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.     

The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non-Hodgkin's lymphoma (2189 cases (68.53%) of B-cell lymphoma, 796 cases (24.92%) of T-cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non-Hodgkin's lymphoma were 33.34% for diffuse large B-cell lymphoma, 8.45% for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T-cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T-cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal-type T/NK cell lymphoma, 2.35% for angioimmunoblastic T-cell lymphoma, and 2.35% for precursor B-cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T-cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large-cell lymphoma of T- and null-cell types (1.53%), and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south-western Japanese island, Kyushu, an endemic area of human T-cell leukemia virus type 1 (HTLV-1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV-1.     

A Case of Adult T-cell Leukemia/Lymphoma, Histologically Presenting CD30-Positive Large Cell Lymphoma

A 48 year old Japanese woman with adult T-cell leuke-mia/lymphoma (ATLL), histologically presenting CD30 positive large cell lymphoma is reported. The patient, who was from an ATLL endemic area in Japan, had cutaneous nodules in the head, trunk, and extremities, and cervical lymph node swelling; these had been found three months before her admission to our hospital. A biopsy specimen of a skin lesion showed diffuse large cell lymphoma; the lymphoma cells were positively stained with CD30 (Ki 1/ Ber H 2), CD4 (helper T), and CD25 (interleukin 2 receptor) antibodies. Anti HTLV-1 antibody (ATLA) was detected in the serum, and molecular cytogenetic studies of lymphoma cells showed both positive T-cell receptor rearrangement and HTLV-1 specific DNA sequences.     

Expression of the intestinal T-lymphocyte associated molecule HML-1: analysis of 75 non-Hodgkin''s lymphomas and description of the first HML-1 positive T-lymphoblastic tumour

The expression of the gut intra-epithelial T-cell associated molecule HML-1, a trimeric protein of 150, 125, 105 kD, was studied in 75 T-cell lymphomas of different subtypes: 20 T-lymphoblastic lymphomas/leukaemias; 50 nodal peripheral T-cell lymphomas; and five intestinal T-cell lymphomas. Our results confirm: (i) the usefulness of the HML-1 monoclonal antibody as an immunohistochemical marker for intestinal T-cell lymphomas: and (ii) the lack of reactivity of HML-1 with nodal peripheral T-cell lymphomas. Moreover, expression of the HML-1 molecule was found for the first time in a case of T-lymphoblastic lymphoma/leukaemia. The patient presented with a mediastinal mass which consisted of HML-1 + neoplastic cells displaying a phenotypic profile consistent with early thymocytes. Genes coding for the alpha, beta, gamma and delta chains of the T-cell receptor were in a germline configuration. The neoplastic cells could have been derived from the small subset of HML-1 + thymocytes detectable in the cortex of normal human thymus.     

Non-HTLV-1-associated primary gastric T-cell lymphomas show cytotoxic activity: clinicopathological,immunohistochemical characteristics and TIA-1 expression in 31 cases

AIMS: Most primary gastrointestinal lymphomas are of B-cell origin and T-cell origin is very rare. Recent studies have suggested that human T-cell lymphotrophic virus type 1 (HTLV-1) may be involved in the development of primary gastric T-cell lymphoma. We analysed 31 patients with primary gastric T-cell lymphoma in south-west Japan, an area endemic for HTLV-1, and determined their phenotypes, genotypes, and HTLV-1 status. METHODS AND RESULTS: Here we present 31 cases of primary gastric T-cell lymphoma in a HTLV-1-endemic area in Japan and analyse the clinical status, histology, phenotype and virus status. The median age at onset of primary gastric T-cell lymphoma was 57 years with a gender ratio of M:F = 1.58:1. Six of the 31 primary gastric T-cell lymphoma cases had HTLV-1 proviral DNA (five males, one female), nine of the 31 cases were positive for anti-adult T cell leukaemia antibody, without examination of HTLV-1 proviral DNA (five males, four females), eight were non-HTLV-1-associated primary gastric T-cell lymphoma (four males, four females) and the other eight cases were unknown. Primary gastric T-cell lymphoma usually presented as a large ulcerated tumour at the corpus to the antrum and histologically consisted of anaplastic large cell type (n = 2), pleomorphic large cell type (n = 3), pleomorphic medium and large cell type (n = 14), pleomorphic medium cell type (n = 11), and angioimmunoblastic T-cell lymphoma type (n = 1). There were no clear macroscopic and microscopic differences between HTLV-1-associated and non-HTLV-1-associated primary gastric T-cell lymphoma. Most patients died within 2 years of diagnosis, and both types of primary gastric T-cell lymphoma (with and without HTLV-1) were associated with poor prognosis. Cytotoxic marker analysis showed that HTLV-1-associated lymphomas were negative for TIA-1, while non-HTLV-1-associated lymphomas were positive for TIA-1. CONCLUSIONS: Our results suggest that in HTLV-1-endemic areas, patients with HTLV-1-associated primary gastric T-cell lymphoma should be managed carefully and that TIA-1 seems to be useful for identifying the aetiology of this lesion.     

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.     

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.     

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.     

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.     

Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas

Degradation of the extracellular matrix by matrix metalloproteinases (MMPs) is a crucial step in tumour invasion and metastasis. In human carcinomas, tumour cell-fibroblast interactions (TFIs) have been demonstrated to play a role in the up-regulation of MMP levels in tumours, and emmprin is a surface molecule on tumour cells that stimulates nearby fibroblasts to produce MMP-1, 2, and 3. T-cell lymphomas frequently show extranodal organ involvement and skin invasion, but a role for TFIs in their invasion has not been examined in detail. This study investigated TFIs in T-cell lymphomas with special reference to emmprin expression and MMP production. Immunohistochemically, only germinal centre cells and some histiocytes expressed emmprin in non-neoplastic lymph nodes (ten cases), while all T-cell lymphomas [14 cases of adult T-cell leukaemia/lymphoma (ATLL), six cases of lymphoblastic lymphoma, seven cases of anaplastic large cell lymphoma, and nine cases of angio-immunoblastic T-cell lymphoma] expressed emmprin strongly and diffusely. FACS analysis of peripheral blood from normal individuals revealed that small fractions of B-cells, T-cells, and monocytes expressed emmprin, whereas emmprin-expressing T-cells were much increased in number, and expressed this protein to a higher level, in ATLL patients. In vitro co-cultures of emmprin-positive HTLV-1-transformed lymphocytes (MT-2) and emmprin-negative human fibroblasts enhanced the production of pro-MMP-2 (gelatinase A) and active MMP-2, compared with cultures of either cell type alone. This stimulation was inhibited by an activity-blocking peptide against emmprin. Moreover, in histopathological sections from patients with ATL skin involvement, MMP-2 was demonstrated in fibroblasts around infiltrating ATL cells, but not in fibroblasts in non-diseased areas. In conclusion, emmprin is overexpressed by T-lymphoma cells, when compared with normal counterparts, and facilitates MMP-2 production via interactions with fibroblasts, which could play a role in stromal invasion by lymphoma cells.     

T-cell lymphomas of the stomach: Morphological and immunological studies characterizing two cases of T-cell lymphoma

Summary Using cytochemical, electron microscopic and immunohistochemical techniques in 20 primary malignant lymphomas of the stomach, we found 18 B-cell and 2 T-cell lymphomas. Primary T-cell lymphoma in the stomach has not been previously reported. The T cells in both cases were reminiscent of T immunoblasts with prominent nucleoli and a basophilic cytoplasm. Case 1 showed a cytological relationship to pleomorphic T-cell lymphoma, large cell type. Case 2 contained in addition some cells not previously described in T-cell lymphomas, resembling immature plasma cells with abundant rough endoplasmic reticulum. Focal positivity to acid phosphatase and dipeptidylaminopeptidase IV suggests the T-cell nature of both lymphomas. In both cases the tumour cells were OKT 11 and OKT 4 positive, and negative for OKT 8. Thus, both cases represent high-grade malignant T-cell lymphomas which correspond phenotypically to T-helper cell lymphoma. Case 2 revealed a further immunohistochemical peculiarity: atypical immunoblasts reacted positively with Ki-1 antibody. Thus, it is a Ki-1 lymphoma of T-cell type.     

Monoclonal antibody HML-1, a marker for intraepithelial T cells and lymphomas derived thereof, also recognizes hairy cell leukemia and some B-cell lymphomas

Current views regard monoclonal antibody HML-1 as an exquisite marker for intraepithelial T cells and primary intestinal and cutaneous T-cell lymphomas. We show that HML-1 reacted with 11 of 12 cases of hairy cell leukemia, with 1 of 13 cases of primary gastrointestinal B-cell lymphoma, and with an unclassified large-cell B lymphoma of the thoracic wall. We conclude that HML-1 is not restricted to the T-cell lineage and that the HML-1 antigen is expressed in a small subset of both T- and B-cell neoplasms.     

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.     

A case of adult T-cell leukemia/lymphoma, histologically presenting CD30-positive large cell lymphoma.

A 48-year-old Japanese woman with adult T-cell leukemia/lymphoma (ATLL), histologically presenting CD30-positive large cell lymphoma is reported. The patient, who was from an ATLL endemic area in Japan, had cutaneous nodules in the head, trunk, and extremities, and cervical lymph node swelling; these had been found three months before her admission to our hospital. A biopsy specimen of a skin lesion showed diffuse large cell lymphoma; the lymphoma cells were positively stained with CD30 (Ki-1/Ber H-2), CD4 (helper-T), and CD25 (interleukin-2 receptor) antibodies. Anti HTLV-1 antibody (ATLA) was detected in the serum, and molecular cytogenetic studies of lymphoma cells showed both positive T-cell receptor rearrangement and HTLV-1 specific DNA sequences.     

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.     

Frequent expression of gp46 in adult T-cell leukemia/lymphoma: an immunohistochemical study of 40 cases

Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. HTLV-1 is spread by cell-to-cell transmission via the gp46-197 region, from Asp197 to Leu216, in the envelope protein gp46. A correlation exists between the prevalence and titer of the antibody recognizing the gp46-197 region (anti-gp46-197 antibody) and the severity of ATLL. In the present study, immunohistochemical staining was performed on samples of paraffin embedded lymph nodes of three different histological types of ATLL (anaplastic large cell type, n = 10; pleomorphic type, n = 10; and Hodgkin's-like type, n = 10) from 30 cases and 10 cases of HTLV-associated lymphadenitis. Of the three ATLL subtypes, gp46 expression was highest in the anaplastic large cell type, followed by the pleomorphic type and Hodgkin's-like type (mean: 53.4%, 34.9% and 16.0%, respectively; P= 0.0003). In HTLV-1 associated lymphadenitis cases, gp46 positive cells were rarely seen (4.0%). These results suggest that gp46-197 immunohistochemical staining can be a useful histological indicator for prediction of the aggressiveness of ATLL and prognosis for ATLL patients.     

Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas

Jaw1, also known as lymphoid-restricted membrane protein (LRMP), is an endoplasmic reticulum-associated protein. High levels of Jaw1/LRMP mRNA have been found in germinal centre B-cells and in diffuse large B-cell lymphomas of 'germinal centre' subtype. This paper documents Jaw1/LRMP expression at the protein level in human tissues by immunohistochemical and western blotting analysis using an antibody reactive with paraffin-embedded tissues. Jaw1/LRMP was highly expressed in germinal centre B-cells (in keeping with gene expression data), in 'monocytoid B-cells', and in splenic marginal zone B-cells. It was absent, or present at only low levels, in mature T-cells, although cortical thymocytes were weakly positive. Among lymphoid neoplasms, Jaw1/LRMP was found in germinal centre-derived lymphomas (follicle centre lymphoma, Burkitt's lymphoma, lymphocyte-predominant Hodgkin's disease) but not in T-cell neoplasms (with the exception of a single T lymphoblastic lymphoma). Classical Hodgkin's disease and myeloma lacked Jaw1/LRMP but many cases of chronic lymphocytic leukaemia (but not mantle zone lymphoma) were Jaw1/LRMP-positive. Approximately half of the marginal zone lymphomas were Jaw1/LRMP-positive. In diffuse large B-cell lymphomas, Jaw1/LRMP was found in three-quarters (24/32) of the cases classified phenotypically as being of 'germinal centre' type, but it was also expressed in almost half (13/28) of the 'non-germinal centre' cases. A similar proportion of 'non-germinal centre' cases were positive for the protein products of two other genes expressed highly in germinal centre cells (HGAL/GCET2 and PAG). The fact that all three of these proteins are expressed in a significant proportion of diffuse large B-cell lymphomas assigned to the 'non-germinal centre' category indicates that the immunophenotypic categorization of diffuse large B-cell lymphoma according to cellular origin may be more complicated than currently understood. Finally, the expression of Jaw1/LRMP in other types of lymphoma and in non-lymphoid tissues/tumours may be of interest in differential diagnosis and research.     

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.     

Epstein–Barr virus-associated primary gastrointestinal lymphoma in non-immunocompromised patients in Korea

We examined 81 cases of primary gastrointestinal lymphomas in Korea, including 64 gastric lymphomas and 17 intestinal lymphomas, for EBV expression by EBER-1 in situ hybridization (ISH) and EBNA-1 PCR. In EBER-1 positive cases, we performed immunohistochemistry for latent membrane protein-1 (LMP-1) and EBV diffuse early antigen (EA(D)) to compare EBV latent gene expression and lytic process.   EBER-1 was detected in 15 of 81 cases of lymphomas. EBER-1 expression showed three different patterns on tumour cells; diffuse 4/81 (5%), localized 4/81 (5%), and a few scattered pattern 7/81 (9%). We regarded diffuse pattern and localized pattern as EBER-1 positive group (8/81: 10%). Diffuse pattern of EBER-1 was shown in all three T-cell lymphomas and one B-cell lymphoma. A localized pattern was seen all in B-cell lymphomas. The EBER-1 expression was 11% in the stomach (7/64) and 6% in the intestine (1/17). Five of the eight EBER-1 positive gastric lymphomas were histologically diffuse large B-cell lymphomas, and the other three were peripheral T-cell lymphoma, unspecified, one angiocentric lymphoma, and one intestinal T-cell lymphoma by REAL classification. Eight MALT type gastric B-cell lymphomas showed no EBV association. EBV nuclear antigen (EBNA-1) was detected in 15 of 45 resected cases (33%) by PCR. EBER-1 positive cases were all EBNA-1 positive. Twelve EBNA-positive/EBER-negative cases consisted of seven cases showing a few scattered EBER-1 positive lymphocytes. LMP-1 and diffuse early antigen (EA(D)) was detected in five and three cases, respectively. Although follow-up information in our series was incomplete, it seemed that there was no significant difference in their staging or prognosis between EBER-positive cases and EBER-negative group. It is concluded that EBV is associated with some lymphomas among Koreans without overt pre-existing immunodeficiency, especially in T-cell lymphomas.     

Histopathology and immunohistochemistry of peripheral T cell lymphomas: a proposal for their classification.

Based on the results of histological and immunohistochemical observations of a large number of peripheral T cell lymphomas from China, England, Germany and Japan, histological and cytological morphology were correlated with immunophenotype, aetiological association with HTLV-1, and clinical behaviour to produce a working classification of the T cell lymphomas. This classification, based mainly on cytological criteria, divides the peripheral T cell lymphomas into tumours of low grade and high grade malignancy. Adult T cell lymphoma/leukaemia (ATLL) is caused by HTLV-1 and belongs chiefly to the high grade category. Some tumours are characterised by an admixture of other cells (epithelioid cells, follicular dendritic cells, etc) and structures (high endothelial venules, follicles), which may indicate the secretion of lymphokines by the tumour cells. Clear cells seem to be specific for T cell lymphomas and may occur in various types of peripheral T cell lymphoma.