Sandbox: T cell

Pathogenesis

Adult T‐cell leukaemia/lymphoma (ATLL) is a mature T‐cell neoplasm of post‐thymic lymphocytes Etiologically linked to the human T‐cell lymphotropic virus, HTLV‐I, HTLV‐I serology is a mandatory investigation Long latency, virus exposure usually occurs very early in life Transmission of HTLV-1 is believed to occur from mother to child; by sexual contact; and through exposure to contaminated blood, either through blood transfusion or sharing of contaminated needles HTLV-I p40 tax viral protein: non structural protein that causes transcriptional activation of many genes in infected lymphocytes Enhancement of c-AMP response element binding transcription factor (CREB) phosphorylation HTLV-I basic leucine zipper factor (HBZ): causes T cell proliferation and oncogenesis JAK/STAT pathway constitutively activated in HTLV-I infected cells

The disease manifests in 75% of cases with leukaemia and in the remaining as a pure lymphomatous form widely disseminated disease which may involve liver, skin dermis layer, peripheral blood involvement , bone, and CNS anaemia and thrombocytopenia is variable patchy infiltrates Bone marrow infiltration Neutrophilia and eosinophilia Present

lytic bone lesions tumor-induced osteolysis hypercalcaemia increased osteoclastic activity elevated serum levels of IL-1, TGFβ, PTHrP, macrophage inflammatory protein (MIP-1α), and receptor activator of nuclear factor-κB ligand (RANKL) have been associated with hypercalcemia

Diffuse infiltration of the lymph node leading expansion of the paracortical area Infiltration of the dermis skin infiltration, epidermotropism present and Pautrier's microabcesses antibodies to HTLV‐I are demonstrable defects of cell-mediated immunity recurrent infections

Genetic

+3, +7, +21, monosomy X,deletion of chromosome Y and chromosomes 6 and 14q; 14q11 and break points e TCR‐alpha and ‐delta chain genes TCRA and TCRD 14q32 of TCL1 mutations of tumour‐suppressor genes CDKN2A (p16), CDKN2B (p15) and TP53 (p53)

Gross

Nodules skin

Micro

pleomorphic, a medium size lymphocyte conndensed chromatin convoluted or polylobated nucleus nucleoli are not visibl cytoplasm agranular “flower cell” Reed-Sternberg like cells may also be present

CD4 positive CD8 positive CD2 and CD5 positive CD7 negativ CD3 and T‐cell receptor (TCR)‐β may be down‐regulated CD2, CD3, CD4, CD5, CD25, TCR α/β, CD45ROCD56 expressionCCR4, FOXP3, HLA-DR, L-selectin (CD62), MUM-1