The diagnostic history of a case of T-cell large granular lymphocytic leukemia

Preamble

T-cell large granular lymphocytic leukemia (T-LGLL) is a rare chronic lymphoproliferative disease
.
Presents with a chronic course of the disease, with blood routine often showing a primary or secondary line of cytopenias, with neutropenia being more common
.
We encountered a case of T-LGLL with neutropenia as the first manifestation and successfully diagnosed after five years, which is reported below
.

Case history

The patient is a 79-year-old man presenting to the Department of
Respiratory Medicine with "chronic bronchitis".
Personal or family history is not special
.
Physical examination: superficial lymph nodes such as bilateral neck and supraclavicular are not large, and the hepatosplenic and subcostal lymph nodes are not palpated
.
The blood routine of this admission was: absolute neutrophil value 1.
32×10^9/L↓, hemoglobin 82 g/L↓, average red blood cell volume 109.
8 fL↑, mean red blood cell hemoglobin amount 36.
4 pg↑, platelet count 174 ×10^9/L
.

Hemomyeloid image: the proportion of T lymphocytes in the bone marrow is increased, combined with flow cytometry immunophenotyping can not exclude T-cell lymphoma (large granular T lymphocytic leukemia), but please rule out reactive changes first, please combine clinical, bone marrow smear and other examinations, and do TCR rearrangement examination
.
(About 60% of lymphocytes are sent for smear, and about 46% of visible granulosa lymphocytes are sent.
)

Bone marrow immunophenotyping: the proportion of lymphocytes in the bone marrow increased, accounting for about 54.
50% of nucleated cells, mainly T lymphocyte hyperplasia; Detectable and abnormal phenotypic T lymphocytes, accounting for about 15.
29% of nucleated cells, the immunophenotype can be seen in T cell tumors (large granular T lymphocytic leukemia) and some reactive changes, please combine clinical, morphological and TCR, IGH gene rearrangement and other examination results for further diagnosis
.

TCR clonal assay: Monoclonal TCR rearrangement
detected.

Diagnosis: T-cell large granular lymphocytic leukemia

Case studies

T-LGLL is a chronic lymphoproliferative disorder
.
Its onset is insidious and slow, and there is still insufficient clinical understanding
of the disease.
In one study, the median time from onset of clinically ill symptoms to definitive diagnosis was five (0.
2-96) months [1].

The main clinical manifestation is fatigue, and the common physical examination is splenomegaly
.
Routine blood tests often show monophyletic neutropenia or anaemia
.

Neutropenia occurs more frequently in Western countries and anaemia is more
frequent in Asian countries.
Large lymphocytosis
may be seen on bone marrow and/or peripheral blood.
The typical T-LGLL immunophenotype is mainly CD3+CD4-CD8+CD56-CD57+TCRαβ+
.

Since some autoimmune or infectious diseases may also present with circulating large lymphocytosis, but reactive LGL is polyclonal, determining whether LGL is monoclonal is key
to diagnosing T-LGLL.
At present, polymerase chain reaction (PCR) and/or flow cytometry (FCM) is mainly used to detect TCR rearrangement to determine the clonality of T cells[2].

Normal T lymphocytes or reactive T lymphocytosis are polyclonal sources, T-LGLL T lymphocytes are monoclonal sources, TCRβ rearrangements are derived from the same leukemia clone, monoclonal bands can appear on PCR testing, and FCM detection can show a significant increase
in the proportion of TCRV-β subfamilies.
In addition, lymphoma, multiple myeloma, hairy cell leukemia, myelodysplastic syndrome, myeloproliferative tumors have been reported with T-LGLL [3], care should be taken to avoid missing other hematological diseases
while diagnosing T-LGLL.

This patient was not paid attention to the fact that mild neutropenia was found in preoperative examination due to trauma 5 years ago, and since then a progressive decrease in neutrophils and anemia have gradually developed during routine annual physical examination, but it has remained undiagnosed
.
This time, he was admitted to the hospital due to fatigue, and the diagnosis was successful
in menstrual blood myeloid image, bone marrow immunophenotyping, TCR clonal analysis, etc.
Treatment can be treated with single-agent cyclophosphamide, cyclosporine, or COP regimen chemotherapy
.

Summary

Neutropenia is broadly divided into three categories according to etiology and pathogenesis: decreased neutrophil production, neutrophil destruction or excessive consumption, and abnormal
distribution of neutrophils.
Although isolated neutropenia is clinically common, the cause is difficult
to find.
Mild to moderate neutropenia on the first or several short-interval blood tests, but no other abnormal signs or symptoms, persuade patients to undergo bone marrow examination, which is often difficult for patients to accept
.
Long-term follow-up and prompt peripheral blood cell morphology in patients with unexplained neutropenia may help in the timely diagnosis
of T-LGLL.

References:

[1] Dong Yuting, Zhou Minran, Li Miao, et al.
Clinical analysis and literature review of 21 cases of T-cell macrogranular lymphocytic leukemia.
Chinese Journal of Oncology.
2020.

HUANG Qiaorong, WEN Bo, LI Xue, et al.
Establishment of a nine-color flow cytometry protocol for the detection of TCRVβ lymphocyte subset activation and apoptosis in human peripheral blood.
Journal of Sichuan University:Health Sciences.
2016;47(2):5.

SHI Yin, HE Dashui, GUO Guiqing, et al.
Clinical and laboratory features of proliferation of myeloid tumors with clonal T-large granular lymphocytes.
Chinese Journal of Hematology.
2020;41(4):6.