Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (371 page)

Suggested Reading

Swerdlow SH, Webber SA, Chadburn A, et al. Post-transplant lymphoproliferative disorders. In:
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
, 4th ed. Lyon, France: International Agency for Research on Cancer; 2008:343–349.

LYMPHOPLASMACYTIC LYMPHOMA (LPL)/WALDENSTRÖM MACROGLOBULINEMIA (WM)

   Definition

LPL/WM results from the accumulation, predominantly in the bone marrow, of clonally lymphoplasmacytic cells that secrete a monoclonal IgM protein, resulting in elevated serum IgM paraprotein. Most cases of LPL are IgM associated, a few secrete IgA or IgG, and some are nonsecretory, hence falling outside the classical denomination of WM. Clinically, classical WM can be distinguished from lymphoplasmacytic lymphoma on the basis of symptoms of hyperviscosity. However, there seems no rationale for separating these entities. We will use the terms interchangeably, as LPL/WM. The term LPL/WM should be reserved for a distinct neoplasm of small lymphoid cells that are CD5
⁻
, CD10
⁻
, CD23
⁻
, and have a pan-B-cell marker– positive phenotype. There is variable involvement of bone marrow, lymph nodes, and spleen. Monoclonal gammopathy of undetermined significance (MGUS) of IgM class (defined as <10% marrow infiltration and <3 g/dL of serum monoclonal IgM) and smoldering WM (defined by the presence of ≥3 g/dL IgM and/or ≥10% lymphoplasmacytic infiltration, but no evidence of end-organ damage) have been associated with an increased risk of developing LPL/WM.

   Who Should Be Suspected?

Patients with lymphadenopathy, hepatosplenomegaly, oronasal bleeding, and constitutional symptoms (weakness, fatigue, weight loss, fever, night sweats, recurrent infections—especially pneumonias with pleural effusion). The presentation may be characteristic of the hyperviscosity syndrome: blurring or loss of vision, headache, vertigo, dizziness, diplopia retinal vein engorgement and flame-shaped hemorrhages, and papilledema.
Severe hyperviscosity is a medical emergency.
Patients with type I or II cryoglobulinemia and cold agglutinin hemolytic anemia should also be investigated for LPL/WM. The disease may also present with pulmonary symptomatology or with CNS infiltration (Bing-Neel syndrome).

   Laboratory Findings

   
CBC

   Red cells: Moderate to severe normochromic, normocytic anemia with rouleaux formation on the peripheral blood smear (PBS). The anemia is multifactorial, in part due to bone marrow infiltration, but to a large extent being the result of red cell dilution by increased plasma volume. Autoimmune hemolytic anemia may develop on the basis of cold or warm antibodies.

   WBC: Lymphocytosis or monocytosis is common. Occasionally, leukopenia is present.

   Platelets: Thrombocytopenia may be present; it is occasionally immune in etiology. Platelet function is impaired secondary to coating of the platelet surface receptors by IgM paraproteins, resulting in impaired platelet adhesiveness. Platelet aggregation may show a thrombocytopathy.

   
Immunoglobulins

   Serum protein electrophoresis reveals a homogenous spike (M component), almost always of γ mobility.

   Total serum protein and globulin are markedly increased.

   Quantitation of immunoglobulins reveals increased IgM (>30 g/L in most cases, but no specific cutoff is required for the diagnosis). There is reciprocal decrease of IgG and of IgA. Serial quantitation of serum IgM is used to monitor the effect of therapy or disease progression.