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CHAPTER 3 be preferable to the sternum gained hold, and another 10 years passed
before a practical marrow biopsy instrument was put to use. Regular
EXAMINATION OF THE use of the posterior iliac crest for aspiration and biopsy and regular use
of biopsy to complement aspiration did not occur until the 1970s, when
MARROW staging of lymphoma made biopsy a frequent procedure and new sim-
pler biopsy instruments became readily available.

Daniel H. Ryan INDICATIONS FOR MARROW ASPIRATE
OR BIOPSY
SUMMARY The International Council for Standardization in Hematology has pub-
lished guidelines for marrow aspirate and biopsy to promote consis-
2
Microscopic examination of the marrow is a mainstay of hematologic diagno- tency in performance and reporting. Although marrow aspiration and
sis. Even with the advent of specialized biochemical and molecular assays that biopsy techniques are safe, they should be performed with a clear idea as
to how the results will help distinguish the differential diagnoses under
capitalize on advances in our understanding of the cell biology of hematopoie- consideration or provide followup of treatment. In many hematologic
3–5
sis, the primary diagnosis of hematologic malignancies and many nonneoplas- disorders, such as most cases of iron-deficiency anemia, thalassemia,
tic hematologic disorders relies upon examination of the cells in the marrow. and acquired and inherited hemolytic anemia, examination of the blood
An aspirate and biopsy of the marrow can be obtained with minimal risk and and specialized laboratory tests usually suffice to make the diagnosis
only minor discomfort and are quickly and easily processed for examination. without the need for a marrow examination.
The marrow should be examined when the clinical history, blood cell counts, When examination of the marrow is indicated, the decision as
blood film, or laboratory test results suggest the possibility of a primary or sec- to whether an aspirate or an aspirate plus biopsy is desired should be
ondary hematologic disorder for which morphologic analysis or special studies made. Aspiration is always attempted because of the superior morphol-
of the marrow would aid in the diagnosis. Leukopenia or thrombocytopenia ogy offered by examination of the aspirate smear. However, a marrow
may require a marrow examination for diagnosis. Nonhemolytic anemia that biopsy is superior to the aspirate in quantifying marrow cellularity and
is not readily diagnosed by blood cell examination and supporting labora- diagnosing infiltrative diseases of the marrow and should be performed
when these conditions are part of the differential diagnosis. Marrow
6,7
tory tests often requires a marrow examination. Abnormal cells in the blood, biopsy is useful for diagnosing and following the course of disorders
such as nucleated red cells, white cell precursors, abnormal lymphocytes not that are commonly associated with reticulin fibrosis, such as megakary-
explained by concurrent infection, and blast cells, usually require a marrow oblastic leukemia, hairy cell leukemia, and the chronic myeloprolifera-
examination. In addition to determining the cellularity and morphology of tive neoplasms. In myelodysplastic syndromes, marrow biopsy is useful
8
precursor cells, or infiltration by nonhematopoietic cells, the study provides for evaluating abnormal localization of immature precursor cells and
marrow cells for immunophenotyping, cytogenetic, molecular and genomic abnormal megakaryocytes. Marrow necrosis and gelatinous transfor-
studies, culture of infectious organisms, and storage of marrow cells for further mation are more readily detected in marrow sections than in aspirate
analysis. films. Marrow aspirate alone may be appropriate in some clinical set-
tings where the diagnostic question is very targeted, such as diagnosis
of childhood immune thrombocytopenia purpura or surveillance fol-
lowup of leukemia patients in apparent remission.
Depending on the diagnostic question, availability of material, and
HISTORY OF THE MARROW expected frequency of the abnormal cells, an appropriate selection of
EXAMINATION specialized diagnostic methods may be needed to support the clinical
diagnosis. Morphology of marrow cells is still the gold standard for diag-
The first recorded examinations of marrow in living patients occurred nosis of hematologic malignancy and allows construction of a good dif-
in the first decades of the 20th century, first using the tibia as the source ferential diagnosis for nonmalignant disorders. Immunocytochemistry
of marrow and then surgical bone biopsies. Neither technique led to provides excellent phenotype–morphology correlation on an individual
routine examination of the marrow, because in the former case the tibia cell basis, but is limited to epitopes that resist destruction by fixation,
was usually hypocellular in adults, and in the latter case, because of decalcification, and paraffin embedding. Flow cytometry allows study
the invasiveness of an open procedure and the discomfort and risk of of almost any surface or intracellular protein, with the added ability to
infection and bleeding. In 1923, Arinkin devised the marrow aspiration detect important quantitative changes in cellular proteins and simulta-
technique, which was the prototype for our current aspiration proce- neous determination of multiple proteins within the same cell. How-
1
dure. Thirty years passed before the suggestion that the pelvis might ever, flow cytometry requires that cells be viable and dissociated from
tissue. Gene expression arrays allow analysis of complex patterns of
RNA expression by sophisticated mathematical algorithms to discover
diagnostic patterns based on gene expression. These studies may point
Acronyms and Abbreviations: CD, cluster of differentiation; CLL, chronic lym- the way to a smaller more practical set of proteins that can be studied by
phocytic leukemia; CML, chronic myelogenous leukemia; DMSO, dimethylsulfoxide; immunocytochemistry or immunofluorescence. Molecular assays tar-
EDTA, ethylenediaminetetraacetic acid; FISH, fluorescence in situ hybridization; GPI, get oncogenic DNA sequence alterations from the chromosome to the
glycosylphosphatidylinositol; MDS, myelodysplastic syndrome; M:E, myeloid-to- nucleotide, and include classic metaphase cytogenetics, fluorescence in
erythroid cell ratio; MRD, minimal residual disease; PCR, polymerase chain reaction. situ hybridization (FISH), reverse transcriptase polymerase chain reac-
tion (PCR), and targeted or whole-genome sequencing.

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