Adult T-cell leukemia/lymphoma in Jujuy,north-west Argentina

Human T-cell leukemia virus type 1 (HTLV-1) infection is prevalent in native Americans living in the Andes. Some of their malignant lymphomas (ML) show a peculiar histology suggestive of adult T-cell leukemia/lymphoma (ATLL). To determine whether ML resembling ATLL are indeed ATLL, re-analysis of 34 cases occurring in Jujuy, a province of Argentina, was conducted, concentrating on immunological phenotype, integration of HTLV-1 proviral DNA, expression of HTLV-1 p40Tax and p27Rex, and infection of Epstein-Barr virus (EBV). The ML were 22 cases of mature peripheral T-cell and natural killer (NK)-cell neoplasm (mT/NKN), 11 B-cell malignant neoplasms and one Hodgkin's lymphoma. Polymerase chain reaction against the HTLV-1 proviral DNA, using DNA extracted from paraffin sections, indicated integration of the HTLV-1 proviral DNA in three cases of eight mT/NKN. Two other cases of mT/NKN were positive for anti-HTLV-1 antibodies. Expression of p40Tax and p27Rex was detected in all five of these mT/NKN cases associated with HTLV-1. As such, these five mT/NKN were rediagnosed as ATLL. In situ hybridization signals for EBV-encoded small nuclear early region-1 were detected in nine cases of mT/NKN, of which five cases of NK-cell lymphoma were found to have cytoplasmic CD3 expression, a CD56 phenotype and positivity of TIA1. According to the new World Health Organization classification, the mT/NKN class includes five cases of ATLL and five cases of NK-cell lymphomas. The five cases of ATLL were of native American extraction from an HTLV-1-endemic area around Jujuy, north-west Argentina.     

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.     

Frequent expression of CD30 antigen in the primary gastric non-B, non-Hodgkin lymphomas

Most primary gastric lymphomas are of B-cell origin. Fourteen cases of primary gastric non-B, non-Hodgkin lymphomas were studied to evaluate their clinicopathological and immunophenotypic findings. The cases were comprised of 11 men and three women, with a median age of 56.5 years. Most patients underwent surgery either with or without chemotherapy, exhibiting a 5 year survival rate of 57.5%. Morphologically, the neoplastic cells showed various histological features, such as anaplastic large cell lymphoma (ALCL) (n = 3), peripheral T-cell lymphoma, unspecified, large (n = 4), medium-sized (n = 2) and mixed cell (n = 5). Two cases displayed a non-B, non-T cell phenotype, whereas the remaining cases displayed a T-cell phenotype. Six cases were CD4+, while two were CD8+. The neoplastic cells were CD30+ in 10 cases. TIA-1 was positive in six cases. In one case, anaplastic large cell lymphoma kinase (ALK) was identified with immunostaining and chromosomal rearrangement of ALK was detected by fluorescence in situ hybridization (FISH). In conclusion, although the mechanism of CD30 expression is unknown, primary gastric non-B, non-Hodgkin lymphomas tend to express CD30. We consider that some of the cases in the present study may be derived from cytotoxic T cells, similar to systemic and cutaneous ALCL, the majority of which exhibit TIA-1.     

Primary non-Hodgkin's lymphoma of the intestine: a morphological, immunohistochemical and clinical study of 31 Chinese cases

Thirty-one cases of primary non-Hodgkin's lymphoma of the intestine were investigated. Twenty-one were of B-cell and 10 of T-cell origin. The B-cell lymphomas comprised two cases of low-grade B-cell lymphoma of mucosaassociated lymphoid tissue (MALT), one of centroblastic/centrocytic type, three of high-grade B-cell lymphoma coexisting with a low-grade B-cell lymphoma of MALT, nine of centroblastic, three of immunoblastic and three of Burkitt type. Of the T-cell lymphomas, eight were of pleomorphic medium-to large-sized cell type and two of large cell anaplastic type. All the B-cell lymphomas expressed CD20 (L26) and/or Ki-B5; in six there was monotypic immunoglobulin light chain restriction. Membrane positivity for CD45RO (UCHL1) was observed in the 10 cases of T-cell lymphoma, but the tumour cells did not express monocyte-macrophage markers. Clinically, the patients with T-cell lymphomas were usually young males with constitutional symptoms and their prognosis was significantly worse than those of patients with intestinal B-cell lymphoma.     

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.     

T-cell lymphoma in Hashimoto's thyroiditis

An elderly Caucasian woman with a 2-year-history of hypothyroidism, treated with thyroxine, presented with a rapidly growing mass in the thyroid. The morphological and immunological features of this thyroid tumour were those of a peripheral T-cell lymphoma with an immunophenotype commonly associated with HTLV-1 positive-adult T-cell leukaemia/lymphoma, although serology for HTLV1 antibody was negative. Monoclonal gene rearrangements were demonstrated with T-cell receptor beta- and gamma-specific primers. There are several interesting features in this case (i): although primary B-cell lymphomas (MALT-associated lymphomas) of thyroid are a well-recognized sequel to thyroiditis, primary T-cell lymphomas are rare, even in areas of the world where adult T-cell lymphomas predominate; (ii) the tumour showed the typical immunophenotype of an HTLV-1 positive T-cell lymphoma but the patient is English, has not visited endemic areas, and is serologically negative for HTLV–1; (iii) the residual thyroid gland showed a florid lymphocytic thyroiditis with Hu¨rthle cell change, typical of Hashimoto's thyroiditis; (iv) unlike other reports of thyroid T-cell lymphoma, which have presented with stage III-IV disease, this tumour presented in the favourable clinical stage of IE.     

The World Health Organization classification of malignant lymphoma: incidence and clinical prognosis in HTLV-1-endemic area of Fukuoka

New insights into the pathogenesis of lymphoid malignancies have been gained through novel genetic, molecular and immunological techniques. A new classification system for lymphoid malignancies, known as the new World Health Organization (WHO) classification, has been proposed recently based on these findings. The relative incidence of the subtypes of malignant lymphoma is known to differ according to geographic location. Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type 1 (HTLV-1), and the Kyushu islands are an HTLV-1 endemic area. To clarify the relationship between the histological classification and prognosis of lymphoid malignancies, we reclassified previous cases in our department and summarized our previous reports using the WHO classification. Of 933 cases of lymphoid malignancies, 471 (50%) were B-cell lymphoma, 396 (42%) T/natural killer (NK)-cell lymphoma and 41 (4%) Hodgkin lymphoma (HL). Analysis of clinical outcome showed favorable prognosis for HL, intermediate for B-cell lymphoma and poor prognosis for T-cell lymphoma. Among B-cell lymphomas, the commonest type was diffuse large B-cell lymphoma (n = 281; 60%). Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) was diagnosed in 82 cases (17%), follicular lymphoma in 52 (11%) and mantle cell lymphoma in 24 (5%). Other less common lymphomas were Burkitt lymphoma (n = 9; 2%) and lymphoblastic lymphoma (n = 5; 1%). Using overall survival rates, the various B-cell lymphoma types could be divided into three broad groups for prognostic purposes: (i) low-risk group comprising follicular lymphoma and MALT; (ii) intermediate-risk group comprising diffuse large B-cell lymphoma and Burkitt lymphoma; and (iii) high-risk group comprising mantle cell lymphoma and lymphoblastic lymphoma. Among the T/NK-cell lymphomas, the commonest type was ATLL (n = 191; 48%), followed by peripheral T-cell lymphoma, unspecified (n = 83; 21%), angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) (n = 38; 10%), anaplastic large cell lymphoma (ALCL) (n = 22; 6%). Less common types were lymphoblastic lymphoma (n = 17; 4%), nasal and nasal-type NK/T-cell lymphoma (n = 17; 4%), mycosis fungoides (MF) (n = 9; 2%) and other rare types. With respect to clinical prognosis, T/NK-cell lymphomas fell into three groups: (i) relative low-risk group comprising ALCL, AILD, MF and lymphoblastic lymphoma; (ii) relative intermediate-risk group comprising NK/T-cell lymphoma and unspecified lymphoma; and (iii) extremely high-risk group comprising ATLL. Among the lymphoblastic lymphomas, B-cell type and T-cell type lymphomas exhibited different clinical outcomes. We conclude that the histological, phenotypic and genotypic classification of the new WHO system should be beneficial for the clinical approach to these tumors.     

Phenotyping of T-cell lymphomas in paraffin sections–which antibodies?

Five antibodies, MT1 (CD43), UCHL1 (CD45RO), OPD4, poly-CD3 and beta F1, were assessed for their reactivity with 50 archival cases of T-cell lymphoma in formalin-fixed paraffin-embedded tissue. All cases had been previously characterized as T-cell lymphomas, and the histological types included 14 cases of small cerebriform lymphoma, six cases of angioimmunoblastic lymphadenopathy-like T-cell lymphoma, four cases of T-zone lymphoma, five cases of pleomorphic small cell lymphoma, 12 cases of pleomorphic medium and large cell lymphoma, four cases of anaplastic large cell lymphoma, two cases of T-lymphoblastic lymphoma and three cases of enteropathy-associated T-cell lymphoma. UCHL1 and MT1 showed reactivity with the highest percentage of cases (94 and 86% respectively) but lack absolute specificity for T-cells, especially in high-grade lymphomas. Poly-CD3 is highly specific for T-cells, and stained neoplastic cells in almost 80% of the cases. beta F1 stained the lowest percentage of cases (40%). UCHL1 and poly-CD3 together identified 98% of cases, and this combination is recommended for the diagnosis of T-cell lymphomas in paraffin sections.     

T-cell lymphoma in Singapore: pathology, clinical findings and association with HTLV-1 antibodies

Of 128 cases of malignant lymphomas studied in Singapore between 1986 and 1988, 28 were identified as peripheral T-cell lymphomas. Sera from two of the 128 cases were positive for HTLV-1 antibodies and both cases had the clinical and pathological features of adult T-cell leukaemia/lymphoma. The pathological and clinical features of the 28 cases of peripheral T-cell lymphoma are presented in detail. Survival data indicated no significant difference between the low grade and high grade histological types. Three of the patients had previous or concomitant malignancies. The percentage of T-cell lymphomas associated with HTLV-1 infection in Singapore is low compared to those areas in which HTLV-1 is endemic.     

CD30 (Ki-1) expression in adult T-cell leukaemia/lymphoma is associated with distinctive immunohistological and clinical characteristics

Twenty-one patients with CD30 (Ki-1) positive lymphoma were studied from a group of 91 patients with adult T-cell leukaemia/lymphoma. The patients were grouped into three types: diffuse CD30 positive anaplastic large cell lymphoma in 11 patients (group 1); pleomorphic type lymphoma with diffuse CD30 expression in five patients (group 2); and pleomorphic type lymphoma with positive CD30 expression in large cells but negative in medium-sized and small cells in five patients (group 3). The patients with diffuse CD30 positive lymphomas (groups 1, 2) frequently presented with extranodal tumours (68.8%) and lymph node enlargement greater than 2 cm in diameter (50%), and rarely with leukaemic changes, bone marrow involvement and hypercalcaemia (one case of each). Patients in group 3 rarely had extranodal tumours, but had frequent leukaemic changes. Expression of intercellular adhesion molecule (ICAM-1; CD54) by the lymphoma cells in 13 patients (81.3%) with diffuse CD30 positive lymphomas, was significantly higher than that in 33 patients (9.1%) with CD30 negative adult T-cell leukaemia/lymphomas. No positive reaction for epithelial membrane antigen (EMA) was found in the lymphoma cells of CD30 positive cases. The overall survival in patients with diffuse CD30 positive lymphomas was better than that of CD30 negative adult T-cell leukaemia/lymphoma patients, but showed no significant difference. These findings suggest that diffuse CD30 positive adult T-cell leukaemia/lymphoma has unusual clinical and immunohistological findings. It is also speculated that local tumour formation and leukaemic changes in such diffuse CD30 positive cases are influenced by CD54 (ICAM-1) expression by the lymphoma cells.     

An immunocytochemical study of T-cell lymphomas using monoclonal and polyclonal antibodies effective in routinely fixed wax embedded tissues

Formalin fixed and paraffin wax embedded tissue from 24 cases of T-cell lymphoma diagnosed using immunocytochemistry on cryostat sections was examined using a panel of eight monoclonal and three polyclonal antisera. The monoclonal antibodies UCHL1 and MT1 proved to be comparable and reliable markers of neoplastic cells in T-cell lymphomas. The B-cell specific marker, MB1, strongly stained all cells in two cases of pleomorphic large cell T-cell lymphoma, large cells in two cases of pleomorphic mixed medium and large cell lymphoma, and isolated clusters of blast cells in four cases of T-zone and angioimmunoblastic lymphadenopathy-like T-cell lymphoma. The cells stained by MB1 expressed T suppressor/cytotoxic surface markers on frozen section. Epithelial membrane antigen, as detected by a polyclonal anti-EMA and the monoclonal antibody HMFG2, was expressed in 36% of tumours especially those of monomorphic large cell and pleomorphic large cell phenotype. Single granules or finely dispersed cytoplasmic granularity was seen in four tumours using the anti-granulocyte reagent Leu M1. Tumour cells in one case stained in a pattern identical to Reed-Sternberg cells in Hodgkin's disease. Granular alpha-1-antitrypsin staining was found in 10 cases of pleomorphic large cell and monomorphic large cell lymphoma. No staining was observed using anti-lysozyme or the monoclonal macrophage specific marker Mac411. Monomorphic and pleomorphic large cell lymphomas tended to show a common immunophenotype with the majority of cells co-expressing alpha-1-antitrypsin HLA-DR and epithelial membrane antigen. Scattered large transformed blast cells in cases of angioimmunoblastic lymphadenopathy-like T-cell lymphomas and T-zone lymphomas shared a similar immunophenotype with the large cell lymphomas. Using a panel of monoclonal antibodies effective in paraffin embedded tissue, diagnostically useful staining profiles which correlate with the morphological phenotype can be established in T-cell lymphomas.     

Laboratory Diagnosis of HTLV-1-Associated Myelopathy

Human T-lymphotropic virus type 1 (HTLV-1), a human retrovirus, is endemic in certain regions of the world and affects millions of people worldwide. Infected individuals are at risk of developing adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. Vertical and parenteral transmission are the main routes of infection. Diagnosis of HTLV-1 infection can be made by detection of HTLV-1-specific antibodies in plasma, serum, or cerebrospinal fluid using a combination of initial and supplemental serologic assays. In contrast, quantitative proviral DNA in peripheral blood mononuclear cells has been used to predict and monitor disease progression. This review provides an overview of the virology, epidemiology, transmission, pathophysiology, clinical manifestations, and laboratory testing methods for HTLV-1 infection.     

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.     

Classification of cell lineage and anatomical site, and prognosis of extranodal T-cell lymphoma – natural killer cell, cytotoxic T lymphocyte, and non-NK/CTL types

Due to their minority among the non-Hodgkin lymphomas, classification of extranodal T-cell lymphomas, including those of the natural killer (NK) cell type, has long been controversial and unclear, and the clinical outcome is not well clarified. Recently, new well-defined disease entities have been described based on tumor cell biology combined with anatomical site, clinical features, Epstein-Barr virus (EBV) status, and cell lineage as determined by immunophenotype and genotype. Cytological features are usually not specific, and there are no morphologic correlates with the classification of extranodal T/NK-cell lymphomas. From a human T-cell lymphotropic virus type 1 (HTLV-1) endemic area in Japan, we report here the analysis of 144 cases of extranodal T-cell lymphoma, from which fresh tissues were available. As the clinicopathological features were known, we simply reclassified the cases according to cell lineage and anatomical site. The extranodal T-cell lymphomas were classified into three types on the basis of cell lineage: (1) natural killer cell (NK) type [sCD3-, CD56+, T-cell receptor gene (TCR) germline], (2) cytotoxic T lymphocyte (CTL) type [sCD3+, TIA-1+, TCR rearranged, CD8+/-, CD4-/+], and (3) non-NK/CTL type [sCD3+, TIA-1-, TCR rearranged, CD4+/-, CD8-/+]. In addition to cell lineage, the anatomical site and clinical features were added for subclassification. NK type tumors (35 cases) included the lymphoblastic type, nasal/nasal-type NK lymphoma, and NK leukemia. The CTL type (46 cases) included anaplastic large cell lymphoma (ALCL), cutaneous type, intestinal, gamma delta T-cell type, and an unspecified type. The non-NK/CTL type (63 cases) included adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides (MF), and an unspecified type. With the exception of ATLL and MF, most extranodal T-cell lymphomas had a cytotoxic phenotype of NK type or CTL type and were often associated with EBV infection. MF and the unspecified type within the non-NK/CTL tumors, with the exception of ATLL, had a favorable prognosis. However, NK and CTL types, with the exception of ALCL, were associated with a poor prognosis. Our results indicate that anatomical site and cell lineage are useful predictors of clinical outcomes of extranodal T-cell lymphomas.     

Comparative ultrastructural study of cytotoxic granules in nasal natural killer cell lymphoma, intestinal T-cell lymphoma, and anaplastic large cell lymphoma

Comparative immunohistochemical and ultrastructural studies were performed on five nasal natural killer (NK) cell lymphoma cases, two intestinal T-cell lymphoma cases, and eight anaplastic large cell lymphoma (ALCL) cases to clarify morphological differences in cytotoxic granules among these cytotoxic lymphomas. Nasal NK-cell lymphomas and intestinal T-cell lymphomas had fine azurophilic granules and displayed dot-like immunostaining of granzyme B- and T-cell intracellular antigen 1 (TIA-1), predominantly in the central area of the cytoplasm. Ultrastructurally, these NK-cell lymphomas and intestinal T-cell lymphomas had two types of cytotoxic granules, type-I granules (dense core granules) and type-II granules (multivesicular bodies), which have been demonstrated in normal large granular lymphocytes in peripheral blood. However, ALCLs did not have azurophilic granules, and only type-II cytotoxic granules were found ultrastructurally, even though they showed similar dot-like immunostained patterns of granzyme B and TIA-1, as seen in NK-cell lymphomas and intestinal T-cell lymphomas. Immunoelectron microscopy revealed that TIA-1 was primarily located at the periphery of the cytoplasmic granules in the NK-cell lymphoma and ALCL cases. These findings suggest that malignant lymphomas with a cytotoxic phenotype can be divided into two types, (azurophilic granule)+, (type-I granule)+, (type-II granule)+ lymphomas and (azurophilic granule)-, (type-I granule)-, (type-II granule)+ lymphomas.     

Immunoreactivity of B-cell markers (CD79a, L26) in rare cases of extranodal cytotoxic peripheral T- (NK/T-) cell lymphomas.

The monoclonal antibodies L26 (CD20) and CD79a are very useful reagents for the immunohistochemical assessment of B-cell lineage in lymphoproliferative disorders. Although very few CD20-positive peripheral T-cell lymphomas (PTL) have been reported, comprehensive analyses of CD79a reactivity in extranodal PTL and NK/T-cell lymphomas have not been performed previously. This study investigated CD79a (clone JCB117) and CD20 reactivity in 94 extranodal non-B-cell lymphomas (enteropathy-type intestinal T-cell lymphoma [n = 52], nasal NK/T-cell lymphoma [n = 11], and primary cutaneous PTL [n = 31]) and in 17 cases of nodal PTL, unspecified. In four cases (enteropathy-type intestinal T-cell lymphoma [n = 3] and nasal NK/T-cell lymphoma [n = 1]), the majority of tumor cells stained for CD79a (all CD20 negative) and one cutaneous PTL, unspecified, was CD20 positive (CD79a negative). Extensive immunophenotyping and polymerase chain reaction-based molecular analyses revealed that all five B-cell marker-positive extranodal lymphomas had a cytotoxic phenotype and did indeed represent monoclonal peripheral T-cell proliferations. To minimize the risk of misinterpretation of lymphoma cell lineage, especially in cases of extranodal, lymphoproliferative disease, we suggest the use of both CD79a and CD20 in combination with a panel of antibodies reactive to T cells, such as betaF1 and CD5, and to T cells and NK cells, such as CD3, CD2, CD56, and TIA-1.     

Primary gastric apoptosis-rich T-cell lymphoma co-expressing CD4, CD8, and cytotoxic molecules

In contrast to primary gastric lymphomas of B-cell type, little is known about primary gastric T-cell lymphomas. We describe three cases with remarkably similar features: diffuse growth, epitheliotropism, medium too large cell size, high apoptotic rates, and a CD3+, CD4+, CD8+, CD45RO+ immunophenotype. Clonal TCRγ gene rearrangement was shown in two cases. Epstein-Barr virus infection was excluded in two cases. Taking advantage of fresh-frozen material, we analyzed two cases further, revealing CD5–, CD16+, CD56–, CD57–, CD25+, CD30+, CD103 (αEβ7)+, bcl-2 protein+, CD95+, CD95 ligand(L)–. CD95L, however, was detected in histiocytic and fibroblastoid by stander cells. The lymphomas expressed granzyme B, perforin, and the TIA-1 antigen in various combinations. All three cases had a very unfavorable clinical course characterized by local recurrence and/or dissemination to other epithelial sites, leading to death within 6–12 months after the initial diagnosis despite surgery and aggressive antineoplastic treatment. These data suggest a novel variant of peripheral T-cell lymphoma operationally characterized as primary gastric, apoptosis-rich, CD103+, EBV-, T-cell lymphoma co-expressing CD4, CD8, CD16 and cytotoxic molecules. Received: 20 August 1999 / Accepted: 2 November 1999     

T-cell lymphomas in adults: a clinicopathological study of eighteen cases

Eighteen cases of adult T-cell lymphoma have been studied with respect to clinical presentation, response to treatment, histology, enzyme histochemistry, immunocytochemistry, and gene rearrangement. Seven cases (39 per cent) presented at extra-nodal sites, and the age range was from 18 to 79. Treatment was with combination chemotherapy in most cases, and 11 of the 18 patients died within the three year follow-up period. The lymphomas were classified morphologically into six types; T-lymphoblastic lymphoma (TLL), angioimmunoblastic lymphadenopathy (AIL)-like T-cell lymphoma, T-zone lymphoma, pleomorphic mixed medium and large cell T-cell lymphoma (PMMLC), pleomorphic large cell T-cell lymphoma (PLC), and monomorphic large cell T-cell lymphoma (MLC). Enzyme histochemistry was found to be of limited value in the identification of T-cell lymphomas. Immunocytochemistry showed a degree of correlation between the immunological profile and morphology, with cases in the PLC and MLC groups showing limited expression of T-cell antigens. Re-arrangement of the beta chain of the T-cell receptor gene was detected in 12 of the 14 cases studied, and all showed germ-line immunoglobulin genes. The study emphasizes the varied morphological and clinical appearances of adult T-cell lymphoma.     

Testicular natural killer/t-cell lymphoma,nasal type,of true natural killer-cell origin

The majority of primary testicular lymphomas are of B-cell type. Other primary lymphomas are rarely encountered in the testes. Natural killer (NK)/T-cell lymphomas of nasal type are aggressive extranodal lymphomas associated with Epstein-Barr virus infection that are usually encountered in the upper aerodigestive tract. They also occur in the skin, soft tissue, and colon. Primary testicular NK/T-cell lymphomas are rarely reported. We describe the case of a 66-year-old Korean man who presented with right-sided painless testicular enlargement and underwent radical orchiectomy. Histologic examination revealed an angiocentric and angioinvasive infiltrate of medium to large tumor cells with moderately abundant pale pink cytoplasm and folded and indented pleomorphic nuclei. Paraffin immunohistochemical studies showed positivity of the tumor cells for CD45, TIA-1, granzyme B, CD56, and CD3 epsilon. In situ hybridization showed diffuse positivity for Epstein-Barr virus-encoding RNA. The results of gene rearrangement studies for the gamma chain of the T-cell receptor were negative. The results of paraffin immunohistochemical studies for CD20, CD8, CD45RO, beta f1, and ALK-1 were negative. An extensive workup showed no evidence of lymphoma outside the testes. We report a rare case of primary testicular NK/T-cell lymphoma of the nasal type of true NK-cell origin.     

Cytotoxic protein expression in natural killer cell lymphomas and in αβ and γδ peripheral T-cell lymphomas

Lymphomas with T-cell phenotype represent a heterogeneous group of diseases differing in histopathology, tumour site, and cell origin. They include peripheral T-cell lymphomas (PTCLs) derived from αβ cells, but also some recently recognized entities such as γδ hepatosplenic lymphomas and natural killer (NK) cell lymphomas. Only a few studies have investigated the possibility that at least some PTCLs could be derived from lymphocytes with cytotoxic potential. In order to investigate this possibility, 60 cases of PTCL, including 27 cases expressing the αβ T-cell receptor (TCRαβ), 15 TCRγδ cases and 18 cases expressing neither TCR (TCR silent), as well as 14 cases of NK-cell lymphomas, were studied by immunohistochemistry for the expression of TIA-1, perforin, and granzyme B proteins. Expression of TIA-1 is characteristic of cytotoxic cells regardless of their activation status, whereas expression of perforin and granzymes is highly increased in activated cytotoxic cells and correlates with the induction of cytolytic activity. All NK-cell lymphomas (11 sinonasal, three systemic cases) expressed TIA-1, perforin, and granzyme B in most tumour cells. All γδ PTCLs (15 cases) expressed TIA-1 protein in most tumour cells, with a different cytotoxic antigen profile in hepatosplenic γδ PTCL (TIA-1+, perforin−, granzyme B−) and in non-hepatosplenic γδ PTCLs (three nasal, one skin, one lung), the latter expressing the three cytotoxic proteins. Of the 45 cases of αβ and TCR silent PTCL, 15 (33 per cent) were considered to be derived from cytotoxic lymphocytes with expression of at least one cytotoxic protein (TIA-1, 15/45; perforin, 10/41; granzyme B, 14/38) in tumour cells. This cytotoxic protein expression appeared to be related to the site of localization, since 7/13 (54 per cent) extranodal and only 8/32 (25 per cent) nodal αβ and TCR silent PTCLs expressed TIA-1, and to histology, since this pattern was observed in a proportion of anaplastic (6/8, 75 per cent) and pleomorphic (8/17, 47 per cent) lymphomas, but not in AILD-type NHL (0/16). Taken together, our data suggest that NK-cell lymphomas and non-hepatosplenic γδ PTCLs represent tumours of activated cytotoxic NK cells and γδ T cells, respectively; that hepatosplenic γδ PTCLs represent tumours of non-activated cytotoxic γδ T cells; and that a small proportion of αβ and TCR silent PTCLs, mostly extranodal cases, or nodal anaplastic lymphomas, represent tumours of cytotoxic T cells. © 1997 John Wiley & Sons, Ltd.