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Clinical manifestations, pathologic features, and diagnosis of adult T cell leukemia-lymphoma

Arnold S Freedman, MD
Jon C Aster, MD
Section Editor
Andrew Lister, MD, FRCP, FRCPath, FRCR
Deputy Editor
Alan G Rosmarin, MD


Adult T cell leukemia-lymphoma (ATL), according to the 2016 World Health Organization (WHO) classification of lymphoid neoplasms, is defined as a peripheral T cell neoplasm associated with infection by the human T-lymphotropic virus, type I (HTLV-I) [1,2]. Although it is often highly aggressive, the disease course of ATL is variable and in some cases it is quite indolent. (See "Classification of the hematopoietic neoplasms".)

Other distinct T cell neoplasms include mycosis fungoides (cutaneous T cell lymphoma), T cell large granular lymphocytic leukemia, T cell prolymphocytic leukemia, anaplastic large cell lymphoma, peripheral T cell lymphoma, and precursor T cell lymphoblastic leukemia/lymphoma. These disorders are not caused by HTLV-1.

Epidemiologic studies suggest that HTLV-I is primarily transmitted by breastfeeding, although spread via blood transfusion, sharing of needles, and sexual intercourse also occurs. This is discussed in more detail separately. (See "Human T-lymphotropic virus type I: Virology, pathogenesis, and epidemiology".)

The epidemiology, pathogenesis, clinical features, pathology, and diagnosis of ATL will be discussed here; the treatment of ATL is discussed separately. (See "Treatment and prognosis of adult T cell leukemia-lymphoma".)


Adult T cell leukemia-lymphoma (ATL) is an uncommon lymphoid neoplasm that occurs in patients with human T-lymphotropic virus, type I (HTLV-I) infection. Incidence varies by population according to the prevalence of HTLV-I infection [3]. Infection with HTLV-1 is endemic in several islands in southern Japan, the Caribbean basin (eg, Jamaica and Trinidad), western Africa, Peru, northeast Iran, and the southeastern portion of the United States; most affected patients live in or originate from these areas [4-10].

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Literature review current through: Nov 2017. | This topic last updated: Jul 10, 2017.
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  1. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
  2. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
  3. Vose J, Armitage J, Weisenburger D, International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008; 26:4124.
  4. Jaffe ES, Blattner WA, Blayney DW, et al. The pathologic spectrum of adult T-cell leukemia/lymphoma in the United States. Human T-cell leukemia/lymphoma virus-associated lymphoid malignancies. Am J Surg Pathol 1984; 8:263.
  5. Picard FJ, Coulthart MB, Oger J, et al. Human T-lymphotropic virus type 1 in coastal natives of British Columbia: phylogenetic affinities and possible origins. J Virol 1995; 69:7248.
  6. Hjelle B, Khabbaz RF, Conway GA, et al. Prevalence of human T cell lymphotropic virus type II in American Indian populations of the southwestern United States. Am J Trop Med Hyg 1994; 51:11.
  7. Bitar N, Hajj HE, Houmani Z, et al. Adult T-cell leukemia/lymphoma in the Middle East: first report of two cases from Lebanon. Transfusion 2009; 49:1859.
  8. Phillips AA, Shapira I, Willim RD, et al. A critical analysis of prognostic factors in North American patients with human T-cell lymphotropic virus type-1-associated adult T-cell leukemia/lymphoma: a multicenter clinicopathologic experience and new prognostic score. Cancer 2010; 116:3438.
  9. Laurini JA, Perry AM, Boilesen E, et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood 2012; 120:4795.
  10. Chihara D, Ito H, Matsuda T, et al. Differences in incidence and trends of haematological malignancies in Japan and the United States. Br J Haematol 2014; 164:536.
  11. Yamamoto JF, Goodman MT. Patterns of leukemia incidence in the United States by subtype and demographic characteristics, 1997-2002. Cancer Causes Control 2008; 19:379.
  12. Adams SV, Newcomb PA, Shustov AR. Racial Patterns of Peripheral T-Cell Lymphoma Incidence and Survival in the United States. J Clin Oncol 2016; 34:963.
  13. Matutes E. Adult T-cell leukaemia/lymphoma. J Clin Pathol 2007; 60:1373.
  14. Hanchard B. Adult T-cell leukemia/lymphoma in Jamaica: 1986-1995. J Acquir Immune Defic Syndr Hum Retrovirol 1996; 13 Suppl 1:S20.
  15. Smith MR, Greene WC. Molecular biology of the type I human T-cell leukemia virus (HTLV-I) and adult T-cell leukemia. J Clin Invest 1991; 87:761.
  16. Nagai Y, Kawahara M, Hishizawa M, et al. T memory stem cells are the hierarchical apex of adult T-cell leukemia. Blood 2015; 125:3527.
  17. Gessain A, Cassar O. Epidemiological Aspects and World Distribution of HTLV-1 Infection. Front Microbiol 2012; 3:388.
  18. Murphy EL, Hanchard B, Figueroa JP, et al. Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I. Int J Cancer 1989; 43:250.
  19. Matsuoka M. Human T-cell leukemia virus type I and adult T-cell leukemia. Oncogene 2003; 22:5131.
  20. Chen YC, Wang CH, Su IJ, et al. Infection of human T-cell leukemia virus type I and development of human T-cell leukemia lymphoma in patients with hematologic neoplasms: a possible linkage to blood transfusion. Blood 1989; 74:388.
  21. Hoshida Y, Li T, Dong Z, et al. Lymphoproliferative disorders in renal transplant patients in Japan. Int J Cancer 2001; 91:869.
  22. Tamaki H, Matsuoka M. Donor-derived T-cell leukemia after bone marrow transplantation. N Engl J Med 2006; 354:1758.
  23. Matsuoka M, Jeang KT. Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat Rev Cancer 2007; 7:270.
  24. Taylor G. Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma. J Clin Pathol 2007; 60:1392.
  25. Matsuoka M, Watanabe T, Kannagi M, et al. Meeting report on the 13th International Conference on Human Retrovirology: human T-cell leukemia virus research 30 years after adult T-cell leukemia. Cancer Res 2007; 67:10638.
  26. Migone TS, Lin JX, Cereseto A, et al. Constitutively activated Jak-STAT pathway in T cells transformed with HTLV-I. Science 1995; 269:79.
  27. Ju W, Zhang M, Jiang JK, et al. CP-690,550, a therapeutic agent, inhibits cytokine-mediated Jak3 activation and proliferation of T cells from patients with ATL and HAM/TSP. Blood 2011; 117:1938.
  28. Jeong SJ, Radonovich M, Brady JN, Pise-Masison CA. HTLV-I Tax induces a novel interaction between p65/RelA and p53 that results in inhibition of p53 transcriptional activity. Blood 2004; 104:1490.
  29. Nagata Y, Kontani K, Enami T, et al. Variegated RHOA mutations in adult T-cell leukemia/lymphoma. Blood 2016; 127:596.
  30. Kataoka K, Nagata Y, Kitanaka A, et al. Integrated molecular analysis of adult T cell leukemia/lymphoma. Nat Genet 2015; 47:1304.
  31. Sakashita A, Hattori T, Miller CW, et al. Mutations of the p53 gene in adult T-cell leukemia. Blood 1992; 79:477.
  32. Cesarman E, Chadburn A, Inghirami G, et al. Structural and functional analysis of oncogenes and tumor suppressor genes in adult T-cell leukemia/lymphoma shows frequent p53 mutations. Blood 1992; 80:3205.
  33. Hangaishi A, Ogawa S, Imamura N, et al. Inactivation of multiple tumor-suppressor genes involved in negative regulation of the cell cycle, MTS1/p16INK4A/CDKN2, MTS2/p15INK4B, p53, and Rb genes in primary lymphoid malignancies. Blood 1996; 87:4949.
  34. Nakayama K, Yamada Y, Koji T, et al. Expression and phosphorylation status of retinoblastoma protein in adult T-cell leukemia/lymphoma. Leuk Res 2000; 24:299.
  35. Kataoka K, Shiraishi Y, Takeda Y, et al. Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers. Nature 2016; 534:402.
  36. Motokura T, Fukumoto S, Matsumoto T, et al. Parathyroid hormone-related protein in adult T-cell leukemia-lymphoma. Ann Intern Med 1989; 111:484.
  37. Ikeda K, Ohno H, Hane M, et al. Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma. J Clin Endocrinol Metab 1994; 79:1322.
  38. Nakamura Y, Bando H, Shintani Y, et al. Serum parathyroid hormone-related protein concentrations in patients with hematologic malignancies or solid tumors. Acta Endocrinol (Copenh) 1992; 127:324.
  39. Ishibashi K, Ishitsuka K, Chuman Y, et al. Tumor necrosis factor-beta in the serum of adult T-cell leukemia with hypercalcemia. Blood 1991; 77:2451.
  40. Wano Y, Hattori T, Matsuoka M, et al. Interleukin 1 gene expression in adult T cell leukemia. J Clin Invest 1987; 80:911.
  41. Nosaka K, Miyamoto T, Sakai T, et al. Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor kappaB ligand on adult T-cell leukemia cells. Blood 2002; 99:634.
  42. Bunn PA Jr, Schechter GP, Jaffe E, et al. Clinical course of retrovirus-associated adult T-cell lymphoma in the United States. N Engl J Med 1983; 309:257.
  43. Yamaguchi T, Hirano T, Kumagai K, et al. Osteitis fibrosa cystica generalizata with adult T-cell leukaemia: a case report. Br J Haematol 1999; 107:892.
  44. Oshiro A, Tagawa H, Ohshima K, et al. Identification of subtype-specific genomic alterations in aggressive adult T-cell leukemia/lymphoma. Blood 2006; 107:4500.
  45. Katsuya H, Ishitsuka K, Utsunomiya A, et al. Treatment and survival among 1594 patients with ATL. Blood 2015; 126:2570.
  46. Tsukasaki K, Tanosaki S, DeVos S, et al. Identifying progression-associated genes in adult T-cell leukemia/lymphoma by using oligonucleotide microarrays. Int J Cancer 2004; 109:875.
  47. Ravandi F, O'Brien S. Chronic lymphoid leukemias other than chronic lymphocytic leukemia: diagnosis and treatment. Mayo Clin Proc 2005; 80:1660.
  48. Uchiyama T, Yodoi J, Sagawa K, et al. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood 1977; 50:481.
  49. Foss FM, Aquino SL, Ferry JA. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-2003. A 72-year-old man with rapidly progressive leukemia, rash, and multiorgan failure. N Engl J Med 2003; 348:1267.
  50. Yamada Y, Kamihira S, Murata K, et al. Frequent hepatic involvement in adult T cell leukemia: comparison with non-Hodgkin's lymphoma. Leuk Lymphoma 1997; 26:327.
  51. Sawada Y, Hino R, Hama K, et al. Type of skin eruption is an independent prognostic indicator for adult T-cell leukemia/lymphoma. Blood 2011; 117:3961.
  52. Okada F, Ando Y, Kondo Y, et al. Thoracic CT findings of adult T-cell leukemia or lymphoma. AJR Am J Roentgenol 2004; 182:761.
  53. Kawasaki C, Ikeda H, Fukumoto T. Cerebral mass lesions associated with adult T-cell leukemia/lymphoma. Int J Hematol 1995; 61:97.
  54. Takasaki Y, Iwanaga M, Imaizumi Y, et al. Long-term study of indolent adult T-cell leukemia-lymphoma. Blood 2010; 115:4337.
  55. Chadburn A, Athan E, Wieczorek R, Knowles DM. Detection and characterization of human T-cell lymphotropic virus type I (HTLV-I) associated T-cell neoplasms in an HTLV-I nonendemic region by polymerase chain reaction. Blood 1991; 77:2419.
  56. Verdonck K, González E, Van Dooren S, et al. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis 2007; 7:266.
  57. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol 1991; 79:428.
  58. Kikuchi M, Mitsui T, Takeshita M, et al. Virus associated adult T-cell leukemia (ATL) in Japan: clinical, histological and immunological studies. Hematol Oncol 1986; 4:67.
  59. Ohnita K, Isomoto H, Mizuta Y, et al. Helicobacter pylori infection in patients with gastric involvement by adult T-cell leukemia/lymphoma. Cancer 2002; 94:1507.
  60. Roncador G, Garcia JF, Garcia JF, et al. FOXP3, a selective marker for a subset of adult T-cell leukaemia/lymphoma. Leukemia 2005; 19:2247.
  61. Karube K, Ohshima K, Tsuchiya T, et al. Expression of FoxP3, a key molecule in CD4CD25 regulatory T cells, in adult T-cell leukaemia/lymphoma cells. Br J Haematol 2004; 126:81.
  62. Waldmann TA, Greene WC, Sarin PS, et al. Functional and phenotypic comparison of human T cell leukemia/lymphoma virus positive adult T cell leukemia with human T cell leukemia/lymphoma virus negative Sézary leukemia, and their distinction using anti-Tac. Monoclonal antibody identifying the human receptor for T cell growth factor. J Clin Invest 1984; 73:1711.
  63. Aisenberg AC, Krontiris TG, Mak TW, Wilkes BM. Rearrangement of the gene for the beta chain of the T-cell receptor in T-cell chronic lymphocytic leukemia and related disorders. N Engl J Med 1985; 313:529.
  64. Sanada I, Tanaka R, Kumagai E, et al. Chromosomal aberrations in adult T cell leukemia: relationship to the clinical severity. Blood 1985; 65:649.
  65. Itoyama T, Chaganti RS, Yamada Y, et al. Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki. Blood 2001; 97:3612.
  66. Tsukasaki K, Krebs J, Nagai K, et al. Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course. Blood 2001; 97:3875.
  67. Hatta Y, Yamada Y, Tomonaga M, et al. Detailed deletion mapping of the long arm of chromosome 6 in adult T-cell leukemia. Blood 1999; 93:613.
  68. Pombo-de-Oliveira MS, Dobbin JA, Loureiro P, et al. Genetic mutation and early onset of T-cell leukemia in pediatric patients infected at birth with HTLV-I. Leuk Res 2002; 26:155.
  69. Takasaki Y, Yamada Y, Sugahara K, et al. Interruption of p16 gene expression in adult T-cell leukaemia/lymphoma: clinical correlation. Br J Haematol 2003; 122:253.
  70. Tsukasaki K, Hermine O, Bazarbachi A, et al. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol 2009; 27:453.
  71. Wattel E, Vartanian JP, Pannetier C, Wain-Hobson S. Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy. J Virol 1995; 69:2863.
  72. Tsukasaki K, Tsushima H, Yamamura M, et al. Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease. Blood 1997; 89:948.