ALK+ Diffuse Large B-cell Lymphoma

ALK+ Diffuse Large B-cell Lymphoma

Tariq Muzzafar, MBBS

ALK(+) diffuse large B-cell lymphoma involving lymph node. The neoplastic cells have large nuclei with prominent central nucleoli. Apoptotic cells image and a mitotic figure image are present.

ALK(+) diffuse large B-cell lymphoma (DLBCL). ALK is expressed in a granular and cytoplasmic pattern consistent with t(2;17)(p23;q23)/CLTC-ALK.



  • Diffuse large B-cell lymphoma (DLBCL), anaplastic lymphoma kinase (ALK)


  • Diffuse large B-cell lymphoma expressing ALK protein and associated with ALK gene abnormalities



  • No known association with infectious or environmental factors


  • ALK gene abnormalities at chromosome 2p23 appear to be key transforming event

    • Result in formation of fusion genes

      • Clathrin heavy-chain gene (CLTC)-ALK

      • Nucleophosmin (NPM)-ALK

      • SEC31A-ALK

    • Overexpression of ALK protein



  • Incidence

    • < 1% of all cases of DLBCL

    • Approximately 80 cases reported to date

  • Age

    • Range: 9-85 years

      • Median: ˜ 40 years

  • Gender

    • Male to female ratio: ˜ 5 to 1

  • Ethnicity

    • No apparent ethnic predisposition


  • Lymph nodes are most commonly involved and biopsied (˜ 75%)

  • Extranodal sites of involvement include

    • Bone marrow in ˜ 25% of patients

    • Nasal cavity, nasopharynx, oral cavity

    • Stomach, small intestine

    • Spleen, ovary

    • Bones, soft tissues

    • Epidural mass, brain

  • Enlarged mediastinal lymph nodes can present as mediastinal mass

  • Patients can present with leukemic involvement


  • Systemic (B-type) symptoms common

  • 60-70% of patients have stage III or IV disease

    • Widespread lymphadenopathy

  • Aggressive clinical course

Laboratory Tests

  • Serum lactate dehydrogenase (LDH) levels elevated in ˜ 50% of patients

  • HIV serology is (-)


  • Drugs

    • Most patients have been treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen

      • Based on survival data, this therapeutic approach is not optimal


  • 5-year overall survival is ˜ 25%

    • ˜ 50% of patients die within 1 year

  • Survival is shorter for patients with advanced-stage disease

  • Children appear to have better prognosis

    • Prolonged survival (> 156 months) has been reported


Histologic Features

  • Lymph node

    • Partial or diffuse effacement of lymph node architecture

    • Lymphoma cells infiltrate sinusoids in many cases

    • ± focal necrosis

    • ± binucleated HRS-like cells

    • ± multinucleated giant lymphoma cells

    • Mitotic figures easily identified

  • Extranodal sites

    • Similar morphologic features

    • Sinusoidal infiltration usually not appreciated at extranodal sites

  • Bone marrow

    • Variable degree of involvement

    • Sinusoidal involvement is uncommon in bone marrow

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on ALK+ Diffuse Large B-cell Lymphoma

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