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1352 Part X: Malignant Myeloid Diseases Chapter 87: Myelodysplastic Syndromes 1353

of anemia. A small proportion of patients have infections related to and bactericidal capability may be impaired. 239–241 Formyl-leucyl-
216
severe neutropenia or neutrophil dysfunction, or hemorrhage related methionyl-phenylamine receptor signaling and actin polymerization
to severe thrombocytopenia or platelet dysfunction at the time of diag- can be abnormal. 242,243 Muramidase (lysozyme) activity in blood and
nosis. Patients with severe depressions of neutrophil and platelet counts urine may be increased, reflecting granulocytic hyperplasia, heightened
at diagnosis usually have more advanced disease. Rarely, patients have monocytopoiesis, and monocyte turnover.
fever unrelated to infection. Arthralgia is the initial complaint in some
patients. The presentation, infrequently, can mimic a rheumatologic Platelets
disease. Hepatomegaly or splenomegaly occurs in approximately 5 or Approximately 25 to 50 percent of patients have mild to moderate
10 percent of patients, respectively. thrombocytopenia at the time of diagnosis. 228,234 Mild thrombocyto-
sis also can occur. 228,234 Platelets may be abnormally large, have poor
granulation, or have large, fused central granules (see Fig. 87–3H). 244,245
LABORATORY FEATURES Abnormal platelet function can contribute to a prolonged closure time,
easy bruising, or exaggerated bleeding. Decreased platelet aggrega-
BLOOD tion in response to collagen or epinephrine is a frequent functional
Red Cells abnormality. 246
Anemia is present in greater than 85 percent of patients. 217–219 In approx-
imately 4 percent of patients, the anemia results from erythroid apla- Lymphocytes
sia. Mean cell volume often is increased. Red cell shape abnormalities Patients with clonal hemopathies may have immunologic deficiencies,
220
include oval, elliptical, teardrop, spherical, and fragmented cells. Red such as a decrease in NK cells in the blood but no decrease in LGLs, 247–250
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cell findings occur in a spectrum. Some patients have only slight aniso- a decrease in helper T lymphocytes, and a decrease in Epstein-Barr
cytosis. Elliptical red cells sometimes dominate. Basophilic stippling virus receptors on B lymphocytes. 248–251 Antibody-dependent cellu-
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of red cells occurs (see Fig. 87–3). Nucleated red cells are seen in the lar cytotoxicity is normal. Thymidine incorporation after mitogenic
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blood film in approximately 10 percent of cases. Reticulocyte counts stimulation 252,253 and colony growth of T lymphocytes are decreased.
253
are low for the degree of anemia. Other abnormalities of red cells occur, Lymphocytes may have an increased sensitivity to irradiation. The
such as an increased proportion of hemoglobin F and decreased red defects in lymphoid cells could reflect the level of the somatic muta-
221
cell enzyme activities, especially acquired pyruvate kinase deficiency. tion in a primitive multipotential cell in different cases. Intrinsic, rather
222
Hemolysis has occurred in some patients with the latter deficiency. than secondary, alterations in lymphocytes are determined by whether
Enhanced sensitivity of membranes to complement and modification no lymphocytes are generated from the clone, B cells are part of the
223
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of red cell blood group antigens may be observed. Acquired hemo- clone, or B and T cells are part of the clone. Clonally derived, CD8+C-
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globin H disease, a rare superimposition, results in red cell morphology D57+CD244+CD28–CD62L– T lymphocytes are present in marrow
similar to thalassemia (microcytosis, anisocytosis, basophilic stippling, and to a lesser extent in blood in approximately 50 percent of patients,
poikilocytosis with target cells, fragmented cells, and teardrop cells). independent of type of MDS, age, and sex of the patient, 255,256 as are NK
Intracellular precipitates of β-chain tetramers (identified by crystal vio- and B cells (see “Pathogenesis” above). 256
let stain) reflect an acquired decrease in the rate of α-chain synthesis
in erythroblasts. 225–227 The decrease in α-globin–chain synthesis is pro- PLASMA ABNORMALITIES
found, involves each of the four α-chain loci, and results from a tran- Serum iron, transferrin, and ferritin levels may be elevated as a result
scription abnormality. No gross alterations in genes (e.g., insertions, of anemia and the shift of erythron iron to plasma and storage com-
deletions) are seen in these cases. Acquired hemoglobin H disease in partments. Lactic dehydrogenase and uric acid concentrations can be
227
this setting has been dubbed the α-thalassemia–myelodysplastic syn- increased as a result of ineffective hematopoiesis and a high death frac-
drome and is the consequence of acquired mutations in ATRX, the gene tion of maturing marrow precursors. Monoclonal gammopathy, poly-
associated with the X-linked α-thalassemia/mental retardation (ATR-X) clonal hypergammaglobulinemia, and hypogammaglobulinemia each
syndrome. 225
occur with increased frequency. 257,258 The frequency of autoantibodies
was increased in one report but not in another. β -Microglobulin
258
240
2
Granulocytes and Monocytes serum levels are increased in proportion to the prognostic category of
Neutropenia is present in approximately 50 percent of patients at the the disease. 259
time of diagnosis. The proportion of monocytes often is increased,
228
and monocytosis per se can be the dominant manifestation of the
hematopoietic abnormality for months or years. 229–231 Morphologic MARROW
abnormalities of neutrophils can occur, sometimes resulting in the Cellularity
acquired Pelger-Huët anomaly (see Fig. 87–3E). In this condition, Marrow cellularity usually is normal or increased. 234,260,261 Cellularity
neutrophils have very condensed chromatin and unilobed or bilobed is decreased in approximately 15 percent of cases and may simulate
260
nuclei that often have a pince-nez shape. The neutrophils may be in hypoplastic or aplastic anemia. However, islands of dysmorphic cells,
262
the process of apoptosis. Ring-shaped nuclei also can occur in neu- especially atypical megakaryocytes, usually are present (see Fig. 87–3L).
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trophils (see Fig. 87–3F). Neutrophil alkaline phosphatase activity is An increased proportion of blast cells in this setting suggests hypoplas-
233
decreased in some patients. Expression of normal surface antigens on tic myelogenous leukemia (Chap. 88).
234
neutrophils and monocytes is decreased, and abnormal surface anti-
gen expression occurs in some cases. Defective primary granules of Erythropoiesis
235
abnormal size and shape with decreased myeloperoxidase content can Erythroid hyperplasia is frequent. Very large or small erythroblasts,
be present. Specific neutrophil granules are often decreased in num- nuclear fragmentation, stippled erythroblasts, and poor hemoglobini-
236
ber, producing hypogranular cells. Neutrophil granule membranes zation may be seen. 234,260,261 Proerythroblasts may be present in excess,
237
frequently are deficient in glycoproteins. Chemotactic, phagocytic, and the marrow may lack normal clusters or islets of erythroblasts.
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Kaushansky_chapter 87_p1341-1372.indd 1353 9/21/15 11:05 AM