Salivary gland mucosa-associated lymphoid tissue lymphoma immunoglobulin V(H) genes show frequent use of V1-69 with distinctive CDR3 features.

Salivary gland mucosa associated lymphoid tissue (MALT) type lymphomas are B-cell neoplasms that develop out of a reactive infiltrate, often associated with Sjögren's syndrome. Previous reports from our laboratory involving 10 patients suggested these lymphomas expressed a restricted immunoglobulin (Ig) V(H) gene repertoire with over use of V1-69 gene segments. To better determine the frequency of V1-69 use and whether there may also be selection for CDR3 structures, we sequenced the V(H) genes from 15 additional cases. Over half of the potentially functional V(H) genes (8 of 14) used a V(H)1 family V1-69 gene segment, whereas the other cases used different gene segments from the V(H)1 (V1-46), V(H)3 (V3-7, V3-11, V3-30.3, V3-30.5), and V(H)4 (V4-39) families. The 8 V1-69 V(H) genes used 5 different D segments in various reading frames, but all used a J4 joining segment. The V1-69 CDR3s showed remarkable similarities in lengths (12-14 amino acids) and stretches of 2 to 3 amino acids between the V-D and D-J junctions. They did not resemble CDR3s typical of V1-69 chronic lymphocytic leukemias. This study extends our earlier work in establishing that salivary gland MALT lymphomas represent a highly selected B-cell population. Frequent use of V1-69 appears to differ from MALT lymphomas that develop at other sites. The high degree of CDR3 similarity among the V1-69 cases suggests that different salivary gland lymphomas may bind similar, if not identical epitopes. Although the antigen specificities are presently unknown, similar characteristic CDR3 sequences are often seen with V1-69 encoded antibodies that have anti-IgG or rheumatoid factor activity. (Blood. 2000;95:3878-3884)

Ongoing Ig gene hypermutation in salivary gland mucosa-associated lymphoid tissue-type lymphomas.

Salivary gland mucosa-associated lymphoid tissue (MALT) type lymphomas are typically indolent B-cell neoplasms that are often associated with Sjogren's syndrome. To better define the cell of origin and evaluate whether antigen receptor stimulation may be playing a role in tumor growth, the Ig heavy and light chain variable genes (VH and VL) expressed by five salivary gland MALT lymphomas were cloned and sequenced. Comparison to known germline sequences indicated that three of the lymphoma VH genes were derived from 51p1, a member of the VH1 family, while the other two used different VH gene segments from the VH3 family, 22-2B and HG19. All five of the VL genes belonged to the VkIII family, with three derived from Humkv325 and the other two from the Vg and Humkv328 genes. Numerous point mutations relative to the proposed germline genes were present in all of the lymphoma VH and VL genes. In addition, the VH and VL genes from each lymphoma showed intraclonal sequence heterogeneity indicative of ongoing somatic hypermutation. Because the process of Ig gene hypermutation is thought to occur at the germinal center stage of B-cell development, these findings suggest the MALT lymphoma cell of origin may be a germinal center B cell. Selection against mutations that result in replacement of amino acids suggested that Ig stimulation may be important for lymphoma growth. The possibility that antigen receptor stimulation may be involved in the growth of salivary gland MALT lymphomas is further suggested by the noted restricted use of VH and VL gene segments.

A clonally distinct recurrence of Burkitt's lymphoma at 15 years.

A human immunodeficiency virus-negative male was successfully treated for two occurrences of Burkitt's lymphoma, 15 years apart. As consolidation of his second remission, he underwent high-dose chemotherapy with peripheral blood stem cell transplantation. In an effort to prove whether the second lymphoma was a relapse of the first or a second primary lymphoma, we obtained paraffin-embedded material from both lymphomas. DNA was extracted from this material and amplified by polymerase chain reaction (PCR) using consensus JH and VH region primers. Analysis of the PCR products, which mostly reflects VDJ joints, showed two sharp bands of different molecular size, proving the monoclonal nature of the lymphomas and suggesting that each had different Ig gene rearrangements. Sequencing of both PCR products showed a marked dissimilarity in nucleotide sequence in the clonally unique VDJ joint region, providing strong evidence for the separate cellular genesis of each lymphoma. These results suggest that late relapses of Burkitt's lymphoma should be examined for clonal distinctiveness. If the second lymphoma is distinct from the primary one, it might be treated as a primary lymphoma rather than as recurrent disease.

Radiation dose to positron emission tomography technologists during quantitative versus qualitative studies.

Positron emission tomography technologists were monitored with thermoluminescent dosimeters (TLDs) during qualitative and quantitative studies. Doses to technologists during specific tasks were also measured. The technologists received at least twice as much radiation during the quantitative as the qualitative studies. The average dose per study for qualitative studies was 0.017 mSv (1.7 mrem) shallow and 0.014 mSv (1.4 mrem) deep. The average dose per study for the quantitative studies was 0.05 mSv (5 mrem) shallow and 0.04 mSv (4 mrem) deep. The average dose per study was based on the TLD dose accumulated over studies conducted over four 2-mo and one 1-mo intervals. The dose incurred by the technologists each time they drew a radioactive dose was 0.002 mSv (0.2 mrem) shallow and 0.001 mSv (0.1 mrem) deep. The doses received during injection were 0.014 mSv (1.4 mrem) shallow and 0.007 mSv (0.7 mrem) deep. Doses received during blood sampling were 0.016 mSv (1.6 mrem) shallow and 0.014 mSv (1.4 mrem) deep. During quantitative studies, the technologist received a much greater dose than during its qualitative counterpart due to the blood sampling process and increased time in the room with the radioactive patient.

Performance testing of the environmental TLD system for the Three Mile Island Nuclear Station.

Panasonic UD-801 thermoluminescent dosimeters ( TLDs ) containing two calcium sulfate phosphors were tested under Performance Specification 3.1 established by the American National Standard Institute ( ANSI75 ) and in the U.S. Nuclear Regulatory Commission's Regulatory Guide 4.13 ( NRC77 ). The specific qualifying tests included TLD uniformity, reproducibility, energy dependence and directional dependence. The overall measurement uncertainties and associated confidence levels are within the prescribed guidelines defined in the qualifying requirements for environmental TLDs .