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Waldenström’s macroglobulinemia – a review
Rev Assoc Med B ras 2014; 60(5):490-499 493
to lymphoplasmacytic (42%), with predominantly small
lymphocytes and plasma cells. The polymorphic state
(11%) is characterized by a broad spectrum of these many
cells.
A high number of mast cells in the medullary infil-
trate is frequent, and this finding may help in the diffe-
rential diagnosis.
LPL may eventually evolve into a more aggressive
form of lymphoma such as as diffuse large B-cell lym-
phoma. 54 This evolution is accompanied by worsening
of clinical symptoms, with development of profound
cytopenia, organomegaly and extramedullary cellular
infiltration.54
In the peripheral blood, plasmacytoid lymphocytes
are sometimes observed, but leukemic symptoms are ra-
rely observed.
Immunophenotyping should be interpreted simul-
taneously, verifying its consistency with the results of a
bone marrow biopsy. In practice, IgM monoclonal gam-
mopathy associated with the expression of IgM on neo-
plastic B-lymphocytes with a CD19+, CD20+, CD5-, CD10-
and CD23- phenotype and intertrabecular pattern of bone
marrow infiltration is sufficient for the diagnosis of MW 16
(Table 1). Nevertheless, the phenotypic characteristics are
not always typical and in about 10-20% of cases positivity
for CD5, CD10 or CD23 has been described.17.55,56 Other
common phenotypic features which are not specific but
may be useful for the differential diagnosis with other
lymphoproliferative diseases are the expression of sIgD,
CD22, CD79a, PAX5, Bcl2, FMC7, CD25 and CD27 and
the absence of expression of BCL6, CD103 , CD138, CD56
and CD75. Some of these markers are particularly useful
for studying the bone marrow infiltrate in the bone biopsy
through immunohistochemical and other studies for the
immunophenotypic characterization of B-lymphocytes
by flow cytometry.
Extramedullary infiltration is uncommon, and may
affect the articular and periarticular structures, gastroin-
testinal tract, lungs, kidneys, skin, eyes and central ner-
vous system.17,27,42
The symptoms of malabsorption, diarrhea, obstipa-
tion or bleeding may indicate involvement of the gastroin-
testinal tract.43-46 Some patients have cellular infiltration
at the pulmonary parenchymal level,47,48 being coughing
the most common symptom, followed by dyspnea and
chest pain. Renal infiltration has also been reported,49 as
well as cutaneous infiltration (maculopapular lesions,
plaques or nodules)7,50 and infiltration of periorbital struc-
tures, such as the tear gland and retro-orbital lymphoid
tissue (ocular tremors).51,52
The infiltration of malignant cells in the central
nervous system is responsible for a rare neurological
disorder called Bing-Neel syndrome. Associated symp-
toms are nystagmus, diplopia, vertigo, memory loss,
mental confusion, motor dysfunction and eventually
coma.17,53
Diagnosis
Table 1 presents the diagnostic criteria for WM. The de-
tection of IgM monoclonal gammopathy is important
for diagnosis, but the serum concentration presents a
great variability between individuals.16
For diagnosis, a bone marrow biopsy is crucial to as-
sess the extent of neoplastic infiltration, the infiltration
pattern and cellular morphology. In WM, medullary in-
filtrate consists of a monoclonal cellular population of
small B-lymphocytes, in different maturation stages: small
lymphocytes, lymphoplasmocytoid lymphocytes and plas-
ma cells.
The level of differentiation of the infiltrate is varia-
ble, ranging from lymphoplasmocytoid (47% of cases),
consisting of small cells and plasmacytoid lymphocytes,
Table 1Clinical and laboratory characteristics of Waldenström’s macroglobulinemia
IgM monoclonal gammopathy of varying concentration
Bone marrow biopsy: ≥10% infiltration by small B-lymphocytes with plasmacytoid/plasmacytic differentiation
Bone marrow biopsy: generally intertrabecular infiltration pattern
Immunophenotyping of B-lymphocytes: CD19+, CD20+, CD5- , CD10-, CD23 -, sIgM+ (monoclonal)
Other immunophenotypic characteristics of neoplastic B-lymphocytes: sIgD+, CD22+, CD79a+, PAX5+, Bcl2+, FMC7+, CD25 +, CD27 +, BCL6 -,
CD103- , CD138-, CD56 -, CD75-
Cytogenetic studies: over 50% of cases present deletions (del) 6q
sIgM – Surface immunoglobulin M.
Note: Immunophenotypic variations may occur. Other lymphoproliferative diseases, including marginal zone B-cell lymphoma, chronic lymphocytic leukemia and mantle cell lymphoma should be
excluded.