Adult T-cell leukemia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]

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). On gross pathology, skin nodules, maculopapular eruption, and erythema 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 polylobulated nucleus and agranular cytoplasm.

Pathogenesis

The exact mechanism of pathogenesis of the adult T‐cell leukemia is unknown.

  • Adult T‐cell leukemia arises from post‐thymic lymphocytes, which are normally involved in the process of cell-mediated immune response.[1][2][3][4][5]
  • Adult T‐cell leukemia is mainly caused by an infection with human T‐cell lymphotropic virus (HTLV) [6].
  • HTLV is usually transmitted via breast feeding early in life. Other minor routes of transmission for HTLV may include sexual contact, exposure to contaminated blood, or vertical maternal transmission [7].
  • There appears to be a long latent period between HTLV-1 infection and the development of adult T‐cell leukemia.
  • The oncogenesis of HTLV infection, which results in the development of adult T-cell leukemia, is due to:
  • 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.
  • Hematopathological features of adult T-cell leukemia are variable, which may include:
  • Hypercalcemia among adult T-cell leukemia patients has been associated with elevated serum concentrations of:
  • 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 organomegaly among adult T-cell leukemia patients.
  • Cutaneous manifestations of adult T-cell leukemia is due to the infiltration of leukemic cells along the dermis layer of the skin.
  • Cutaneous Pautrier's microabscesses 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

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

Gross Pathology

Microscopic Pathology

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

References

  1. 1.0 1.1 Matutes E (2007). "Adult T-cell leukaemia/lymphoma". J. Clin. Pathol. 60 (12): 1373–7. doi:10.1136/jcp.2007.052456. PMC 2095573. PMID 18042693.
  2. 2.0 2.1 Adult T-cell leukemia/lymphoma. Wikipedia (2015) https://en.wikipedia.org/wiki/Adult_T-cell_leukemia/lymphoma Accessed on November, 3 2015
  3. 3.0 3.1 Human T-lymphotropic virus. Wikipedia (2015) https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus#Transmission Accessed on November, 3 2015
  4. 4.0 4.1 Lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Lymphoma#Adult_T-cell_leukemia.2Flymphoma Accessed on November, 3 2015
  5. 5.0 5.1 5.2 Adult T-cell Leukemia. PathologyOutlines (2015) http://www.pathologyoutlines.com/topic/lymphomanonBatlv.html Accessed on November, 3 2015
  6. Oliveira PD, Farre L, Bittencourt AL (October 2016). "Adult T-cell leukemia/lymphoma". Rev Assoc Med Bras (1992). 62 (7): 691–700. doi:10.1590/1806-9282.62.07.691. PMID 27925051.
  7. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (December 1980). "Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma". Proc. Natl. Acad. Sci. U.S.A. 77 (12): 7415–9. PMC 350514. PMID 6261256.
  8. Pezeshkpoor F, Yazdanpanah MJ, Shirdel A (2008). "Specific cutaneous manifestations in adult T-cell leukemia/lymphoma". Int J Dermatol. 47 (4): 359–62. doi:10.1111/j.1365-4632.2008.03526.x. PMID 18377598.
  9. Bittencourt AL, da Graças Vieira M, Brites CR, Farre L, Barbosa HS (November 2007). "Adult T-cell leukemia/lymphoma in Bahia, Brazil: analysis of prognostic factors in a group of 70 patients". Am. J. Clin. Pathol. 128 (5): 875–82. doi:10.1309/2YGD1P0QCVCWBLDX. PMID 17951212.