Lymphoma & related disorders

• Lymphoplasmacytic lymphoma (LPL) is a B cell neoplasm of small lymphocytes, plasmacytoid lymphocytes and plasma cells
• Usually involves bone marrow, sometimes lymph nodes and spleen
• Does not fulfill the criteria for any other small B cell lymphoid neoplasm
• Waldenström macroglobulinemia (WM): lymphoplasmacytic lymphoma involving the bone marrow associated with IgM monoclonal paraprotein of any concentration in the blood

• Blood
  • Often shows lymphocytosis with a spectrum of lymphocytes, plasmacytoid lymphocytes and plasma cells
  • Rouleaux formation of red blood cells is routinely seen
  • Cold agglutinin or cryoglobulin may be present
• Bone marrow (Arch Pathol Lab Med 2013;137:580)
  • Involvement in almost all cases
  • Aspirate is the most helpful sample in morphologic diagnosis
    • Predominantly small lymphocytes with a variable number of plasmacytoid lymphocytes and plasma cells
    • Mast cells are typically increased; most prominent within particles on aspirate smears
  • Core biopsy (Am J Surg Pathol 2005;29:1549, Am J Clin Pathol 2015;143:797)
    • Most common pattern is the combination of paratrabecular and nonparatrabecular lymphoid nodules
    • Less common patterns include paratrabecular or intrasinusoidal with or without interstitial infiltrate
    • Pseudointranuclear (Dutcher bodies) and intracytoplasmic inclusions (Russell bodies) are most prominent on core biopsy section
    • Amyloid deposition may be present within vessel walls or interstitial deposits
• Lymph node (Arch Pathol Lab Med 2013;137:580)
  • 2 main patterns of nodal involvement
    • Classic pattern
      • Subtotal architecture effacement
      • Retention of small primary or enlarged reactive follicles
      • Patent dilated sinuses
      • Interfollicular areas contain monomorphous infiltrate of small lymphocytes, plasmacytoid lymphocytes and plasma cells
      • Dutcher bodies, increased number of mast cells and hemosiderin deposition may be present
    • Polymorphous pattern
      • Complete architectural effacement
      • Nodular to diffuse polymorphous infiltrate
        • Small lymphocytes
        • Plasmacytoid lymphocytes
        • Plasma cells
      • Greater numbers of large transformed cells
      • Clusters of epithelioid histiocytes may be conspicuous
        • Termed polymorphous immunocytoma
    • Extracellular immunoglobulin in the form of amyloid may be present
• Spleen (Am J Surg Pathol 2003;27:1104)
  • Not well described
  • Older published series and review
    • Presence of nodular and diffuse infiltrates of lymphoplasmacytic cells involving red pulp
    • Spectrum of lymphoma cells analogous to bone marrow
    • Sparing of white pulp with absence of marginal zone growth pattern

Contributed by Ling Zhang, M.D.

Contributed by Ling Zhang, M.D. and Caroline An, M.D.

Contributed by Ling Zhang, M.D.

• IgM monoclonal gammopathy of undetermined significance (IgM MGUS):
  • All 3 criteria must be met
    • Serum IgM monoclonal protein < 3 gm/dL
    • Bone marrow lymphoplasmacytic infiltration < 10%
    • No evidence of anaemia, constitutional symptoms, hyperviscosity, lymphadenopathy or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder
• IgG and IgA MGUS:
  • More closely related to plasma cell myeloma
  • Negative for MYD88
• Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma:
  • B cell lymphoma composed of small mature forms
  • Often coexpresses dim CD20, CD5 and CD23 by flow cytometry
  • Frequent nodal presentation with generalized lymphadenopathy, vaguely nodular proliferation with identifiable pseudoproliferation centers; the latter is lacked in LPL / WM
  • Frequent peripheral involvement, mature lymphocytosis with clumped chromatin (soccer ball chromatin pattern), > 5,000/uL neoplastic B cells, CLL phenotype is required to diagnose CLL
  • Usually negative for MYD88 mutation
• Marginal zone lymphoma (MZL):
  • B cell lymphoma with monocytoid or plasmacytoid differentiation
  • Immunophenotypically similar to LPL / WM, triple negative for CD5, CD10 and CD23
  • Bone marrow involvement: mostly interstitial and intrasinusoidal infiltration pattern
  • Lymph node, spleen and extranodal involvement might not be easy to distinguish it from LPL / WM
  • Presence of MYD88 L265P mutation favors LPL / WM over MZL
  • Plasmacytoid differentiation with Dutcher bodies is less frequently in MZL than in LPL

Which of the following immunoglobulins is most commonly seen in lymphoplasmacytic lymphoma?

1. IgA
2. IgD
3. IgE
4. IgG
5. IgM

E. IgM. More than 90% of patients with LPL / WM show an overt elevated IgM level. Answer A is incorrect because non-IgM LPL / WM, mainly IgM or IgA, is reported in ~5% of cases. Answer D is incorrect because concurrent IgM and IgG LPL is rarely reported. Answers B and C are incorrect because IgD and IgE LPL / WM might occasionally exist but have not been well reported.

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Reference: Lymphoplasmacytic lymphoma

What somatic mutation is associated with lymphoplasmacytic lymphoma and can aid in diagnosis?

1. BCL2
2. BRAF
3. KRAS
4. MYD88 L265P

D. MYD88 L265P. MYD88 is considered the driver mutation and detected in 93 - 97% of patients with LPL / WM. The particular mutation leads to constitutive activation of NFkB pathway. While answer D is correct, be cautious, as the presence of MYD88 is not 100% specific for LPL / WM. The mutation has also been found in monoclonal gammopathy of unknown significance (MGUS), diffuse large B cell lymphoma, activated B cell (DLBCL ABC) type, etc. Integrating with other clinical and pathologic results is necessary for an accurate diagnosis. Answers A - C are incorrect because other mutations are infrequently reported in LPL / WM and are not helpful for diagnosis.

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Reference: Lymphoplasmacytic lymphoma