Sandbox: T cell

Pathogenesis

• Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated and humoral immune responses.
• Adult T‐cell leukemia is mainly caused by an infection with human T‐cell lymphotropic virus (HTLV‐I).
• HTLV-1 is usually transmitted via breast feeding early in life.
• Other routes of transmission for HTLV-1 may include sexual contact, exposure to contaminated blood, or vertical maternal transmission.
• There appears to be a long latent period between HTLV-1 infection and the development of adult T‐cell leukemia.

• The oncogenesis of HTLV‐I infection is due to:
• The development of adult T‐cell leukemia as a result of HTLV‐I infection is related to:

• HTLV-I p40 tax viral protein
• HTLV-I basic leucine zipper factor
• Enhancement of CREB by HTLV-I
• Activation of JAK/STAT signaling pathway by HTLV-I

• The disease manifests in 75% of cases with leukemia 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

• Infiltration of the liver and spleen lead to the development of organomegally

• 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