Clonal T‐cell large granular lymphocyte proliferations in childhood and young adult immune dysregulation conditions

Abstract

Background Proliferation of large granular lymphocytes (LGL) and T‐cell LGL (T‐LGL) in peripheral blood along with demonstration of clonality are the hallmarks of a heterogeneous group of disorders, including T‐LGL leukemia or T‐LGL lymphocytosis. They are often associated with neutropenia and responsive to immunosuppression. The true nature of this entity is not well understood. Some cases are reported as reactive phenomena with very limited experience in pediatric population. Methods Hematology/Oncology Flow Cytometry Laboratory database has been reviewed retrospectively. Patients with identifiable distinct CD5‐dim T‐cell population and positive clonal T‐cell receptor rearrangement were included in the analysis. Clinical and laboratory data were then reviewed. Results Sixteen cases of children and young adults with increased peripheral blood clonal T‐LGL population characterized by dim CD5 expression with wide range of underlying immune dysregulation/stimulation disorders were reviewed. Extended follow up with repeat testing suggested the reactive nature of persistent clonal T‐LGL proliferations in this group. Conclusions Our observations indicate that clonal T‐LGL proliferations in children and young adults are reactive in nature and some can be persistent with an indolent course with unknown consequentiality. Clonal T‐LGL cells could be targeting the most prominent immunogenic stressor(s) involved as a control mechanism.

Uncovering the significance of expanded CD8+ large granular lymphocytes in inclusion body myositis: Insights into T cell phenotype and functional alterations, and disease severity

“…Initially, a diagnosis of T-LGLL was based on the accumulation of T-LGLs greater than 2x10 9 /L of blood ( 20 ). More recently, the utility of this threshold has been debated, with several studies defining T-LGLL using lower cell counts (>0.5x10 9 /L of blood), when appropriate clinical criteria were met ( 16 – 18 , 21 ). Furthermore, the classification of T-LGLL as a neoplastic disease is often debated, and despite its reported monoclonal nature, T-LGLL is rarely aggressive like other lymphoproliferative diseases ( 22 ).…”

Pediatric Recurrent Rosai-Dorfman Disease with germline heterozygous SLC29A3 and somatic MAP2K1 mutations

“…Increased T-LGL (18-41%) with clonal TCR rearrangement pattern likely reflect persistent immune dysfunction. 5 Despite very high vitamin B12 levels, a known feature of autoimmune lymphoproliferative syndrome (ALPS) and known link between ALPS and RDD, he neither has increased double-negative TCR alpha/beta T-cells, another hallmark of ALPS nor any known ALPS-related mutations. [6][7] Homozygous germline SLC29A3 mutations are described in Faisalabad histiocytosis and familial, but not sporadic RDD.…”

Expanding clinical spectrum of female X‐linked lymphoproliferative syndrome 2

“…A currently 18-year-old female presented with fever, abdominal pain, diffuse lymphadenopathy, splenomegaly, and pancytopenia LGL expansion may be related to EBV and/or immune deficiency. 4 Low vitamin B12 raises the possibility of impairment in absorption; the presence of proctitis raises possible subclinical inflammation in the distal ileum. Observed conditions in this case add to the spectrum of this rare entity (Table 1).…”

“…Persistent high EBV EA‐IgG titers is suggestive of ongoing EBV challenge due to immune deficiency, and emphasizes the significance of EBV serology testing. Clonal T‐LGL expansion may be related to EBV and/or immune deficiency 4 . Low vitamin B12 raises the possibility of impairment in absorption; the presence of proctitis raises possible subclinical inflammation in the distal ileum.…”