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Leukemia and lymphomas (Acute leukemia (Dx (Immunophenotyping (B…

- - - - Acute promyelocyte leukemia (APL)
      - DIC risk in severe infection
      - t(15;17) involving the PML and RARA gene
      - Dx
        
        BM aspirate - >30% abnormal promyelocytes
        
        PS - heavy, dense granulation in promyelocytes, faggot cells that contain Auer rods sometimes in bundles
      - Need urgent dx, risk of bleeding, rapid death
      - Tx
        
        All trans-retinoid acid therapy
        
        Arsenic therapy
        
        Conventional cytotoxic chemotherapy
    - - Leukemic infiltration of the skin
    - - Gum infiltration - gingival hypertrophy
  - - - Dx - PS large lymphoblasts with cytoplasmic vacuolation, basophilic cytoplasm, salt and pepper chromatin pattern, low N/C ratio, prominent nucleoli, stippled nuclear chromatin
      - B-ALL
        
        B-ALL with hyperdiploidy
        
        B-ALL with t(9;22) (BCR-ABL1)
        
        Mature B-ALL with t(8;15) - Burkitt's leukemia
      - T-ALL
  - - - Down's syndrome
      - Fanconi's anemia
      - Bloom syndrome
  - - - Ecchymoses, IC hemorrhage
      - Hyperviscosity - leucocytosis
    - - Hepatosplenomegaly
      - LN
      - Skin
      - Brain
      - Testes
  - - - AML - large clusters of blast cells, abundant cytoplasm, fine granules, Auer rods, fine chromatin, prominent nucleoli
      - ALL - darker blast cells, not as clumped, agranular cytoplasm, high N:C ratio, clumped chromatin, indistinct nucleoli
    - - B-lymphoblasts - CD22, 19, 79a
      - T-lymphoblasts - cytoplasmic CD3
      - Myeloblasts - cMPO
    - - AML mutations
        
        FLT3-ITD - internal tandem duplication
        
        Poor prognosis
        
        FLT3 inhibitor - targeted therapy
        
        NPM1 mutation
        
        Favorable prognosis
        
        Aberrant cytoplasmic localization of nucleophosmin
        
        CEBPA gene - biallelic
        
        Favorable prognosis
        
        APL - t(15;17)(q22;q12) - PML-RARA gene
      - ALL mutations
        
        t(4;11)
        
        Poor prognosis
        
        t(9;22) - Burkitt's leukemia
        
        Poor prognosis
- - - - Follicular lymphoma (most common)
        
        Middle aged or elderly
        
        Benign for many years
        
        Due to Bcl-2 overexpression
      - MALT lymphoma
        
        Lymphoepithelial lesions
        
        Destroyed glands
        
        AE1 and AE3 antibody
        
        Common in stomach and other parts of GI tract or other regions
        
        A/w pre-existing inflamm or autoimmune diseases - H pylori chronic gastritis, Sjogren's syndrome, Hashimoto's thyroidits
      - Extranodal NK/T cell lymphoma
        
        Lethal midline granuloma
        
        Extranodal, common in nasal cavity
        
        A/w EBV
        
        Angiocentric, angiodestructive
      - Diffuse large B-cell lymphoma
        
        Classical high grade
        
        De novo or progression from less aggressive lymphoma
        
        Large neoplastic B lymphoid cells
        
        Aggressive but potentially curable with multi-agent chemotherapy
      - Burkitt's lymphoma
        
        Highly aggressive
        
        A/w EBV
        
        Can be endemic, sporadic or immunodeficiency associated
        
        Dx -PS starry sky pattern caused by apoptosis and high proliferation index
    - - HTLV1 - adult T cell lymphoma
      - EBV - Burkitt's, NK/T cell
      - H pylori infection - MALT
      - Inherited or acquired immunodeficiency - B cell lymphoma
      - AIDS - high grade B cell lymphoma
    - - Burkitt's - t(8;14)
      - Follicular - t(14;18), BCl break apart +ve, CD20
      - Mantle cell - t(11;14)
      - Anaplastic large cell - t(2;5)
  - - - Nodular sclerosing (most common)
        
        CD30 immunostain, highlights RS cells, lacunar cells
        
        In young adults
        
        Mediastinal involvement, pleural effusion, SVCO
      - Mixed cellularity
      - Lymphocyte depleted
      - Lymphocyte rich/predominant (best prognosis)
    - - CD20, CD45
      - Popcorn cells - lymphocyte predominant cells
    - - PS - Reed-Sternberg cells (owl eye appearance), multinucleate, reactive inflamm components, lymphocytes, eosinophils, plasma cells, histiocytes
      - EBV genome in 50% of cases
      - Cervical LN involvement and splenomegaly