The clonality of nodular lymphocyte-predominant Hodgkin's disease (NLPHD) and the relationship to composite or sequential large-cell lymphomas (LCLs) is poorly understood. Clonal Ig heavy-chain gene rearrangements (lgHGR) have infrequently been observed in NLPHD by Southern hybridization. The goals of this study were (1) to determine if IgHGR could be identified by polymerase chain reaction (PCR) techniques in the LCL associated with NLPHD; (2) to determine if the lgHGR identified in the LCL could also be found in the associated NLPHD; and (3) to determine if Epstein-Barr virus (EBV) played a role a role in histologic progression to LCL. Using consensus primers to conserved regions in the lgH variable (V) and joining (J) region genes, we analyzed formalin-fixed paraffin-embedded sections from the biopsies of 25 patients referred to the National Cancer Institute (NCI) registry for NLPHD and LCL using both single-step and seminested V-J PCR. The histologically aggressive component was further subclassified as frank LCL or as L&H-cell-rich, but not fulfilling criteria for LCL. Matched samples representing both NLPHD and aggressive components were available in 13 cases. In 12 cases, only one component was available (aggressive, n = 8; NLPHD, n = 4). In addition, we also amplified, with 32P labeling, 12 cases of NLPHD without associated LCL. Two clonal IgHGR were identified in 29 cases (7%) of typical NLPHD, both of which were associated with LCL containing a similar sized band by PCR. The clonal identity of the bands in the NLPHD and associated LCL was confirmed by sequencing the products in these two cases. Eight of 10 cases (80%) of LCL associated with NLPHD contained a clonal band by this technique. By contrast, none of the cases classified as L&H-cell- rich contained an IgHGR. The single-step and seminested PCR methods produced identical results. All clonal LCLs were studied for EBV sequences by in situ hybridization using the EBER1 probe, and were negative. We conclude that the LCLs associated with NLPHD are clonal B- cell malignancies. However, by these methods, the same clone can be identified in only a minority of cases of NLPHD and LCL. EBV does not appear to play a role in histologic progression. Moreover, our results suggest that many cases suspected of being LCL may actually represent NLPHD with increased numbers of L&H cells. In histologically equivocal cases, the diagnosis of LCL should be reserved for those cases in which a clonal B-cell neoplasm can be demonstrated.

Malignant lymphomas (ML) with t(3;14) or variant t(2;3) and t(3;22) have recently been recognized. These translocations have been shown to associate predominantly with B-cell diffuse large cell lymphoma (DLCL) and less frequently with follicular lymphoma (FL). The molecular alterations associated with these translocations involve one of the immunoglobulin gene (Ig) loci and a recently cloned gene, bcl-6 located at 3q27 which codes for a zinc-finger protein that may function as a transcription factor. We have identified by cytogenetic analysis 22 cases of ML with a 3q27/Ig translocation. The pathologic diagnoses of these cases include DLCL, FL, small non-cleaved non-Burkitt lymphoma and chronic lymphocytic leukaemia. Molecular analysis confirmed a bcl-6 rearrangement in 10/12 cases tested. The karyotype in 5/22 cases revealed the t(3;14) or variant in association with another lymphoma-specific translocation, t(14;18) in three cases and t(8;14) in two cases. ML with dual translocations that implicate Ig genes in the deregulation of proto-oncogenes are being increasingly recognized and may represent distinct subtypes or 'hybrid' forms of malignant lymphoma.

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This study calibrated and validated the FORE-SIGHT Elite tissue oximeter to accurately measure SctO2 in pediatric patients with the medium sensor.