Page 58 - Williams Hematology ( PDFDrive )

34 Part I: Clinical Evaluation of the Patient Chapter 3: Examination of the Marrow 35

After the low-power survey, the films should be examined at neutrophils have two to four lobes. Basophil nuclei may be obscured by
higher power and under oil-immersion magnification to determine the the abundant basophilic granules.
various hemopoietic cell types present and assess adequacy of differen-
tiation in each hematopoietic lineage. For most diagnostic questions, MONOCYTES
careful and systematic visual examination of the marrow is sufficient
to assess differentiation, but a marrow differential cell count can be Monocytes in normal marrow are identical morphologically to those in
performed to quantify blasts or other abnormal cells. Based on the the blood. Promonocytes (Chap. 67) have delicate lace-like chromatin
diagnostic question at issue, the marrow differential count may require similar to a monoblast, but with indented or convoluted nuclear out-
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examination of 300 to 500 nucleated cells. Table 3–1 lists the normal line. These are important cells to identify as they are considered blast
values for these determinations, including data for infants from birth equivalents in the evaluation of myelodysplastic syndrome (MDS) and
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to age 18 months. Between birth and age 1 month, lymphocytes acute leukemia.
increase and erythroid and granulocytic precursors decrease. After 1
month, the marrow differential count varies little to age 18 months, MACROPHAGES (HISTIOCYTES)
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the duration of the study. The proportion of segmented neutrophils
increases with large volumes of aspirate, probably because of dilution of These cells are derived from monocytes but are larger, reaching 20 to
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marrow cells by mature granulocytes in the blood. The range of nor- 30 μm in the longest dimension (Chap. 67). The nucleus is oval with del-
mal for all cell types is broad, and differential counts and M:E ratios icate reticular chromatin and one or two small nucleoli. The cytoplasm
should be considered rough guides to the character of the marrow as a ranges from blue-gray to pale and colorless, and often contains phago-
whole. cytosed cells, degenerating cell debris, and vacuoles. Normally, intact
Progenitors of all lineages typically are unremarkable cells with- red cells are rarely visible inside marrow macrophages. Erythrophago-
out distinctive morphologic attributes. Precursors and mature cells of cytic macrophages are a feature of autoimmune hemolytic anemia,
the hematopoietic lineages show characteristic diagnostic morphologic hemophagocytic lymphohistiocytosis (HLH), a severe uncontrolled
changes as described below. Further details of the morphology of these hyperinflammatory reaction that can occur in a variety of clinical set-
cells are discussed in the relevant specific chapters of this book as ref- tings, such as infection, neoplasia, and autoimmune disorders (where it
erenced below. is termed macrophage activation syndrome), in addition to certain rare
genetic disorders of cytotoxic granule function or immunodeficiency
states (Chap. 71).
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GRANULOCYTES
Granulocytes are precursors or mature forms of leukocytes character- ERYTHROID CELLS
ized by neutrophilic, eosinophilic, or basophilic granules in their cyto- During erythroid differentiation, the nucleus progressively becomes
plasm in the more mature stages of development. This series sometimes smaller and nuclear chromatin more condensed, as the cell’s prolifera-
is referred to as the myeloid series (Chap. 60). The overall trend is a grad- tive capacity decreases. The cytoplasm gradually loses the bluish color
ual decrease in nuclear size and enhanced clumping of nuclear chroma- imparted by RNA, which is replaced by the pink-staining hemoglobin.
tin as cells lose proliferative capacity, while granules of varying types Cells in the erythroid series are termed erythroblasts (previously the
progressively appear in the cytoplasm. term “normoblast” was used to distinguish the normal sequence from
The myeloblast is round and large, with a nucleus occupying most the sequence observed in megaloblastic anemia). These stages are arbi-
of the cell. The nuclear chromatin is very fine, and two to five nucleoli trary divisions within a continuum of differentiation. Chapter 31 pro-
are present. The cytoplasm is basophilic, but less so than the cytoplasm vides more detailed descriptions of normal red cell precursors.
of the erythroid series. Few azurophilic granules may be present. The The proerythroblast is a large, round cell measuring from 15 to
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promyelocyte is larger than the myeloblast, with a coarser chromatin, 20 μm in diameter. The nucleus occupies most of the cell and contains
but still containing nucleoli. The cytoplasm is basophilic with a clear nucleoli. The chromatin is present in a fine reticular or stippled pattern
Golgi area and a small number of prominent, large red granules—the but is usually more densely stained than the chromatin of the myeloblast.
primary, nonspecific, or azurophilic granules. The myelocyte is slightly The cytoplasm typically is more basophilic than the myeloblast. The
smaller than the promyelocyte, and is the most mature mitotic cell in basophilic, polychromatophilic, and orthochromatophilic erythroblasts
the myeloid lineage. Its nucleus is round or oval and often eccentrically are characterized by cytoplasm gradually changing from blue to gray to
located. The chromatin pattern is coarser than that of the promyelocyte, pink in color as hemoglobin is produced and RNA reduced. The erythro-
and nucleoli usually are not visible. The defining feature is the presence cyte is the mature anucleate red cell. Polychromatophilic erythrocytes are
of specific granules in the perinuclear cytoplasm, which identify the mature anucleate red cells that are just released from the marrow (corre-
cell lineage. The granules may be neutrophilic (fine, variable size, lilac sponding to early reticulocytes) and still have sufficient residual RNA to
color), eosinophilic (larger, round, orange–red), or basophilic (larger impart a slight grayish tinge to the cytoplasm (Chap. 32).
still, irregular in size, deep blue). The metamyelocyte is about the same
size as the myelocyte and resembles it closely, except that the nucleus
is indented, the chromatin is more coarse, and the cytoplasm is less EVALUATION OF IRON STORES
basophilic. The band cell is characterized by a nucleus that is horse- Marrow examination often should include evaluation of the iron
shoe shaped or lobular but is not narrowly segmented. The cytoplasm is stores, especially if the patient is anemic. The examination is accom-
yellowish–pink or nearly colorless with abundant lineage specific gran- plished by staining a marrow film or section by the Prussian blue tech-
ules. Segmented (polymorphonuclear) granulocytes differ from band cells nique. Because decalcification of marrow biopsy specimens results in
by the multilobed character of the nucleus. At least two separate lobes decreased recovery of stainable iron, a nondecalcified specimen or
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are defined by a complete rounded shape, whether or not the thin fila- aspirate should be stained when evaluating iron stores in the differen-
ment joining them is seen. Nuclear chromatin is very dense. The mature tial diagnosis of anemia. Marrow macrophages (seen best in the aspi-
eosinophil typically has only two lobes, whereas the nuclei of most rate particle preparation) are evaluated for storage iron (see Fig. 3–3),

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