Adult T-cell Leukemia/Lymphoma



Adult T-cell Leukemia/Lymphoma


Aaron Auerbach, MD, PhD





Key Facts


Etiology/Pathogenesis



  • Long latency period between HTLV-1 infection and tumor development


  • Small risk of ATLL in HTLV-1 infected people


  • Tax viral oncoprotein linked to tumorigenesis


Clinical Issues



  • 4 clinical presentations: Acute, chronic, lymphoma, and smoldering


Microscopic Pathology



  • Skin with T-cell infiltrate in epidermis, dermis, &/or subcutis



    • Epidermotropism &/or Pautrier microabscesses


  • Peripheral blood with multilobated “flower” cells


  • Lymph nodes with effaced architecture and diffuse infiltrate


Ancillary Tests



  • Confirmation of HTLV-1 infection by serology


  • Immunophenotype: Regulatory T cells CD3(+), CD4(+), CD25(+), FOXP3(+), CCR4(+); often loses CD7; cytotoxic markers negative


  • Clonal T-cell receptor gene rearrangement


  • Complex chromosomal abnormalities; no one abnormality is characteristic of ATLL


Top Differential Diagnoses



  • Mycosis fungoides



    • Similar clinical picture with epidermotropism and peripheral blood lymphocytosis


    • Also CD4(+), CD8(−) T cells, but CD25(−), FOXP3(−), and CD30(−)


  • Anaplastic large cell lymphoma







This clinical photograph shows an ulcerating lesion image, which is 2.5 cm in greatest dimension, from the foot of a person from the Caribbean region with ATLL, HTLV-1(+).






This ATLL involves the mucosa. Note the small lymphocytes with irregular hyperchromatic nuclei infiltrating squamous mucosa, forming Pautrier-like microabscesses image. (Courtesy C. Bueso-Ramos, MD.)


TERMINOLOGY


Abbreviations



  • Adult T-cell leukemia/lymphoma (ATLL)


Synonyms



  • Adult T-cell leukemia


Definitions



  • T-cell lymphoma/leukemia of regulatory T cells (CD4[+], CD25[+], FOXP3[+]) caused by human T-cell leukemia virus type 1 (HTLV-1)


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Human T-cell leukemia virus type 1



    • Progresses to leukemia/lymphoma in < 5% of infected individuals


    • Long latency period



      • Most exposed as infants/children


      • Tumor often after 20 years of viral exposure


    • Transmitted through blood or breast milk


    • Also causes tropical spastic paraparesis


    • Encodes Tax (a viral oncoprotein)



      • Plays a role in development of ATLL


      • Activates transcription factors for T-cell proliferation genes


CLINICAL ISSUES


Epidemiology



  • Age



    • Adults, most commonly in 50s or 60s


  • Gender



    • Male:female = 1.5:1.0


  • Ethnicity



    • Endemic to southwest Japan, Caribbean islands, South America, and central Africa


Presentation



  • Skin lesions



    • Develop in 50% of ATLL patients


    • Usually multiple nodules/tumors, papules, plaques, or macules



      • Papules may cover large segments of body


    • Rarely, erythroderma, purpura, prurigo, or erythema multiforme


  • Other sites of disease include lymph nodes, peripheral blood, bone, spleen and sometimes lung, liver, and CNS



    • Most patients have generalized lymphadenopathy


    • Hypercalcemia from increased osteoclast bone resorption


  • 4 clinical presentations: Acute, chronic, lymphoma, and smoldering



    • Acute subtype



      • Most common subtype


      • Severe peripheral blood lymphocytosis, ↑ WBC, ↑ LDH, skin lesions, lymphadenopathy


      • Hypercalcemia and lytic bone lesions


      • Immunodeficiency leads to other opportunistic infections


    • Chronic subtype



      • Lymphocytosis, but ↓ WBC than acute subtype


      • No hypercalcemia, exfoliative skin rash


    • Lymphomatous subtype



      • ↑ lymphadenopathy; usually no peripheral blood involvement


      • Less hypercalcemia than acute subtype; skin often involved


    • Smoldering subtype



      • > 5% tumor cells in peripheral blood, even though normal WBC count


      • Tumor cells small with less pleomorphism and lobation


      • No hypercalcemia or lymphadenopathy

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Adult T-cell Leukemia/Lymphoma

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