T-prolymphocytic leukemia. Atypical presentation of a rare disease
Introduction/Background/Significance: T-prolymphocytic leukemia (T-PLL) is a rare mature T-cell neoplasm, accounting for approximately 2% of adult leukemias. It primarily affects older adults but may occasionally present in younger individuals. It typically involves the blood, bone marrow, and lymph nodes and carries a poor prognosis.
The typical immunophenotype includes negative expression of TdT, CD30, and CD1a, with strong positivity for CD2, CD3, CD7, TCR, and IRF4/MUM1. CD52 is frequently overexpressed and serves as a therapeutic target. Cytogenetic abnormalities are common, especially involving 14q, 8q, del(17p), 11q, 6q, 12p, and 13q or complex karyotype.
Diagnosis requires either three major criteria (T-lymphocytosis >5 × 109/L, T-cell clonality, and abnormalities involving 14q32/Xq28 or expression of TCL1A/B or MTCP1), or two major criteria plus one minor criterion (abnormalities in chromosomes 11, 8, 5, 12, 13, 22, or complex karyotype).
Materials and Methods/Case Presentation/Objective: A 42-year-old Hispanic woman with no significant medical history was referred to hematology for mild anemia and marked leukocytosis (139,000/μL), with 120,000/μL lymphocytes and normal platelet count. She was asymptomatic, with no lymphadenopathy, hepatosplenomegaly, or skin lesions on examination.
Initial labs: Hemoglobin 10.3 g/dL, MCV 90 fL, leucocytes 139 000, lymphocytes 120 000. Platelets 130.000. Peripheral smear showed small, mature lymphocytes without atypia or projections. CT imaging, endoscopy, and colonoscopy were unremarkable.
Bone marrow biopsy showed mature T-cells (CD3+, CD5+, CD8+, CD7+++, TCL1A-), initially interpreted as peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), CD8+. HTLV-1/2 tests were negative.
Flow cytometry (EuroFlow):
Mature T-cells (83%) with asynchronous maturation. Positive markers: CD99, CD2, CD3 (cytoplasmic and membrane), CD5, CD7, CD8, CD45RA, CD44. Negative markers: CD4, CD10, CD1a, CD56, CD117, HLA-DR, TCR α/β, and TCR γ/δ. CD52 and CD98 were not tested.
Cytogenetics: Normal female karyotype (46,XX)
NGS findings: del(4q31), del(11q22), and del(13q14).
Results/Description/Main Outcome Measures: This case was diagnostically challenging due to the absence of classical morphology, an unusual CD4-/CD8+ immunophenotype, and negative TCL1A expression. However, the patient met two major criteria (marked lymphocytosis and T-cell clonality) and two minor criteria (abnormalities in chromosomes 11 and 13), fulfilling diagnostic requirements for T-PLL.
Typically, 60% of T-PLL cases are CD4+/CD8-, 25% coexpress both, and only 15% are CD4-/CD8+, as in this case. Differentiation from other entities, such as PTCL-NOS, often requires molecular testing.
Conclusions: This case represents an atypical T-PLL presentation in a young, asymptomatic patient without classical features. NGS played a key role in establishing the diagnosis. The patient remains under close surveillance without treatment. When needed, therapy may include anti-CD52 agents or novel combinations involving BTK and BCL-2 inhibitors.
References
1.- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): T-Cell Prolymphocytic Leukemia. Version 1.2025. [Internet]. Plymouth Meeting (PA): National Comprehensive Cancer Network; 2025. https://www.nccn.org/professionals/physician_gls/pdf/t-cell_prolymphocytic_leukemia.pdf
2.- Gonzalez Rodriguez E, et al. T-cell prolymphocytic leukemia: a case report and review of the literature. Oncol Res. 2025;doi:10.32604/or.2025.058175.
3.- Gutierrez M, Bladek P, Goksu B, Murga-Zamalloa C, Bixby D, Wilcox R. T-cell prolymphocytic leukemia: diagnosis, pathogenesis, and treatment. Int J Mol Sci. 2023;24:12106. doi:10.3390/ijms241512106.
