Hematology/Oncology

Board Review
05/20/11

Vaibhav Sahai MD MSc

Hem/Onc Fellow
Northwestern University
 Benign Hematology
Cytopenias
Anemia, thrombocytopenia, leukopenia

Thrombosis/Anticoagulation
Heparin, Warfarin

Thrombolytics
Streptokinase, urokinase, alteplase, anistreplase

Antiplatelets
Aspirin, Clopidogrel, Abciximab
 Benign Hematology
Cytopenias
Anemia, thrombocytopenia, leukopenia

Thrombosis/Anticoagulation
Heparin, Warfarin

Thrombolytics
Streptokinase, urokinase, alteplase, anistreplase

Antiplatelets
Aspirin, Clopidogrel, Abciximab
 Anemia
How to think about anemias?

Congenital/Acquired

Microcytosis/Normocytosis/Macrocytosis

Production/Destruction/Blood loss
 Microcytic anemia
MCV <80

Types Iron deficiency

Sideroblastic anemia
Thalassemia
Lead poisoning
 Question
32 year old Caucasian female comes to establish with a
new physician. No significant past medical history except
anemia for which she has been on OTC iron for past year.
Vitals and examination normal except for mild scleral pallor.
Hgb 11.7, MCV 78, WBC 5k, platelets 180k & ferritin 20.
Her peripheral smear is shown. What is the most likely
diagnosis:

Pernicious anemia
Iron deficiency
Anemia of chronic disease
Thalassemia
 Schrier, S. ASH Image Bank 2002;2002:100325

Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.

 Question
32 year old Caucasian female comes to establish with a
new physician. No significant past medical history except
anemia for which she has been on OTC iron for past year.
Vitals and examination normal except for mild scleral pallor.
Hgb 11.7, MCV 78, WBC 5k, platelets 180k & ferritin 20.
Her peripheral smear is shown. What is the most likely
diagnosis:

Pernicious anemia
Iron deficiency
Anemia of chronic disease
Thalassemia
 Iron deficiency anemia
Etiology Blood loss GI, GU bleed, menstruation
Malabsorption Celiac disease
Insufficient intake Elderly

Iron studies Serum Fe low

TIBC high
Ferritin low
 Question
12 year old boy is brought to the pediatrician for poor
school performance and colicky abdominal pain. Laboratory
studies reveal leukocytes 5.5, hemoglobin 9.5 g/dL,
platelets 400k. Peripheral smear is shown. Physical
examination shows a dark line along the gingival lines.
Which of the following is the most likely explanation?

Attention deficit disorder

Folate deficiency
Lead intoxication
Mercury intoxication
Vitamin B12 deficiency
 Question
12 year old boy is brought to the pediatrician for poor
school performance and colicky abdominal pain. Laboratory
studies reveal leukocytes 5.5, hemoglobin 9.5 g/dL,
platelets 400k. Peripheral smear is shown. Physical
examination shows a dark line along the gingival lines.
Which of the following is the most likely explanation?

Attention deficit disorder

Folate deficiency
Lead intoxication
Mercury intoxication
Vitamin B12 deficiency
 Question
47 year old male presents with anemia and you just
diagnosed him with acute hemolytic anemia (way to go!).
You expect the following findings EXCEPT:

Decreased haptoglobin
Increased indirect bilirubin
Increased reticulocyte count
Microcytosis
 Hemolytic anemia
Extravascular Intravascular
(Liver/Spleen) (Blood vessels)

Examples Autoimmune Microangiopathic

Hereditary spherocytosis PNH
 Hemolytic anemia
Autoimmune hemolytic anemia

Type Warm Cold

Antibody IgG IgM
Examples Drugs Mononucleosis
SLE Mycoplasma pneum
Coombs test + +

If RBCs are coated with Ig --> Direct Coombs’ positive

If serum has Ig --> Indirect Coombs’ positive
 Hemolytic anemia
Hereditary Spherocytosis Paroxysmal nocturnal
Hemoglobinuria

How Inherited Acquired

Why Membrane defect Membrane defect

(Spectrin/ankyrin) (PIGA)

Where Extravascular Intravascular

Test Osmotic fragility Flow cytometry CD55, 59

Clues Splenomegaly, gallstones Aplastic anemia, thrombosis

 Question
47 year old male with vitiligo comes to you for evaluation of
fatigue. He states that he has no energy throughout the
day even though he is sleeping or eating well. His weight
has been stable and mood is good. Examination reveals
mild pallor and hypopigmentation consistent with vitiligo
but otherwise normal. His peripheral smear is shown. What
is the most likely diagnosis:

Pernicious anemia
Iron deficiency
Anemia of chronic disease
Thalassemia
 Question
47 year old male with vitiligo comes to you for evaluation of
fatigue. He states that he has no energy throughout the
day even though he is sleeping or eating well. His weight
has been stable and mood is good. Examination reveals
mild pallor and hypopigmentation consistent with vitiligo
but otherwise normal. His peripheral smear is shown. What
is the most likely diagnosis:

Pernicious anemia
Iron deficiency
Anemia of chronic disease
Thalassemia
 Macrocytic anemia
MCV >98

Types Megaloblastic versus Non-megaloblastic

Etiology B12 deficiency Alcoholism

Folate deficiency Liver failure
Chemotherapeutics Reticulocytosis
 Question
60 year old female with history of acid reflux on proton
pump inhibitor for past several years presents with
decreased proprioception and gait instability. WBC 7,000,
Hgb 10.6, MCV 105, platelet 135,000. Folate level 5, B12
206. What test would confirm B12 deficiency?

Elevated homocysteine level

Macrocytosis
Negative Schilling test
Elevated methymalonic acid level
 Question
32 year old Indian female comes to establish with a new
physician. No significant past medical history except
anemia for which she has been on iron for past year. Vitals
and examination normal except for mild scleral pallor. Hgb
11.7, MCV 64, WBC 5k, platelets 180k & ferritin 150. Her
peripheral smear is shown. What is the most likely
diagnosis:

Pernicious anemia
Iron deficiency
Anemia of chronic disease
Thalassemia
 Question
32 year old Indian female comes to establish with a new
physician. No significant past medical history except
anemia for which she has been on iron for past year. Vitals
and examination normal except for mild scleral pallor. Hgb
11.7, MCV 64, WBC 5k, platelets 180k & ferritin 150. Her
peripheral smear is shown. What is the most likely
diagnosis:

Pernicious anemia
Iron deficiency
Anemia of chronic disease
Thalassemia
 Thalassemia
Definition Defective globin synthesis
Epidemiology Southeast Asians, Mediterranean, Blacks
Types Alpha
⍺-/⍺⍺ minor
--/⍺⍺ minor
--/-⍺ HbH disease
--/-- Hydrops fetalis
Beta
β/- minor/trait
β0/- intermedia
-/- major
Test Hemoglobin electrophoresis
 Benign Hematology
Cytopenias
Anemia, thrombocytopenia, leukopenia

Thrombosis/Anticoagulation
Heparin, Warfarin

Thrombolytics
Streptokinase, urokinase, alteplase, anistreplase

Antiplatelets
Aspirin, Clopidogrel, Abciximab
 Question
55 year old male was admitted to the hospital yesterday
due to pneumonia. Blood cultures were obtained &
empirical antibiotic therapy was initiated. On admission his
Hgb was reported to be 13 g/dL, WBC 11,000 and platelet
count 70,000. The next laboratory study that should be
done is:

Coagulation studies
Antiplatelet antibody test
Platelet aggregation studies
Peripheral smear
Bone marrow aspiration and biopsy
 Question
32 year old Caucasian female presents with fever &
confusion. T 38.2 C, P 100/minute, RR 20/minute, and BP
100/60 mm Hg. She has widespread petechiae. Lab studies
show BUN 32 mg/dL, Cr 2.3 mg/dL, Hgb 12.2 g/dL, MCV 93
fL, platelet 19,000 and WBC count 8.1. Schistocytes are
seen on her peripheral blood smear. Which of the following
is the most likely diagnosis?

Disseminated intravascular coagulopathy

Idiopathic thrombocytopenia purpura
Thrombotic thrombocytopenic purpura
Warm antibody hemolytic anemia
 Question
32 year old Caucasian female presents with fever &
confusion. T 38.2 C, P 100/minute, RR 20/minute, and BP
100/60 mm Hg. She has widespread petechiae. Lab studies
show BUN 32 mg/dL, Cr 2.3 mg/dL, Hgb 12.2 g/dL, MCV 93
fL, platelet 19,000 and WBC count 8.1. Schistocytes are
seen on her peripheral blood smear. Which of the following
is the most likely diagnosis?

Disseminated intravascular coagulopathy

Idiopathic thrombocytopenia purpura
Thrombotic thrombocytopenic purpura
Warm antibody hemolytic anemia
 TTP
• 5 cardinal features of TTP
Neurological symptoms (confusion/headache/stroke)
Fever
Thrombocytopenia
Microangiopathic hemolytic anemia
Acute renal insufficiency

• ADAMTS-13 (von Willebrand metalloproteinase) deficiency

E.coli (EHEC 0157:H7) -->diarrhea in children --> TTP/HUS

• Treatment
Plasmapheresis/plasma exchange
Steroids
 ITP
• Immune/Idiopathic Thrombocytopenic Purpura
Like name suggests the etiology mostly unknown
Diagnosis after ruling out other causes
?Antibodies against platelets
 Disseminated Intravascular
Coagulation
Abnormal activation of coagulation cascade leading to
global consumption of platelets, fibrin & coagulation factors

Caused by sepsis (gram negative), trauma, obstetric

complication, malignancy, acute pancreatitis

Elevated PT, PTT

Thrombocytopenia
Elevated d-dimer (fibrin split products)
Schistocytes
 Benign Hematology
Cytopenias
Anemia, thrombocytopenia, leukopenia

Bleeding/Thrombosis/Anticoagulation
Hemophilia, vWD, Heparin/Warfarin

Thrombolytics
Streptokinase, urokinase, alteplase, anistreplase

Antiplatelets
Aspirin, Clopidogrel, Abciximab
 Question
32 year old Caucasian female 32 weeks pregnant with 2
prior spontaneous 1st trimester abortions. She has swollen
& painful R leg and ultrasounds reveals acute RLE deep
venous thrombosis. No significant past medical history, CBC
and CMP normal. Vitals and examination normal. How
would you treat her thrombosis?

Observation
Aspirin
Heparin
Warfarin
 Heparin
MOA Thrombin & potentiate anti-thrombin III

Measure aPTT (extrinsic pathway)

Use Acute use in anticoagulation (onset secs)

IN PREGNANCY

Types Unfractionated half-life ~1 hour

Low molecular half life ~6 hours

Reversal Protamine
 Warfarin (a rodenticide)

MOA Inhibits g-carboxylation of clotting factors II, VII,

IX, X, Protein C & S

Measure PT (extrinsic pathway)

Use Chronic use in anticoagulation (onset days)

NOT IN PREGNANCY! (teratogenic)

Half life Long

Reversal Vitamin K/Fresh frozen plasma

 Question
35 year old G0P0 female with no past medical/surgical
history had a molar extraction. She continues to bleed for 2
days after the surgery and then finally comes to your office
to get it evaluated. Physical examination reveals bleeding
at the site of extraction. Labs show Hgb 11.6, platelets
200,000, PT 13 (normal <15), PTT 38 (normal <41). On
further questioning, she has no history of bleeding but her
mother had a bleeding problem. What is the diagnosis?

Hemophilia A
Hemophilia B
Von Willebrand’s disease
 Von Willebrand’s disease
Most common inherited bleeding disorder

Type 1 Quantitative defect (mild) Most common

Type 2 Qualitative
Type 3 Quantitative defect (severe)

vWF is a protein produced & secreted by the endothelial cells.

Its function is to bind & protect Factor VIII in circulation

Treatment
- Desmopressin (stimulates release of vWF)
- Factor VIII concentrate
 Hemophilia A and B
Inheritance Both are x-linked recessive
Gender Mostly males (females possible)
Deficiency Factor VIII – Hemophilia A
Factor IX – Hemophilia B
Incidence 1:5000 births – Hemophilia A
1:25000 births – Hemophilia B
Presentation Bleeding into joints, muscles, GI tract
Complications Hemarthrosis
Infections (Hepatitis, HIV, B19)
Iron overload (heart/liver failure)
Screening tests Elevated PTT
Confirmatory Factor level
 Benign Hematology
Cytopenias
Anemia, thrombocytopenia, leukopenia

Thrombosis/Anticoagulation
Heparin, Warfarin

Thrombolytics
Streptokinase, urokinase, alteplase, anistreplase

Antiplatelets
Aspirin, Clopidogrel, Abciximab
 Benign Hematology
Cytopenias
Anemia, thrombocytopenia, leukopenia

Thrombosis/Anticoagulation
Heparin, Warfarin

Thrombolytics
Streptokinase, urokinase, alteplase, anistreplase

Antiplatelets
Aspirin, Clopidogrel, Abciximab
 Malignant Hematology
Multiple myeloma
Acute leukemia
Chronic leukemias
Hodgkin’s lymphoma
Non-Hodgkin Lymphoma
Viruses associated with malignancies
Oncogenes
Tumor suppressor genes
Tumor markers
Paraneoplastic syndrome
 Question
18 year old Hispanic female presents with nose bleed for
past 6 hours and headache to ER. Labs show WBC 13,000,
Hgb 9.2, platelet count 7,000. CT head wo contrast shows
intracranial bleeding. Peripheral smear is reviewed (shown)
and Hematology/Oncology fellow is paged at 2 am. He
drives to the hospital, confirms the diagnosis and starts
chemotherapy within one hour. What is the diagnosis?

Acute myeloid leukemia

Acute promyelocytic leukemia
Chronic myeloid leukemia
Chronic lymphocytic leukemia
Acute lymphocytic leukemia
 Acute Leukemias
• Acute promyelocytic leukemia
Auer rods in myeloid blast cells
Present with thrombocytopenia, bleeding, fever, infection
PML-RARA or t(15;17)
Treatment with ATRA or Arsenic trioxide

• Acute myeloid leukemia

Usually elderly with elevated WBC count
Treatment with chemotherapy, stem cell transplant

• Acute lymphocytic leukemia

Usually young children
Treatment with chemotherapy, stem cell transplant
 Question
59 year old woman with weakness, fatigue, easy bruising
and nosebleeds. Analysis of her blood work reveals a
reciprocal translocation between chromosomes 22 and 9
and low leukocyte alkaline phosphatase. These findings
confirm a diagnosis of

ALL
AML
CML
CLL
 Chronic Myeloid Leukemia
Associated with t(9;22) or bcr-abl

Presentation Usually with an elevated WBC count

Splenomegaly
May present in “blast crisis”

Treatment Imatinib (tyrosine kinase inhibitor)

 Question
67 year old male presents with low back pain and
weakness, worsening over past 6 months. Lab examination
reveals anemia with rouleaux formation of erythrocytes.
Urine shows proteinuria and hypercalciuria. X-rays reveal
diffuse osteoporosis of spine and small lytic lesions in ribs &
skull. The diagnosis is:

Osteosarcoma
Metastatic prostatic adenocarcinoma
Multiple myeloma
Fibrous dysplasia
 Question
67 year old male presents with low back pain and
weakness, worsening over past 6 months. Lab examination
reveals anemia with rouleaux formation of erythrocytes.
Urine shows proteinuria and hypercalciuria. X-rays reveal
diffuse osteoporosis of spine and small lytic lesions in ribs &
skull. The diagnosis is:

Osteosarcoma
Metastatic prostatic adenocarcinoma
Multiple myeloma
Fibrous dysplasia
 Multiple Myeloma
Disorder of plasma cells (fried-egg appearance)

Presentation Hypercalcemia
Lytic lesions in bones
Renal failure

Tests Serum protein electrophoresis (M protein)

Lights chains (Bence Jones proteins)
Anemia
 Question
24 year old computer analyst presents with a complaint of
persistent, non-productive cough & chest tightness. He has
lost 18 lbs over past 6 months and has had intermittent
fevers and drenching sweats with acetaminophen.
Examination normal. Chest X-ray shows an anterior
mediastinal mass. The most likely diagnosis is:

Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma
Tuberculosis
Retrosternal goiter
Featherstone C et al. JCO 2003;21:1420-1421
 Hodgkin’s lymphoma
Reed-Sternberg B-cells, binucleate/bilobed, “owl’s eyes

B-symptoms fever, night sweats, >10% weight loss

EBV 50% cases associated

Distribution Bimodal (20s and then in 60s)

Types Nodular sclerosing (65-75%)

Mixed cellularity (25%)
Lymphocyte predominant (6%)
Lymphocyte depleted (rare)
 Non-Hodgkin’s lymphoma
I. B-cell
Indolent (difficult to cure)
Follicular lymphoma
Small lymphocytic lymphoma

Aggressive (may be curable)

Diffuse large B-cell
Burkitt’s lymphoma

II. T-cell
Aggressive
Lymphoblastic lymphoma
Diffuse large T-cell
 Question
46 year old Asian female with no past medical history
presents with fatigue, weight loss for past 2 months.
Mammogram, PAP smear normal. Chest x-ray reveals a
mediastinal mass. CT scan shows widespread
lymphadenopathy throughout chest, abdomen & pelvis. A
lymph node biopsy shows T-cell lymphoma. Which of the
following viruses are most commonly associated with this
disorder?

Ebstein-Barr virus
HTLV
HIV
Cytomegalovirus
HPV
 Question
26 year old Asian female with no past medical history
presents with fatigue, weight loss for past 2 months.
Mammogram, PAP smear normal. Chest x-ray reveals a
mediastinal mass. CT scan shows widespread
lymphadenopathy throughout chest, abdomen & pelvis. A
lymph node biopsy shows Hodgkin’s lymphoma. Which of
the following viruses are most commonly associated with
this disorder?

Ebstein-Barr virus
HTLV
HIV
Cytomegalovirus
HPV
 Question
26 year old Asian female with no past medical history
presents with fatigue, weight loss for past 2 months.
Mammogram, PAP smear & chest x-ray normal. CT scan
shows a nasopharyngeal mass which on biopsy is revealed
to be nasopharyngeal carcinoma. Which of the following
viruses are most commonly associated with this disorder?

Ebstein-Barr virus
HTLV
HIV
Cytomegalovirus
HPV
 Oncogenic viruses
HTLV-1 Adult T-cell leukemia/lymphoma
Hepatitis B virus Hepatocellular carcinoma
Hepatitis C virus Hepatocellular carcinoma
Ebstein-Barr virus Burkitt’s lymphoma, Hodgkin’s
lymphoma, Nasopharyngeal carcinoma
HPV Cervical carcinoma (HPV 16,18),
penile/anal carcinoma
HHV-8 Kaposi’s sarcoma, B-cell lymphoma body
cavity
Oncology
 Tumor markers
Screening
Prostate specific antigen (PSA) Prostate
Alpha-fetoprotein (AFP) Hepatocellular

Surveillance
Carcinoembryonic antigen (CEA) Colorectal, pancreatic
Beta-HCG Hydatidiform moles
Choriocarcinomas
Gestational trophoblastic
CA-125 Ovarian, epithelial tumors
S-100 Melanoma, neural tumors
Alkaline phosphatase Metastases to bone,
Paget’s ds., biliary ds.
CA19-9 Pancreatic, GI tract
 Oncogenes
Oncogene Associated tumor

abl CML
c-myc Burkitt’s lymphoma
bcl-2 Follicular lymphoma
erb-B2 Breast, ovarian & gastric
k-ras Colon carcinoma
l-myc Lung cancer
n-myc Neuroblastoma
ret Multiple endocrine neoplasia
 Tumor suppressor genes
Gene Chr Associated tumor

Rb 13q Retinoblastoma, osteosarcoma

BRCA1 & 2 17q, 13q Breast, ovarian cancer
p53 17p Most cancers; Li-Fraumeni syndrome
p16 9p Melanoma
APC 5q Colorectal cancer
WT1 11q Wilm’s tumor
NF1 17q Neurofibromatosis type 1
NF2 22q Neurofibromatosis type 2
DPC 18q Pancreatic cancer
DCC 18q Colon cancer
 Question
35 year old Caucasian sexually active male presents with a
swollen R testicle for past few weeks which he noticed
incidentally. He blames in on a cycling accident a month
ago when he had trauma to his testciles. On examination,
he has a firm rubbery non-tender mass in R testicle.
Transillumination reveals an opaque mass. Labs show
elevated LDH, normal AFP, normal WBC count and B-HCG.
What is the diagnosis?

Seminoma
Orchitis
Hydrocele
Dysgerminoma
Non-seminoma
Epididymitis
 Testicular tumors
• Seminoma
Elevated LDH
Normal B-HCG (elevated in 20% cases)

• Non-seminoma
Elevated AFP
 Question cont…
What is the next step?

Fine needle aspiration biopsy

CT scan chest/abdomen/pelvis w contrast
Orchiectomy
Observation since this is a benign tumor
 Question
59 year old female with a 60 pack-year smoking history
was diagnosed with lung cancer 2 months ago. She now
enters the hospital in coma. Her serum calcium is 16
mg/dL. Which of the following would be the first thing you
would for this patient?

Intranasal calcitonin
Furosemide
Normal saline
Bisphosphonates
 Paraneoplastic syndrome
Small cell lung ca ACTH Cushing’s syndrome
ADH SIADH
Squamous cell lung ca PTHrp Hypercalcemia
Renal cell ca
Breast ca
Multiple myeloma
Bone metastasis

Renal cell ca Erythropoietin Polycythemia

Hemangioblastoma
Thymoma Antibodies Lambert-Eaton syndrome
Leukemia/Lymphoma Uric acid Gout, nephrolithiasis
 Question
35 year old female with stage II breast cancer dx 15 years
ago s/p lumpectomy, radiation followed by Tamoxifen for 5
years. She presents with acute onset low back pain to ER at
2am. MRI shows moderate spinal cord compression due to
a L2 vertebral mass. On further questioning, she has
bilateral leg weakness. Physical examination normal except
for 4/5 muscle strength bilateral lower extremities. What
would be your next step?

Consult neurosurgery for surgical decompression

High dose steroids
Consult radiation oncology for radiation
 Spinal cord compression
Examination findings Muscle weakness
Hyperreflexia
Positive Babinski’s sign
Urine/bowel incontinence

Treatment(s) High dose steroids

Radiation
Surgical decompression

Differential diagnosis Lymphoma

Breast, prostate, lung, renal ca

Biopsy, biopsy, biopsy

 Question
19 year old female who is a Jehovah’s witness requires
emergent orthopedic surgery and the surgeon expects
major blood loss. Which one of the following options would
you consider?

Erythropoietin injection
Convince the patient to undergo blood transfusion
Replace body fluids but not give blood transfusion
Give normal saline and fresh frozen plasma
Give the transfusion if necessary and inform her later
Obtain court order
Obtain permission from her parents
Thank you