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Case 274 - Discussion

Uploaded: 2012-10-18, Updated: 2012-10-18

 
CD20 CD138
kappa Lambda
   

 

Lymphoplasmacytic Lymphoma

/ Waldenström's Macroglobulinemia

 

CLINICAL FEATURES

  • Spectrum of small B cells, plasmacytoid lymphocytes, and plasma cells

  • Associated with an IgM gammopathy

  • ~ 5% of B-cell lymphoproliferative disorders, slight male predominance, median age 60-65 years

  • Maybe associated with HCV infection

  • Bone marrow consistently involved, and extensive replacement can result in peripheral cytopenias. Lymph node and spleen may be also involved

PERIPHERAL BLOOD FINDINGS

  • Lymphocytosis, but not significantly elevated

  • Tumor cells are small, with condensed nuclei and inconspicuous nucleoli. A subset of lymphocytes can demonstrate plasmacytoid cytoplasmic features characterized by eccentric nuclei and slightly more abundant basophilic cytoplasm. Rare plasma cells may be seen

  • Red blood cell rouleau formation

BONE MARROW FINDINGS

  • Aspirate smear: a spectrum of small round lymphocytes, plasmacytoid lymphocytes, and plasma cells.

  • Trephine biopsy:

    • May form ill-defined patchy interstitial collections, nodular aggregates, loose paratrabecular foci, interstitial or even diffuse sheet infiltration

    • Mixed small lymphocytes, plasmacytoid lymphocytes and plasma cells with scattered centroblasts or immunoblasts

    • Dutcher bodies (intranuclear pseudoinclusions of immunoglobulin) frequently found in plasma cells and lymphocytes

    • Increased mast cells in the marrow

LYMPH NODE FINDINGS

  • Paracortex and perisinusoidal distribution, spotty or subtle, preserved nodal architecture with patent trabecular sinuses

  • Or, replacement of lymph node by a vaguely nodular or more diffuse effacing pattern

  • Lack of proliferation center foci as noted in SLL or monocytoid/marginal zone cytologic features as seen in MZL

  • Small lymphocytes and varying numbers of plasma cells. Plasma cells in small, distinct clusters or admixed with small lymphocytes. Scattered centroblasts or immunoblasts, but may be predominant (5-10%) with polymorphous morphology

  • Dutcher bodies common

  • Mast cells common

  • Hemosiderin deposition typically noted

  • Rarely, abundant epithelioid histiocytes with a nonnecrotizing granulomatous appearance

  • Rarely, extracellular immunoglobulin or amyloid deposition

  • Generally low mitotic rate

SPLEEN FINDINGS

  • Mainly involve white pulp manner with patchy red pulp lymphoid aggregates

  • Lack of monocytoid features or marginal zone growth pattern as seen in SMZL

IMMUNOPHENOTYPE

  • Positive: pan–B-cell antigens, CD19, CD20, CD22, CD79a, PAX5

  • A significant subset of cases can coexpress CD5 or CD23, or both

  • Plasma cells positive for CD138,  MUM-1 (IRF4), and CD19+

CYTOGENETICS AND GENETICS

  • 6q−,  most common abnormality in LPL, 40 - 60% of cases

DIFFERENTIAL DIAGNOSES

  • Reactive conditions

    • Autoimmune diseases or infectious processes can result in significant plasmacytosis in both lymph nodes and bone marrow

    • IgG4-associated sclerosing disease: lack of a clonal B-cell and plasma cell population,  presence of increased serum IgG4

    • Castleman's disease, plasma cell type: may demonstrate some features reminiscent of LPL in lymph nodes, especially when shows interfollicular plasmacytosis. Castleman's disease can be associated with monoclonal plasma cells, but lack of a monoclonal B-cell component

  • MZL

    • Often exhibits plasmacytic differentiation and shares a relatively nonspecific B-cell immunophenotype with LPL

    • Rarely associated with the clinical features of WM and IgM paraprotein production

    • Monocytoid features, follicular colonization and lymphoepithelial lesions

    • Extranodal cases may have BIRC3 (API2), BCL10, and MALT1 translocations

  • Gamma heavy-chain disease (GHCD)

    • Very rare and considered as a variant of LPL

    • LPL-like infiltrates involving lymph nodes, spleen, liver, bone marrow, and blood, with resultant lymphadenopathy and hepatosplenomegaly

    • Common autoimmune cytopenias and peripheral eosinophilia

    • Secrete gamma immunoglobulin heavy chains without light chains

    • Infiltration of a variable population of small lymphocytes, centroblasts, plasma cells, and eosinophils, which mimics classical Hodgkin's lymphoma or peripheral T-cell lymphoma

    • More aggressive than typical LPL/WM

  • IgM MGUS

    • IgM monoclonal protein < 3 g/dL

    • Absence of histopathologic bone marrow involvement (<10%) by a lymphoid or plasmacytic neoplasm

    • Risk of developing B-cell malignancies over time, particularly LPL/WM and, to a lesser extent, CLL/SLL

  • Multiple myeloma, IgM type

    • Extremely rare, ~1% of de novo cases

    • Similar presentation to non-IgM plasma cell tumors, with osteolytic lesions and hypercalcemia

    • No lymphoid marrow infiltration, concurrent monoclonal B-cell population, peripheral lymphadenopathy, or splenomegaly

TREATMENT AND PROGNOSIS

  • Low grade, median overall survival approximately 5 years
  • Complications of cytopenia, hyperviscosity, and bleeding
REFERENCES
  • Hematopathology, 2011. By Elaine Sarkin Jaffe, MD, Nancy Lee Harris, James Vardiman, MD, Elias Campo, MD and Daniel MD Arber, MD