Tumour-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group.

AIMS: To evaluate the role of tumour-associated macrophages (TAMs) of the M1 and M2 types in the behaviour of diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS: Double immunohistochemical staining of HLA-DR/CD68 (M1) or CD163/CD68 (M2) was performed in 101 cases of DLBCL. CD68+ cells represent the total number of TAMs. The average number of double-positive cells was counted, and the cut-off value was set at the mean number of counts, i.e. 30.7 and 27.0 for M1 TAMs and M2 TAMs, respectively. That for total TAMs was set at the 90th percentile number of total counts, i.e. 132.3. Cases were categorized into three pairs: high (34 cases) and low (67 cases) M1 TAM groups, high (39 cases) and low (62 cases) M2 TAM groups, and high (10 cases) and low (91 cases) total TAM groups. The difference in overall survival rates was statistically significant between the high and low M2 TAM groups (P < 0.01) and between the high and low total TAM groups (P < 0.05). Multivariate analysis revealed that the presence of a bulky mass and a higher number of M2 TAMs were significant factors for poor prognosis (P < 0.05). CONCLUSIONS: Estimation of specific type of macrophages, of the M1 and M2 types, is superior to the estimation of TAMs as a whole (CD68+ cells) for prediction of the prognosis of DLBCL patients.

Diffuse large B cell lymphoma with an interfollicular pattern of proliferation shows a favourable prognosis: a study of the Osaka Lymphoma Study Group.

AIMS: Diffuse large B cell lymphoma (DLBCL) occasionally shows an interfollicular pattern of proliferation (DLBCL-IF) preserving lymphoid follicles. In this study, clinicopathological findings in 31 cases of DLBCL-IF were analysed. METHODS AND RESULTS: The study group comprised 20 males and 11 females, with ages ranging from 41 to 87 (median 69) years. The primary site was lymph node in 25 cases, and unknown in six due to advanced stage at diagnosis. Eight cases were clinical Stage I, 10 were Stage II, four Stage III, and nine Stage IV. A polymorphous pattern of proliferation containing large B cells and inflammatory cells was found in about 60% of cases. The overall survival rate of the DLBCL-IF patients was better than that of a DLBCL control group (log-rank test; P < 0.05). Multivariate analysis revealed that an interfollicular pattern of proliferation showed marginal significance for favourable prognosis (P = 0.069). Immunohistochemical double staining with antibodies for HLA-DR/CD68 (markers for M1-tumour-associated macrophage [M1-TAM]) or CD163/CD68 (M2-TAM) revealed that all DLBCL-IF patients with a low M2 count were alive at the end of observation. CONCLUSIONS: These findings suggest that DLBCL-IF is a clinicopathological entity distinct from ordinary DLBCL. The possible origin of tumour cells in DLBCL-IF from marginal zone B cells is discussed.

Presence of B-cell clones in T-cell lymphoma.

OBJECTIVES: The presence of B-cell clones in 76 cases with peripheral T-cell lymphoma (PTCL) and precursor T-lymphoblastic lymphoma (T-LBL) and its correlation with Epstein-Barr virus (EBV) was studied. METHODS: DNA was extracted from paraffin sections and/or fresh-frozen samples and then used for clonality analysis using a modified BIOMED-2 polymerase chain reaction (PCR)-based method. RESULTS: T- and B-cell clones were detected in 59 (77.6%) and 14 (18.4%) of 76 patients, respectively: 90% and 30% of cases with PTCL, not otherwise specified, 76.4% and 17.6% of cases with angioimmunoblastic T-cell lymphoma, 77% and 7.6% of cases with adult T-cell lymphoma, 50% and 0% of cases with anaplastic large T-cell lymphoma, 62.5% and 12.5% of cases with T-LBL, and 50% and 0% of cases with intestinal T-cell lymphoma, respectively. Histological and immunohistochemical analyses revealed the presence of large B cells in lesional tissues, which were occasionally monoclonal. The presence of B-cell clones was highly associated with EBV positivity, as revealed by in situ hybridization. In two cases that were evaluated by serial histological and molecular examination, EBV-positive cells persisted in one and disappeared in the other. CONCLUSIONS: These findings suggest a role for EBV in the evolution of B-cell clones in T-cell lymphomas.

Epidemiology and pathogenesis of nasal NK/T-cell lymphoma: a mini-review.

Nasal NK/T-cell lymphoma (NKTCL) frequently presents with necrotic, granulomatous lesions in the upper respiratory tract, and usually shows a highly aggressive clinical course. Thus, it was initially included in the clinical condition of lethal midline granuloma. Recently, the disease has been recognized as a neoplastic proliferation of NK/T cells. The disease is much more frequent in Asian and Latin American countries than in Western countries, and is universally associated with Epstein-Barr virus (EBV) infection. Analyses of gene mutations, especially p53 and c-kit, revealed the different frequencies by district. Abnormalities of other genes have also been reported. Case-control studies showed that the exposure to pesticides and chemical solvents could be causative of NKTCL. Further studies including HLA antigen typing of patients is necessary to further clarify the disease mechanism.

Prognostic implication of types of tumor-associated macrophages in Hodgkin lymphoma.

To evaluate roles of tumor-associated macrophages (TAMs) for prognosis of classical Hodgkin lymphoma (CHL). Expression of markers for TAMs, CD68, HLA-DR, CD163, HLA-DR/CD68 (M1), and CD163/CD68 (M2) was immunohistochemically examined in 82 cases with CHL. Positively stained cells were counted and correlation of number of TAMs and patients' survival time was analyzed. Number of CD163+ cells and M2 cells was significantly correlated with shorter overall survival (P < 0.05), while it was marginally significant for CD68+ cells (P = 0.0827). HLA-DR + cells and M1 cells showed no significant correlation with overall survival. When confined to mixed cellularity subtype, number of M1 cells was correlated with favorable prognosis (P < 0.05), while M2 did not (P = 0.7). Older age and male sex were unfavorable factors for prognosis. At multivariate analysis, number of CD163+ cells, M2+ cells, and age were independent factors for poor overall survival (P = 0.03, 0.02, and 0.01, respectively). CD163+ cells and M2 cells might work to be tumor promotive in CHL. M1 cells might be tumor suppressive in mixed cellularity type.