Page 55 - Williams Hematology ( PDFDrive )

30 Part I: Clinical Evaluation of the Patient Chapter 3: Examination of the Marrow 31

a useful sample. An unspoken assumption is that the piece of marrow Cellularity of individual lineages is best assessed by examination of
provided for diagnostic evaluation is representative of the marrow as a the biopsy specimen. Erythroid cells typically are arranged in clusters,
whole. Based on reproducibility of bilateral biopsies, this more likely whereas megakaryocytes are scattered throughout the biopsy. Erythroid
is true in leukemia and myeloma than in lymphoma and metastatic and megakaryocytic cellularity is best appreciated at low power. In the
tumor. A biopsy specimen should contain at least a 0.5-cm length aspirate, a myeloid-to-erythroid (M:E) ratio frequently is calculated to
32
of marrow cavity. However, for detection of lymphoma or metastatic give some impression of the relative cellularity of these two major lin-
tumor, current recommendations suggest a biopsy length of 1.6 to 2.0 eages. As a rule of thumb, the M:E ratio normally should be between 2:1
33
cm. A significant proportion of biopsies obtained in routine practice and 4:1 (Table 3–1 lists the normal ranges in men and women). The rela-
may fall short of this recommended length. 34 tive proportions of cell types should be assessed only on the direct mar-
The marrow cavity was entered if the aspirate contains marrow row film, biopsy imprint, or particle preparation, not a concentrate film,
particles or hematopoietic precursors (e.g., megakaryocytes, nucleated which has been manipulated by centrifugation. A decreased M:E ratio
red cells) not found in the blood film. However, this finding does not can be interpreted as either myeloid hypocellularity or erythroid hyper-
ensure the specimen is adequate for diagnosis, because the amount of plasia, depending on the overall marrow cellularity. Megakaryocyte
marrow actually aspirated can vary significantly in disease states. Also, numbers can be assessed from the direct marrow aspirate film, where
some cell types, notably fibroblasts and metastatic tumor cells, are not at least five megakaryocytes should be present in the optimal portion of
as readily removed from the marrow space by aspiration as are normal the film. In the particle preparation, most large particles should contain
precursors. Lack of particles or precursor cells does not prove the mar- one or more megakaryocytes. Megakaryocyte number varies markedly
row cavity was not entered, because marrow packed with leukemic cells in direct marrow aspirate films of normal subjects and depends on the
or infiltrated with fibroblasts may yield few cells (“dry tap”). Marrow degree of admixture of the specimen with blood. Megakaryocytes are
35
aspirations resulting in a dry tap usually are a consequence of signifi- enriched at the feathered edge of concentrate films.
35
cant pathology (only 7 percent show normal histology on biopsy ) and
indicate the need to examine a biopsy specimen, which should include
a touch imprint. 21
INFILTRATIVE DISEASES OF THE MARROW
Malignant Neoplasms
MARROW CELLULARITY Metastatic nonhematopoietic tumor in the marrow biopsy is charac-
The “gold standard” for overall marrow cellularity is examination of an terized by disruption of the marrow architecture with groups of cyto-
adequate marrow biopsy specimen. The normal cellularity percentage logically abnormal cells. Assessment of the tissue of origin is primarily
36
of marrow space occupied by hematopoietic cells as opposed to fatty based on morphology, clinical history, and immunocytochemical stain-
and nonhematopoietic tissue of iliac crest marrow decreases from a ing. The tendency of carcinoma cells to form tightly adherent clusters
mean of 80 percent in early childhood to 50 percent by age 30 years, frequently is helpful in recognizing these neoplasms (Chap. 45). The
with further decreases after age 70 years. Consequently, marrow cel- clumps can appear on the marrow aspirate, but the aspirate is less sen-
37
lularity should be evaluated with reference to normal individuals of the sitive than the biopsy for detecting metastatic tumor. Tumor clumps
same age as the patient. When evaluating cellularity, consider that the may occur only on side or feathered edges of the film, or only in the
38
marrow spaces directly adjacent to cortical bone frequently are fatty and concentrate preparation. These tumor clumps must be distinguished
are not representative of the cellularity of the deeper marrow spaces. A from clumps of damaged hematopoietic cells, which commonly appear
grid can be used to estimate marrow cellularity of a biopsy. 39 in aspirate preparations, especially the concentrate film. The distinction
Cellularity assessment by examination of the direct marrow aspi- is best accomplished by examining cells at the periphery of the clumps
rate film is more difficult because of loss of histologic structure and to determine if the cells show the morphology of hematopoietic precur-
mixture with blood. The aspirate may suggest the marrow is more sors or are cytologically atypical cells. Isolated nonhematopoietic tumor
hypocellular than indicated by the biopsy. Marrow particles (seen in cells are seen infrequently in aspirate preparations, even when tumor is
40
the direct film or a particle preparation) are the best indicators of cel- obvious in the biopsy, because of the adherent nature of most nonhe-
lularity. These particles are like “mini-biopsies” and contain sufficient matopoietic tumors. Examination of multiple films may be necessary to
hematopoietic and fatty elements to give some idea of marrow cellu- find isolated tumor cell clumps. Methods for identifying rare microm-
44
larity. Cellularity estimates based on careful examination of particles in etastatic tumor cells (disseminated tumor cells) in marrow aspirates and
the aspirate preparation agree well with cellularity estimated from the blood have continued to evolve, but have not yet found an established
marrow biopsy. 38 role in guiding clinical prognosis or therapy. 45,46
The degree of dilution of marrow aspirate specimens with blood Myeloma and lymphomas are nonhomogeneously distributed
48
47
during the aspiration is variable and may affect interpretation of mar- and more reliably detected on the biopsy preparation. Abnormal lym-
row cellularity. Adult marrows with greater than 30 percent lymphocytes phoid aggregates should be distinguished from lymphoid aggregates
plus monocytes likely are substantially admixed with blood, as shown by found in reactive conditions or in older patients. Neoplastic aggregates
cytokinetic studies of paired marrow aspirate and biopsy preparations. show cytologic atypia and a monomorphous cellular population, and
41
A higher-than-expected proportion of mature neutrophils in the marrow they often are adjacent to bony trabeculae, but the distinction can be
differential is another clue to a hemodilute marrow aspirate. In patients difficult in some cases. The cellular morphology often can be better
with hematologic disease, from 6 to 93 percent of the nucleated cells appreciated on the marrow aspirate, but the key histologic features
were derived from the blood. The greatest admixture was observed in are lost. Lymphoma cells do not form the tight clusters seen in non-
42
patients with leukemia. Substantial dilution with blood may occur in dif- hematopoietic tumors on the marrow aspirate film. In hairy cell leu-
ficult aspirates or when multiple draws were taken from the same punc- kemia (Chap. 93), the hematopoietic cells are sufficiently adherent to
ture site. For instance, contamination of marrow aspirates with blood each other and the marrow matrix with variably increased collagen
cells was only 8 percent in the first 1 mL, but 20 percent in subsequent matrix that the aspirate specimen is often markedly hypocellular (dry
draws. 43 tap), whereas biopsy specimens show extensive infiltration with hairy

Kaushansky_chapter 03_p0027-0040.indd 31 17/09/15 5:37 pm