adult T-cell leukemia/lymphoma

ATLL arises from HTLV-1 infection of CD4+ T cells, transmitted via breastfeeding, sexual contact, blood transfusion, or IV drug use (shared needles). The virus integrates into the host genome and expresses the Tax protein, which activates NF-κB and dysregulates cell cycle control, promoting clonal proliferation and malignant transformation—typically after decades of latency. Only a small percentage (~5%) of HTLV-1 carriers develop ATLL in their lifetime.

Clinical subtypes include acute (most common, aggressive), lymphomatous, chronic, and smoldering forms. The acute form presents with the classic tetrad: hypercalcemia (due to PTHrP-like cytokines and osteoclast-activating factors produced by tumor cells, causing lytic bone lesions), generalized lymphadenopathy, hepatosplenomegaly, skin lesions (rash, nodules, erythroderma), and opportunistic infections due to immunosuppression (e.g., Strongyloides hyperinfection, Pneumocystis).

Peripheral blood smear shows pathognomonic 'flower cells'—lymphocytes with highly lobulated, cloverleaf-shaped nuclei. Immunophenotyping reveals CD4+/CD25+ (IL-2 receptor alpha) T cells. Diagnosis requires confirmation of HTLV-1 seropositivity along with clinicopathologic features.

Prognosis is generally poor, especially in acute and lymphomatous subtypes, with median survival often less than a year without aggressive therapy. Treatment includes combination chemotherapy, antiretroviral therapy (zidovudine) plus interferon-alpha, and allogeneic stem cell transplant in eligible patients. HTLV-1 is also associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a distinct neurologic complication.