T-cell large granular lymphocyte leukemia
| T-cell large granular lymphocyte leukemia | |
| ICD-O: | 9831/3 |
|---|---|
| MeSH | D054066 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [8]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [9]
Synonyms and keywords: LGL leukemia; Tγ-lymphoproliferative disorder; T-cell chronic lymphocytic leukemia; Proliferation of large granular lymphocytes (LGLs)
Overview
T-cell large granular lymphocyte leukemia is a disease that exhibits a unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.[1]
Pathophysiology
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]
Genetics
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.[2]
Gross Pathology
The leukemic cells of T-LGL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.[1][3]
Microscopic Pathology
Peripheral blood
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.[4]
Bone marrow
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]
Epidemiology and Demographics
T-LGL is a rare form of leukemia, comprising 2-3% of all cases of small lymphocytic leukemias.[1]
Natural History, Complications ans Prognosis
- This disease is known for an indolent clinical course and incidental discovery.[1]
- The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.[5]
Diagnosis
Symptoms
- B symptoms are seen in a third of cases - fever, night sweats, and weight loss
- Symptoms of anemia - shortness of breath, fatigue, palpitations
- Abdominal discomfort
- Recurrent infections due to the associated neutropenia are seen in almost half of cases.[3][6][7][8]
- Joint pains - rheumatoid arthritis is commonly observed in patients with T-LGL, leading to a clinical picture similar to Felty's syndrome.
Physical Examination
Skin
Abdomen
Laboratory Findings
- Complete blood count and differential count - neutropenia
- The requisite lymphocytosis of this disease is typically 2-20x109/L.
- Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.[8][9][10][11]
Immunophenotype
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.[6][7] Variable expression of CD11b, CD56, and CD57[8] are observed. Immunohistochemisty 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 |
Treatment
Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.[12]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 [1] Jaffe E.S., Harris N.L., Stein H., Vardiman J.W. (eds): World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues. IARC Press: Lyon 2001
- ↑ [2] Vie H, Chevalier S, Garand R, Moisan JP, Praloran V, Devilder MC, Moreau JF, Soulillou JP. "Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder." Blood. 1989 Jul;74(1):285-90. PMID: 2546620
- ↑ 3.0 3.1 [3] Lamy T, Loughran TP. "Large Granular Lymphocyte Leukemia." Cancer Control. 1998 Jan;5(1):25-33. PMID: 10761014
- ↑ [4] Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP Jr. "The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis." Blood. 1997 Jan 1;89(1):256-60. PMID: 8978299
- ↑ Bareau, B; Rey, J; Hamidou, M; Donadieu, J; Morcet, J; Reman, O; Schleinitz, N; Tournilhac, O; Roussel, M (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.
- ↑ 6.0 6.1 [5] Chan WC, Link S, Mawle A, Check I, Brynes RK, Winton EF. "Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes." Blood. 1986 Nov;68(5):1142-53. PMID: 3490288
- ↑ 7.0 7.1 [6] Pandolfi F, Loughran TP Jr, Starkebaum G, Chisesi T, Barbui T, Chan WC, Brouet JC, De Rossi G, McKenna RW, Salsano F, et al. "Clinical course and prognosis of the lymphoproliferative disease of granular lymphocytes. A multicenter study." Cancer. 1990 Jan 15;65(2):341-8. PMID: 2403836
- ↑ 8.0 8.1 8.2 [7] Lamy T, Loughran TP Jr. "Clinical features of large granular lymphocyte leukemia." Semin Hematol. 2003 Jul;40(3):185-95. PMID: 12876667
- ↑ Oshimi K, Yamada O, Kaneko T; et al. (1993). "Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders". Leukemia. 7 (6): 782–8. PMID 8388971. Unknown parameter
|month=ignored (help) - ↑ Loughran TP, Starkebaum G, Aprile JA (1988). "Rearrangement and expression of T-cell receptor genes in large granular lymphocyte leukemia". Blood. 71 (3): 822–4. PMID 3345349. Unknown parameter
|month=ignored (help) - ↑ Loughran TP, Kadin ME, Starkebaum G; et al. (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. PMID 3966754. Unknown parameter
|month=ignored (help) - ↑ Rosenblum MD, LaBelle JL, Chang CC, Margolis DA, Schauer DW, Vesole DH (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. Unknown parameter
|month=ignored (help)