Sandbox: T cell
Overview
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. These cutaneous lesions are actually indistinguishable from the lesions found in both Sézary syndrome and mycosis fungoides.
- 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