May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Molecular Analysis of IgH Gene Rearrangements in 61 Patients With Primary Intraocular Lymphoma
Author Affiliations & Notes
  • J. A. Gonzales
    Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland
  • D. Shen
    Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland
  • G. Levy-Clarke
    Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland
  • R. R. Buggage
    Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland
  • M. Mochizuki
    Department of Ophthalmology, Tokyo Medical and Dental University School of Medicine, Tokyo, Japan
  • D. G. Callanan
    Department of Ophthalmology, University of Texas Southwestern Medical School, Dallas, Texas
  • R. B. Nussenblatt
    Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland
  • C.-C. Chan
    Laboratory of Immunology, National Eye Institute/National Institutes of Health, Bethesda, Maryland
  • Footnotes
    Commercial Relationships J.A. Gonzales, None; D. Shen, None; G. Levy-Clarke, None; R.R. Buggage, None; M. Mochizuki, None; D.G. Callanan, None; R.B. Nussenblatt, None; C. Chan, None.
  • Footnotes
    Support National Eye Institute Intramural Research Program
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1582. doi:https://doi.org/
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    • Get Citation

      J. A. Gonzales, D. Shen, G. Levy-Clarke, R. R. Buggage, M. Mochizuki, D. G. Callanan, R. B. Nussenblatt, C.-C. Chan; Molecular Analysis of IgH Gene Rearrangements in 61 Patients With Primary Intraocular Lymphoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1582. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Histopathological identification of malignant lymphoma cells from biopsied tissue is required to diagnose primary intraocular lymphoma (PIOL), but differentiation of reactive and atypical lymphoid proliferations from true malignancy can be challenging. Thus, adjunctive testing identifying monoclonality, a hallmark feature of malignancy, is useful. Confirmation of a monoclonal or malignant process is crucial for treatment to commence in patients with PIOL. This retrospective study identifies patterns of monoclonality in cases of PIOL diagnosed from tissues submitted to our laboratory.

Methods:: A retrospective review of pathology reports between 1997 and 2006 from submitted biopsy specimens (vitreous, cerebrospinal fluid, aqueous, retina, iris, or brain) of 60 HIV-negative patients with clinical PIOL/primary CNS lymphoma was performed. Biopsy specimens had undergone microdissection of at least 15 atypical lymphoid cells and subsequent polymerase chain reaction (PCR) to reveal monoclonality within the variable region of the third complementary determining region (CDR3) in the immunoglobulin heavy chain (IgH) gene using primers of FR2A (5’-TGGRTCCGMCAGSCVYCNGG-3’), FR3A (5’-ACACGGCYSTGTATTACTGT-3’), and CDR3 (5’-CCGGRAARRGTCTGGAGTGG-3’). T-cell receptor (TCR) gene rearrangement was identified using primers for the CDR3 and the variable region of the gamma (γ) chain gene.

Results:: Biopsy tissue was submitted for 37 females and 23 males (1.6:1 ratio) for diagnosis of PIOL. Notably, 29/60 patients were previously diagnosed and treated for an inflammatory condition before PIOL was confirmed. Atypical cells from 57/60 patients exhibited monoclonality demonstrated as rearrangement of IgH at the CDR3 region, most sensitive with the FR3A (90% cases positive) and CDR3 (56.7% cases positive) primers. A TCR, not IgH, gene rearrangement was found in 3/60 cases indicating a T-cell origin for the malignant cells.

Conclusions:: Atypical lymphoid cells can be identified genotypically via microdissection and PCR analysis of IgH or TCR rearrangements thereby indicating a malignant origin. While most PIOL is B-cell in origin, T-cell lineage rarely occurs, especially in patients with cutaneous or nasal mucosal involvement.#

Keywords: oncology • pathology: human • tumors 
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