Hematology and Clinical Microscopy Glossary - College of American ...
Hematology and Clinical Microscopy Glossary - College of American ...
Hematology and Clinical Microscopy Glossary - College of American ...
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Bone Marrow Cell Identification<br />
Microorganisms<br />
The bone marrow <strong>of</strong> infected patients can demonstrate<br />
nonspecific reactive changes, such as granulocytic<br />
hyperplasia, reduced erythropoiesis or megakaryocytic<br />
hyperplasia. Macrophages, occasionally with<br />
hemophagocytosis, may be observed. The morphologic<br />
detection <strong>of</strong> organisms within cells is uncommon in the<br />
marrow <strong>and</strong> blood <strong>and</strong>/or bone marrow culture testing<br />
is indicated in evaluating a patient for infection.<br />
Macrophage With Phagocytized Fungi,<br />
Leishmania, Toxoplasma<br />
Histoplasma capsulatum is a 1- to 2-μm budding yeast<br />
that typically is present in large numbers within the<br />
cytoplasm <strong>of</strong> macrophages within the bone marrow.<br />
The organisms may manifest a crescent or ring shape,<br />
<strong>and</strong> also may be surrounded by a small halo, both <strong>of</strong><br />
which are artifacts, but helpful in diagnosis. The<br />
amastigote form <strong>of</strong> the parasite Leishmania has a similar<br />
size <strong>and</strong> appearance within marrow macrophages, but<br />
is recognized by the additional presence <strong>of</strong> a dot-like<br />
kinetoplast associated with each organism. The<br />
unicellular tachyzoites <strong>of</strong> Toxoplasma gondii also imitate<br />
Histoplasma morphologically, but do not stain positively<br />
with the Gomori’s methenamine silver (GMS) stain. The<br />
biggest diagnostic problem with this group <strong>of</strong> organisms<br />
is their ability to imitate each other, but they can also<br />
be confused with other budding yeast organisms, large<br />
bacterial cocci, or phagocytized material, particularly<br />
cells. If the macrophage has ruptured, extracellular<br />
organisms may be mistaken for platelets.<br />
Macrophage With Phagocytized<br />
Mycobacteria<br />
The mycobacteria are responsible for a variety <strong>of</strong><br />
clinical infections, with tuberculosis <strong>and</strong> leprosy being<br />
the best known. At least 25 species <strong>of</strong> mycobacteria are<br />
causative agents <strong>of</strong> human disease <strong>and</strong> several species<br />
can infect the bone marrow. The two species that<br />
most commonly involve the bone marrow are<br />
Mycobacterium tuberculosis <strong>and</strong> Mycobacterium avium<br />
complex. M. tuberculosis elicits a granulomatous<br />
response with or without caseous necrosis typically<br />
identified in the biopsy, while M. avium-intracellulare is<br />
usually seen in large numbers within bone marrow<br />
macrophages with or without a granulomatous<br />
response. When a granulomatous response is present,<br />
organisms may be rare <strong>and</strong> difficult to find. The<br />
mycobacteria are straight to slightly curved bacilli<br />
varying from 0.2 to 0.6 μm in width <strong>and</strong> 1 to 10 μm in<br />
length. They are acid-fast (due to the high lipid content<br />
in the cell wall) <strong>and</strong> may appear beaded on acid-fast<br />
stain. The organisms appear as nonrefractile<br />
“negative images” or clear or red refractile beaded<br />
rods on Romanowsky-stained preparations. The<br />
incidence <strong>of</strong> disseminated M. avium-intracellulare<br />
infection has greatly increased as the population <strong>of</strong><br />
patients infected with HIV has exp<strong>and</strong>ed.<br />
Fungi<br />
Probably the most frequently seen fungus in the bone<br />
marrow is Histoplasma capsulatum, but the organisms<br />
are nearly exclusively present within macrophages<br />
as 1- to 2-μm budding yeast forms but can be seen<br />
in neutrophils. They are only rarely seen in an<br />
extracellular location, usually when the cell membranes<br />
<strong>of</strong> the macrophages have ruptured. Other organisms,<br />
such as Coccidioides, Cryptococcus, C<strong>and</strong>ida, <strong>and</strong><br />
Aspergillus, occur less frequently but are more<br />
commonly extracellular. The appearance is<br />
dependent upon the specific organism. Coccidioides<br />
typically shows mature spherules ranging between 20 to<br />
60 μm, <strong>and</strong> contains endospores ranging from 2 to 4 μm.<br />
Cryptococcus is a round to oval yeast-like fungus<br />
ranging from 3.5 to 8 μm or more in diameter, usually<br />
with a thick mucopolysaccharide capsule, <strong>and</strong><br />
demonstrating a narrow neck when budding. C<strong>and</strong>ida<br />
can appear in bone marrow as either yeast-like<br />
organisms with budding or as pseudohyphae. Aspergillus<br />
is typically identified by its septate 4-μm–wide hyphae<br />
with characteristic 45° branching. Most organisms<br />
will stain with a periodic acid-Schiff (PAS) stain (<strong>and</strong> the<br />
Gomori’s methenamine silver stain for fungi).<br />
Anaplasma/Ehrlichia<br />
Recognized as an arthropod-borne infectious agent in<br />
humans, members <strong>of</strong> the genus Anaplasma (previously<br />
Ehrlichia) are small, Gram-negative, obligate<br />
intracellular organisms currently classified as rickettsiae.<br />
On Wright-stained preparations, Anaplasma species<br />
appear as round, dark purple-stained dots or clusters <strong>of</strong><br />
dots (morulae) in the cytoplasm <strong>of</strong> either granulocytes<br />
in human granulocytic anaplasmosis due to Anaplasma<br />
phagocytophilum or monocytes <strong>and</strong> macrophages<br />
in human monocytic Ehrlichiosis due to Ehrlichia<br />
Chafeensis. The morulae are microcolonies <strong>of</strong><br />
elementary bodies.<br />
Parvovirus<br />
The virus preferentially infects erythroid precursors <strong>and</strong><br />
very large pronormoblasts with eosinophilic nuclear<br />
inclusions can be seen.<br />
<strong>College</strong> <strong>of</strong> <strong>American</strong> Pathologists 2012 <strong>Hematology</strong>, <strong>Clinical</strong> <strong>Microscopy</strong>, <strong>and</strong> Body Fluids <strong>Glossary</strong>