Tag Archives: EBV

Organ Systems, Bone Marrow, Lymph Node, WHO Classification

Lymphomatoid Granulomatosis

Lymphomatoid Granulomatosis (LYG) is a B-cell neoplasm of EBV + B-cells with characteristic anglocentric and angiodestructive features typically associated with some form of immunodeficiency.
 
LYG is an uncommon lymphoproliferative disorder and is not usually found in lymph nodes or spleen.  Pulmonary involvement is present in >90% of cases, and other organs (e.g. brain, kidney, skin, liver) can be variably affected.  
Morphology
LYG can have a varied appearance, but usually has a predominate background of small lymphocytes (T-cells), plasma cells, and histiocytes.  Eosinophils and neutrophils are not a typical finding.  Neoplastic EBV + B-cells can have a variable appearance ranging from immunoblast-like cells to morphologies similar to Hodgkin cells.  The lymphoid infiltrate has an anglocentric and angiodestructive pattern, which may result in necrosis.  If the pattern is of large cells in diffuse sheets, then the diagnosis of EBV+ diffuse large B-cell lymphoma should be made.
 
Differential diagnosis – Extranodal NK/T-cell lymphoma, nasal type is also an EBV+ tumor with an angiodestructive growth pattern.
Immunophenotype
  • EBV+ Neoplastic B-cells
  • CD20+
  • CD30 variably positive
  • Background T-cells
Grading
  • Grade 1 – < 5 EBV+ cells/HPF, polymorphic lymphoid infiltrate (large atypical cells rare/absent), No/focal necrosis.
  • Grade 2 – 5-20 EBV+ cells/HPF (small clusters of B-cells by CD20), occasional large atypical/transformed cells.
  • Grade 3 – > 50 EBV+ cells/HPF, numerous large atypical CD20+ B-cells (may form large aggregates)
References
WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues.  SH Swerdlow, et al. International Agency for Research on Cancer. Lyon, 2008. p. 247-249
Antibody List, A - F Antibodies

EBV (EBER)

Detection of EBV virus may be performed as stains in tissue sections in one of two ways:  (1) EBV IHC or (2) EBER (EBV-encoded RNA) ISH.  EBV IHC antibody reacts with the BNLF1 gene product that forms the latent membrane protein (LMP).  This marker has limited sensitivity in the 30% range.
 
EBER expression is localized to the nucleus, while the IHC LMP stains the surface membrane.
Pitfalls
EBER expression can identify lymphocytes latently infected with EBV.  Therefore, in CHL for example, the tumor cells must show expression for the case to be considered EBV-related.  On the other hand IHC stains for LMP rarely mark latently infected cells in the background, but may show false positivity in poorly fixed tissue, cells in the nervous system, and some uninfected hematopoietic elements (eosinophils and plasma cells).  False negative results are more common with IHC LMP in decalcified tissues.
 
Inter-observer agreement is greater for the interpretation of EBER compared to LMP.
EBV Expression Profile
  • DLBCL – EBV is identified in cases of EBV+ DLBCL of the elderly.
  • Hodgkin Lymphoma – Approximately 40% of Hodgkin lymphoma cases express EBV in the Hodgkin cells. (Mixed cellularity HL is ~70%+)
  • Burkitt Lymphoma – Endemic form
  • Nasopharyngeal Carcinoma
  • Infectious Mononucleosis
Photomicrographs
EBV (EBER)
EBV (EBER)
References
American Journal of Clinical Pathology. 2002;117(2)