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.     

Malignant lymphoma of the thyroid. A 30-year clinicopathologic experience and an evaluation of the presence of Epstein-Barr virus.

Lymphoma of thyroid is uncommon, and Epstein-Barr virus (EBV) is found in many lymphomas. We studied the clinicopathologic characteristics in Hong Kong Chinese and analyzed the presence of EBV in thyroid lymphomas by reviewing data collected during 3 decades. We studied EBV gene expression by in situ hybridization and immunohistochemistry. Primary thyroid lymphomas were found in 23 patients (diffuse large B-cell lymphoma, 18; marginal zone B-cell lymphoma, 4; plasmacytoma, 1), and secondary lymphomas were found in 9 patients (diffuse large B-cell lymphoma, 3; Burkitt lymphomas, 2; Burkitt-like lymphoma, 1; hairy cell leukemia, 1; nasal T-cell and natural killer cell lymphoma, 1; and intestinal T-cell lymphoma, 1). Primary thyroid lymphomas were large (mean, 7 cm), found commonly in older women, and often misdiagnosed as undifferentiated carcinomas. Fine-needle aspiration was not helpful for diagnosis. Fifteen patients had Hashimoto thyroiditis. A history of thyrotoxicosis was found in 3 patients, and coexistence of 3 diseases (papillary microcarcinomas, primary thyroid lymphoma, and Hashimoto thyroiditis) was found 4 patients. The 5-year survival rate for primary thyroid lymphoma was 53%. Combined surgery and radiotherapy seemed to be the best treatment. Secondary thyroid lymphomas often were asymptomatic. EBV messenger RNAs were detected in 1 primary and 1 secondary thyroid lymphoma. The EBV gene expression in primary thyroid lymphoma showed a type II latency pattern. Thyroid lymphomas in Chinese had important clinicopathologic features. EBV may have a role in a subset of cases.     

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.     

Immunohistochemical detection of p53 and Bcl-2 proteins in Hashimoto's thyroiditis and primary thyroid lymphomas.

AIMS--To investigate whether immunohistochemical staining using p53 and/or bcl-2 distinguishes between florid Hashimoto's thyroiditis and low grade mucosa associated lymphoid tissue (MALT) lymphoma of the thyroid. METHODS--Ten cases of Hashimoto's thyroiditis and eight of primary thyroid lymphoma were stained with monoclonal antibodies directed against p53 and bcl-2. RESULTS--In Hashimoto's thyroiditis most small lymphoid cells in mantle zones, within the thyroid parenchyma and in lymphoepithelial lesions expressed bcl-2 protein. Very occasional centroblasts in reactive germinal centres were positive for p53, but all other lymphoid cells from cases of Hashimoto's disease were negative for p53. In diffuse, low grade lymphomas bcl-2 protein was uniformly expressed by most tumour cells. However, low grade lymphomas with a follicular pattern did not express bcl-2. The diffuse, low grade lymphomas were negative for p53, while occasional larger cells in the follicular subtype were positive. Both high grade lymphomas were bcl-2 negative but strongly p53 positive. CONCLUSIONS--This study indicates that there is an inverse correlation between p53 and bcl-2 immunostaining in thyroid lymphomas (low grade lymphomas: bcl-2 positive, p53 negative; high grade lymphomas: bcl-2 negative, p53 positive). Furthermore, immunohistochemical staining for bcl-2 and p53 proteins does not distinguish florid Hashimoto's thyroiditis from diffuse, low grade thyroid lymphoma.     

Post-transplant T-cell lymphoproliferative disorder/T-cell lymphoma: a report of three cases of T-anaplastic large-cell lymphoma with cutaneous presentation and a review of the literature

AIMS: To report the clinical, pathological and immunohistochemical features of three cases of post-transplant T-cell lymphoproliferative disorder (T-PTLD) T-cell lymphoma with primary cutaneous presentation. METHODS AND RESULTS: Three cases of primary cutaneous post-transplantation anaplastic large-cell lymphomas occurred in renal transplant recipients and were shown to display a T-cell immunophenotype; all were ALK 1 protein and EMA negative and two were Epstein-Barr virus positive using in-situ hybridization. Two displayed a CD4+ phenotype, two were focally CD56+ and all three were negative for the cytolytic enzyme granzyme B. In two cases monoclonality was established by T-cell receptor gene rearrangement study. All presented with nodular cutaneous involvement and all were ultimately fatal. CONCLUSION: T-PTLDs are uncommon histological subtypes both in a general context and associated with cutaneous presentation. Our findings suggest clinicopathological and immunophenotypic similarities to primary cutaneous anaplastic large-cell lymphoma but with a progressive clinical behaviour similar to previously reported T-PTLD and to systemic nodal ALK- anaplastic large-cell lymphoma.     

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.     

Investigation of the clonality of lymphocytes in Hashimoto's thyroiditis using immunoglobulin and T-cell receptor gene probes

Southern blotting and DNA hybridization were used for the detection of immunoglobulin and T-cell receptor gene rearrangements in thyroid tissue from six patients with Hashimoto's thyroiditis, three patients with B-cell lymphoma complicating Hashimoto's thyroiditis, and two patients with nonspecific lymphocytic thyroiditis. Immunoglobulin gene rearrangements were detected only in patients with histologic evidence of lymphoma. A single T-cell receptor beta-chain gene rearrangement was detected in one of the patients with uncomplicated Hashimoto's thyroiditis. Based on our knowledge of primary thyroid lymphomas, it is highly unlikely that this case represents an early, histologically occult T-cell lymphoma. The uniform lack of immunoglobulin gene rearrangements in Hashimoto's thyroiditis supports the use of genotypic analysis in differentiating between uncomplicated Hashimoto's thyroiditis and non-Hodgkin's lymphoma. The finding of a T-cell receptor gene rearrangement in a case of Hashimoto's thyroiditis suggests that the immune response in this disease occasionally may be clonally restricted.     

Malignant lymphomas of the nasal cavity and Waldeyer's ring--clinicopathologic and immunohistochemical study.

The clinicopathologic and immunohistochemical finding of 10 cases of nasal non-Hodgkin's lymphoma (NHL) and 23 cases of Waldeyer's ring NHL were studied. Immunohistochemically, nasal NHL expressed T-cell markers exclusively, whereas the NHL of Waldeyer's ring were of both T-cell (56.5%) and B-cell lineages (43.5%). Angioinvasiveness by tumor cells was exclusively noted in the T-lineage lymphomas. Epithelial hyperplasia, epitheliotropism by tumor cells, and extensive invasion of adjacent normal tissue were more prominent in T-cell lymphomas than in B-cell lymphomas. T-lineage lymphomas showed distant extranodal spread pattern involving the skin, soft tissue, stomach, spleen, and the liver, whereas B-lineage lymphomas tended to localize in the lymph nodes. The survival rate of Nasal NHL was similar to that of Waldeyer's ring NHL. Although not statistically significant because of small sample numbers, immunophenotype, histologic groups of monomorphic lymphoma, and stage had prognostic importance. In general, T-lineage lymphomas presented with a higher stage than B-lineage lymphomas (p < 0.05)-and overall survival was poor. Stage I disease showed a much more favorable prognosis than stage II disease. Monomorphic lymphomas had a shorter survival than polymorphic reticulosis (PR) or lymphomas with features of PR. This result in conjunction with the morphologic transition between them suggested that monomorphic lymphoma may represent the most advanced stage in the spectrum of PR, lymphoma with features of PR, and monomorphic lymphoma.     

Klinisch-pathologische Formen peripherer T- und NK-Zell-Lymphome

Malignant lymphomas, originating from peripheral T or NK cells, are rare tumours in Europe and account for less than 10% of all malignant lymphomas. In this review, the salient features of the more frequently occurring entities derived from T or NK cells will be presented. Nasal NK/T cell lymphoma is mainly found in the nose and paranasal sinuses and often, but not always, display an angiocentric growth pattern leading to coagulation necrosis. The tumor cells consistently express CD56, CD2 and the EBER molecules encoded by the Epstein-Barr virus. Clonal T cell receptor gene rearrangements are often absent indicating, in the majority of cases, a derivation of these tumors from NK cells. Enteropathy-type intestinal T-cell lymphomas often arise in patients with celiac disease and have a dismal prognosis. The tumour cells express T cell antigens, CD103 and cytotoxic molecules, but are negative for CD4. Approximately 20% of the cases display CD56 mostly in combination with CD8. Recently, an early purely intraepithelial form of this tumour was identified. Histologically these cases resemble celiac disease, however the intraepithelial lymphocytes often exhibit an abnormal immunophenotype with absent CD8 and T-cell-receptor protein expression, and, they are clonal by molecular analysis. Clinically, the patients suffer from refractory sprue or ulcerative jejunitis. The prognosis is bad with the patients often dying from malnutrition or an invasive tumour-forming T-cell lymphoma. Angioimmunoblastic T-cell lymphoma is defined by characteristic morphological findings (atypical lymphoid cells in part with pale cytoplasm, arborizing high endothelial venules and large FDC-meshworks) as well as clinical features (systemic symptoms, signs of a dys-regulated immune response). Peripheral T-cell lymphomas, that do not fit into a distinct entity, are classified in the REAL and the new WHO classifications as peripheral T-cell lymphomas unspecified. These display a broad morphological spectrum (including the T-cell lymphomas of different cell sizes, Lennert's lymphoma and T-zone lymphoma of the Kiel-classification) and in general are clinically aggressive.     

Primary lymphoma of the thyroid: a clinical, histological and immunohistochemical study of 20 cases

Twenty cases of malignant lymphoma arising in the thyroid gland were studied clinically, histologically and immunohistochemically. Nineteen cases were non-Hodgkin's lymphoma (15 diffuse and four follicular lymphoma) and one was a plasmacytoma. Immunohistochemical analysis of the lymphomas using paraffin-embedded sections disclosed that 17 lymphomas were B-cell type and two were T-cell type. The plasmacytoma was of IgG kappa type. The large majority of the lymphomas were associated with an underlying chronic thyroiditis. The 5-year survival rate of the patients was 70%. An unfavourable diagnosis was more likely when the tumour was diffuse rather than follicular, when it was of diffuse large cell type or of immunoblastic type and when there was cervical lymph node involvement.     

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.     

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.     

Stage is a better prognostic indicator than morphologic subtype in primary noncutaneous T-cell lymphoma

The authors reviewed 28 primary noncutaneous T-cell lymphomas, referred to the Comprehensive Cancer Center Amsterdam, using the updated Kiel classification. Clinical course was related with stage of disease, morphologic subtype, and immunophenotype of the tumor cells. The incidence of primary noncutaneous T-cell lymphomas was 4.1 cases per 1,000,000 people per year. Morphologic classification was difficult and arbitrary. Immunohistochemistry contributed considerably in diagnosis of this group of tumors. All primary noncutaneous T-cell lymphomas had a poor prognosis, with no significant difference between predominantly small cell (low-grade) and large cell (high-grade) tumors. The only parameter significantly correlating with survival was the stage of the disease at presentation. The results suggest that all types of primary noncutaneous T-cell lymphoma are to be considered high grade and that primary localization (cutaneous vs. noncutaneous) and stage of disease at presentation appear to be more important as predictors of clinical outcome than morphologic or immunophenotypic subtype.     

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.     

Nodal T/NK-cell lymphoma of nasal type: a clinicopathological study of six cases

Aims:  To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein–Barr virus (EBV)+ T/natural killer (NK)-cell lymphoma, a putative nodal counterpart of nasal NK/T-cell lymphoma (nodal T/NK-cell lymphoma of nasal type) in comparison with nasal NK/T-cell lymphoma with secondary lymph node involvement ( n  = 24) and peripheral T-cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type ( n  = 21).
Methods and results:  All cases of nodal T/NK-cell lymphoma of nasal type exhibited diffuse infiltration of pleomorphic medium-sized to large tumour cells, reminiscent of those in CTM+ EBV+ PTCL. The tumour cells had a typical phenotype of nasal NK/T-cell lymphoma: CD2+, CD3ε+, CD4−, CD5−, CD56+, T-cell intracellular antigen-1+, granzyme B+, perforin+ and EBV+. However, four of six cases demonstrated clonal T-cell receptor γ-gene rearrangement on polymerase chain reaction analysis, unlike nasal NK/T-cell lymphoma. Comparison of clinical parameters and overall survival among the three groups demonstrated only minor differences.
Conclusions:  Nodal T/NK-cell lymphoma may occupy the grey zone between extranodal nasal-type NK/T-cell lymphoma and nodal CTM+ PTCL in a spectrum of NK to T-cell lymphomas that are EBV+. The close relationship between NK/T-cell lymphomas and cytotoxic T-cell lymphomas was also substantiated.     

A reassessment of primary thyroid lymphoma: high-grade MALT-type lymphoma as a distinct subtype of diffuse large B-cell lymphoma

AIMS: Primary lymphoma of the thyroid gland (PTL) is a relatively rare disease. During an 18-year period, 53 cases of primary non-Hodgkin's lymphoma involving this extranodal site were seen at our institutions. The aims of this study were to evaluate the spectrum of PTLs using current lymphoma classification concepts and immunocytochemical markers, determine whether features of MALT-type lymphoma were evident in PTL, and if there was any clinical significance of such a finding. METHODS AND RESULTS: The cases were retrospectively studied clinically, histologically and immunohistochemically. The tumours were classified according to the Revised European-American Lymphoma Classification of lymphoid malignancies (REAL classification). Thirty-eight patients were females, 15 were males and mean age at diagnosis was 66.3 years (range 38-90). Three cases were low-grade marginal zone lymphomas (low-grade MALT-type lymphomas). There were 45 diffuse large B-cell lymphomas (DLBCL) of which there were 27 DLBCL-NOS and 18 high-grade MALT-type lymphomas. Within the diffuse large B-cell lymphoma (DLBCL) category, cases were subdivided into those without (DLBCL-NOS) and those with features of 'high-grade' MALT-type lymphoma based on presence of a low-grade component or large cell lymphoepithelial lesions (HG MALT-type lymphoma). In addition there were three follicle centre lymphomas, one anaplastic large cell lymphoma and one peripheral T-cell lymphoma. Twenty cases were stage IE, 18 stage IIE, and four stage IV. All patients with low-grade MALT-type lymphoma are alive without disease. The 5-year survivals for DLBCL-NOS and HG MALT-type lymphoma were 75% and 25%, respectively. Univariate analysis (log rank) among the DLBCLs showed stage (P < 0.001) and subtype (P = 0.005) were associated with survival. Stage was associated with type of DLBCL, 65% of DLBCL-NOS being stage IE compared to 20% of HG MALT-type lymphomas. CONCLUSIONS: We conclude that primary thyroid lymphomas occur most commonly in elderly women and are frequently present in clinical stage IE and IIE. Low-grade MALT-type lymphomas are relatively uncommon but appear to have a favourable prognosis. DLBCL is the most common lymphoma and features of MALT can be seen in over one-third of cases. As a group, HG MALT-type lymphomas had a worse outcome than DLBCL-NOS, primarily due to higher clinical stage at diagnosis. These two subtypes of DLBCL appear to be distinct clinical and histological entities.     

Primary natural killer/T-cell lymphomas of the oral cavity are aggressive neoplasms

Thirty-four cases of primary non-Hodgkin’s lymphoma of the oral cavity were investigated for their clinical findings, histopathological features, immunophenotypes and association with Epstein-Barr virus (EBV). Four cases (12%) were natural killer/T-cell lymphomas, 3 (9%) were T-cell lymphomas and 27 (79%) were B-cell lymphomas. Compared with T- and B-cell lymphomas, NK/T-cell lymphomas had a male predominance (M:F 4:0), and most presented as ulceration of the palate and/or maxillary gingiva. Histologically, the lesions showed diffuse infiltration of medium-sized or large lymphoid tumour cells. Angiocentricity and/or angioinvasion were found in all 4 cases. The immunophenotypes of the NK/T-cell lymphomas were CD3+, CD43+, CD45RO+, CD56+ and TIA-1+. EBV was detected in 2 NK/T-cell lymphomas by in situ hybridization (ISH) and polymerase chain reaction (PCR) methods, and was not detected in T- and B-cell lymphomas. The survival rate of patients with NK/T-cell lymphoma was zero, but the survival rates for patients with T-cell and B-cell lymphomas were 67% and 38%, respectively. It appears that NK/T-cell lymphomas of the oral cavity have a predilection for originating in the palate and maxillary gingiva and are aggressive neoplasms. EBV positivity might be associated with more aggressive behaviour. Received: 21 January 1999 / Accepted: 14 April 1999     

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 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.     

Sinonasal non-Hodgkin's lymphomas and Wegener's granulomatosis: A clinicopathological study

Summary Reports of sinonasal non-Hodgkin's lymphomas, analysed with monoclonal antibodies, are scarce, and differentiation of these lymphomas from Wegener's granulomatosis can be difficult. In this study, we investigated histopathologically and immunohistologically 20 cases of non-Hodgkin's lymphoma, primary in the sinonasal region, and sinonasal biopsies from 11 patients with Wegener's granulomatosis. All T-cell lymphomas (n=7) and plasmacytomas (n=4) were stage I at clinical presentation, while all B-cell lymphomas (n=9) presented at higher stages. T-cell lymphomas tended to be more frequent in the nasal cavity and paranasal sinuses; B-cell lymphomas more often presented in the nasopharynx. Remarkably, 1 B-cell lymphoma expressed MT1, and 1 T-cell lymphoma expressed L26 (CD 20). The follow-up of 2 patients with a clinical diagnosis of Wegener's granulomatosis was suggestive of non-Hodgkin's lymphoma. Retrospective immunohistochemical analysis revealed that the original histological diagnosis of non-specific inflammation had to be changed to T-cell lymphoma, pleomorphic small cell type. We conclude that a biopsy from the sinonasal region with a dense inflammatory infiltrate, consisting predominantly of Tlymphocytes, renders a diagnosis of Wegener's granulomatosis unlikely and is at least suspicious of T-cell lymphoma. Immunohistochemical analysis is warranted for this type of biopsy.