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

• Hematopathology, 2011. By Elaine Sarkin Jaffe, MD, Nancy Lee Harris, James Vardiman, MD, Elias Campo, MD and Daniel MD Arber, MD