Clinical, Histopathological, and Immunogenetic Analysis of Ocular Adnexal Lymphoproliferative Disorders: Characterization of Malt Lymphoma and Reactive Lymphoid Hyperplasia

Mod Pathol. 2001 Jul;14(7):641-9. doi: 10.1038/modpathol.3880366.


Malignant lymphomas and reactive lymphoid hyperplasia (RLH) in the ocular adnexa are sometimes difficult to differentiate morphologically and have often been categorized together as a lymphoproliferative disorder. Immunogenotypic characters of these diseases have not yet been well clarified. This study included 76 cases of ocular adnexal lymphoproliferative disorders. These consisted of 52 cases of malignant lymphoma (43 primary and 9 secondary), 22 of RLH, and 2 borderline cases. There were slightly more male than female subjects. Diagnoses were based on morphology and immunophenotypic characteristics. Clonalities were detected by means of polymerase chain reaction (PCR), and immunoglobulin heavy-chain variable region (VH) genes were sequenced in 10 cases of mucosa-associated lymphoid tissue (MALT) lymphoma. MALT lymphoma constituted 86% (37 cases) of the primary lymphomas. MALT lymphomas were more indolent, more rarely disseminated, and had a lower death rate than the other primary lymphomas. Two patients exhibited coexistence of MALT and diffuse large B-cell lymphoma. The average age of patients with RLH was 5.5 years younger than that of those with MALT lymphoma. One of the cases of RLH later progressed to malignant lymphoma. B-cell clonality was detected by PCR in 57%, 55%, and 0% of primary lymphomas, MALT lymphomas and RLHs, respectively. Sequencing of VH genes revealed that the VH3 family was the most commonly expressed germline VH family (70%) and that DP-63, DP-54 and DP-47 genes were frequently found in the MALT lymphomas examined. PCR analysis was useful for differentiation between MALT lymphoma and RLH. Sequence analysis of VH genes showed that an autoimmune mechanism may be involved in the lymphomagenesis of ocular adnexal MALT lymphoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA, Neoplasm / genetics
  • Eye Neoplasms / genetics
  • Eye Neoplasms / immunology
  • Eye Neoplasms / pathology*
  • Female
  • Gene Rearrangement
  • Genes, Immunoglobulin / genetics
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Immunophenotyping
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / immunology
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / immunology
  • Lymphoproliferative Disorders / pathology*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Pseudolymphoma / genetics
  • Pseudolymphoma / immunology
  • Pseudolymphoma / pathology


  • DNA, Neoplasm
  • Immunoglobulin Variable Region