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Correlative morphologic and molecular genetic analysis demonstrates three
distinct categories of posttransplantation lymphoproliferative disorders
DM Knowles, E Cesarman, A Chadburn, G Frizzera, J Chen, EA Rose and RE Michler
Department of Pathology, New York Hospital-Cornell Medical Center, NY
10021.
The posttransplantation lymphoproliferative disorders (PT-LPDs) are a
morphologically heterogeneous group of Epstein-Barr virus (EBV)-driven
lymphoid proliferations of varying clonal composition. Some PT-LPDs regress
after a reduction in immunosuppression, while others progress in spite of
aggressive therapy. Previously defined morphologic categories do not
correlate with clonality, and neither morphology nor clonality has reliably
predicted the clinical behavior of PT-LPDs. We investigated 28 PT-LPD
lesions occurring in 22 patients for activating alterations involving the
bcl-1, bcl-2, c-myc, and H-, K- and N-ras proto-oncogenes and for mutations
involving the p53 tumor suppressor gene. We correlated the results of these
studies with the morphology of the lesions, their clonality based on Ig
heavy and light chain gene rearrangement analysis, and the presence and
clonality of EBV infection. We found that the PT-LPDs are divisible into
three distinct categories as follows: (1) plasmacytic hyperplasia: most
commonly arise in the oropharynx or lymph nodes, are nearly always
polyclonal, usually contain multiple EBV infection events or only a minor
cell population infected by a single form of EBV, and lack oncogene and
tumor suppressor gene alterations; (2) polymorphic B-cell hyperplasia and
polymorphic B-cell lymphoma: may arise in lymph nodes or various extranodal
sites, are nearly always monoclonal, usually contain a single form of EBV,
and lack oncogene and tumor suppressor gene alterations; and (3)
immunoblastic lymphoma or multiple myeloma: present with widely
disseminated disease, are monoclonal, contain a single form of EBV, and
contain alterations of one or more oncogene or tumor suppressor genes
(N-ras gene codon 61 point mutation, p53 gene mutation, or c-myc gene
rearrangement). The PT-LPDs are divisible into three categories exhibiting
distinct morphologic and molecular genetic characteristics. Alterations
involving the N-ras and c-myc proto- oncogenes and the p53 tumor suppressor
gene may play an important role in the development and/or progression of
the PT-LPDs.
Volume 85,
Issue 2,
pp. 552-565,
01/15/1995
Copyright © 1995 by The American Society of Hematology
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