Sandbox: T-cell large granular lymphocyte leukemia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [3] Maria Fernanda Villarreal, M.D. [4]
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 (also known as T-GLL) is a rare type of leukemia that exhibits a unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.[1]
Historical Perspective
- T-cell large granular lymphocyte leukemia was first discovered by McKenna, in 1977.
Classification
- T-cell large granular lymphocyte leukemia may be classified into 2 groups:
- T-cell large granular lymphocyte leukemia (T-LGL)
- Natural-killer (NK) granular lymphocyte leukemia (NK-LGL)
- Other variants of T-cell large granular lymphocyte leukemia include
Pathophysiology
- The pathogenesis of T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells.
- The postulated cells of origin of T-LGL leukemia are 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.
- The leukemia cells of T-cell large granular lymphocyte leukemia can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.
- The [gene name] gene/Mutation in [gene name] has been associated with the development of T-cell large granular lymphocyte leukemia, involving the [molecular pathway] pathway.
- On gross pathology, characteristic findings of T-cell large granular lymphocyte leukemia, include:
- T-LGL can be found in peripheral blood, bone marrow, spleen, and liver
- On microscopic histopathological analysis, characteristic findings of T-cell large granular lymphocyte leukemia, include:
- Neoplastic lymphocytes (large in size)
- Presence of azurophilic granules (contains proteins involved in cell lysis such as perforin and granzyme B)
- 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
- On immunohistochemistry, characteristic findings of T-cell large granular lymphocyte leukemia, include:
- Positive perforin
- Positive TIA-1
- Positive granzyme B
Causes
- Common causes of T-cell large granular lymphocyte leukemia, include:
Differentiating T-cell Large Granular Lymphocyte Leukemia from Other Diseases
- T-cell large granular lymphocyte leukemia must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
Epidemiology and Demographics
- T-cell large granular lymphocyte leukemia is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders.
Age
- Patients of all age groups may develop T-cell large granular lymphocyte leukemia.
- T-cell large granular lymphocyte leukemia is more commonly observed among patients aged [age range] years old.
- T-cell large granular lymphocyte leukemia is more commonly observed among middle aged adults.
Gender
- T-cell large granular lymphocyte leukemia affects men and women equally.
Race
- There is no racial predilection for T-cell large granular lymphocyte leukemia.
Risk Factors
- Common risk factors in the development of T-cell large granular lymphocyte leukemia, include:
Natural History, Complications and Prognosis
- The majority of patients with T-cell large granular lymphocyte leukemia may be initially asymptomatic.
- Early clinical features include fever, night sweats, and weight loss.
- If left untreated, patients with T-cell large granular lymphocyte leukemia may progress to develop infections.
- Common complications of T-cell large granular lymphocyte leukemia, include:
- Prognosis is generally good, and the 5 year survival rate of patients with T-cell large granular lymphocyte leukemia is approximately 89%.
Diagnosis
Diagnostic Criteria
- The diagnosis of T-cell large granular lymphocyte leukemia is made when the following diagnostic criteria is met:
- Clonal rearrangements of the T-cell receptor (TCR) gene
- Chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood
- [criterion 3]
- [criterion 4]
Symptoms
- T-cell large granular lymphocyte leukemia may be initially asymptomatic.
- Symptoms of T-cell large granular lymphocyte leukemia may include the following:
Physical Examination
- Patients with T-cell large granular lymphocyte leukemia usually appear pale and malnourished.
- Physical examination may be remarkable for:
- Cardiac flow murmur
- High-grade fever
- Hepatomegaly
- Splenomegaly
Laboratory Findings
- Laboratory findings consistent with the diagnosis of T-cell large granular lymphocyte leukemia, include:
- Neutropenia
- Anemia
- Hypergammaglobulinemia
- Lymphocytosis
Imaging Findings
- There are no specific imaging findings associated with T-cell large granular lymphocyte leukemia.
Other Diagnostic Studies
- T-cell large granular lymphocyte leukemia may also be diagnosed using the following studies:
Immunophenotyping
- The following table demonstrates common immunophenotype findings.
- 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. Variable expression of CD11b, CD56, and CD57 are observed.
| 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 |
Karyotyping
Peripheral blood smear
- Large neoplastic lymphocytes
- Azurophilic granules
Treatment
Medical Therapy
- The mainstay of therapy for T-cell large granular lymphocyte leukemia is targeted-chemotherapy.
- Alemtuzumab is the treatment of choice for patients with refractory T-cell large granular lymphocytic leukemia.
Surgery
- Surgery is the mainstay of therapy for T-cell large granular lymphocyte leukemia.
- [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of T-cell large granular lymphocyte leukemia.
Prevention
- There are no primary preventive measures available for T-cell large granular lymphocyte leukemia.
- Once diagnosed and successfully treated, patients with T-cell large granular lymphocyte leukemia are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].