Hemapathology

case

ADRIAN JOE G. CABALLES

CASE
A woman in her late 80s is referred to the
hematology/oncology clinic for anemia detected during
routine laboratory workup. The patient is asymptomatic for
anemia. She has multiple concurrent conditions, including
chronic kidney disease, obesity, diabetes, lipidemia,
hypertension, hypothyroidism, diverticulosis, and gastric
reflux. Her complete blood count shows decreased
hemoglobin (8.1 g/dL), decreased hematocrit (24.5%),
increased platelets (488,000/uL), and increased red cell
distribution width (19.2%) . Her medical record shows that her
last normal hemoglobin and hematocrit levels were 3 years
prior, and the levels have been steadily decreasing over that
period. The patient also uses omeprazole chronically for her
gastric reflux.
LABORATORY TEST decreased
hemoglobin and
hematocrit which is a
sign of anemia
increased platelets
indicative of
thrombocytosis or
Write a significant observation between
the company and its competitors thrombocythemia
Briefly elaborate on the observation increased red cell
distribution width
(variation in the size
of red blood cells
LABORATORY TEST
erythropoietin level is
elevated (as a
response to low red
blood cells or
increasing abnormal
Write a significant observation between RBC
the company and its competitors High folic acid (to
compensate for low
RBC)
Bone marrow biopsy and aspirate images
MORPHOLOGY

Biopsy of bone marrow showing

hypercellularity with erythroid hyperplasia
(indicates a stimulation of erythropoiesis or a
compensatory response to anemia)
Trilineage hematopoiesis is noted
(production of three types of blood cells)
Note the presence of Megakaryocyte and a
number of Erythroid precurssors
Erythroid precursors demonstrates dysplasia,
including irregular nuclear contours, nuclear
budding, megaloblastic change (light purple)
Bone marrow biopsy and aspirate images
MORPHOLOGY

Megakaryocytes are increased, with some

clustering noted and some atypical forms
(some are hypolobated and monolobated
forms which is dysplastic and associated
with a myelodysplastic syndrome) (dark
purple)
Iron stain demonstrates a moderate number
of ring sideroblasts (pink)
Note the presence of perinuclear iron
granules
Sideroblasts
abnormal blasts that take
over the bone marrow and
prevent the production of
adequate numbers of other
types of blood cells
presence of RS usually
signifies ineffective
erythropoiesis and
mitochondrial iron overload
 History of chronic alcoholism
Acquired
Elevated serum aspartate aminotransferase
sideroblastic
(AST):alanine aminotransferase (ALT) ratio
anemia due to
Macrocytic anemia
chronic alcohol use
< 15% ring sideroblast

Drug induced
The presence of sideroblastic History of medication use
bone marrow ring anemia - May have pure red cell aplasia
chloramphenicol, Reversible after discontinuation of drug
sideroblasts
penicillamine,
linezolid, isoniazid

Clonal disorder
MDS / MPN with
Platelet count of ≥ 450 × 109/L (persistent)
ring sideroblasts
Large, atypical megakaryocytes
and thrombocytosis

 Myelodysplastic Syndrome

a heterogeneous group of hematologic neoplasms classically

described as a clonal disorder of hematopoietic stem cells
leading to dysplasia and ineffective hematopoiesis in the bone
marrow
Highlighted as morphological dysplasia with presence of ring
sideroblasts (erythroid precursors with ≥ 5 iron granules
encircling a third or more of the nucleus)
Myelodysplastic Syndrome
Etiology
Mutations in the SF3B1 gene which lead to altered splicing of
mitochondrial iron transporter gene and other metabolic genes,
which in turn leads to the ineffective erythropoiesis and formation
of ring sideroblasts
Abnormality in signaling adapters JAK2 which promotes myeloid
proliferation which result in excessive production of either RBC
WBC or PLATELET
Epidemiology
incidence increases with age occurring after age 65 and most
frequently seen in patients over 80 years old, with a rate of 58
per 100,000
PATHOGENESIS

production of MDSCs
Hematopoietic stem cells
(pathologically activated
functional activity declines triggers the Mutations in the
neutrophils and monocytes
with age genetic insult JAK2 and SF3B1 MSD
with potent

gene
immunosuppressive activity)
 MUTATION OF JAK2 MUTATION OF SF3B1

Dysregulated Kinase ↑EPO Hyperstimulates Ineffective

activity megakaryocyte production erythropoiesis

↑bone marrow cellularity Disordered Cellular FORMATION OF

(due to megakaryocyte Maturation SIDEROBLAST
hyperplasia

↑RBC Destruction
Poor regulation of
megakaryocyte maturation
may cause ↑ platelets
Normocytic Anemia
Primary Thrombocytosis
Thrombocytosis
(platelet elevation due to
(↑platelets in Reduced Oxygen
changes in bone marrow
peripheral blood) Carrying capacity
production)
 Reduced Oxygen
Carrying capacity

HIF-1 causes kidney epithelial

cells to regress to a less-
differentiated cell type causing
fibrosis

formation of internal scar tissue

Chronic Kidney Disease

Renal Parenchymal
Peripheral Vascular
Damage Hypertention
Resistance

Vascular Endothelial
Damage Increase Endothelin