Bilateral development of biclonal ocular adnexal marginal zone lymphoma at a 2-year interval.

Ocular adnexal marginal zone B-cell lymphoma (OAMZL) of the mucosa-associated lymphoid tissue is a distinct subtype of B-cell lymphoma. OAMZL occasionally occurs on both sides with a varied sequence in the time course. However, few case reports have described clonal analysis of bilateral OAMZ. Here we present a case of biclonal OAMZL, that developed bilaterally at a 2-year interval. A 38-year-old woman was diagnosed with OAMZL in the right lower eyelid conjunctiva and received local radiation therapy, resulting in the disappearance of the tumor. Two years later, she developed another tumor in the left lower eyelid and was diagnosed with relapse of OAMZL. She was re-treated successfully with radiation therapy. Analysis of immunoglobulin (Ig) gene rearrangement in the bilateral tumor samples showed different clonotypic VDJ recombination within the Ig heavy chain gene and different patterns of rearrangement of the Ig light chain genes. The results indicated that independent B-cell clones causing the specific subtype of lymphoma had generated in both eyes. The biclonal nature of the lymphoma that developed sequentially in the same anatomic site in this case suggests that underlying inherent or environmental factors may lead to ongoing emergence of new tumor clones.

Biallelic BCL6 rearrangements by dual t(3;14)(q27;q32) and t(3;22)(q27;q11) translocations in diffuse large B-cell lymphoma.

3q27 chromosomal translocation involving the BCL6 gene is one of the most frequent forms of cytogenetic abnormality observed in B-cell lymphoma. We report a case with diffuse large B-cell lymphoma (DLBCL) presenting dual 3q27 translocations. The patient was a 71-year-old man who presented with swelling of multiple abdominal lymph nodes (LNs) and obstructive jaundice. LN biopsy exhibited dense proliferation of atypical large cells expressing CD20, MUM1/IRF4, BCL2, BCL6, and MYC, but not CD10. He was diagnosed with non-GCB/ABC type DLBCL and showed an initially good response to R-CHOP chemotherapy, but relapsed soon after the completion of therapy. Chromosomal analysis of the biopsied LN exhibited multiple abnormalities including t(3;14)(q27;q32) and t(3;22)(q27;q11). Fluorescence in situ hybridization (FISH) using BCL6 break-apart probes confirmed chromosomal breaks occurring on both BCL6 alleles. Molecular analysis revealed two independent rearrangements of BCL6, either with the IGH or the IGL gene. 3q27 breakpoints were located 1.2kb apart from each other within the first intron of BCL6, while the IGH and IGL breaks occurred at the 5' of IGHG2 and within IGLV3-1, respectively. The results suggest that biallelic BCL6 rearrangements might be a rare but recurrent genetic event in B-cell lymphoma.

[Case with hairy cell leukemia-Japanese variant following radiotherapy for orbital adnexal MALT lymphoma].

We report a patient with hairy cell leukemia Japanese variant (HCL-Jv) that developed after radiotherapy for orbital adnexal MALT lymphoma. A 78-year-old man was diagnosed as having MALT lymphoma in the left conjunctiva in December 2003. The patient was treated by local radiotherapy and the tumor disappeared. Thereafter, he gradually developed leukocytosis and mild splenomegaly. In May 2009, the leukocyte count was 34,300 with 80% lymphoid cells. A diagnosis of HCL-Jv was made since the lymphoid cells showed a hairy morphology with round nuclei and indistinct nucleoli. These cells expressed CD11c, CD19, CD20, CD103 and showed weak reaction for tartrate-resistant acid phosphatase (TRAP). Bone marrow was infiltrated by atypical cells with an intrasinusoidal pattern. No treatment was needed as the patient was asymptomatic without anemia, thrombocytopenia or lymphadenopathy. Results of the immunoglobulin light chain expression and the heavy chain rearrangement in the tumor cells indicated that the two mature B-lymphoid neoplasms, MALT lymphoma and HCL-Jv, in this patient were derived from independent clones. This appears to be the first reported case of HCL-Jv associated with other lymphoid tumor. Further analysis is needed to clarify the risk of secondary malignancy in HCL-Jv.

A molecular analysis of biclonal follicular lymphoma: further evidence for bone marrow origin and clonal selection.

We report a follicular lymphoma (FL) case presenting the coexistence of two tumor cell subpopulations in lymph node (LN) and bone marrow (BM), which exhibited an inverse pattern of immunoglobulin light (IgL) chain gene rearrangement and expression: Igkappa-lambda+ in LN and Igkappa+lambda- in BM. These tumor clones shared an identical BCL2-IgH recombination, accompanying t(14;18)(q32;q21) translocation, and an identical variable, diversity and joining segments joining with clone-specific VH somatic hypermutations on the untranslocated IgH allele. Our study provides further evidence that FL clones, originating from common progenitor cells, can be developed independently at different sites and with different IgL expression after immune selection.

The GAS5 (growth arrest-specific transcript 5) gene fuses to BCL6 as a result of t(1;3)(q25;q27) in a patient with B-cell lymphoma.

The BCL6 gene is frequently disrupted at its 5' noncoding region by 3q27 chromosomal translocations in B-cell lymphoma. As a result of translocation, BCL6 is juxtaposed to reciprocal partners, such as the immunoglobulin (Ig) gene family. Besides the Ig loci, multiple non-Ig partners of the BCL6 translocation have been reported. Here we describe the identification of the GAS5 (growth arrest-specific transcript 5) gene as a novel partner of the BCL6 in a patient with diffuse large B-cell lymphoma, harboring the t(1;3)(q25;q27). In this case, the chromosome 1 breakpoint was located within the intronic small nucleolar RNA (snoRNA) sequence of GAS5 and the chromosome 3 breakpoint at 4 kb upstream of BCL6 exon 1a. As the result of chromosomal translocation, the GAS5-BCL6 chimeric transcripts were expressed, in which the 5'-terminal oligopyrimidine (5'TOP) sequence of GAS5 was fused to the whole coding sequence of BCL6. The GAS5 gene on chromosome 1q25 is the second BCL6 partner, to the SNHG5 on 6q15, which is classified as a non-protein-coding multiple snoRNA host and 5'-TOP class gene.