Rose Valerie P.

Manalo

I. Acute Myeloid Leukemia Pathophysiology/Determinants

M1- Acute Myeloblastic Leukemia Examination of the peripheral blood reveals that granulocy
without maturation cells, and platelets are reduced in number. The num
circulating blast cells is variable and usually is directly prop
to the total white count. In the early stages of AML, th
count may be normal or low, with few or no blasts
peripheral blood although blasts are increased in th
marrow. The majority of cases were present with leuk
secondary to high numbers of circulating blasts.

Characteristically the bone marrow is hypercellular. Nu

morphologic abnormalities are found in all marrow cell
observed by the presence of dismyelopoietic ne
maturation, dyserythropoiesis and morphologically a
megakaryocytes.
M2- Acute Myeloblastic Leukemia The peripheral blood findings commonly include a reductio
with maturation number of normal blood cells and leukocytosis secon
citculating blast cells. The bone marrow is hypercellular
same morphologic in all marrow cell lines that are describe
Some cases of M2 demonstrate a marked increase in b
eosinophils or both.

M3- Hypergranular Promyelocytic The majority of cells seen in M3 acute leukemia are a
Leukemia promyelocytes, with heavy granulation filling the cytpola
sometimes overlying the nucleus. Indeed, the granules m
abundant that they obscure the outlines of the nuc
contrast, M2 promyelocytes have less granulation, and gra
not obscure the nucleus. The cytochemical profile of M3 l
is similar to that of M1 and M2 except that in this case ,
the abnormal cells are intensely positive.
M3m- Microgranular Promyelocytic A microgranular variant of acute promyelocytic leuk
Leukemia designated M3m. Although clinically similar t
morphologically , it is dissimilar in that the cells appear d
granules. In fact, numerous granules are present i
promyelocytes but are below the normal resolution of t
microscope and therefore can be detected only by
microscopy.
M4- Acute Myelomonocytic Leukemia Most of the circulating cells in the peripheral blood are bl
abnormal cells. Some of the highest white counts to occu
ANLLs are seen in M4. Both granulocytic and m
Rose Valerie P. Manalo
M5- Acute Monocytic Leukemia
M6- Acute erythroleukemia
M7-Acute Megakaryocytic Leukemia
II. Acute Lymphoblastic Leukemia
L1- Small  cell, homogenous
differentiation is observed in the peripheral blood an
marrow.
Morphologically, M5A is characterized in both blood an
marrow by large blast cells with delicate, lacy chromatin
three large, prominent vesicular nucleoli also are prese
cytoplasm of these cells is voluminous, and often one
pseudopods of basophilic cytoplasm are seen.Azu
granulation is rare. Some monocytes are found, along with
percentage of promonocytes.
Peripheral blood findings include a variable white
pancytopenia , and most notably numerous nucleated re
cells (NRBCs). The presence of NRBCs in the circul
accompanied by a wide variety of changed in red cell morp
including anisocytosis, poikilocytosis, macrocytes, oval mac
schistocytes, or mixed populations of hypochrom
normochromic red cells. None of these changes is specific
but together, they are an indication of dyserythropoietic
in the bone marrow.
The blast cells of M7 were classified as undifferenti
previous FAB criteria because of the cytochemical negati
Sudan Black B , peroxidase, and esterase. Blast cells in som
are small and round with scanty cytoplasm and nuclear ch
that is dense and heavy, giving the cells a lymphoid appear
Pathophysiology/Determinants
In L1, the blasts are predominantly small; up to twice the d
of a small lymphocyte. They are generally uniform, and this
variation in size creates a homogenous picture of similar ce
chromatin is usually finely dispersed but may appear more
clumped in smaller cells. Chromatin and cell size may show
variation from case to case, but the homogenous features w
each particular case are a primary feature. Nuclear shape is
regular, however there may be some degree of clefting, fol
indentation. Nucleoli often are not visible or , if present are
Rose Valerie P. Manalo
L2- Large cell, hete
Type L3: Burkitt type
III. Chronic Myeloproliferative
Disorders
Polycythemia Vera
Chronic Myelogenous Leukemia
and indistinct. The cytoplasm is usually scanty (high nuclea
cytoplasmic ratio) amd only slightly to moderately basophi
Cytoplasmic vacuoles may or may not be present.
The majority of immature cells are more than twice the dia
of a small lymphocyte. In many cases, there is a marked
heterogeinity of cell size. Cjrp,atom ramhes from fine and
dispersed to coarsed and condensed, thus presenting a mix
picture. Nuclear clefting, indentation, and folding are
characteristic, and gross irregularities of nuclear shape are
common. Nucleoli are nearly always visible and and of vario
and numbers. Tje degree of cytoplasmic basophilia is also v
The Burkitt form is a relatively rare type of ALL (3%-5% of c
The blasts are ;arge and present a characteristically homog
picture. They have a dense but rather finely stippled chrom
The nucleus is oval to round, with a regular contour. One o
prominent vesicular nucleoli are visible in most cells. The
cytoplasm is intensely basophilic and moderately abundant
Cytoplasmic as well as nuclear cacuolation is often promine
These vacuoles stain positively with oil red O, making this s
valuable in the diagnosis of Burkitt leukemia (L3) or lympho
Pathophysiology/Determinants
The most obvious finding in the peripheral blood is an extre
high erythrocyte count, which may reach 10x 1012/ L. This le
increased HB levels (males greater than 17.5 g/dL; females
than 15.5 g/dL) and HCTs (male greater than 0.55 L/L; fema
greater than 0.47 L/L). The MCV and MCHC values are often
normal to slightly reduced because of the decreased or abs
stores in the marrow as a result of chronic bleeding and
phlebotomy and increased red blood cell production and tu
An occasional normoblast maybe found. The reticulocyte co
generally is not significantly increased.
A marked leukocytosis is the obvious feature in the periphe
blood. Generally, leukocyte counts range from 50 to 600 x 1
prior to treatment. However, much higher counts have bee
reported. If anemia is present, it is usually normocytic
normochromic. Platelet counts may be increased (approxim
600x109/L or decreased with occasional giant forms. Freque
the leukocyte and platelet counts are inversely related: the
the leukocyte count, the lower the platelet count. This effec
probably attributable to a “squeezing out” of marrow
megakaryocytes by the over abundance of granulocytic cell
 Rose Valerie P. Manalo
Juvenile CML
Agnogenic Myeloid Metaplasia
Essential Thrombocythemia
Chronic Neutrophilic Leukemia
IV. Chronic Lymphoproliferative
Leukemia
Prolymphocytic Leukemia
Hairy cell Leukemia
Although not a chronic MPD, is seen in children who have a
variant with Ph1 (-) cells. The peak incidence occurs at 1 to
of age. The prognosis is extremely unfavorable. There is a
dyserythropoiesis and a marked increased in serum and
urine/muramidase levels secondary to leukocyte destructio
Leukocyte counts are usually below 100 x 109/L and typicall
lower than those in adult Ph1 (+) CML. Increased fetal hemo
is common. Other characteristics of fetal erythrocytes are a
common, including a decreased Hb A2 level and low levels o
enzymes G6PD, lactate dehydrogenase and pyruvate kinase
among others).
Leukocytes and platelets may be increased , normal or decr
number. A mild anemia may be present, and It is usually of
normocytic, normochromic type. Ocassionally, a microcytic
is found, especially if patients have had repeated episodes o
gastrointestinal bleeding.
The most striking finding is the persistence of a marked
thrombocytosis , with platelet counts exceeding 1100 x 10 9/
masses of platelets aggregates are seen on the blood film, w
many abnormal-appearing giant and bizzare forms. Marked
anisocytosis (large and small forms) and occasional megaka
fragments are characterictics.
Classically, there is persistent neutrophilic leukocytosis with
left shift. Toxic granulation and a few Dohle bodies are pres
on rare occasions, an NRBC is found. Leukocyte counts may
high as 100x109/L with normal to slightly decreased platelet
and mild anemia. Hemoglobin is usually around 11 g/dL.
Pathophysiology/Determinants
The proliferation and accumulation of abnormal lymphoid cells in
the spleen, bone marrow, and to a lesser extent, the liver account
for the signs and symptoms of PLL. Immunologic deficiencies, such
as low levels of gamma globulins and generally low leves of othe
immunoglobulins, are frequently found. Additionally, the number
of T lymphocytes is below normal.
Hairy cell leukemia has a rather indolent course in most patients.
However, these patients are subject to many medical problems.
The growth and accumulation of hairy cells in the spleen, blood and
bone marrow account for the complications, which fall into the two
groups, those related to cytopenias and splenomegaly, such as
anemia, bleeding, and infection, and paraneoplastic complications,
 Rose Valerie P. Manalo
V. Lymphoma
Hodgkin’s Lymphoma
Non-Hodgkin’s Lymphoma
Mycosis Fungoides and Sezary
Syndrome
VI. Plama Cell Dysrasias (Paraproteinemias)
Multiple Myeloma
including autoimmune syndrome and less often, para proteinemia.
The mean survival has been said to be 5 years.
Pathophysiology/Determinants
The presence of clonal malignant Hodgkin and Reed-Sternberg (H-
RS) cells amid a hyperplastic background of normal reactive
lymphocytes, plasma cells, histiocytes, neutrophils, eosinophils, and
stromal cells characterizes Hodgkin's disease (HD).There is an
absolute increase in monocytes and eosinophils. Platelets are
normal in number. A transitory increase in lymphocytes may be
noted. The blood film may show large, abnormal-appearing
lymphocytes, which have a very little cytoplasm and irregular
nuclear chromatin. In advance disease, granulocytes often display
toxic granulation. Hyperuricemia may be found because of
excessive cell turnover.
Blood counts are normal in most patients with NHL, even in those
cases in which the bone marrow is involved. Other laboratory
findings depend on the classification of the lymphoma. Leukemic
phase of the disease can be seen with diffuse small-cell lymphocytic
lymphoma and in lymphoblastic lymphoma.
Cells are thought to be pathognomonic of this condition. The
lymphocyte involved is larger than normal with scanty cytoplasm,
and the nucleus is large with clefting. . Nuclear folding can be so
extensive as to suggest an image of the brain, and these nuclei are
thus described as cerebriform. The nuclear chromatin is fine with
little condensation. There may or may not be visible nucleoli.
Pathophysiology/Determinants
Multiple myeloma is the most common malignant
disease of plasma cells and generally affects older
individuals (50-75 years) . Etiology is uknown, both
genetics and chronic antigenic stimulation have
been suggested as predisposing factors. Clonal
proliferation of malignant plasma cells begin in the
bone marrow, and multiple tumors appear as
patchy infiltrates in skeletal structures, producing
osteoporosis and lytic bone disease. As the
neoplastic mass grows, pathologic bone fractures
and vertebral collapse may occur. Infiltration can
spread to lymph nodes, spleen and other ograns.
 Rose Valerie P. Manalo
Plasma Cell Leukemia
Waldenstrom Macroglobulinemia
Heavy Chain Disease
Amyloidosis
The homogenous protein synthesized by the
abnormal clone may be complete Igs or an L-chain
subunit (kappa/lambda). However myeloma cells
have decreased ability to synthesize normal Igs
against specific antigen. In fact, these cells supreess
normal lymphocytic function. Imbalance in the
plasma proteins with an absolute increase in
monoclonal Ig sometimes increases plasma
viscocity.
A patient is said to have plasma cell leukemia when
circulating plasma cells exceed 2x109/L. A leukemic
blood picture can occur as late manifestation of
plasma cell myeloma but plasma cell leukemia has
been reported as discrete entity. Greater than 2x
109 abnormal plasma cells/L, pancytopenia with
leukoerythroblastic findings, and an elevated ESR
are found in the peripheral blood. Morphologically,
the abnormal plasma cells are small with little
cytoplasm and with pronounced nuclear:
cytoplasmic asynchronism.
Characterized by large concentration of monoclonal
IgM as described by Waldenstrom. The abnormal B
lymphocytes involved in this rare malignancy are
primarily in the extramedullary nodes and have the
ability to differentiate into large plasmacytoid
lymphocytes and plasma cells. IgM exceeds 15% of
the gammaglobulin concentration. Rarely causes
osteolytic lesions.
The heavy chain diseases are rare
immunoproliferative disorders characterized by
abnormal synthesis of the Fc portion of a particular
H chain. Incomplete H chains of three major classes
of Igs are produced by the tumor cells: alpha,
gamma and mu. The tumor cells involved resemble
activated lymphocytes and plasma cells and present
a clinical feature similar to that of malignant
lymphoma.
Amyloidosis is a condition in which proteinaceous
deposits (amyloid) occur throughout the body,
producing symptoms and disease. Primary
amyloidosis is closely associated with monoclonal
gammopathies such as plasma cell myeloma. The
proteinaceous material amyloid is composed od L-
chain fragments from the variable region of Ig.
Rose Valerie P. Manalo

Lambda chains have a better potential for amyloid

formation than kappa chains. Secondary
amyloidosis is associated with chronic illness, and
the amyloid protein is unrelated to Ig. Treatment
addresses the associated plasma cell dyscrasia or
underlying disease to control further amyloid
deposition and subsequent loss of organ function.