Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (357 page)

   Laboratory Findings

   Findings vary with subtype of MDS (see above). Common findings will be described, as well as those distinguishing ones for various subtypes.

   
CBC
. Unilineage, bilineage, or trilineage cytopenias are common, but in the absence of dysplastic features, they are insufficient for the diagnosis of MDS.

   Red cells: commonly macrocytic anemia (high MCV); hypochromic, microcytic cells in RARS; ovalomacrocytosis; basophilic stippling; Howell-Jolly bodies; and megaloblastoid nucleated red cells may be present on peripheral blood smear (PBS).

   WBC: Leukopenia resulting from neutropenia is present at diagnosis in half the patients. Granulocytes have reduced or absent granulation, reduced segmentation of nuclei (pseudo-Pelger-Huet nuclei), clumped chromatin pattern, ring-shaped nuclei, and nuclear sticks. The granulocytes may be dysfunctional, leading to infections. Lymphopenia due to a reduction of T4 lymphocytes is seen in hypertransfused patients. Mild monocytosis is common, but if the monocytes are markedly elevated, consider CMML.

   Platelets: Varying degrees of thrombocytopenia are present at the time of diagnosis in about 25% of patients. Giant or agranular platelets can be seen on peripheral blood smear (PBS). Platelets may be functionally defective, and platelet aggregation is often abnormal. Thrombocytosis may be present in some patients with RARS; thrombocytosis is also part of the 5q
⁻
syndrome or in patients with translocations involving chromosome 3.

   
Bone marrow examination
is mandatory for diagnosis and classification of the MDS subtype. Marrow fibrosis can be seen in approximately 10% of the MDS cases, and it is usually associated with excess blasts and aggressive clinical course. In most cases, the bone marrow is hyperplastic, and erythroid hyperplasia, in association with ineffective erythropoiesis. The erythroid precursors show alterations in their nuclei. Approximately 10–15% of patients have a hypocellular marrow that is difficult to distinguish from aplastic anemia.

   Defective maturation in the myeloid series is common, and counting the number of blasts is essential to determine subtype and prognosis.

   Megakaryocytes are normal or increased in number; they sometimes occur in clusters. Abnormal morphology of megakaryocytes is common.

   Cytochemical stains of the bone marrow (especially iron stains of erythroblasts) are helpful in the diagnosis of the various subtypes of MDS.

   Immunophenotyping of the bone marrow is useful in determining percentage of CD34+ cells, which usually parallels the number of blasts on the aspirate smear. Assessment of maturation patterns of myeloid and monocytic elements can also provide supporting evidence for the diagnosis of MDS.

   
Cytogenetic studies
are helpful for diagnosis, may provide prognostic information, and are useful for monitoring response to therapy. Patients with the 5q
⁻
anomaly (isolated or in combination with other abnormalities) may be treated differently, as they often respond to immunomodulatory therapy. Clonal cytogenetic abnormalities are seen in approximately 50–75% of cases and are not specific to subtypes, although certain cytogenetic abnormalities may be associated with characteristic morphology, for instance the association of
EVI1
rearrangements at 3q26 with abnormal megakaryocytes. Recurrent abnormalities include
⁻
5/5q
⁻
,
⁻
7/7q
⁻
, trisomy 8, and 20q
⁻
. In the International Prognostic Scoring System (IPSS) for MDS, normal chromosomes,
⁻
Y, 5q
⁻
, and 20q
⁻
are considered good prognosis;
⁻
7/7q
⁻
or complex karyotype (≥3 abnormalities) are considered poor prognosis, and other findings are considered intermediate. Del(17p) is associated with the presence of pseudo-Huët granulocytes containing small vacuoles, a deletion of TP53, and a relatively high risk of leukemic transformation. Abnormalities of
MLL
at 11q23 often represent therapyrelated MDS and are associated with poor prognosis. Certain clonal cytogenetic abnormalities, for example,
⁻
Y and 20q
⁻
, are not diagnostic of MDS in the absence of positive morphologic findings.