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]
Epidemiology and Demographics
T-LGL is a rare form of leukemia, comprising 2-3% of all cases of small lymphocytic leukemias.[1]
Pathology
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][3]
Gross Pathology
The leukemic cells of T-LGL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.[1][4]
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.[5]
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]
Natural History, Complications ans Prognosis
This disease is known for an indolent clinical course and incidental discovery.[1]
Diagnosis
Symptoms
- B symptoms are seen in a third of cases - fever, night sweats, and weight loss
- Abdominal discomfort
- Recurrent infections due to the associated neutropenia are seen in almost half of cases.[4][6][7][8]
Physical Examination
Abdomen
Laboratory Findings
- Complete blood count and differential count - neutropenia
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 |
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
- ↑ 4.0 4.1 [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
- ↑ 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 [7] Lamy T, Loughran TP Jr. "Clinical features of large granular lymphocyte leukemia." Semin Hematol. 2003 Jul;40(3):185-95. PMID: 12876667