CD4+Ki-67+ cells based on the total number of cells present in the specimen. Of these, 13 (87%) showed TCR beta rearrangement. In eight cases, containing a maximum of 20% CD4+Ki-67+ cells, only one (13%) showed any rearrangement. In addition, TCR beta rearrangement was observed in five of the nine cases of LeL, including two cases with only 12% CD4+Ki-67+ cells. For each of the three types, the proportion of CD4+ cells among the Ki-67+ population showed a relatively good correlation with the clonal TCR beta gene rearrangement. Moreover, there was a significant difference (P less than 0.05) in survival curves between groups with and without TCR beta rearrangement, although no obvious plateau was seen. These results suggest that the paucity of tumor cells in these lesions may account for the absence of a detectable band of rearrangements in some patients with one of these three specific types of low-grade peripheral T-cell lymphoma.     

Peripheral T-cell lymphoma. A clinicopathologic study of a morphologically diverse entity

We analyzed the clinicopathologic features of 13 patients with immunologically confirmed peripheral T-cell lymphoma. The lymphomas were classified into poorly differentiated lymphocytic, mixed cell, and large cell types. Marked morphologic heterogeneity was noted within the mixed cell and large cell categories, and the various subtypes are described. Twelve of the 13 patients received multiagent chemotherapy. Only three of the nine patients with poorly differentiated or mixed cell lymphomas achieved a complete remission, and the median survival for this group was 11 months. In contrast, all three of the treated patients with large cell lymphomas achieved a complete remission, two of whom are alive without disease (14 and 29 months, respectively). Classification of peripheral T-cell lymphomas into lymphocytic, mixed cell, and large cell types, as well as further subclassification within the heterogeneous groups, is suggested so that pathologic features of prognostic significance can be identified.     

Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases

We analysed the clinical and pathologic features of 42 patients with immunologically confirmed peripheral T-cell lymphoma. The median age was 60 years and the male to female ratio was 1:1. A prior lymphoproliferative or autoimmune disorder was present in 14 per cent of the patients. Signs of advanced disease were usually present from the onset, such as B symptoms (55 per cent), generalized lymphadenopathy (57 per cent), stage III/IV disease (62 per cent), and elevated levels of serum lactate dehydrogenase (68 per cent). Primary extranodal disease (14 per cent), hepatomegaly (12 per cent), splenomegaly (12 per cent), lung/pleural involvement (12 per cent), skin involvement (21 per cent), and bone marrow involvement (28 per cent) were uncommon. Lymphocytopenia was present in 64 per cent of the patients, and none of nine patients tested were serologically positive for human T-cell leukemia/lymphoma virus (HTLV-I) infection. Among 38 patients receiving combination chemotherapy, 20 (53 per cent) achieved a complete remission. The actuarial median survival of all patients was 17 months. Age greater than 60 years and stage III/IV disease predicted a poor clinical outcome, whereas the large cell histological subtype predicted a favourable outcome. Prospective clinical studies using uniform treatments and a uniform histologic classification scheme are needed to confirm these findings.     

Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases

Clinical and histopathologic material from 42 patients with peripheral T-cell lymphoma (PTCL) was reviewed. The median age was 63.5 years (range, 11-97 years). The male:female ratio was 2.8:1. Prior immune or lymphoproliferative diseases occurred in 36% of the patients. PTCL was advanced at presentation with B symptoms (67%), generalized adenopathy (69%), and stage III/IV disease (79%). Suspected lung or pleural involvement (21%), hepatomegaly (29%), and splenomegaly (43%) were common; marrow involvement was documented in 37% of the patients at presentation and in 51% of patients during the illness. Hypercalcemia and eosinophilia occurred in 19% and 29% of patients, respectively. Among patients receiving combination chemotherapy (BCOP, CHOP, BACOP, COMLA), eight (24%) of 33 achieved a complete remission and only four (12%) of 33 had a sustained complete remission. The median survival for PTCL was 11 months. Because of the poor response to standard therapy, clinical trials should identify cases of PTCL and evaluate newer regimens in this subset of aggressive lymphoma.     

Adult T-cell leukemia/lymphoma in Taiwan. A clinicopathologic observation

The retrovirus-associated adult T-cell leukemia/lymphoma (ATL) has not been previously documented in Taiwan. Five cases identified recently by the authors are reported. Three of the patients were women, and their ages ranged from 36 to 60 years. The most important diagnostic clue was the observation of polylobated lymphoid cells in the peripheral blood. Other variably observed significant features included hypercalcemia, cutaneous eruptions, osteolytic bone lesion, hepatomegaly, and lymphadenopathy. Surface marker studies revealed that the leukemic or lymphoma cells were T-helper cells. Histopathologic examination revealed one case of pleomorphic type and three cases of medium-sized cell type. No tissue was available for study in one case. The diagnosis of ATL was confirmed by the indirect immunofluorescence test on MT-1 cell for antibodies to adult T-cell leukemia virus-associated antigen (ATLA). Three patients were dead within 6 months, and two patients had been in clinical remission for 7 and 10 months, respectively. These two latter cases were similar to the so-called smoldering type of ATL. Two descendents among nine relatives of the patients were also positive for anti-ATLA (22%). Two husbands were negative. Four of the five patients lived in the same county in northeastern coastal Taiwan, which suggested a possible clustering of ATL in that region.     

Lymphoma type adult T-cell leukemia--a clinicopathologic study of HTLV related T-cell type malignant lymphoma

The clinical and pathological features of T-cell type malignant lymphoma related to human T-cell leukemia virus (HTLV) were investigated in eight patients presenting lymphadenopathy. Biopsy of lymph nodes showed an histology of diffuse non-Hodgkin's lymphoma. All patients were positive for anti-ATLA antibody and HTLV proviral DNA in the lymph node cells. Most patients showed pronounced hypercalcemia and high serum levels of lactic dehydrogenase. All patients died between 3 and 17 months (mean 8 months) after the onset of disease. HTLV-related malignant lymphoma should be added to the spectrum of ATL, being classified as a lymphoma type ATL.     

A clinicopathologic study of orbital and adnexal non-Hodgkin's lymphoma.

An analysis of non-Hodgkin's lymphoma involving the orbital structures was performed at the University of Iowa between 1937 and 1975. Sixteen cases of primary orbital lymphoma were diagnosed. Histopathologic reclassification according to the Rappaport scheme and the clinical course of each histologic sub-category was described. There were 5 patients with reactive hyperplasia, 2 patients with well-differentiated lymphoid proliferation with Dutcher bodies which were also felt to be reactive, 3 patients with diffuse poorly differentiated lymphocytic lymphoma, 4 patients with nodular poorly differentiated lymphocytic lymphoma, and 2 patients with diffuse histiocytic lymphoma. It was concluded that the Rappaport classification is applicable to orbital lymphoid tumors and that those lymphomas which do present as primary tumors should be staged as one would stage the same histologic category of lymphoma presenting in other sites. Radiation therapy appears to be an effective treatment for local control; however, patients with primary orbital lymphoma should undergo observation for systemic disease similar to patients with lymphoma presenting in other sites. Excisional biopsy is recommended to facilitate precise classification.     

Cytogenetic and immunohistochemical analysis of lymphoepithelioid cell lymphoma (Lennert's lymphoma): further substantiation of its T-cell nature

In 1968 a special variant of Hodgkin's disease, epithelioid cellular lymphogranulomatosis--later on termed lymphoepithelioid cell lymphoma/Lennert's lymphoma--was defined. There are increasing indicators that Lennert's lymphoma is of T-cell origin. Seven cases of Lennert's lymphoma are studied with cytogenetic as well as immunohistochemical techniques. Six of them have cytogenetic abnormal clones always including aberrations of chromosome No. 3 (+3, break in q22, dup q22----q24). In all cases band 3q22 is either broken or duplicated. Immunohistochemically it is clearly demonstrated that the proliferating cells are of T-cell nature (Ki67+, Leu4+, Leu1+). Under consideration in the literature it can be stated in conclusion that (1) lymphoepithelioid cell lymphoma (Lennert's lymphoma) with aberrations has to be designated as malignant lymphoma, (2) immunohistochemical double labeling proved the T-cell nature of this lymphoma, (3) there are remarkable similarities between the chromosomal patterns of lymphoepithelioid cell lymphoma, lymphogranulomatosis X/angioimmunoblastic lymphadenopathy and probably Hodgkin's disease: many normal mitoses and abnormalities of chromosome No. 3, especially trisomy. It is discussed that abnormalities of chromosome No. 3 involving band q22 are an indicator of a common genetic background of these lymphomas.     

Anti-human T-cell lymphotrophic virus type I antibody-positive adult T-cell leukemia/lymphoma with no monoclonal proviral DNA. A clinicopathologic and immunologic study

Proviral DNA of adult T-cell leukemia virus (HTLV-I) was examined by the standard Southern blotting method in lymph nodes of 45 patients with anti-HTLV-I antibody (ATLA)-positive adult T-cell leukemia/lymphoma (ATLL). Six of these patients revealed no monoclonal proviral HTLV-I DNA in tumor cells. These six patients showed typical flower cells in peripheral blood; they comprised five cases of the smoldering type and one of lymphoma type. They showed a longer clinical course than ATLL patients with integrated proviral HTLV-I DNA. Five of the six patients were alive from 8 to 36 months after onset; the other patient died 9 months after onset. Histologically, they exhibited features of T-cell malignancy but with absence of the typical cerebriform giant cells that are usually present in ATLL. The tumor cells represented T-cell markers, usually CD4, but CD25 was negative. Rearrangement of the T-cell receptor gene C beta was found in four of the six cases. On the basis of these results, cases of ATLL with no monoclonal proviral HTLV-I DNA should be clinicopathologically differentiated from those with integrated proviral DNA.     

Primary gastrointestinal lymphoma. A clinicopathologic study of 102 patients

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

IMMUNOBLASTICLYMPHADENOPATHY－LIKE T－CELLL YMPHOMA：A CLINICOPATHOLOGIC AND IMMUNOPHENOTYPIC ANALYSIS OF 24 CASES

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Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma. Clinical, histopathologic, and immunohistochemical analyses

An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which usually shows the same phenotype as CTCL, i.e., a helper/inducer T-cell phenotype (CD4+CD8-), and usually involves the skin. Clinically, both CTCL and ATL are heterogeneous in nature. In this study, we demonstrated differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant clinical findings were peripheral lymph node involvement, skin lesions, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, by contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was demonstrated. Phenotypic heterogeneity of ATL in the skin, i.e., CD4-CD8-, CD4+CD8-, and CD4-CD8+, was demonstrated. Expression of Leu8, CD7 (Leu9), and CD45RA (2H4) was high in both the skin-infiltrating ATL cells and peripheral blood and lymph node ATL cells compared with that in the skin-infiltrating CTCL cells. Expression of CD25 (IL-2R), CD71 (OKT9), HLA-DR, and HLA-DQ was higher in the skin-infiltrating ATL cells than in CTCL cells. Expression of CD29 (4B4) was high, and that of CD45RA (2H4) was low in both the skin-infiltrating ATL and CTCL cells compared with the peripheral blood and lymph node ATL cells. Expression of CD45RO (UCHL-1) was not significantly high in the skin-infiltrating CTCL cells compared with that in ATL cells. The most significant phenotypic difference between ATL cells and CTCL cells was the expression of Leu8 (lymph node homing receptor), CD7 and CD25 antigens on the cell surface, and the main phenotypic difference between skin-infiltrating ATL and CTCL cells and peripheral blood and lymph node ATL cells was the expression of CD29 and CD45RA. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL, and suggest that the predominant phenotype of peripheral blood and lymph node ATL cells is that of naive, relatively immature or activated T-cells, and that CTCL cells are previously activated (memory) T-cells. In other words, CTCL cells do not share the same origin as ATL cells. These observations support the concept that ATL is a disease distinct from CTCL.     

Management of peripheral T-cell non-Hodgkin's lymphoma

PURPOSE OF REVIEW: Peripheral T-cell lymphomas are an uncommon and heterogeneous group of non-Hodgkin's lymphomas that are noted for their particularly poor prognosis. Their rarity has resulted in few data being available to allow formulation of optimal treatment approaches. There remains no widely accepted standard therapy. A new and increasing interest in studying these lymphomas is leading to advances in our understanding, which is widening options for management. RECENT FINDINGS: Historically, peripheral T-cell lymphomas were treated with strategies borrowed from management of aggressive B-cell lymphomas. Investigators have recognized the inadequacy of these approaches, and we are beginning to receive results, often preliminary, of studies specifically designed to evaluate T-cell lymphomas. These range from transplantation approaches, to better prognostic schemes and to attempts at molecular characterization, and new drugs are being developed specifically for their activity against T-cell lymphomas. SUMMARY: Research in T-cell lymphomas is still mainly preliminary and studies tend to be small. Nonetheless, our understanding of these disorders is increasing, and data on new and hopefully better approaches are emerging.     

外周T细胞淋巴瘤治疗进展

外周T细胞淋巴瘤(PTCL)是我国较为常见的一种非霍奇金淋巴瘤亚型,临床多具有高度侵袭性,疾病进展迅速,目前治疗方法效果差,总体预后不良。第62届美国血液学会年会上报道了PTCL分子靶向及免疫治疗方面的进展,包括程序性死亡受体1/程序性死亡受体配体1抗体、JAK抑制剂和维布妥昔单抗等,为患者带来了更好的前景。     

Treatment of a patient with a nodal peripheral T-cell lymphoma (Angioimmunoblastic T-cell lymphoma) with a human monoclonal antibody against the CD4 antigen (HuMax-CD4)

A patient with a CD4+ refractory peripheral T-cell lymphoma (PTL), subtype angioimmunoblastic T-cell lymphoma (AILD), was treated with a human monoclonal anti-CD4 antibody (HuMax-CD4) iv once weekly for 10 wk. Early during treatment all palpable enlarged lymph nodes disappeared. A decline of normal CD4+ T-cells in the blood mirrored the treatment effect. Shortly after stopping treatment the patient relapsed with new enlarged lymph nodes. This time no antitumor effect was seen when HuMax-CD4 treatment was reinstituted. No severe side effects were observed during the antibody treatment. This case report is the first describing that HuMax-CD4 has antilymphoma activity in PTL and is an interesting drug to study further in patients with CD4+ PTL.     

T-cell/histiocyte-rich large B-cell lymphoma: a distinct clinicopathologic entity.

PURPOSE: Although it has proven difficult to delineate diagnostically reproducible and clinically relevant subgroups, the heterogeneity of diffuse large B-cell lymphomas (DLBCL) is widely acknowledged. In 1992, we reported on six cases that suggested that large B-cell lymphoma rich in stromal histiocytes and T cells may be identified as a distinct clinicopathologic entity within DLBCL. PATIENTS AND METHODS: An integrated clinicopathologic study of 40 cases of this DLBCL subtype is presented. RESULTS: Distinguishing a DLBCL rich in histiocytes and reactive T cells, designated T-cell/histiocyte--rich large B-cell lymphoma (THR-BCL), may be justified from a clinical point of view. The disease typically affects middle-aged male patients who usually present with advanced-stage disease that is not adequately managed with current therapeutic strategies. Whereas proliferation fraction and p53 overexpression, in addition to the clinical variables incorporated in the International Prognostic Index (IPI), significantly correlate with response to treatment and survival in a univariate analysis, only the IPI score identifies relevant prognostic THR-BCL subpopulations in a multivariate model. The morphologic and immunophenotypic profile of the neoplastic B cells in THR-BCL suggests that they may originate from a germinal center ancestor. CONCLUSION: THR-BCL constitutes a distinct clinicopathologic entity that is characterized by an aggressive behavior. Experimental therapeutic strategies may be indicated to obtain a more favorable response to treatment in this disease.     

Peripheral T-cell lymphoma. A clinical, histologic, and immunologic study of five cases

The authors describe five white patients with peripheral T-cell lymphoma. Four patients were older than 65 years. All cases presented with a short clinical course and advanced stage at the time of diagnosis. Clinical manifestations included asthenia, weight loss, peripheral and abdominal lymphadenopathy. One case showed tonsillar involvement and subcutaneous lymph node enlargement; hepatomegaly was present in four cases, two of them with splenomegaly. Only one case presented peripheral lymphocytosis and antibodies to human T-leukemia virus. Although three cases were classified as diffuse mixed lymphomas and two as poorly differentiated lymphocytic lymphomas, there were some common characteristics: diffuse infiltration by different proportions of small lymphoid cells and large immunoblasts, some of them multinucleated and similar to Reed-Sternberg cells; accumulation of histiocytes, plasmacytosis, eosinophilia, venular proliferation and compartmentalization were also found. Bone marrow infiltration was observed in two patients. Results of monoclonal markers showed four cases to be OKT4+ and the other OKT8+. The morphologic and immunologic characteristics of these patients were typical and similar to those reported from other geographical areas.