Abstract
Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1). Most ATLL cases are CD4-positive and CD8-negative. Though rare, there are a few dual negative (CD4-CD8-), dual positive (CD4+CD8+), and CD4-CD8+ cases reported in literature. ATLL is associated with HTLV-1 infection, but HTLV-1 alone cannot cause the malignant transformation of infected T cells. Additional genetic and/or epigenetic events are required for the development of the disease. Here, we report an unusual CD4-CD8+ATLL in a 76-year-old male with a unique molecular genetic profile. Molecular studies revealed alterations in 10 genes. Three of them are predicted to be pathogenic by the computational models, including the frameshift change in ZFHX4 and missense mutations in RHOA and POT1. The specific mutations of POT1 (c.281A > G; p.Q94R), RHOA (c.47G > A; p.C16Y), and ZFHX4 (c.2871delC; p.F958Sfs (∗) 31) have never been previously reported in ATLL to the best of our knowledge. The clinical significance of other genetic alterations is unknown. Further research is warranted to correlate this patient's molecular findings with other ATLL cases. Correlation specifically with other cases of CD8+ ATLL could prove to be useful in understanding the pathogenesis of this rare variant of an already rare form of leukemia/lymphoma.