https://orcid.org/0000-0002-6451-6503
Key Points
We rigorously showed that T-cell neoplasms other than adult T-cell leukemia/lymphoma occur in HTLV-1 carriers.
In situ hybridization and quantitative PCR using formalin-fixed paraffin-embedded specimens are useful for the differential diagnosis.
Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Although most T-cell neoplasms that develop in HTLV-1 carriers are considered ATLL, non-ATLL T-cell lymphomas (TCLs) could also occur, as documented in only a few case reports. Herein, we presented 14 cases of non-ATLL TCLs arising in HTLV-1 carriers. All TCL cases were serologically positive for HTLV-1 antibody; Southern blot analysis for the viral integration of HTLV-1, in situ hybridization for HTLV-1 basic leucine zipper factor (HBZ-ISH), quantitative real-time PCR for HTLV-1 proviral load (HTLV-1-qPCR), the entire HTLV-1 genome sequence, and target capture sequencing rigorously excluded the possibility of ATLL. Various histological subtypes, such as six nodal T follicular helper cell lymphomas, angioimmunoblastic type/not otherwise specified (nTFHL-AI/NOS), two monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL), two peripheral T-cell lymphomas, NOS (PTCL, NOS), and two anaplastic large cell lymphomas (ALCL), ALK-negative, were included. Each case exhibited immunophenotypes and genetic profiles consistent with its respective histological subtype, but atypical for ATLL. Three nTFHL-AI cases exhibited co-mutations of RHOA p.G17V, TET2, and IDH2 p.R172, characteristic of nTFHL-AI but not of ATLL. Among the molecular analytic modalities included in this study, the combination of HBZ-ISH and HTLV-1-qPCR represented the results obtained from the other more expensive modalities, indicating that this combination is effective in daily practice. When T-cell neoplasms arise in HTLV-1 carriers and exhibit atypical clinical, phenotypical, or genetic features for ATLL, it is recommended to perform HBZ-ISH and HTLV-1-qPCR to distinguish non-ATLL TCLs.
