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.


TERMINOLOGY


Abbreviations



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


Definitions



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


ETIOLOGY/PATHOGENESIS


Etiology



  • No known association with infectious or environmental factors


Genetics



  • 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


CLINICAL ISSUES


Epidemiology



  • 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


Site



  • 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


Presentation



  • 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 (-)


Treatment



  • Drugs



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



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


Prognosis



  • 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


MICROSCOPIC PATHOLOGY


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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