Sandbox: T cell

Overview

Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response. Development of adult T-cell leukemia is the result of multiple genetic mutations induced by an infection with human T‐cell lymphotropic virus (HTLV‐I). On gross pathology, skin nodules, maculopapular eruption, and erythroderma are characteristic skin findings of adult T-cell leukemia. On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include pleomorphic, medium sized lymphocytes with a polylobated nucleus and agranular cytoplasm.

Pathogenesis

• Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response.
• 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 concentrations 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 a defective cell-mediated immunity.

Genetic

• Development of adult T-cell leukemia is the result of multiple genetic mutations.

• Genes involved in the pathogenesis of adult T-cell leukemia include:

• 14q11 gene mutation
• TCR‐alpha chain gene mutation
• TCR‐delta chain gene mutation

Gross Pathology

• On gross pathology, skin nodules, maculopapular eruption, and erythroderma are characteristic findings of adult T-cell leukemia cutaneous manifestations.

Mircoscopic Pathology

• On microscopic histopathological analysis, characteristic findings of adult T-cell leukemia include:

• Pleomorphic, medium sized lymphocytes
• Convoluted or polylobated nucleus with condensed chromatin (cloverleaf nuclei)
• Nucleoli are not visible
• Agranular cytoplasm
• “Flower cells”
• Reed-Sternberg like cells may also be present

• On immunohistochemical analysis, characteristic findings of adult T-cell leukemia include:

• CD2 +ve
• CD4 +ve
• CD5 +ve
• CD8 +ve
• CD7 -ve
• CD3 and T‐cell receptor (TCR)‐β may be down‐regulated