Lymphoma and plasma cell neoplasms
T / NK cell disorders
T cell large granular lymphocytic leukemia

Author: Dragos Luca, M.D. (see Authors page)

Revised: 24 March 2017, last major update September 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: T cell large granular [title] lymphocytic leukemia

Cite this page: T cell large granular lymphocytic leukemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomanonBtLGL.html. Accessed August 20th, 2017.
Definition / general
  • T cell large granular lymphocytic leukemia (T-LGL) is a heterogeneous disorder characterized by a persistent ( > 6 months) increase in the number of peripheral blood large granular lymphocytes (LGL), usually 2 - 20 × 109/L, without a clearly identified cause (WHO 2008, Blood 1997;89:256)
Epidemiology
  • Uncommon; 2 - 3% of mature lymphocytic leukemias
  • M:F ratio 1:1
  • No clearly defined age peak, majority between 45 - 75 years (73%)
Sites
  • Peripheral blood, bone marrow, liver, spleen
  • Lymph node involvement – very rare
Etiology
  • Possibly due to sustained immune stimulation
  • Frequently associated with autoimmune disorders
  • Absence of homeostatic apoptosis (high levels of FAS / FASL) suggests activation of prosurvival pathways
  • Rarely occurs as a form of posttransplant lymphoproliferative disorders
  • Clonal populations of T-LGL also seen in association with low grade B cell malignancies (HCL, CLL) but no progression to clinical disease
Clinical features
  • Modest lymphocytosis (usually between 2 - 20 × 109/L) and often severe neutropenia with or without anemia; splenomegaly in 50%
  • May have rheumatoid factor, rheumatoid arthritis, autoantibodies, circulating immune complexes and hypergammaglobulinemia
  • Severe anemia due to red cell aplasia may occur
  • CD4+ cases are often associated with an underlying malignancy (30%)
Case reports
Prognosis and treatment
  • Indolent course in most cases, median survival 13 years in study with 68 patients
  • Morbidity and mortality mostly due to cytopenias, especially neutropenia and other accompanying diseases
  • If treatment is necessary: cyclosporine A, cyclophosphamide, corticosteroids, methotrexate, pentostatin
Postulated normal counterpart
  • CD8 positive T cell subset for the common type
  • Subset of T lymphocytes for the rare TCRγδ-positive type
Microscopic (histologic) description
  • Peripheral blood: medium / large lymphocytes with abundant cytoplasm containing coarse azurophilic granules
  • Bone marrow: variable cellularity, myeloid series shifted to immaturity, mild to moderate reticulin fibrosis, interstitial / intrasinusoidal involvement highlighted by CD8; nonneoplastic nodular aggregates of B cells surrounded by a rim of CD4+ T-cells
  • Spleen: red pulp infiltration / expansion and hyperplastic white pulp
Microscopic (histologic) images

Images hosted on other servers:

Peripheral blood

Bone marrow - CD8

Bone marrow - Granzyme B

Nonneoplastic nodule

Immunohistochemistry
Positive stains
  • CD3, CD8, TCRαβ, CD16 & CD57 (80%), CD94 and KIR isoforms ( > 50%), TIA1, granzyme B, granzyme M
  • Uncommon: CD4+ TCRαβ positive cases; TCRγδ positive cases (60% CD8+, 40% CD4- / CD8-)
Negative staining
Flow cytometry description

Images hosted on other servers:

Various images

Electron microscopy description
  • Parallel tubular arrays
Molecular / cytogenetics description
  • T cell receptor gene rearrangement
  • No consistent karyotypic abnormalities
Differential diagnosis
  • Reactive hyperplasia: no T cell receptor gene rearrangement