Diagnostic Impact of Molecular Lineage Analysis on Paraffin-Embedded Tissue in Hematolymphoid Neoplasia Reclassified by
- PDF / 4,246,289 Bytes
- 25 Pages / 592.44 x 751.18 pts Page_size
- 11 Downloads / 148 Views
ORIGINAL RESEARCH ARTICLE
© 2007 Adis Data Information BV. All rights reserved.
Diagnostic Impact of Molecular Lineage Analysis on Paraffin-Embedded Tissue in Hematolymphoid Neoplasia Reclassified by Current WHO Criteria Leonard Hwan Cheong Tan,1,2 Lily-Lily Chiu3 and Evelyn Siew Chuan Koay1,3 1
Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2
Department of Pathology, Singapore General Hospital, Singapore
3
Molecular Diagnosis Centre, Department of Laboratory Medicine, National University Hospital, Singapore
Abstract
Background and Objective: By current WHO criteria, most – though not all – cases of hematolymphoid neoplasm can be diagnosed immunomorphologically, diminishing the role of molecular tests for lymphoid antigen receptor clonality in lymphoma diagnosis. Hence, our objective was to glean immunomorphological and molecular correlates from hematolymphoid neoplasms that had remained unresolvable without diagnostic molecular input. Methods: Thirty-five such cases were reviewed histologically and with standard immunoperoxidases. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNAs (EBER) was performed on selected cases. PCR amplification of genes encoding T-cell receptors (TcR) and immunoglobulin heavy chains (IgH) [TR and IGH genes, respectively] was performed on whole tissue in all cases, and on microdissected cells in two cases. Results: Twenty-five cases (71%) requiring diagnostic molecular genotyping had some form of peripheral T-cell lymphoma (PTCL). Twenty (80%) of these were complicated by a proliferation of B-lineage cells, either within the same tissue (‘syntopic’) as large B cells (LBC) or Reed-Sternberg (RS)-like cells (17 cases), florid lymphoid hyperplasia (two cases, one also with syntopic LBC) or monotypic plasma cells (one case), or at a separate (‘metatopic’) site as a B-cell lymphoma (two cases, one of which also had syntopic LBC) or Hodgkin lymphoma (HL; one case, also showing syntopic LBC). Fifteen (75%) of these 20 PTCLs with B-lineage proliferation yielded monoclonal TR gene rearrangements, and only two (10%) showed IGH monoclonality, which was transient in one case. Three (18%) of the PTCLs with LBC had originally been misinterpreted as some form of HL. Conversely, of the remaining cases, three of four (75%) that had been diagnosed initially as some form of large cell non-HL (NHL), including two of three that were called ‘anaplastic’, had to be revised to grade II/syncytial nodular sclerosing (NS) HL, yielding polyclonal TcRγ gene (TRG) rearrangements, with one case, in addition, disclosing a biallelic clonal IGH gene rearrangement that excluded anaplastic large cell lymphoma. Discussion/Conclusion: Paradoxically, monoclonality of TR rather than IGH gene rearrangement may more often be detectable in a predominantly dispersed (‘hodgkinoid’), large B-lineage cell proliferation, consistent with release from immune regulation in the milieu of impaired immunosurveillance within a PTCL. This is compounded by the difficul
Data Loading...
