Sandbox: T cell

Pathogenesis

• Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated 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 minor 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, which results in the development of adult T-cell leukemia, is due to:

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

• Adult T‐cell leukemia can manifests as either a leukemic form (75% of the cases) or a pure lymphomatous form (25% of the cases).
• Adult T‐cell leukemia is a widely disseminated disease which may involve the peripheral blood cells, bone marrow, lymph nodes, liver, spleen, skin, and CNS.
• Haematopathological features of adult T-cell leukemia are variable, patients may present with:

• Anemia
• Thrombocytopenia
• Neutrophilia
• Eosinophilia

• Patchy bone marrow infiltration among adult T-cell leukemia patients may result in:

• Tumor-induced osteolysis due to increased osteoclastic activity
• Multiple lytic bone lesions
• Hypercalcemia

• Hypercalcemia among adult T-cell leukemia patients has been associated with elevated serum levels of:

• IL-1
• TGFβ
• PTHrP
• MIP-1α
• RANKL

• Infiltration of malignant leukemic cells results in the expansion of the lymph nodes paracortical region, which may lead to the development of peripheral lymphadenopathy among adult T-cell leukemia patients.
• Infiltration of the liver and spleen may lead to the development of organomegally among adult T-cell leukemia patients.
• Cutaneous manifestations of adult T-cell leukemia is due to the infiltration of leukmeic cells along the dermis layer of the skin.
• Cutaneous Pautrier's microabcesses formation (due to epidermotropism) may also be present among adult T-cell leukemia patients. These cutaneous lesions are indistinguishable from the ones found in Sézary syndrome and mycosis fungoides.
• Immune deficiency occurs in adult T-cell leukemia due to the defect of patients cell-mediated immunity.

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