Primary pulmonary non-Hodgkin's lymphomas

We report a retrospective study of the pathological features in 69 primary pulmonary non-Hodgkin's lymphomas which have previously been clinically reviewed. The tumours consisted of 61 (88%) low-grade and eight (12%) high-grade malignant lymphomas. Fifty-four of the low-grade malignant lymphomas were MALT lymphomas. Lymphoepithelial lesions were observed in bronchial, bronchiolar and alveolar lining. All tumours were composed of nodules, forming a lymphangitic pattern at the periphery and a confluent central mass. Invasion of pleura and vessels was often seen but this without any consequence on survival. Granulomas were found in 20% of cases. Six of the eight high-grade tumours were centroblastic and another two were B-cell lymphomas of undetermined type. In four cases, associated areas of low-grade malignant lymphoma with lympho-epithelial lesions indicated a preexisting MALT lymphoma. Clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasms. However, non-invasive diagnostic methods need to be developed.     

Primary malignant lymphoma of the intestine: Clinicopathologic and immunohistochemical studies of 39 cases

Clinicopathologic and immunohistochemical features in 39 cases of primary intestinal non-Hodgkin's lymphoma (NHL) in Japanese patients were studied. Only resection materials in stage I_E and II_E-1 were included in this study because of the certainty that the intestine was the primary site of the lymphoma. The updated Kiel classification was used to classify NHL Histologically, only two cases (5.1%) were follicular lymphomas, and the others were diffuse lymphomas. Twenty-eight patients (71.8%) had high-grade NHL and 11 (28.2%) had low-grade NHL. Twenty (71.4%) of the 28 high-grade NHL were centroblastic lymphomas, and 14 (70.0%) of these 20 cases of centroblastic lymphoma were the polymorphic variant. Ten (90.9%) of the 11 low-grade NHL were low-grade mucosa-associated lymphoid tissue (MALT) lymphomas. Macroscopically, 18 patients had polypoid masses, 17 ulcerative tumors and four had diffusely infiltrating NHL. Seven of the 10 low-grade MALT lymphomas were polypoid masses. Immunohistochemically, 35 lesions (89.7%) were of the B cell phenotype and three (7.7%) were of the T cell phenotype. In the remaining case, the cell lineage could not be determined. No lesions were considered to be Of histio-cytic origin. The 5 year survival rate for high-grade B cell lymphomas was poorer than for low-grade B cell lymphomas, and the present study indicated that the histological grade of the intestinal B cell lymphomas was a prognostically significant factor.     

Biased VH family usage in primary gastric B cell lymphoma of mucosa-associated lymphoid tissue-type and the selected Vβ expression of T cells infiltrating into the lymphoma cells

Seven cases of primary gastric low-grade B cell lymphoma of mucosa-assoclated lymphoid tissue (MALT) type, two cases of high-grade B cell lymphoma with a low-grade component and three cases of pure high-grade lymphoma were selected for the current study. The Ig VH gene use of lymphoma cells and the Vβ repertoires of infiltrating T cells were Investigated. The VH gene analysis showed multiple VH family usage In 12 cases, but the MALT-type lymphoma cell usage was found to be biased for the families that have a low number of VH genes (VHIV and V). Another analysis of lymphoma-lnfiltrating T cells showed restricted expressions of the Vβ repertoire in all seven low-grade cases and three high-grade cases. In those 10 cases, a considerable number of CD4-postttve T cells Infiltrated Into lymphoma cells and RAG-1 was also prominently expressed. Based on these findings, It was thus assumed that the normal counterpart of gastric B cell lymphoma of MALT type is different from the conventional B cell lymphoma, and the restricted expression of Vβ repertoires Is therefore considered to be a characteristic finding in low-grade B cell lymphomas of MALT type as well as in a proportion of high-grade lymphomas (the so called 'high-grade lymphoma of MALT type').     

Follicular dendritic cells in extranodal non-Hodgkin lymphomas of MALT and non-MALT type

Extranodal lymphomas of the thyroid (n=19), kidney (n=15) and testis (n=30) were investigated histologically and immunohistochemically for follicular dendritic cell pattern using the monoclonal antibody Ki-FDC1P. This recognizes follicular dendritic cells in paraffin sections. Follicular dendritic cells were most predominant in lymphomas of the thyroid. These thyroid lymphomas showed the morphological features of mucosa-associated lymphoid tissue (MALT) type lymphomas in 18 of 19 cases and were classified as high-grade malignant lymphoma of MALT type with evidence of a low-grade malignant component (n=18). Ten of these cases contained destroyed reactive follicles of follicular dendritic cells. In 6 of these 10 cases follicular dendritic cells occurred in a pattern of tumour-associated abortive follicle type. The remaining lymphoma of the thyroid was an immunoblastic lymphoma of B-cell type showing no detectable follicular dendritic cells. In extranodal lymphomas of non-MALT type follicular dendritic cells occurred in only two cases where immunocytoma involved the kidney. Malignant lymphomas of the kidney (chronic lymphocytic leukaemia,n=2; immunocytoma,n=4; centroblastic lymphoma,n=9) and of the testis (immunocytoma,n=2; centroblastic lymphoma,n=27; immunoblastic lymphoma of B-cell type,n=1) revealed no characteristics of MALT type lymphoma, cytologically or with respect to follicular dendritic cells. Classical lymphoepithelial lesions formed by centrocyte-like cells, a hallmark of MALT, occurred exclusively in thyroid lymphomas of MALT type. Although occurrence of classical lymphoepithelial lesions formed by centrocyte-like cells was limited to thyroid lymphomas of MALT type, a growth pattern of lymphoid blasts, with formation of lesions mimicking lymphoepithelial lesions superficially, was found in 6 of 27 testicular centroblastic lymphomas. Follicular dendritic cells in non-Hodgkin's lymphomas of MALT type show distinct follicular patterns not found in other extranodal lymphomas such as those found in the kidney and testis.     

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type in Waldeyer's ring

Amongst a total of 329 cases of low-grade B-cell lymphoma of Waldeyer's ring, we identified 12 cases that corresponded histomorphologically to low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. These lymphomas are characterized by an extrafollicular growth pattern, often with a marginal zone-like arrangement, and by the centrocyte-like morphology of the tumour cells. They have not been described previously in this location. They predominantly affected the palatine tonsil. Ten cases were primary lymphomas of Waldeyer's ring. In two cases there was a simultaneous high-grade component. Two cases showed regional spread to cervical lymph nodes, but there was no widespread nodal involvement at the time of diagnosis. Immunohistochemically, all cases displayed B-cell markers and light chain restriction. Tropism of tumour cells for the epithelium was a consistent finding. In two cases involvement of Waldeyer's ring was secondary; in one of them the primary tumour was a gastric low-grade B-cell lymphoma of MALT type and in the other a high-grade B-cell non-Hodgkin's lymphoma of the stomach. These findings indicate that low-grade B-cell lymphomas of MALT type occurring in Waldeyer's ring should be included amongst the tumours of the MALT system. We surmise that in Waldeyer's ring such tumours are derived from the marginal zone, as has already been postulated for similar gastric tumours.     

Clinicopathological analysis of 143 primary malignant lymphomas in the small and large intestines based on the new WHO classification

AIM: To study the clinicopathological and immunohistochemical features of 143 cases of primary small and large intestinal non-Hodgkin's lymphoma (NHL) in Japanese patients who presented between 1981 and 2000. METHODS AND RESULTS: The new World Health Organization (WHO) classification was used to classify NHL. The patients included 109 males and 34 females, with an average age of 54.1 years. Tumour sites were as follows: ileocaecal (n = 51, 35.7%), ileum (n = 29, 20.3%), rectum (n = 13, 9.1%), and duodenum (n = 11, 7.7%). Macroscopically, 124 cases (86.7%) were classified as tumorous type, 12 (8.4%) as diffuse infiltration type (erosion, superficial ulceration), five (3.5%) as polyposis type, and only two cases (1.4%) as ulceration type. Immunohistochemically, 122 lesions (85.3%) were of B-cell phenotype and 21 lesions (14.7%) were of T-cell phenotype. According to the WHO classification, of the B-cell lymphomas, 84 cases (68.9%) were large cell, 16 (13.1%) were Burkitt, 10 (8.2%) were marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT), and seven (5.7%) were mantle cell tumours. Among the T-cell lymphomas, 15 (71.4%) were of unspecified type, two (9.5%) were natural killer type, two were anaplastic large-cell lymphomas, one was lymphoblastic, and one was an adult T-cell leukaemia lymphoma. The survival rate for T-cell lymphomas was poorer than for B-cell lymphomas. Among the B-cell lymphomas, mantle cell lymphoma tended to have a poorer prognosis, whereas MALT lymphomas had a better prognosis than other B-cell tumour types. CONCLUSIONS: Our retrospective study of patients with primary malignant lymphomas in the small and large intestines has illustrated the clinical features and outcomes of patients with this disease.     

Primary gastric lymphomas: Morphologic, immunohistochemical and immunogenetic analyses

Morphologic, lmmunohistochemical and lmmunogenetic studies were performed on 28 cases of primary gastric lymphoma from fresh frozen tissue. Eight cases were diagnosed as diffuse large B-cell lymphoma, four as follicular center lymphoma (follicular), five as mucosa-associated lymphoid tissue (MALT) lymphoma, three as plasmacytoma, and three as T-cell lymphoma, two as mantle cell lymphoma, one as follicular center lymphoma (diffuse, predominantly small cell), and one as lymphoplasmacytoid lymphoma, and one as Hodgkin's disease.
From lmmunohistochemical studies, four types of morphologically similar low-grade lymphomas can be differentiated by a combination of various monoclonal antibodies. Cases of diffuse large B-cell lymphoma may have a germinal center origin. We observed lympho-epithelial lesions in cases of non-MALT lymphomas. We therefore consider that the current diagnostic criterion for MALT lymphoma may not always be valid.
Except for cases of T-cell lymphoma and Hodgkin's disease, 17 out of 22 cases revealed clonal rearrangement bands of the JH gene. In situ hybridization (ISH) and polymerase chain reaction (PCR) studies revealed the presence of Epstein-Barr (EB) virus genomes in two and three cases, respectively. Epstein-Barr virus may play a role in lympho-magenesis, although on relatively rare occasions.     

Ploidy, proliferative activity, cluster differentiation antigen expression and clinical remission in highgrade non-Hodgkin''s lymphoma

Using a large range of monoclonal antibodies to specific cluster differentiation antigens the phenotypes of a series of high-grade non-Hodgkin's lymphomas of B- and T-cell type were investigated. Cell ploidy and proliferative fraction were assessed by fluorescent staining of DNA and flow cytometry and data on the incidence of complete clinical remission were obtained. With the exception of some lymphoblastic lymphomas, high-grade B-cell lymphomas normally expressed the pan B-cell antigens CD19 and CD22 but only immunoblastic lymphomas consistently expressed the pan B marker CD20. Variable, generally weak expression of CD21 was observed whilst CD23 expression was most prevalent in rapidly proliferative cases and in Burkitt's and centroblastic lymphomas. A rapidly proliferative, multilobated B-cell lymphoma displayed phenotypic properties intermediate between centroblastic and immunoblastic lymphomas. The T-cell lymphomas generally showed low proliferative activity and expression of CD4 prevailed over CD8. Most cases also showed CD2 and CD5 positivity with some also showing CD3 and CD7 expression. Patients with rapidly proliferative diploid or DNA aneuploid tumours obtained complete remission more readily than patients with lowly proliferative diploid tumours. An excess of early deaths occurred among T-cell cases.     

Immunohistological characterization of malignant lymphomas of the Waldeyer''s ring other than the nasopharynx

Among extranodal lymphomas, the Waldeyer's ring is the second most frequently involved site after the gastrointestinal tract. Fresh tissue from 23 consecutive cases of malignant lymphoma of the faucial tonsil, palate and base of tongue were studied histologically and with a panel of 25 monoclonal antibodies. Twenty cases were primary Waldeyer's ring lymphoma, and all were found to express B-cell phenotype. Most cases were classified as diffuse centroblastic lymphoma, polymorphic subtype, in which there were immunoblast-like, centrocyte-like and/or multilobated centroblasts. All except one case expressed all three B-cell lineage antigens CD19, CD20 and CD22, but they showed inconsistent expression of the B-cell antigens CD9 and CD24. Four cases lacked surface immunoglobulin. Six cases expressed interleukin-2 receptor, suggesting that they were composed of highly activated B-cells. Three cases represented relapse in the tonsil or tongue in patients with known malignant lymphoma in other sites; one case expressed T-cell and two cases B-cell phenotype (both of which also expressed interleukin-2 receptor). The clinical features and immunohistological findings suggest that Waldeyer's ring lymphomas, other than those of the nasopharynx, share some of the characteristics of 'mucosa-associated lymphoid tissue' lymphomas. In contrast, nasopharyngeal lymphomas are more related to nasal lymphomas, and are almost exclusively peripheral T-cell neoplasms.     

Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue

Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B-cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells.     

Expression of CD10, CD75 and CD43 in MALT lymphoma and their usefulness in discriminating MALT lymphoma from follicular lymphoma and chronic gastritis.

AIMS: While it may be difficult to discriminate between chronic gastritis, MALT lymphoma and a gastric location of a nodal lymphoma using histology of small endoscopic biopsies alone, additional markers like CD10, CD75 and CD43 and proliferative activity may be of value. We assessed the expression of these antigens in MALT lymphoma and their usefulness in discriminating MALT lymphoma from follicular lymphoma and from gastritis. METHODS AND RESULTS: Tissue samples of 38 patients with gastric MALT lymphoma were immunohistochemically stained for expression of CD10, CD75 and/or CD43. Proliferation index was scored using MIB-1 staining. Ten cases of nodal follicle centre B-cell lymphomas (n = 11) and 18 cases of high-grade MALT lymphoma (n = 22) showed moderate to high CD75 expression (25-100% positive cells). All tested low-grade MALT lymphomas (n = 9) and chronic gastritis (n = 6) were negative (0-25%) for CD75. All MALT lymphomas (n = 25) were negative for CD10. High-grade lymphomas show significantly higher proliferation indices (67% vs. 16%) than low-grade lymphomas. Only four of 26 MALT lymphomas were slightly positive for CD43. All gastritis biopsies (n = 4) were negative for CD43. CONCLUSIONS: These data suggest that combining both CD10 and CD75 may be useful in discriminating between low-grade MALT, high-grade MALT lymphoma and extranodal location of follicular lymphoma. However, CD43 expression cannot in the majority of cases be used to distinguish between low-grade MALT lymphoma and gastritis.     

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 lymphomas of the lung: morphological, immunohistochemical and clinical features

Sixty-two cases of primary malignant lymphoma of the were investigated. Fifty-eight lymphomas were of B- and two of T-cell type. Two cases of high-grade homa could not be further classified. The largest group (43 cases) consisted of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue. These showed features similar to low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue of the stomach. The low-grade lymphomas showed a peak occurrence in the sixth decade, the high-grade lymphomas in venth decade. Males predominated slightly. Three-quarters of the patients with low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue showed solitary or multiple sharply defined nodules of the lung. The prognosis of the B-cell-derived lung lymphomas without constitutional symptoms was relatively favourable, regardless of whether they were of low- or high-grade malignancy, whereas patients with constitutional symptoms and the two patients with T-cell lymphomas showed a bad prognosis. However, recurrences and metastases in the lung, stomach, lymph nodes and salivary glands were seen in about 46% of the cases of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue.     

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.     

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.     

Clinicopathological features of gastric B-cell lymphoma: a series of 317 cases

The stomach is a common site of extranodal malignant lymphoma. Here we examined the clinicopathological features of 317 gastric B-cell lymphomas and characterized the differences among low-grade mucosa-associated lymphoid tissue (MALT) lymphomas (LG), high-grade MALT lymphomas (HG), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DL). Cases included 126 DL, 71 HG, 98 LG, 10 FL, three Burkitt's lymphoma and nine of undefined type. The age range of patients was as follows: LG, 14-96 years (mean, 61.1); HG, 20-87 years (mean, 63.9); DL, 16-88 years (mean, 62.8); and FL, 54-76 years (mean, 65.5). There were no differences in age with respect to tumor type. There were more women patients with LG (female:male, 55:43), while males predominated among DL patients (54:72). The sexes were represented almost equally in HG cases (34:37). Histological findings, especially in DL tumors, correlated significantly to the gross appearance of mass formation. Dutcher bodies were encountered mainly in HG or LG cases. Our results showed no differences in age, sex or site of disease between LG, HG and DL tumors. However, the grade of malignancy correlated strongly to gross appearance. Dutcher bodies were important for the diagnosis of gastric MALT lymphoma.     

Significance of C4d deposition in the follicular lymphoma and MALT lymphoma and their relationship with follicular dendritic cells

We evaluated the deposition of C4d in follicular lymphomas (FL) and extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Deposition of C4d was detected in 118 lymphoma tissues from patients with lymphoma and in 20 reactive hyperplasia lymphadens (RHL) using immunohistochemistical methods. FL, MALT lymphoma, and RHL were studied using double staining for CD35/C4d and Bcl-2/C4d. We studied 26 FL tissues, 19 of which showed C4d deposition. C4d deposition was detected around the follicular dendritic cells (FDCs) in the neoplastic follicles. There was no significant difference between the positive ratio of C4d and the grades of FL. We studied 12 MALT lymphoma tissues, six of which displayed C4d deposition. In these tissues, C4d deposition was detected in the peripheral region of partially colonized follicles in the form of an irregular ring, but was not found in the central region. C4d deposition was negative in completely colonized follicles. There was no C4d deposition in diffuse large B-cell lymphomas, mantle cell lymphomas, B-small lymphocytic lymphomas, T-lymphoblastic lymphomas, peripheral T-cell lymphomas, and anaplastic large cell lymphomas. C4d around the FDCs in the neoplastic follicles was a specific indicator for FL. C4d deposition in partially colonized follicles of MALT lymphoma was completely different from that in neoplastic follicles of FL, forming a key point for differential diagnosis.     

Gastrointestinal lymphomas of T- and B-cell types.

Gastrointestinal lymphomas comprise a group of distinctive clinicopathological entities of B- or T-cell type, with primary gastrointestinal Hodgkin's disease being extremely uncommon. Most low-grade B-cell gastrointestinal lymphomas are of mucosa-associated lymphoid tissue (MALT) type, so called because they recapitulate the features of MALT rather than those of lymph nodes. Paradoxically, however, most MALT lymphomas arise in the stomach, which normally contains no organized lymphoid tissue. Gastric MALT lymphomas appear to arise in MALT acquired as a reaction to infection of the stomach by Helicobacter pylori and their growth can be inhibited by eradication of this organism from the stomach. Low-grade MALT lymphomas, which usually have a very favorable clinical course, may undergo high-grade transformation but high-grade diffuse large B-cell lymphomas may also arise de novo. Immunoproliferative small intestinal disease (IPSID) is a special form of MALT lymphoma characterized by synthesis of alpha heavy-chain immunoglobulin and a restricted geographic distribution. Other B-cell lymphomas that tend to arise in the gastrointestinal tract include mantle cell lymphoma, which presents as lymphomatous polyposis, Burkitt's lymphoma, and B-cell lymphomas associated with immunodeficiency states. Enteropathy (celiac disease)-associated T-cell lymphoma (EATL) is the most common primary gastrointestinal T-cell lymphoma This is a clinically aggressive tumor that arises from the intraepithelial T-cell population.     

CD 30 expression in follicular lymphoma

The CD30 antigen is a characteristic phenotypic feature of Sternberg-Reed and Hodgkin cells and is also found in a subset of large cell non-Hodgkin's lymphomas. The finding of CD30 positive cells in some centroblastic/centrocytic (cb/cc) follicular lymphomas prompted us to characterize the presence and distribution of CD30 positive cells in this type of lymphoma, using the monoclonal antibody BerH2. CD30 positive cells were present in 17/19 of the cases studied, located mainly at the edge of the neoplastic follicles, but also in some cases in perinodular or T-cell areas. This distribution resembles that found in reactive tonsils and lymph nodes. The majority of these CD30 positive cells in cb/cc lymphoma seem to be B-cells, as suggested by their reactivity with B-cell markers demonstrated by double immunostaining. The nature of these CD30 positive cells is unclear, but they should be taken into consideration in the differential diagnosis of cb/cc lymphoma with lymphocyte predominance Hodgkin's disease.     

T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphoma

AIMS: An accurate diagnosis of T-cell/histiocyte-rich large B-cell lymphoma needs to take into consideration those forms of Hodgkin's lymphoma also characterized by a predominance of small lymphocytes and histiocytes, i.e. nodular lymphocyte predominance Hodgkin's lymphoma and lymphocyte-rich classical Hodgkin's lymphoma. We have studied the clinical, phenotypic and genetic features of a series of 12 cases of T-cell/histiocyte-rich large B-cell lymphoma along with 18 cases of Hodgkin's lymphoma for comparative purposes. METHODS AND RESULTS: Of the Hodgkin's lymphoma cases, there were 11 lymphocyte predominance type and seven classic type. T-cell/histiocyte-rich large B-cell lymphomas presented usually in advanced stages (III or IV in 11/12 cases), frequently with 'B' symptoms (6/9 cases), and followed a more aggressive course than Hodgkin's lymphoma (4/8 patients died due to the tumour in T-cell/histiocyte-rich large B-cell lymphoma versus 0/15 in Hodgkin's lymphoma). T-cell/histiocyte-rich large B-cell lymphoma cases showed diffuse effacement of the nodal architecture by a proliferation of scattered large atypical B-cells obscured by a background of small T-lymphocytes (more CD8+, TIA1+ than CD57+). Five cases showed also a prominent histiocytic component. The large B-cells expressed CD45 and often EMA (6/10 cases). On the other hand, CD 30, CD15 and latent infection by Epstein-Barr virus (EBV) were generally lacking. bc l6 and CD10 were, respectively, detected in 6/6 and 1/5 cases. Conventional polymerase chain reaction (PCR) showed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements in all T-cell/histiocyte-rich large B-cell lymphomas studied (5/5), but did not detect any case with t(14;18) involving the major breakpoint region (0/4). CONCLUSIONS: The differential diagnosis of T-cell/histiocyte-rich large B-cell lymphoma from Hodgkin's lymphoma is facilitated by the integration of different immunophenotypic, molecular and clinical findings. T-cell/histiocyte-rich large B-cell lymphoma is a monoclonal neoplasm of bc l6+ B-cells with a phenotypic profile similar to lymphocyte predominance Hodgkin's lymphoma, suggesting a germinal centre origin and a possible relation to this disease. Therefore, in order to distinguish it from lymphocyte predominance Hodgkin's lymphoma, characterization of the reactive background, IgH gene rearrangement studies by conventional PCR and clinical features are more useful. In contrast, T-cell/histiocyte-rich large B-cell lymphoma can be distinguished from classical Hodgkin's lymphoma thanks to the presence of monoclonal IgH rearrangement and the CD 30-CD15-CD45+EMA+ immunophenotypic profile of the neoplastic cells in T-cell/histiocyte-rich large B-cell lymphoma.