T-Cell Large Granular Lymphocytic Leukemia with Atypical Immunophenotypes: A Single Center Retrospective Analysis of 17 Cases

Purpose T-cell large granular lymphocytic leukemia (T-LGLL) is characterized by expansion of cytotoxic T cells expressing αβ T cell receptor (TCR), CD2, surface CD3, CD8, CD57 as well as cytotoxic molecules. Atypical immunophenotypes of T-LGLL, including γδ TCR and CD4, reported in a small subset, remains to be well-defined. Methods We retrospectively analyzed immunophotypes and clinicopathologic features of 96 T-LGLL cases. Results We found a total of 17 cases with atypical immunophenotypes including 9 TCRγδ + cases and 8 CD4+ TCRαβ + cases. Pure red cell aplasia was less common in atypical immunophenotypes patients compared to that of typical immunophenotypes [0/17 (0%) vs. 26/79 (32.9%), p=0.005]. STAT3 mutations were also less frequent in atypical immunophenotypes cases, although accompanied with marginal significance (p=0.086). Conclusion Patients with atypical immunophenotypes showed a similar survival outcome to that of typical T-LGLL immunophenotypes. Additional efforts were needed to better understand the pathogenesis of these rare atypical immunophenotypes T-LGLL cases.

[1]  L. Peterson,et al.  T-Cell Large Granular Lymphocytic Leukemia , 2019, Encyclopedia of Pathology.

[2]  S. Swerdlow.  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues , 2017 .

[3]  J. V. van Dongen,et al.  Dysregulated signaling, proliferation and apoptosis impact on the pathogenesis of TCRγδ+ T cell large granular lymphocyte leukemia , 2017, PloS one.

[4]  T. Loughran,et al.  LGL leukemia: from pathogenesis to treatment. , 2017, Blood.

[5]  S. Bortoluzzi,et al.  High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia. , 2016, Blood.

[6]  J. Qian,et al.  Methotrexate therapy of T-cell large granular lymphocytic leukemia impact of STAT3 mutation , 2016, Oncotarget.

[7]  R. Advani,et al.  The World Health Organization Classification of Lymphoid Neoplasms , 2013 .

[8]  R. Cason,et al.  Clinicopathologic, Immunophenotypic, Cytogenetic, and Molecular Features of γδ T-Cell Large Granular Lymphocytic Leukemia: An Analysis of 14 Patients Suggests Biologic Differences With αβ T-Cell Large Granular Lymphocytic Leukemia. [corrected]. , 2015, American journal of clinical pathology.

[9]  W. Xu,et al.  Expression patterns of CD200 and CD148 in leukemic B-cell chronic lymphoproliferative disorders and their potential value in differential diagnosis , 2015, Leukemia & lymphoma.

[10]  J. Qian,et al.  Assessment of clonality in T-cell large granular lymphocytic leukemia: flow cytometric T cell receptor Vβ repertoire and T cell receptor gene rearrangement , 2015, Leukemia & lymphoma.

[11]  Jian-yong Li,et al.  STAT3 mutations are frequent in T-cell large granular lymphocytic leukemia with pure red cell aplasia , 2013, Journal of Hematology & Oncology.

[12]  S. Mustjoki,et al.  Somatic STAT3 mutations in large granular lymphocytic leukemia. , 2012, The New England journal of medicine.

[13]  N. Karandikar,et al.  Laboratory findings in CD4(+) large granular lymphocytoses , 2010, International journal of laboratory hematology.

[14]  W. Au,et al.  T-cell large granular lymphocyte leukemia: an Asian perspective , 2010, Annals of Hematology.

[15]  G. Shaw,et al.  The γδ variant of T cell large granular lymphocyte leukemia is very similar to the common αβ type: report of two cases , 2008, Journal of hematopathology.

[16]  Marcos González,et al.  Monoclonal TCR-Vbeta13.1+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis: evidence for an antigen-driven chronic T-cell stimulation origin. , 2007, Blood.

[17]  A. Órfão,et al.  TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T-cells , 2006, Leukemia.

[18]  A. Órfão,et al.  TCRgammadelta+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRgammadelta+ T-cells. , 2006, Leukemia.

[19]  Ana Helena Santos,et al.  TCRalphabeta+/CD4+ large granular lymphocytosis: a new clonal T-cell lymphoproliferative disorder. , 2003, The American journal of pathology.