Overview and Classification of Mature Leukemias, Immunosecretory Lymphomas

Overview and Classification of Mature Leukemias, Immunosecretory Lymphomas

Kaaren K. Reichard, MD

Typical appearance of chronic lymphocytic leukemia in the blood shows small lymphoid cells with mature clumped chromatin and scant cytoplasm. Occasional “smudge” cells are evident image.

Multiple paratrabecular lymphoid aggregates image are present on low power in this case of follicular lymphoma involving the bone marrow. Mantle cell lymphoma may show a similar histology.



  • Clonal B-cell or plasma cell-derived neoplasms composed of morphologically &/or immunophenotypically mature B or plasma cells

    • Characteristic peripheral blood (PB) and bone marrow (BM) involvement in B leukemias and plasma cell neoplasms

    • Variable involvement of PB/BM with B-cell lymphomas

Classification of Mature B-cell Leukemias

  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)

  • B-cell prolymphocytic leukemia (B-PLL)

  • Hairy cell leukemia (HCL)

  • Splenic B-cell lymphoma/leukemia, unclassifiable

Classification of Mature B-cell Lymphomas That May Involve PB/BM

  • Splenic B-cell marginal zone lymphoma (SMZL)

  • Follicular lymphoma (FL)

  • Mantle cell lymphoma (MCL)

  • Diffuse large B-cell lymphoma (DLBCL)

  • Intravascular large B-cell lymphoma

  • ALK(+) DLBCL

  • Plasmablastic lymphoma

  • Burkitt lymphoma

Classification of Plasma Cell Neoplasms

  • Lymphoplasmacytic lymphoma (LPL)

  • Gamma heavy chain disease

  • Monoclonal gammopathy of uncertain significance (MGUS)

  • Plasma cell myeloma (PCM)



  • Incidence

    • Highly variable

      • CLL/SLL common

      • FL and DLBCL common

      • MGUS common

      • ALK(+) DLBCL rare

  • Age range

    • Highly variable

      • Plasma cell neoplasms typically affect adults

      • Burkitt lymphoma seen in children and adults

      • Other mature B cell leukemias and lymphomas tend to affect adults


  • PB/BM

    • Typical of leukemias

    • Typical of plasma cell neoplasms

  • Extramedullary sites with possible involvement of PB/BM

    • B-cell lymphomas

Presentation and Natural History

  • CLL/SLL, SMZL, HCL generally indolent

  • B-PLL generally aggressive

  • DLBCL, Burkitt lymphoma, plasmablastic lymphoma; aggressive, yet potentially curable

  • Mantle cell lymphoma generally aggressive

Laboratory Tests

  • Complete blood cell count (CBC) with differential

  • PB smear review

  • BM biopsy

  • Flow cytometry

  • Genetics depending on disease type

  • Immunohistochemistry for ALK-, EBV-, and HHV8-related disease


  • Highly variable

  • Depends on disease

  • Patients with indolent disease may not require therapy

  • Chemotherapy &/or other therapies for aggressive tumors


Highly Variable

  • Subtype dependent


  • FL and subset of DLBCL with t(14;18)(q32;q21); IGH@-BCL2 fusion

  • Burkitt lymphoma with t(8;14)(q24;q32); IGH@-MYC or variant MYC translocation

  • Mantle cell lymphoma with t(11;14)(q13;q32); CCND1-IGH@

  • ALK(+) DLBCL with t(v;2p23); ALK1

Viral Oncogenic Role

  • Epstein-Barr virus (EBV) in Burkitt lymphoma and plasmablastic lymphoma



  • Circulating tumor cells in CLL/SLL, B-PLL, SMZL, HCL, MCL

  • Occasional circulating tumor cells in myeloma, LPL, FL, BL

  • Distinctive morphology

    • CLL/SLL: Small, clumped chromatin, scant cytoplasm

    • B-PLL: Prominent central nucleoli

    • HCL: Reniform nucleus, circumferential cytoplasmic projections

    • SMZL: Round nucleus, polar villous projections

    • LPL: Spectrum of lymphoid, lymphoplasmacytic, and plasma cells

    • Myeloma: Plasma cells

    • FL: Small, deeply clefted nuclei, scant cytoplasm

Bone Marrow

  • Distinctive patterns of involvement depending on B-cell leukemia, lymphoma, or PC subtype

    • Focal nonparatrabecular

      • CLL/SLL

    • Focal paratrabecular

      • FL, MCL

    • Diffuse/interstitial

      • B-PLL, HCL, LPL, DLBCL, BL

    • Sinusoidal

      • SMZL, intravascular LBCL



  • Pan B-cell antigens: CD19, CD20, CD79-α

  • Plasma cell-associated antigens: CD38, CD138, cytoplasmic κ, cytoplasmic λ, MUM1

  • Germinal center associated antigens: CD10, Bcl-6

  • ALK

  • EBER

  • Annexin-A1; hairy cell leukemia (HCL)

  • Cyclin D1; mantle cell lymphoma, HCL, PCM

Flow Cytometry

  • Assess surface/cytoplasmic light chain restriction

  • Assess aberrant/restricted antigen expression; CD5, CD10

  • Discriminate mature from immature; CD34, TdT


  • PCR

    • Clonal IGH@ in mature B and PC neoplasms


  • For diagnosis

    • t(14;18)(q32;q21); BCL2-IGH@

      • FL

      • Subset of DLBCLS

      • Subset of double-hit lymphomas

    • t(8;14)(q24;q32); MYC-IGH@ or variant (Ig-MYC)

      • BL

      • Double-hit lymphomas

      • Subset of progressive B-cell lymphomas and myeloma

    • t(11;14)(q13;q32); CCND1/IGH@

      • MCL

  • For prognosis

    • CLL

      • Deletion TP53, ATM, 13q14, 13q34, IGH@ translocations, and trisomy 12 by FISH

    • Plasma cell myeloma

      • Conventional cytogenetics: Hyperdiploid favorable; hypodiploid less favorable

      • FISH: TP53 (17p13) deletion, t(14;16), t(4;14) less favorable

    • Double-hit lymphoma

      • Presence of t(14;18)(q21;q32) and t(8;14) (q24;q32), or t(8;14) and other BCL2 or BCL6 translocation

      • Highly aggressive


Nonneoplastic B-cell or Plasma Cell Proliferations

  • Chronic infection

  • Chronic immune response

  • Collagen vascular diseases

Benign Lymphoid Aggregates

  • Predominance of CD3(+) T cells or equal numbers of CD20(+) B cells/CD3(+) T cells

  • No aberrant antigen expression on B cells

  • Nonclonal

Immature B-cell Process

  • B lymphoblastic leukemia/lymphoma

    • CD34(+), TdT(+), sIg(-), CD45 weak(+) or (-)

Benign Hematogones

  • Characteristic dense nuclear chromatin

  • May mimic mature leukemias/lymphomas

  • Characteristic B-cell maturation pattern by flow cytometry

Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Overview and Classification of Mature Leukemias, Immunosecretory Lymphomas
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