T-cell leukemia/lymphoma seronegative

Abstract

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative malignancy of CD4+/CD25+ T lymphocytes, associated in over 95% of cases with human T-cell lymphotropic virus type 1 (HTLV-1) infection, whose seropositivity is considered an essential diagnostic criterion. However, extremely rare seronegative variants have been reported, posing significant diagnostic and therapeutic challenges. We report the case of a 67-year-old woman with atypical neurological manifestations as the initial presentation of ATLL: severe holocranial headache, somnolence, disorientation, and multiple cranial nerve involvement (II, V, VI, and VII), including bilateral retinal hemorrhages and facial paresthesias. Cerebrospinal fluid analysis showed opening pressure hypertension and mild lymphocytic pleocytosis without infectious findings. Brain MRI revealed periventricular leukoencephalopathy. During progression, the patient developed marked leukocytosis, anemia, thrombocytopenia, and atypical “flower-like” lymphocytes in peripheral blood. Bone marrow flow cytometry revealed a CD4+/CD25+/HLA-DR+ immunophenotype with loss of CD7, CD8, and CD26. Serologies for HTLV-1 and HTLV-2 were repeatedly negative. Literature supports the existence of seronegative ATLL, possibly explained by low viral load, epitope mutations, or silent viral genome integration detectable only through highly sensitive molecular techniques. This case reinforces such hypotheses and illustrates an unusual presentation of ATLL with prominent neurological involvement and persistent seronegativity, challenging traditional diagnostic criteria and emphasizing the need for advanced molecular approaches for timely recognition.