Low level monoclonal B-lymphocyte populations are not associated with an
absolute lymphocytosis and usually comprises less than 1% of the cellular
events analyzed by flow cytometry.
Low level monoclonal B-lymphocyte populations are usually an incidental
finding and persistent in most patients.
One study reported that at least 29% of their cases having small clonal
B-lymphocyte populations represented manifestations of early or clinically
occult NHL but the true risk of progression to overt NHL is unknown and
may take several years to develop.
It would be prudent to monitor a patient’s CBC and general health
at least yearly. Repeat flow cytometric analysis would be dependent on
a change in the patient’s condition, suggesting progression, but
is ultimately at the discretion of the treating physician.
In recent years, flow cytometric analysis of the blood and bone marrow
has become a standard of practice for the evaluation of patients having
hematologic abnormalities, primarily for the identification of hematolymphoid
neoplasms. Multiparameter flow cytometry instrumentation and analysis
software has made it possible to identify small populations of circulating
monoclonal B-lymphocytes in patients with non-Hodgkin lymphoma, as well
as, in patients who are healthy and asymptomatic with no clinical evidence
of lymphoma. The latter group is characterized by the presence of a low
level monoclonal B-lymphocyte population, which is not associated with
an absolute lymphocytosis and usually comprises less than 1% of the cellular
events analyzed by flow cytometry.
The identification of a small clonal B-cell population is almost always
an incidental finding when a patient’s bone marrow or peripheral
blood is being evaluated by flow cytometry for an unrelated reason. The
clonal B-lymphocyte populations are usually persistent in most patients.
They may have a CLL-like immunophenotype characterized by the expression
of CD5 and CD23, or they may exhibit a variety of non-CLL phenotypes,
including: CD5-/CD10-, CD5+/CD23-, CD10+, CD25+/CD103+ (hairy cell-like),
and CD5+/CD23-/FMC7+ (mantle cell-like). The CLL-like phenotype is the
most common, reported to be present in 3.5%-5.5% healthy adults or elderly
persons with normal blood counts, while the non-CLL phenotypes have been
reported in 1%-1.4% of healthy individuals.
The cause and clinical significance of these populations is unknown but
they should not be ignored as evidenced by one study which reported that
at least 29% of their cases having small clonal B-lymphocyte populations
represented manifestations of early or clinically occult NHL. The true
risk of progression to overt NHL is unknown however and may take several
years to develop, if at all, similar to monoclonal gammopathies of undetermined
significance. Some of these populations may be associated with autoimmune
diseases or be age-related. Although no name has been given to this enitiy,
it is perhaps appropriate to use the term, “monoclonal B-lymphocytes
of undetermined significance.”
The clinician having a patient with this finding must address important
two issues. The first is to assess whether the patient has any evidence
of a lymphoproliferative disease. This will require a thorough evaluation,
the extent of which will have to be determined on a case by case basis
and depend on several factors. None the less there will need to be correlation
with the clinical history and physical findings, as well as, the peripheral
blood and bone marrow morphology to determine if there is an underlying
lymphoproliferative disorder that would account for the clonal B-lymphocytes.
If after a thorough evaluation no underlying cause is found, then it is
probably safe to assume that the clonal lymphocyte population is of uncertain
significance and that periodic monitoring of the patient is warranted.
If a patient has a history of NHL, the immunophenotype of the clonal B-lymphocyte
population must be correlated with that of the lymphoma to determine if
it is the same process.
The second issue is how often to monitor the patient for possible progression
or resolution. Given that the risk of progression to clinical disease
is unknown and probably infrequent, it would be prudent to monitor a patient’s
CBC and general health at least yearly. Repeat flow cytometric analysis
would be dependent on a change in the patient’s condition, suggesting
progression, but is ultimately at the discretion of the treating physician.
Chen W, Asplund S, McKenna R, & Kroft, S. Characterization of Incidentally
Identified Minute Clonal B-Lymphocyte Populations in Peripheral Blood
and Bone Marrow. Am J Clin Pathol. 2004;122 (4):588-595
Rawstron AC, Green MJ, Kuzmicki A, et al. Monoclonal B lymphocytes with
the characteristics of “indolent” chronic lymphocytic leukemia
are present in 3.5% of adults with normal blood counts. Blood. 2002; 100:635-639
Ghia P, Prato G, Scielzo C, et al. Monoclonal CD5+ and CD5– B-lymphocyte
expansions are frequent in the peripheral blood of the elderly. Blood.