Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (359 page)

   Who Should Be Suspected?

An elderly patient with persistent monocytosis of >3 months’ duration and massive splenomegaly in 25% of cases. Hepatomegaly, lymphadenopathy, tissue infiltrations, or serous effusions may also be presenting findings.

   Laboratory Findings

   
CBC
: One, two, or all three lineages present dysplastic features.

   RBC: Severe anemia is common.

   WBC: Persistent absolute monocyte count of >1,000/μL (>10% of leukocytes) in the peripheral blood. The monocytes may be morphologically normal or may have dysplastic features. In cases without dysplasia, other causes of monocytosis must be excluded. Neutropenia or neutrophilia may also be present, but neutrophil precursors account for <10% of the leukocytes. They may have dysplastic features. In some cases, eosinophilia is present (CMML with eosinophilia).

   
Platelets
: Moderate thrombocytopenia with atypical, large platelets may be present.

   
Bone marrow
is hypercellular with striking granulocytic and to a less extent monocytic proliferation. Esterase stains distinguish the monocytic line. There are <20% blasts. An increase in erythroid precursors with dyserythropoietic features may also be present. Abnormal megakaryocytes complete the morphologic picture. Lysozyme (muramidase) activity may be elevated in blood and urine.

   
Immunophenotype
: Myeloid antigens CD33 and CD13 are positive; monocytic antigens CD14, CD68, and CD64 are variably expressed. Aberrant features are frequently present. An increasing CD34 population forecasts transformation into acute leukemia.

   
Immunostain
for lysozyme on tissue sections is positive for the monocytic cells.

   
Cytogenetics
: Nonspecific clonal cytogenetic abnormalities are found in 20–40% of patients. The most frequent abnormalities are +8, −7/del(7q), and structural abnormalities of 12p. Some patients with t(5;12)(q33;p13) may have eosinophilia and may respond to therapy with tyrosine kinase inhibitors. This group of patients is no longer included in the CMML category, since they result from fusions of PDGFRB with other genes (see above).

   
Genetic studies
: PDGFRA or PDGFRB are not rearranged. Rearrangements must be excluded in cases with eosinophilia. The BCR-ABL 1 fusion gene must be excluded.

Suggested Reading

Itzykson R, Kosmider O, Renneville A, et al. Clonal architecture of chronic myelomonocytic leukemias.
Blood.
2013;121:2186–2198.

SPLENOMEGALY

   Definition