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Case Reports
. 2022 Nov 2;23(21):13392.
doi: 10.3390/ijms232113392.

Molecular Features and Diagnostic Challenges in Alpha/Beta T-Cell Large Granular Lymphocyte Leukemia

Francesco Gaudio  1 , Pierluigi Masciopinto  1 , Emilio Bellitti  2 , Pellegrino Musto  1 , Elena Arcuti  1 , Olga Battisti  1 , Gerardo Cazzato  2 , Alessandra Solombrino  2 , Filomena Emanuela Laddaga  3 , Giorgina Specchia  4 , Eugenio Maiorano  2 , Giuseppe Ingravallo  2
Affiliations
Case Reports

Molecular Features and Diagnostic Challenges in Alpha/Beta T-Cell Large Granular Lymphocyte Leukemia

Francesco Gaudio et al. Int J Mol Sci. .

Abstract

Large granular lymphocyte leukemia is a rare chronic lymphoproliferative disease of cytotoxic lymphocytes. The diagnosis, according to the WHO, is based on a persistent (>6 months) increase in the number of LGL cells in the peripheral blood without an identifiable cause. A further distinction is made between T-LGL and NK-LGL leukemia. The molecular sign of LGL leukemia is the mutation of STAT3 and other genes associated with the JAK/STAT pathway. The most common clinical features are neutropenia, anemia, and thrombocytopenia, and it is often associated with various autoimmune conditions. It usually has an indolent course. Due to the rarity of the disease, no specific treatment has yet been identified. Immunosuppressive therapy is used and may allow for disease control and long-term survival, but not eradication of the leukemic clone. Here, we discuss the clinical presentation, diagnostic challenges, pathophysiology, and different treatment options available for alpha/beta T-LGL leukemia, which is the most common disease (85%), in order to better understand and manage this often misunderstood disease.

Keywords: T-cell-derived LGL; clonal lymphocyte expansion; leukemia; molecular features.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Molecular pathways involved in LGL leukemia.
Figure 2
Figure 2
Hypercellular bone marrow with erythroid hyperplasia (>50% of total BM cells). (A) Hematoxylin-eosin, original magnification 100×. (B) Immunoreactivity for CD3, immunohistochemistry, 20×. (C) Immunoreactivity for CD8, immunohistochemistry, 100×. (D) Immunoreactivity for CD4, immunohistochemistry, 100×.
Figure 3
Figure 3
Remarkably hypocellular bone marrow. (A,B) Hematoxylin-eosin, original magnification 100×. (C) Immunoreactivity for CD3, immunohistochemistry, 100×. (D). Immunoreactivity for CD8, immunohistochemistry, 100×.
Figure 4
Figure 4
Immunoreactivity for granzyme B; original magnification 100× (A) and 200× (B). Immunoreactivity for CD3 shows intrasinusoidal bone marrow infiltration; see arrows; respectively original magnification 200× (C) and 400× (D).
Figure 5
Figure 5
Diagnostic criteria and treatment options in LGL leukemia.
See this image and copyright information in PMC

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