Cell Inclusions

John Santangelo
Auer rods are elongated, bluish-red rods composed of fused
lysosomal granules, seen in the cytoplasm of myeloblasts,
promyelocytes and monoblasts and in patients with acute
myelogenous leukemia. (AML)
 Lysosomes contain many
hydrolytic enzymes, soluble
at an optimum acid pH.
Howell-Jolly bodies are basophilic nuclear remnants
(clusters of DNA) in circulating erythrocytes.
During maturation in the bone marrow erythrocytes normally expel
their nuclei, but in some cases a small portion of DNA remains.
It is named after William Henry Howell and Justin Marie Jolly.

Appearance
This DNA appears as a basophilic (purple) spot on the
otherwise eosinophilic (pink) erythrocyte.
These inclusions are normally pitted out by the spleen
during erythrocyte circulation, but will persist in individuals
with functional hyposplenia or asplenia.
Description:
Round, dense red cell inclusions of variable size, usually
single with a staining characteristic of the nucleus.
A Howell-Jolly body is a nuclear remnant that results from
incomplete nuclear expulsion as the orthochromic
normoblast exits the bone marrow.
Might also form as a result of karyorrhexis (nuclear rupture).
Small numbers normally are released into the peripheral
blood from the bone marrow, but are not seen on a
peripheral blood smear if the splenic function is normal or
near normal.
Howell-Jolly bodies are also seen in: Severe hemolytic
anemia, Megaloblastic anemia, Hereditary spherocytosis
Myelodysplastic syndrome( MDS).
If a small accessory spleen is present following splenectomy
in an otherwise normal patient, Howell-Jolly bodies usually
are not present.
 Spleen

Accessary Spleen
Howell Jolly Bodies

Red Circle
Pappenheimer Bodies
 Pappenheimer bodies
Pappenheimer bodies appear as violet staining granules usually
found along the periphery of the red cells, often in clusters.

They must be confirmed with an iron stain.

These iron-staining granules are found in sideroblastic and
megaloblastic anemias, alcoholism, following splenectomy, and in
some hemoglobinopathies.
They are smaller than Howell-Jolly bodies.
Pappenheimer bodies are distinctive granules found in a blood
stain that can indicate an excess of iron.
They can interfere with platelet counts in electronic counters
Pappenheimer Bodies
 Toxic Granulation
Toxic granulation refers to changes in granulocyte cells seen on
examination of the peripheral blood film of patients with
inflammatory conditions.
They are commonly found in patients with sepsis.
Toxic granulations are dark coarse granules found in
granulocytes, particularly neutrophils.
Along with Dohle bodies and cytosolic vacuolation, which are two
other findings in the cytoplasm of granulocytes, toxic granulations
are a peripheral blood film finding suggestive of an inflammatory
process.

Cytosolic
Pertains to or relates to the fluid component of the cytoplasm
excluding the organelles and other suspended intracellular
structures.
Toxic granulation neutrophils (TGNs), which have prominent
azurophilic cytoplasmic granules in blood smears stained by the
Wright or May-Grünwald-Giemsa technique, appear in blood when
inflammation occurs.
Serum levels of C-reactive protein (CRP) are also increased in
inflammation as is the ESR.
Toxic Granulation
Toxic Granulation
 Dohle Bodies
The presence of Döhle bodies in mature and immature neutrophils
on a blood smear can be normal if they are present only in small
numbers.
They are also normally more abundant in cats and horses.

Döhle bodies are intra-cytoplasmic structures composed of

agglutinated ribosomes; they will increase in number with
inflammation and increased granulocytopoiesis.
Döhle bodies often are seen together
with toxic granulation.
 Dohle Bodies
Toxic Lymphocyte EBV (Ebstein Barr Virus)
 PUNCTATE BASOPHILIA
(BASOPHILIC STIPPLING)
Seen in:
1. a- and b-thalassaemia.
2. chronic lead poisoning.
3. severe B12 deficiency (megaloblastic
anaemias).
4. pyrimidine 5-nucleotidase deficiency.
5. congenital dyserythropoietic anaemias.*
6. acquired Sideroblastic Anaemias.
7. other myelodysplasias.
Hereditary pyrimidine 5'-nucleotidase deficiency
is the most frequent enzymopathy of red blood cell
nucleotide metabolism that causes hereditary non-
spherocytic haemolytic anaemia.
The disease is usually characterized by mild-to-
moderate haemolytic anaemia, reticulocytosis and
hyperbilirubinemia.
To date, diagnosis ultimately depends upon
demonstration of a reduced level of pyrimidine 5'-
nucleotidase type-I (P5'N-1) activity in red cells and
detection of mutations in the P5'N-1 gene.
Basophilic Stippling
Basophilic Stippling
Basophilic Stippling
Malaria
Four species of human Plasmodium protozoa:

Plasmodium vivax
P.falciparum
P.malariae
P.ovale
 Heinz Bodies
Heinz bodies appear as small round inclusions within the red cell
body, though when stained with Romanowsky dyes they may
appear as projections from the cell.
They appear more clearly when supravitally stained
(e.g., with methylene blue or bromocresyl green).
Heinz bodies can be suspected if bite cells (degmacytes) are seen
on Wright's stained smears.
On the next slide are three bite cells, indicated by the arrows.
The cells appear to have had a bite taken out of them. Heinz
bodies are membrane-bound and bite cells are caused by their
removal. The patient was receiving aspirin-phenacetin-caffeine
(APC) tablets for relief of pain.
Heinz Bodies (Bite Cells)
Platelets overlying erythrocytes sometimes may be mistaken for
inclusions.
Platelets generally have a halo around them if they are seen
over a red cell
 Siderocytes
Red cells that have iron-containing, bluish-green
granules are called siderocytes.
Siderocytes are seen in anaemia's with disordered
haemoglobin synthesis, which include:
sideroblastic anaemia's, thalassemia, refractory
anaemia, dyserythropoiesis, leukaemia, and
preleukemia.
The iron is in the form of ferritin or hemosiderin.
They are particularly evident in any of these diseases
after splenectomy.
Siderocytes
 Cabot Rings
Cabot rings are thin, red-violet staining, threadlike
strands in the shape of a loop or figure-8 that are found
on rare occasions in erythrocytes. They are believed to
be microtubules that are remnants from a mitotic
spindle.

Cabot rings have been observed in a handful of cases

in patients with megaloblastic anaemia, lead poisoning
and other disorders of erythropoiesis.

They were first described in 1903 by American

physician, Richard Clarke Cabot (1868-1939).
Cabot Rings
Cabot Rings
Dimorphic film
 Reticulocytes
Reticulocytes are immature red blood cells, typically composing
about 1% of the red cells in the human body.

Reticulocytes develop and mature in the red bone marrow and

then circulate for about a day in the blood stream before
developing into mature red blood cells.

Like mature red blood cells, reticulocytes do not have a cell

nucleus. They are called reticulocytes because of a reticular
(mesh-like) network of ribosomal RNA that becomes visible under
a microscope with certain stains such as new methylene blue.
(Supravital Stain)

The normal range of values for reticulocytes in the blood depends

on the clinical situation and the lab, but broadly speaking is 0.5%
to 1.5%.
Supravital Staining of
Reticulocytes
Reticulocytes
Acute Myeloid leukaemia with Auer Rods
AML

Auer Rods
 Giant Platelets
Giant platelet syndrome (Bernard-Soulier syndrome):
This condition is a primary problem of platelets in which
the platelets lack the ability to stick adequately to injured
blood vessel walls and as a result of this problem there is
abnormal bleeding.
The giant platelet syndrome usually presents in the
newborn period, infancy, or early childhood with bruises,
nose bleeds (epistaxis), and/or gum (gingival) bleeding.
Later problems can occur with anything which can
induce bleeding such as menstruation, trauma, surgery,
or stomach ulcers.
Giant Platelets
Platelet
 Pelger Huet Anomaly
Pelger-Huët anomaly (PHA) is a benign dominantly
inherited defect of terminal neutrophil differentiation
secondary to mutations in the lamin B receptor (LBR) gene.
Characteristics observed on blood smears include
leukocytes with dumbbell-shaped bilobed nuclei;
a reduced number of nuclear segments;
coarse clumping of the nuclear chromatin in neutrophils,
lymphocytes, and monocytes.
Pelger-Huët cells survive normally in circulation. They have
normal leukocytic function and can phagocytize and kill
micro-organisms.
Examination of a peripheral blood smear in an individual
heterozygous for Pelger-Huët anomaly (PHA) is remarkable
for neutrophils with a predominance of bilobed, spectacle-
shaped nuclei.

Cells that contain twin, joined, and plump nuclei resembling

dumbbells are predominant.
A thin bridge, which is thinner than that observed in a normal
band neutrophil, joins the 2 lobes.
About 69-93% of the neutrophils show nuclear segmentation
that is arrested at the bilobe level.
A small population of neutrophils that possess a nonlobulated
oblong or peanut-shaped nucleus is often present.
Pelger Huet