BCL6 gene amplification/3q27 gain is associated with unique clinicopathological characteristics among follicular lymphoma without BCL2 gene translocation.

Although approximately 10-20% cases of follicular lymphoma lack BCL2 gene rearrangement, there are few reports having described the alternative genetic aberrations and their association about clinicopathological features. In this study, analysis by Fluorescence in situ hybridization of BCL6 gene aberrations in 100 follicular lymphoma cases without IGH/BCL2 rearrangement resulted in the identification of four subgroups. Group I: BCL6 gene rearrangement (n=41); Group II: BCL6 gene amplification/3q27 gain (n=30); Group III: the absence of both (n=23); and Group IV: the presence of both (n=6). Group II showed higher grade morphology (Grade 3a/b: 93%), higher bcl2 and MUM1 expression (73 and 57%, respectively), and more frequent combination with BCL2 gene amplification/18q21 gain (90%) than the other groups. BCL6 gene aberration, especially amplification/3q27 gain, indicates the presence of certain morphological and phenotypical findings in follicular lymphoma cases without IGH/BCL2 rearrangement.

Distribution of malignant lymphoma in Japan: analysis of 2260 cases, 2001-2006.

The World Health Organization classification was used to conduct an analysis of geographic, age, sex, and lesion primarily biopsied/resected distribution of 2260 lymphoid neoplasms diagnosed during 2001-2006 throughout Japan. B-cell neoplasms accounted for 65% of all lymphoid neoplasms, T/natural killer (T/NK)-cell neoplasms for 25% and Hodgkin lymphoma for 7%. The most common type was diffuse large B-cell lymphoma (DLBCL, 33%), followed by follicular lymphoma (18%), and adult T-cell leukemia/lymphoma (ATLL, 10%). The high rate of 18% for follicular lymphoma was similar to that in Western countries (11-33%). T/NK-cell neoplasms accounted for a higher percentage of lymphoid neoplasms in Kyushu (30%) and Okinawa (38%) compared with other areas of Japan (18-20%). Among T/NK-cell neoplasms, ATLL was the most common type in Okinawa (54%) and Kyushu (59%). Extranodal NK/T cell lymphoma was the second most common type of T/NK-cell neoplasms in Okinawa (15%). This epidemiological study shows that the distribution patterns of malignant lymphoma differ especially in Kyushu and Okinawa, the endemic area of human T-cell leukemia/lymphoma virus type 1.

The relationship of FOXP3 expression and clinicopathological characteristics in adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma is an aggressive malignant disease associated with regulatory T cells as discussed in some recent reports. We analyzed the expression of FOXP3, a key molecule of regulatory T cells, in adult T-cell leukemia/lymphoma and its association with clinicopathological features. Of 169 adult T-cell leukemia/lymphoma cases examined, 60 (36%) showed FOXP3 expression in lymphoma cells. Morphologically, 22 cases were classified as anaplastic large cell variant and 147 as pleomorphic cell variant. Only 1 (5%) of the anaplastic large cell variant cases and 59/147 (40%) of the pleomorphic cell variant cases expressed FOXP3. Epstein-Barr virus-infected cells were significantly more frequently found in FOXP3(+) cases (23/60; 38%) than in FOXP3(-) cases (12/109; 11%) (P<0.0001). Cytogenetic analysis showed that FOXP3(+) cases had simpler chromosomal abnormalities than FOXP3(-) cases. Clinically, FOXP3(+) and FOXP3(-) cases did not differ significantly in age distribution, clinical stage, lactate dehydrogenase and calcium in serum and overall survival. However, 8 of 34 FOXP3(+) cases suffered a severe infectious state, an indication of immunosuppression, while only 2 of 62 FOXP3(-) cases did so (P<0.005). FOXP3 expression in adult T-cell leukemia/lymphoma thus reflects morphological features and is clinically and pathologically associated with an immunosuppressive state.

Usefulness of flow cytometry for differential diagnosis of precursor and peripheral T-cell and NK-cell lymphomas: analysis of 490 cases.

Although various CD markers have been analyzed in T-cell and natural killer (NK)-cell lymphomas, the sensitivity and specificity of these phenotypic features have not been satisfactorily characterized. Flow cytometry (FCM) was used to determine the phenotypic pattern of 490 T/NK-cell lymphomas with the aid of a set of surface antigens (CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD16, CD19, CD20, CD25, CD30, CD34, and CD56). In data obtained from 319 patients, CD10 expression was detected in 57% of angioimmunoblastic T-cell lymphomas, CD30 in 93% of anaplastic large cell lymphomas, CD34 in 50% of lymphoblastic lymphomas, and CD56 in 100% of extranodal NK/T-cell lymphomas nasal type. A total of 92% of adult T-cell leukemia/lymphomas (ATLL) had expression of CD25 and downregulation of CD7. Of special interest is that 92 ATLL (50%) were CD4+CD7-CD25+ phenotype while only four peripheral T-cell lymphoma unspecified (9%) and one (9%) cutaneous T-cell lymphoma had this phenotype. Phenotypic analysis using FCM was thus found to be useful for differential diagnosis of T-cell and NK-cell lymphomas.