Large granular lymphocytic leukemia

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Large granular lymphocytic leukemia
Classification and external resources
ICD-O: 9831/3
MeSH D054066

Large granular lymphocytic leukemia is a disease that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.[1]

It is sometimes known as T-cell large granular lymphocyte leukemia (specifying involvement of the T cells). However, NK large granular lymphocyte leukemia (involving natural killer cells) is also possible.[2]

It is also known by the following terms: proliferation of large granular lymphocytes (LGLs), LGL leukemia, Tγ-lymphoproliferative disorder, and, in common with other T cell leukemias such as T-cell prolymphocytic leukemia, T-cell chronic lymphocytic leukemia.[1]

Epidemiology[edit]

T-LGL is a rare form of leukemia, comprising 2-3% of all cases of small lymphocytic leukemias.[1]

Etiology[edit]

The postulated cells of origin are a transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T-cell with clonal rearrangements of γ chain T-cell receptor genes for a minority of cases.[1]

Clinical features[edit]

Clinical presentation[edit]

This disease is known for an indolent clinical course and incidental discovery.[1] The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.[3][4][5][6]

Rheumatoid arthritis is commonly observed in patients with T-LGL, leading to a clinical presentation similar to Felty's syndrome.[7] Signs and symptoms of anemia are commonly found, due to the association between T-LGL and erythroid hypoplasia.[8]

Laboratory findings[edit]

The requisite lymphocytosis of this disease is typically 2-20x109/L.[8]

Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.[6][9][10][11]

Sites of involvement[edit]

The leukemic cells of T-LGL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.[1][3]

Prognosis[edit]

The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.[12]

Morphology[edit]

Peripheral blood[edit]

The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as perforin and granzyme B.[13]

Bone marrow[edit]

Bone marrow involvement in this disease is often present, but to a variable extent. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs.[1]

Molecular Findings[edit]

Immunophenotype[edit]

The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8+ T-cell subset immunophenotype versus other permutations of those markers.[4][5] Variable expression of CD11b, CD56, and CD57[6] are observed. Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive.[1]

Type Immunophenotype
Common type (80% of cases) CD3+, TCRαβ+, CD4-, CD8+
Rare variants CD3+, TCRαβ+, CD4+, CD8-
CD3+, TCRαβ+, CD4+, CD8+
CD3+, TCRγδ+, CD4 and CD8 variable

Genetic findings[edit]

Clonal rearrangements of the T-cell receptor (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.[10][14]

Treatment[edit]

Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.[15]

References[edit]

  1. ^ a b c d e f g h Elaine Sarkin Jaffe, Nancy Lee Harris, World Health Organization, International Agency for Research on Cancer, Harald Stein, J.W. Vardiman (2001). Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors 3. Lyon: IARC Press. ISBN 92-832-2411-6. 
  2. ^ Epling-Burnette PK, Sokol L, Chen X, et al. (December 2008). "Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling". Blood 112 (12): 4694–8. doi:10.1182/blood-2008-02-136382. PMC 2597136. PMID 18791165. 
  3. ^ a b "Large Granular Lymphocyte Leukemia". Cancer Control 5 (1): 25–33. January 1998. PMID 10761014. 
  4. ^ a b Chan WC, Link S, Mawle A, Check I, Brynes RK, Winton EF (November 1986). "Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes". Blood 68 (5): 1142–53. PMID 3490288. 
  5. ^ a b Pandolfi F, Loughran TP, Starkebaum G, et al. (January 1990). "Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study". Cancer 65 (2): 341–8. doi:10.1002/1097-0142(19900115)65:2<341::AID-CNCR2820650227>3.0.CO;2-2. PMID 2403836. 
  6. ^ a b c Lamy T, Loughran, TP (July 2003). "Clinical features of large granular lymphocyte leukemia". Semin. Hematol. 40 (3): 185–95. doi:10.1016/S0037-1963(03)00133-1. PMID 12876667. 
  7. ^ Loughran TP, Starkebaum G, Kidd P, Neiman P (January 1988). "Clonal proliferation of large granular lymphocytes in rheumatoid arthritis". Arthritis Rheum. 31 (1): 31–6. doi:10.1002/art.1780310105. PMID 3345230. 
  8. ^ a b Kwong YL, Wong KF; Wong, K. F. (September 1998). "Association of pure red cell aplasia with T large granular lymphocyte leukaemia". J. Clin. Pathol. 51 (9): 672–5. doi:10.1136/jcp.51.9.672. PMC 500904. PMID 9930071. 
  9. ^ Oshimi K, Yamada O, Kaneko T, et al. (June 1993). "Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders". Leukemia 7 (6): 782–8. PMID 8388971. 
  10. ^ a b Loughran TP, Starkebaum G, Aprile JA (March 1988). "Rearrangement and expression of T-cell receptor genes in large granular lymphocyte leukemia". Blood 71 (3): 822–4. PMID 3345349. 
  11. ^ Loughran TP, Kadin ME, Starkebaum G, et al. (February 1985). "Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia". Ann. Intern. Med. 102 (2): 169–75. doi:10.7326/0003-4819-102-2-169. PMID 3966754. 
  12. ^ Bareau, B; Rey, J; Hamidou, M; Donadieu, J; Morcet, J; Reman, O; Schleinitz, N; Tournilhac, O et al. (2010). "Analysis of a French cohort of patients with large granular lymphocyte leukemia: A report on 229 cases". Haematologica 95 (9): 1534–41. doi:10.3324/haematol.2009.018481. PMC 2930955. PMID 20378561. 
  13. ^ Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP (January 1997). "The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis". Blood 89 (1): 256–60. PMID 8978299. 
  14. ^ Vie H, Chevalier S, Garand R, et al. (July 1989). "Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder". Blood 74 (1): 285–90. PMID 2546620. 
  15. ^ Rosenblum MD, LaBelle JL, Chang CC, Margolis DA, Schauer DW, Vesole DH (March 2004). "Efficacy of alemtuzumab treatment for refractory T-cell large granular lymphocytic leukemia". Blood 103 (5): 1969–71. doi:10.1182/blood-2003-11-3951. PMID 14976065.