What are the hematologic malignancies?

Immature/Acute Immature/Acute
Myeloid Lymphoid
Acute Myelogenous Acute Lymphocytic
Leukemias Leukemias
Myelodysplastic
Syndromes

Mature/Chronic Lymphoid

Monocyte Chronic Lymphocytic Leukemia

Non-Hodgkin Lymphomas
Hodgkin Lymphoma
Megakaryocyte

Mature/Chronic Myeloid Mature/Chronic Lymphoid

Plasma Cell Disorders
Chronic Myeloproliferative Neoplasms MGUS
Chronic Myelogenous Leukemia Multiple Myeloma
Polycythemia Vera Amyloidosis
Essential thrombocythemia
Primary Myelofibrosis The malignancy that arises depends on where the malignant
transforming event occurs and which mutations have been acquired
 Case # 1
A 65 year old man presents with a 6 month history of increasing
fatigue and dyspnea on exertion

WBC 4,000/ul
Hgb 7.5 gm/dL Hct 22% RBC 2.4 x 106/ul MCV 91 fl Pancytopenia
Platelets 120,000/ul

What else do you want to know?

 Case # 1
A 65 year old man presents with a 6 month history of
increasing fatigue and dyspnea on exertion.

WBC 4 x 103 /ul

Hgb 7.5 gm/dL Hct 22% RBC 2.4 x 106/ul MCV 91 fl Pancytopenia
Platelets 120,000/ul
History: No fevers, sweats; has lost about 5 pounds
+lower back pain; Frequent URIs
Diet: worsening appetite
Meds: no antacids, PPIs; tylenol for pain
Exam: no adenopathy, hepatosplenomegaly

Reticulocyte count 1%
Absolute Retics 22,000/ul Reticulocytopenia

Other labs
Normal B12, folate, homocysteine
Total protein 10 gm/dL (elevated) Albumin 3 gm/dL (decreased)
Creatinine 2.3 mg/dL Calcium normal

Blood smear Other labs? Bone Marrow

Case # 1
 Case # 1
Other labs:
Serum Protein Electrophoresis
Serum Immunofixation

IgG lambda monoclonal protein

Normal SPEP
 Case # 1

Plasma Cells

Bone Marrow Aspirate

 Plain x-rays: osteolytic lesions
Bone scan: *no uptake (no bone formation)

Multiple Myeloma (>10% marrow plasma cells)

Calcium (hypercalcemia)
Renal failure
Anemia
Bone lesions (RANK-L  ++osteoclasts  osteolytic lesions)
Infections (hypogammaglobulinemia; neutropenia)
vs MGUS: monoclonal gammopathy only (<10% marrow plasma cells)
vs Waldenstrom’s Macroglobulinemia: IgM monoclonal; low grade NHL; hyperviscosity sx
vs AL Amyloidosis: bx+ deposition of amyloid protein (Congo Red+); can accompany MM

Tho MM patients have elevated monoclonal Ig, it does not provide immunity against a diverse range of pathogens; loss of polyclonal
immunoglobulins (hypogammaglobulinemia) results in risk of infection
 Case # 1.5
A 65 year old man presents with a 6 month history of increasing
fatigue and dyspnea on exertion.

WBC 4,000/ul
Hgb 7.5 gm/dL Hct 22% RBC 2.4 x 106/ul Pancytopenia
Platelets 120,000/ul Reticulocytopenia
Retic count 1%
Absolute Retics 22,000/ul

History: no other symptoms

Diet: eats all Meds: none
Exam: unremarkable Labs??
B12, folate, homocysteine: normal

DDx of (pan)cytopenia + reticulocytopenia ineffective hematopoiesis

Empty marrow, infiltrated marrow, nutritional deficiency,???

Blood Smear Bone Marrow

 Case # 1.5
Bone Marrow
Blood Smear

Bone marrow aspirate: hypercellular;

5% blasts; dyserythropoiesis; megaloblastic
Pseudo Pelger-huet cells erythroid and myeloid maturation; giant bands
Hypolobated PMNs and metamyelocytes
 What’s the Difference?
Myelodysplastic Syndromes
• Clonal, stem cell diseases
• De novo vs secondary
– Chemo, RT, benzene
– Myeloproliferative Neoplasms
– PNH, Aplastic Anemia
• Cytopenias
• Cytogenetic abnormalities
• <20% marrow blasts
• Dysplasia+++
• Hypomethylating agents
• Stem cell transplant
Acute Leukemias
• Clonal stem cell diseases
• De novo vs secondary
– Chemo, RT, benzene
– Myeloproliferative Neoplasms
– PNH, Aplastic Anemia
• Cytopenias
• Cytogenetic abnormalities
• >20% marrow blasts
• No dysplasia
• Chemotherapy
• Stem cell Transplant
 Case # 2
A 23 year old man presents with cervical adenopathy.

WBC 20,000/ul
Leukocytosis
Hgb 11gm/dL Hct 33% RBC 3 x 106/ul
Anemia
Platelets 150,000/ul
 Case # 2
A 23 year old man presents with cervical adenopathy.

WBC 20,000/ul
Leukocytosis
Hgb 11 gm/dL Hct 33% RBC 3 x 106/ul
Anemia
Platelets 150,000/ul

History: ?fevers ?sore throat ?cough ?sweats ?weight loss

?sick contacts
Meds: none
Exam: ?sites of adenopathy ?mobile ?tender ?hard vs rubbery
?hepatomegaly, splenomegaly

WBC Differential: Neutrophils 20% Lymphocytes 80%

Reticulocyte count: 5%
Absolute reticulocytes: 150,000/ul

Other Labs: Normal LFTs; Elevated LDH; T. bilirubin 1.6 mg/dL

Blood smear
 Case # 2

Blood Smear

Mature
lymphocytes What next?
 Case # 2

Flow cytometry: (immunophenotyping):

80% CD3+, CD5+, CD8+ T cells
20% CD20+ B cells
Tdt: negative

Kappa : Lambda staining = 1 : 1

T cell receptor gene rearrangement: no clonal gene

rearrangement detected

Immunoglobulin gene rearrangement: no clonal gene

rearrangement detected
 Case # 2

Why is he anemic?
Why does he have splenomegaly?
 Case # 3
A 40 year old woman presents with right calf pain and
swelling and is found to have a deep vein thrombosis. She has a 6
month history of fatigue, headaches and menometrorrhagia.

WBC 20 x 103/ul Leukocytosis

Hgb 17 gm/dL Hct 50% RBC 7 x 106/ul MCV 71 fl Erythrocytosis
Platelets 700,000/ul Thrombocytosis

What else do you want to know?

 Case # 3
A 40 year old woman presents with right calf pain and swelling and is
found to have a deep vein thrombosis. She has a 6 month history of
fatigue, headaches and menometrorrhagia.

WBC 20 x 103/ul Leukocytosis

Hgb 16 gm/dL Hct 50% RBC 7 x 106/ul MCV 71 fl Erythrocytosis
Platelets 700,000/ul Thrombocytosis
History:
Signs/symptoms infection: no
Prior thrombosis: no Family Hx thrombosis: no
Risk factors for thrombosis: travel, BCPs, pregnancy/postpartum, surgery  no
Meds: Hydrochlorothiazide (for hypertension)
Exam: ?adenopathy ?hepatomegaly ?splenomegaly

WBC differential: PMN 70% Lymphs 20% Monocytes 5% Basophils 5%

Other Labs Blood Smear

 Blood Smear Other Labs:

Serum Iron: low

TIBC: high
Ferritin: low

Normal LFTs
Normal
Chemistries

Hypochromic, microcytic RBCs

Target cells
Thrombocytosis
 Case # 3

Bone Marrow Biopsy Bone Marrow Aspirate

Hypercellular, megakaryocyte hyperplasia, erythroid hyperplasia

What tests might help confirm a diagnosis?

Erythropoietin level: low JAK2V617F mutation: positive
Primary Myeloproliferation vs Reactive Proliferation
 Case #4
A 25 year old woman with a
two month history of night sweats
and right sided cervical adenopathy

Case #5

A 65 year old man with one

month of weight loss, fevers,
enlarging nodes in neck.

Case # 6
An asymptomatic
70 year old woman with small,
non-tender nodes in neck, axilla,
groin
 Lymphomas
History: Diagnosis
Age
Onset/duration of symptoms
Fevers, night sweats, weight loss
HIV? Pathology
Immunophenotype
Exam Genotype
Adenopathy
Splenomegaly Hodgkin
Non-Hodgkin
Histologic subtype Staging determines
Staging determines treatment treatment and prognosis
and prognosis

Treatment
?Curable
?Risk vs benefit

PET, Bone Marrow Primum Non Nocere

Extranodal: CNS, bone, bone marrow,
liver, skin, GI tract
(Spleen counts as a lymph node)
 Case # 4
A 25 year old woman with a two month history of
night sweats and right sided cervical adenopathy

LN biopsy:

Reed Sternberg cells

Staging:
PET: mediastinal and retroperitoneal adenopathy; normal liver,
spleen, GI tract
BM biopsy: negative for lymphoma

Stage? Treatment? Risks? Benefit?

 Case # 5

A 65 year old man with one month of

weight loss, fevers, enlarging nodes in neck.

LN biopsy: Diffuse large

CD20+ B cell lymphoma
CD10+
BCL6+

Staging:
PET: bilateral cervical, axillary, paraaortic, bulky mesenteric
adenopathy; hepatosplenomegaly; +bone lesions
BM biopsy: positive for lymphoma

Stage? Treatment? Risks? Benefit?

 Case # 6 An
asymptomatic 70 year old woman with small,
non-tender nodes in neck, axilla, groin.

LN biopsy: Follicular
lymphoma
CD20+
t(14;18)+
BCL-2+

Staging:
PET: small bilateral cervical, axillary and inguinal adenopathy
BM biopsy: positive for lymphoma

Stage? Treatment? Risks? Benefit?

 Case #7
A 40 year old woman presents with fever, gum
bleeding and rapidly enlarging cervical adenopathy.

WBC 50,000/ul Leukocytosis

Hgb 9 gm/dL Hct 27% Anemia
Platelets 20,000/ul Thrombocytopenia

What else do you want to know?

 Case #7
A 40 year old woman presents with fever, gum
bleeding and rapidly enlarging cervical adenopathy.

WBC 50,000/ul Leukocytosis

Hgb 9 gm/dL Hct 27% Anemia
Platelets 20,000/ul Thrombocytopenia

History: No URI symptoms; No travel, sick contacts

No headache; No sweats; no weight loss
Exam:
Bulky, non-tender, bilateral cervical adenopathy
No hepatosplenomegaly; Normal neurologic exam

WBC Differential: manual differential requested

Reticulocyte count 1%
Absolute reticulocyte count 30,000/ul Blood Smear
Other labs:
EBV PCR positive

Potassium 5.8 mg/dL Uric acid 11 mg/dL Phosphorous 6 mg/dL Calcium 7 mg/dL
 Peripheral Blood Smear

Blood and Bone Marrow flow cytometry:

CD20+, CD10+, TdT negative

Bone Marrow Aspirate

 Lymph Node biopsy

Immunohistochemistry:
CD20+, CD10+, kappa-light chain restricted,
Proliferation index: 100% (Ki-67)
Viruses and Cancer
Virus* Cancer*
EBV Endemic Burkitt’s (some sporadic)
Hodgkin lymphoma
Post transplant lymphoma (PTLD)
Nasopharyngeal Ca
Mononucleosis
HIV Kaposi’s sarcoma
(increased incidence) Anal cancer
Cervical Cancer
Non-Hodgkin lymphoma
Hodgkin Lymphoma
HTLV1 Adult T cell Leukemia Lymphoma
Primary Effusion Lymphoma
HHV8
Kaposi’s sarcoma
H. Pylori MALT lymphoma (marginal zone)
Marginal Zone lymphoma
Hepatitis C
Hepatocellular carcinoma (also Hep B)
Cervical Cancer
HPV
Oropharyngeal (pharynx, tonsil, tongue)
 Disease Cytogenetics* Genes* Protein*
Acute Promyelocytic Leukemia t(15;17) pml-rar transcription factor
t(9;22) bcr-abl tyrosine kinase
Acute lymphoblastic leukemia
11q23 MLL
Myelodysplastic syndromes mono/del 5, 7

Chronic myelogenous leukemia t(9;22) bcr-abl tyrosine kinase

Myeloproliferative Neoplasms
JAK2V617F tyrosine kinase
(P. Vera, ET, Primary Myelofibrosis)

del 13q
Chronic lymphocytic leukemia
del 17p p53 tumor suppressor
del 13q
Multiple myeloma p53 tumor suppressor
del 17p
c-myc (8) transcription factor
Burkitt’s lymphoma t(8;14)
IgH gene
bcl-2 (18) bcl-2
Follicular lymphoma t(14;18) (anti-apoptosis)
IgH gene

bcl-1 (11) cyclin D1 (bcl-1)

Mantle cell lymphoma t(11;14) (drives G1S)
IgH gene
 Mechanism Toxicity Used in:
Targeted Therapy:
Imatinib Tyrosine Kinase Inhibitor (blocks bcr-abl) Diarrhea CML

Rituximab Anti-CD20 monoclonal antibody (ADCC) Infusion reactions CD20+ lymphomas

Trastuzumab Anti-Her2 monoclonal antibody Breast Cancer

(tyrosine kinase)

ATRA Degrades PML-RAR ATRA syndrome APL

Transcription factor
Immunotherapy: sugar, B/P, weight
Corticosteroids Block macrophages, T cells, B cells osteoporosis, moody All of ‘em

Cyclosporine, Tacrolimus Calcineurin inhibitor (block T cells) Renal , neuro Post-transplant IS

Anti-thymocyte Globulin Kills cytotoxic T cells Serum Sickness Aplastic Anemia

IV Gamma Globulin Macrophage Fc Receptor Blockade Infusion Reactions AIHA, ITP, Hypo

PD-1, PDL-1 Inhibitors Activation of T cells against tumor Activation of T cells Being tried in all
(“itis” all organs)
Chemotherapy
Methotrexate Anti-metabolite (anti-folate) Renal, hepatic Leukemia, lymphoma

Vincristine/Vinblastine Spindle (microtubule)poison Neuropathy Leukemia, lymphoma

Adriamycin DNA intercalation/Topoisom. inhib Cardiac, 2O malig. Lymphomas, breast

Bleomycin DNA intercalation, strand breaks Pulmonary Fibrosis Lymphomas

 Labs
• CBC, MCV, MCH
• Reticulocyte count (methylene blue stains RNA in retics)
• B12 level
• Folic acid level
• Homocysteine
• Methylmalonic acid
• Iron, TIBC, Transferrin saturation, Ferritin, soluble transferrin receptor
• Serum Protein Electrophoresis
• Immunoelectrophoresis (serum/urine)
• Hemoglobin electrophoresis
• “Hemolysis” tests:
– Coomb’s test (direct and indirect)
– Bilirubin (direct and indirect)
– Haptoglobin
– LDH
– G6PD
• Erythropoieitin level
 Special Stains

• Prussian Blue/Perl’s: stains iron in marrow

• Methylene blue: stains RNA in retics
• Heinz body stain: stains denatured/oxidized globin chains or
hemoglobin
 Hemostasis Tests
• Peripheral blood smear
• Prothrombin time (Plasma + Ca + PL + TF)
• Partial Thromboplastin time (Plasma + Ca + PL + “Surface”)
• Mixing study
• Clotting factor assays
• Fibrinogen
• Fibrin Degradation Products
• D-Dimer
• Bleeding Time (platelet function studies)
• Platelet Aggregation Studies
 Thrombosis Tests

• Factor V Leiden (APC resistance)

• Prothrombin gene mutation (G20210A)
• Protein C, S
• Anti-thrombin
• Homocysteine
• Lupus anticoagulant
• Anticardiolipin antibody
• Clotting factor levels
 Other Tests

• Staining for Iron (BM; Prussian Blue/Perl’s stain)

• Immunophenotyping (flow cytometry or
immunohistochemistry)
• Cytogenetics
• Molecular analysis:
– FISH
– PCR
– Mutation analysis; next gen sequencing
 Terminology
• Microcytes • Monoclonal gammopathy
• Macrocytes • Light chain restriction
• Schistocytes • Clonality
• Spherocytes • Thrombophilia
• Target cells • Hypercoagulability
• Spur cells (acanthocytes) • Myelophthisis
• Polychromasia • Hemolysis
• Tear drops (dacrocytes) • Hypersplenism
• Leukoerythroblastosis • Work hypertrophy
• Megaloblastosis • Rouleaux
• Hypersegmentation
• Heinz bodies (requires special stain)
• Basophilic stippling (can see on
wright stained blood smear)
A 66 year old man presents with several weeks of back and leg pain which are worse with
movement. He denies any bladder or bowel dysfunction, weakness or numbness. He has
Diabetes Mellitus for which he takes Metformin. He drinks 2 beers/day.

Exam: unremarkable; normal neurologic exam

Xray right leg: shown

Labs: Hgb 9.6 g/dL MCV 92

Creatinine 1.6 mg/dL
Calcium 11 mg/dL
Glucose 220 mg/dL
Total protein 8.8 gm/dL
Albumin 3.8 gm/dL

Which of the following most likely explains the patient’s bone changes?

A Decreased urinary calcium excretion

B Increased 1,25 dihydroxyvitamin D production
C Increased PTH secretion
D Local tumor cell-mediated activation of osteoblasts
E Local tumor cell-mediated activation of osteoclasts
A 34 year old woman presents with a “lump” in her neck. She smokes ½ pack
cigarettes/day and drinks alcohol occasionally. She denies dysphagia, chest pain,
weight loss or fevers.
A biopsy of the enlarged cervical lymph node is positive for t(14;18)

This chromosomal change is most likely to cause which of the following

abnormalities in gene expression?

A bcl2 overexpression
B bcr abl hybrid formation
C c-myc overexpression
D erb-B2 overexpression
E p53 inactivation
A 45 year old man presents with purulent nasal discharge, headache, sore throat and
cough. His PMH is only significant for mononucleosis at age 22. He smokes 1 pack of
cigarettes/day for the past 20 years.
Exam: Febrile; Maxillary tenderness; red throat; small, tender cervical adenopathy,
CBC: WBC 58,000/ul
WBC Differential: PMN 42%, Bands 1%, Metamyelocytes 8%, Myelocytes
30%, Blasts 1%, Eosinophils 6%, Basophils 4%
Leukocyte alkaline phosphatase (LAP) score is low

What is the most likely diagnosis in this patient?

A Acute lymphoblastic leukemia
B Acute myelogenous leukemia
C Burkitt’s lymphoma
D Chronic lymphocytic leukemia
E Chronic myelogenous leukemia
F Diffuse Large B cell lymphoma (DLBCL)
G Follicular lymphoma
H Fungal superinfection
I Leukemoid reaction
J Parasitic superinfection
A 68 year old man presents with fatigue and weight loss. He takes no medications. He
does not smoke cigarettes or drink alcohol
Exam: pale, anicteric; mild hepatomegaly; marked splenomegaly;
CBC: pancytopenia
Blood smear: shown
A bone marrow is inaspirable

What is the bone marrow biopsy likely to show?

A Diffusely fibrotic marrow with clusters megas

B Hypercellular with clusters plasma cells
C Increased iron in macrophages
D Marrow replaced by dysplastic cells
E Severe hypocellular with fat
• Causes of inaspirable marrow:
– Empty (aplastic anemia)
– Myelofibrosis, as in the MPN, primary myelofibrosis
– Hairy cell leukemia: hairy cells secrete TGF which
stimulates fibroblasts to cause fibrosis
– Packed marrow: sometimes a marrow packed with sticky,
leukemic myeloblasts may be inaspirable
A 64 year old man presents with 3 months of back pain and difficulty urinating for the
past year. He has no significant past medical history and takes no medications. He
stopped smoking 10 years ago.

Exam: normal vital signs; no hepatosplenomegaly; enlarged prostate;

Labs: Creatinine 1.9 mg/dL
Urine dipstick: negative
U/A shows waxy, laminated casts
24 hour urine collection shows elevated protein.
Spine x-ray: diffuse osteopenia and multiple irregular, radiolucent lesions in thoracic
and lumbar vertebrae.

A biopsy of one of the bone lesions is most likely to show which of the following?

A Branching papillae lined by cuboidal cells with overlapping nuclei

B Infiltrating glandular cells with adjacent osteoblasts
C Large, malignant cells with keratin and intercellular bridges
D Clusters of mature plasma cells and plasma blasts
E Sheets of round or polygonal cells with abundant clear cytoplasm
A 6 year old boy with presents to the ED with recurrent nosebleeds.
Exam: Diffuse petechiae in mouth and lower legs
CBC: WBC 14,500/ul
Hgb 9 g/dL
Platelets 20,000/ul
BM aspirate : shown
The large cells show positive immunostaining for TdT. They express surface CD19
and CD10 as well.

Which of the following is the most likely diagnosis?

A Precursor B cell ALL
B Precursor T cell ALL
C Mature B cell leukemia
D Mature T cell leukemia
E Hodgkin lymphoma
A 41 year old woman presents with weakness, fatigue, epistaxis and gum
bleeding. Evaluation shows a clonal proliferation of WBCs containing an
abnormal protein. In an experiment, abnormal cells from the patient are purified
and cultured in 2 different plates, one with vitamin A and the second plate
serving as a control (nothing added). After several days, the cells in plate 1 are
well differentiated and clonal proliferation is inhibited.

The patient most likely has which of the following malignancies?

A Acute lymphoblastic leukemia

B Acute myelogenous leukemia
C Chronic lymphocytic leukemia
D Chronic myelogenous leukemia
E Non Hodgkin lymphoma
An 8 year old boy is seen in the office with a right mandibular mass. His family first
noticed the mass a few months ago and it has grown rapidly since that time. He has
not had any fevers, chills, cough or weight loss. The family immigrated to the US from
East Africa. The child has no significant past medical history and takes no medications.
Exam: large tumor right mandible with palpable regional nodes.
Biopsy of the mass shows: diffuse infiltrate of lymphoid cells with numerous mitotic
figures. Interspersed macrophages surrounded by clear spaces are also seen.

The genes translocated in these lymphoid cells produces a protein that is most
directly responsible for which of the following functions?

A Apoptosis inhibition
B DNA repair
C Regulation of G1 to S-phase transition
D Transcription activation
E Tyrosine kinase upregulation
A healthy 16 year old boy is seen with fever, malaise, sore throat and fatigue.
Exam: petechiae on palate and lower legs; bilateral cervical adenopathy; splenomegaly.
Blood smear: shown
Horse erythrocytes agglutinate when exposed to patient’s serum.
The agent causing this patient’s disease is most strongly associated with which of the following
malignancies?
A AML
B Cx carcinoma
C Hepatocellular carcinoma
D Kaposi’s
E MALT lymphoma
F Multiple Myeloma
G Nasopharyngeal
A 24 year old man comes to the oncology clinic for a follow up visit. He was
diagnosed with Hodgkin Lymphoma 4 months ago and received combination
chemotherapy. He has a non-productive cough, and dyspnea with exertion for the
past two weeks.
Exam: there is no jugular venous distension or pedal edema. Heart sounds are normal
with no murmur. Lung exam: bilateral fine inspiratory crackles.
CXR: bilateral reticular interstitial opacities.
PFTs: restrictive pattern with decreased diffusion capacity for carbon monoxide.
CXR and PFTs were normal prior to the start of chemo.

Which of the following is the most likely mechanism of action of medication causing
patient’s current symptoms?

A Disrupts microtubule polymerization causing M-phase arrest

B Impairs DNA synthesis by inhibiting thymidylate synthase
C Induces free radical formation and DNA strand breaks
D Inhibits tyrosine kinases and cellular replication
E Produces cell-cycle arrests and apoptosis by inhibiting proteasomes
An elderly patient is diagnosed with non-Hodgkin lymphoma. Immunohistochemistry
on the lymph node shows positive staining for CD20.

Which of the following biologic agents can be added to the chemotherapy regimen
to improve response?

A Infliximab
B Rituximab
C IL-2
D Imatinib
E Abciximab
A 54 year old woman presents with 2 months of weakness, fatigue, abdominal pain
and early satiety. She has no significant past medical history and denies recent foreign
travel.
Exam: normal vital signs; massive splenomegaly; no adenopathy

CBC: pancytopenia
Bone marrow: Inaspirable

Which of the following is most likely to be seen in this patient?

A Intraerythrocytic ring forms

B Lymphocytes with cytoplasmic projections
C Myeloid cells with azurophilic rodlike granules
D Positive heterophile antibodies
E Ringed sideroblasts
A 57 year old man presents with fatigue and decreased energy. He notes intermittent back pain
that responds to ibuprofen. He has no significant past medical history. His father died of an MI
age 60.

CBC: WBC 7,000/ul

Hct 36% MCV 86 fl
Platelets 170,000/ul

Labs: Fecal occult blood testing negative

Sodium 136 mmol/L
Potassium 4.5 mmol/L
AST 34 IU/L ALT 18 IU/L T. bilirubin 0.8 mg/dL
Creatinine 2 mg/dL
Plasma protein electrophoresis reveals high peak corresponding to gamma-globulins.

Which of the following is the most likely dx in this patient?

A Iron deficiency
B Cobalamin deficiency
C Chronic lymphocytic leukemia
D Aplastic anemia
E Plasma cell neoplasm
F Hodgkin lymphoma
G Hypothyroidism
A 68 year old man presents to his doctor’s office with persistent back pain for several months. He
is a retired veteran and has not seen his PCP for many years. He has smoked a pack of
cigarettes/day for 36 years.
Exam: B/P 145/85 Pulse 88/min Cardiopulmonary exam is normal
Abdomen is soft and non tender; There is focal tenderness over 10th rib and L1-L2 vertebral
region. Neurologic exam normal

A bone scan (radionuclide imaging) shows increased activity in multiple vertebrae and ribs,
corresponding to patient’s painful areas
Plain x-ray shows sclerotic lesions matching bone scan areas of increased uptake, which are highly
suspicious for metastatic cancer.

Which of the following additional findings is most likely to be seen in this patient?

A Hematuria and polycythemia

B A monoclonal immunoglobulin spike
C A lung mass and elevated parathyroid hormone-related peptide
D Lymphadenopathy and BCL-2 overexpression
E A nodular prostate and elevated PSA
F A rapidly enlarging, large, irregular mole
• Osteolytic (lucent on plain films; bone scan negative)
– Multiple myeloma
– Non-small cell lung cancer (secretes PTH-related protein)
– Non-Hodgkin lymphoma
– Melanoma
• Sclerotic/Osteoblastic (sclerotic on plain films; positive bone scan)
– Small cell lung cancer
– Prostate cancer
– Hodgkin lymphoma
• Mixed
– Breast cancer
– GI cancers

Bone scan detects bone growth, a response to destruction

Researchers studying chronic lymphocytic leukemia observe that in some patients the
disease is indolent, with limited growth over more than a decade, whereas in other
patients the disease is more aggressive and becomes symptomatic early on. They find
that genetic abnormalities can be detected in a majority of patients with chronic
lymphocytic leukemia and may play a role in determining the difference between clinical
courses. A clinical study is conducted with the hypothesis that CLL patients with trisomy
12 have a more favorable course than CLL patients with other genetic changes.

Which of the following lab techniques would be most useful for identifying patients
with this genetic abnormality?

A Enzyme-linked immunosorbent assay

B Flow cytometry
C Fluorescence in situ hybridization
D Northern blotting
E Western blotting
30 year old HIV positive woman with a history of IV drug use presents with abdominal
distension and anorexia.
CT scan: mass around small intestine.
CT guided biopsy of mass shows uniform, round, medium-sized tumor cells with
basophilic cytoplasm and a Ki-67 proliferative index of >90%.

Which infectious agent is most likely to be associated with this tumor?

A Epstein Barr Virus (EBV)

B Human papilloma virus (HPV)
C H. pylori
D Human Herpes virus-8 (HHV8)
E Hepatitis B
A 57 year old man is seen in the ED with fevers and painful mouth ulcers. He recently
started taking methotrexate for psoriasis. He mistakenly took the medication daily
instead of three times per week. His past medical history if significant for
hypertension and chronic kidney disease.
Exam: Temp 100.6’ multiple aphthous ulcers in oral pharynx
CBC: WBC 2800/ul
Hgb 10.4 g/dL
Platelets 120,000/ul

Which would be the next appropriate step in management?

A Allopurinol
B Amifostine
C Dexrazoxane
D Filgrastim
E Folinic acid
F Mesna
G Ondansetron
A 65 year old patient presents with 4 months of worsening fatigue. He feels tired with
simple household chores. He has a 15 pack-year smoking history and drinks 2-3
beers/day.
Exam: afebrile; B/P 134/86 Pulse 76/min; late systolic ejection murmur with soft
S2; clear lungs; soft non tender abdomen; no hepatosplenomegaly
Normal neuro exam
CBC Hgb 9 g/dL MCV 93
Blood smear: shown

Which of the following best explains the observed erythrocyte findings in this
patient?

A Chronic gastrointestinal blood loss

B Excessive cold agglutinin production
C Increased serum paraproteins
D Mechanical erythrocyte injury
E Nutritional vitamin B12 deficiency
A 59 year old man presents with 3 months of back pain.
Exam: tenderness on palpation of middle and lower spine
Labs: Hgb 10.2 g/dL
Calcium 12 mg/dL
Bone marrow aspirate: shown

The patient is at greatest risk for which of the following complications?

A Amyloidosis
B Cardiac tamponade
C Hepatic failure
D Hyperthyroidism
E Meningeal carcinomatosis
F Splenic rupture
A 35 year old man presents for evaluation of nontender cervical adenopathy.
A cervical lymph node bx is performed: shown

Cytogenetic analysis would most like show which?

A BCL-2 overexpression
B bcr-abl rearrangement
C c-myc overexpression
D Constitutive tyrosine kinase activation
E N-Myc overexpression
A 62 year old woman is evaluated for a painless neck mass that has been gradually
enlarging over the past several months. She also notes fatigue, night sweats and
unintentional weight loss.
Exam: rubbery, nontender bilateral cervical adenopathy
Imaging shows mediastinal and abdominal adenopathy.
An excisional lymph node biopsy is consistent with diffuse large B cell lymphoma
The patient is treated with combination chemotherapy which leads to rapid lysis of the
neoplastic cells.
She gets rasburicase prior to and during chemotherapy treatment.

This medication helps protect normal organs by which of the following mechanisms?

A Converting uric acid into more soluble metabolites

B Forming insoluble complexes with phosphate
C Inhibiting uric acid formation during cell lysis
D Removing excess potassium by exchanging it with sodium
E Supplying a thiol group to inactivate toxic metabolites
F Supplying necessary cofactors blocked by a chemo agent
A 52 year old man presents with a 2 month history of progressive adenopathy.
Exam: enlarged tonsils; bilateral cervical, axillary and inguinal adenopathy;
splenomegaly.
Cervical lymph node biopsy: diffuse infiltration with sheets of atypical large B cells with
a high nuclear:cytoplasmic ratio
IHC: staining positive for EBV

Which of the following is most strongly correlated with this patient’s condition?

A Advanced HIV infection

B Aspirin and NSAIDS
C Cigarette smoking
D Radiation
E Socioeconomic status
A 70 year old man presents with fatigue and bruising, weight loss and episodic fevers.
Exam: mild splenomegaly and enlarged, non tender adenopathy in cervical, axillary
and inguinal areas
CBC: anemia, thrombocytopenia, leukocytosis.
Blood smear: increased numbers of small, mature-appearing, abnormal lymphocytes
Flow cytometry shows positive staining with CD20+ and Kappa light chain
During treatment the patient receives an agent that inhibits the bcl-2 protein.

Which of the following is the most likely effect of this therapy on abnormal cells?

A Accumulation of ubiquitinated intracellular proteins

B Greater susceptibility to cytotoxic T cells
C Increased activation of caspases
D Increased single-strand DNA breaks
E Interruption of cell growth in S phase
F Targeting of ADCC
A 67 year old man is evaluated for lower back pain and fatigue. He has no significant
past medical history and takes no medications.
Labs:
Hgb 8.5 g/dL
Creatinine 2.2 mg/dL
Calcium 10. 6
Following evaluation he is treated with an infusion of a boronic acid-containing
dipeptide that has a high affinity for the proteasome catalytic site.

Which of the following is the mechanism of action of this medication?

A Amyloid plaque resorption

B Cell apoptosis
C Decreased inflammation
D Decreased serum calcium levels
E Interruption of IgG synthesis
A 61 year old woman is seen for evaluation of tingling in her hands and feet. She has a
history of diffuse large B cell lymphoma and has been treated with several cycles of
systemic combination chemotherapy with “CHOP” (cyclophosphamide, Adriamycin,
vincristine, prednisone). Neurologic examination is notable for symmetric distal
neuropathy in a ‘stocking and glove’ distribution. Electrolytes and blood glucose are
normal.

The drug responsible for this patient’s neurologic symptoms causes cell cycle arrest
during which of the following stages?

A GO
B M
C G1
D S
E G2
A 56 year old with man with non-Hodgkin’s lymphoma has received an overdose of
vincristine.

Which of the following toxicities would you expect?

A Finger numbness and tingling

B Burning on urination and urgency
C Leg swelling and orthopnea
D Dry cough and exertional dyspnea
E Tarry stool and fatigue
F Abdominal pain and jaundice
A 56 year old woman with heart failure is admitted for an orthotopic cardiac
transplant. She developed biventricular failure secondary to idiopathic myocarditis.
Because of persistent NY Heart Association Class IV symptoms refractory to maximal
medication therapy she was placed on the transplant waiting list. An ABO-compatible,
partial human HLA mismatch cadaveric heart became available and cardiac
transplantation was performed. The patient’s T lymphocytes quickly recognized the
foreign HLA molecules of the transplanted cells.

Inhibition of which of the following substances would specifically reduce the

proliferation and differentiation of these T lymphocytes?

A BCL-2
B Calcineurin
C E-cadherin
D Neurofibromin
E p53
A 56 year old woman is seen in ED for evaluation of 3 days of frequent urination,
suprapubic pain, dysuria and progressive hematuria. She has no fever or chills. The
patient has a history of node-positive breast cancer diagnosed following a routine
mammogram. She started systemic chemotherapy one month ago.
Exam: afebrile; suprapubic tenderness on abdominal examination
Labs: Hgb 9.8 g/dL
U/A: numerous RBCs, but no leukocyte esterase or bacteria

Which of the following could have prevented this patient’s current condition?

A Dexrazoxane
B Filgrastim
C Folinic acid
D Mesna
E Ondansetron
A 62 year old woman is seen for progressive chest and back pain She noticed a right
breast lump several months ago, which enlarged. She has no significant past medical
history and has not seen a physician for many years. She has not had any cancer
screenings.
Exam: 5 cm hard mass in right breast; enlarged axillary adenopathy; point tenderness
along right sided ribs and 10th thoracic vertebra
Biopsy of breast mass: ER positive, PR positive, HER2-negative invasive ductal
carcinoma
Skeletal survey: lytic lesions of ribs and thoracic vertebrae
As part of the treatment regimen, the patient receives a medication that is a potent
inhibitor of cyclin-dependent kinase.

Which of the following is the most likely dose-limiting toxicity of this medication?

A Bone marrow suppression

B Cardiomyopathy
C Immune-mediated toxicity
D Peripheral neuropathy
E Sensorineural hearing loss
A 68 year old man has advanced melanoma that is unresectable and has been
resistant to adjuvant regimens of therapy. He recently started monoclonal antibody
infusions for advanced melanoma. The monoclonal antibody blocks a specific cell
surface receptor on T lymphocytes. As a result, T cells capable of recognizing tumor
antigens have improved ability to destroy cancer cells.

Which of the following cell surface receptors is most likely blocked by this
treatment?

A CCR5
B CD4
C CD19
D CD28
E PD-1
A 47 year old woman gravida 2 para 2 is seen after finding a pea-sized lump in her
right breast while showering. She has a 3 pack year smoking history, but stopped 20
years ago. She underwent infertility treatment and in vitro fertilization for both of her
pregnancies. There is no family history of breast or ovarian cancer.
Exam: a firm, fixed nodule is palpated in the right breast with a small patch of
overlying puckered skin
Mammogram: highly suspicious for malignancy
Needle biopsy of nodule: infiltrating ductal carcinoma
The patient is scheduled for a right mastectomy and axillary lymph node dissection.

Overexpression of which of the following markers is most likely to be associated

with the aggressive disease in this patient?

A BCL-2
B Estrogen receptor
C Human epidermal growth factor receptor 2
D Mutated p53
E Progesterone receptor
The cells identified by the special immunohistochemical IHC stain on the breast nodule
biopsy in the patient described above is shown to overexpress 185 kD glycoprotein
that spans the cell membrane and has tyrosine kinase activity in the intracellular
domain.

Which of the following is the most likely function of this protein?

A Accelerates cell proliferation

B Acts as a sex hormone receptor
C Governs intercellular binding
D Induces cytokine release
E Mediates endocytosis
A 51 year old woman is seen following a screening mammogram, done 3 weeks ago, that was
suspicious for malignancy. A sono guided fine needle aspirate showed invasive ductal carcinoma.
The patient underwent a lumpectomy and axillary lymph node dissection. No metastatic disease
was identified. Immunohistochemistry showed the malignant cells to be estrogen receptor
positive, progesterone receptor positive and human epidermal growth factor receptor 2 positive.
Adjuvant therapy with a monoclonal antibody is started.

Which of the following is the most likely target of this drug?

A Estrogen receptor
B Peripheral aromatase enzyme
C Receptor activator of nuclear factor kappa-B ligand
D Tyrosine kinase receptor
E Vascular endothelial growth factor
Two antineoplastic drugs are shown to inhibit intracellular thymidylate formation. The
chemotherapeutic effect of drug X can be overcome by N5 formyl-tetrahydrofolate
supplementation, but that of drug Y is not affected.

The drugs described in this scenario are most likely which of the following?

X Y
A Cytarabine Gemcitabine
B Fluorouracil Leucovorin
C Fludarabine Methotrexate
D Methotrexate Fluorouracil
E Gemcitabine Fludarabine
In vivo studies demonstrate that tumor cell lines can become resistant after exposure
to various anticancer agents.

These cells express a specific cell surface glycoprotein that has which of the
following functions?

A Tyrosine kinase-coupled receptor

B Adenylate cyclase-coupled receptor
C Cell adhesion molecule
D Transmembrane ion channel
E ATP-dependent transporter
A 23 year old woman is seen in the ED with vaginal bleeding and abdominal cramps.
Her last menstrual period was 6 weeks ago and a pregnancy test is positive. She has
no significant past medical history, does not smoke cigarettes or drink alcohol.
Pelvic sono: gestational sac in left fallopian tube without rupture.
She is given 1 dose of methotrexate.

Which of following substances will most likely accumulate in the embroyonic tissues
as a result?

A Dihydrofolate polyglutamate
B Folinic acid
C Para-aminobnezoic acid
D Tetrahydrofolate
E Thymidylic acid
A 34 year old man with an unremarkable past medical history is being evaluated
for an enlarged lymph node in the anterior cervical chain that measures 4 cm in
diameter. He first felt the lymph node several weeks ago and says it has been
steadily increasing in size. He is concerned about whether or not he has cancer
and is referred to a specialist for surgical removal of the enlarged lymph node.
Biopsy reveals abnormal lymph node architecture and numerous lymphocytes.

Which of the following, if present, would be most consistent with malignancy in

this patient?

A Lymphocyte pleomorphism
B Abundant mitotic figures within the lymph node
C Nuclear changes in lymphocytes
D Monoclonal T cell receptor gene rearrangements
E Admixture of several lymphoid cell types within the lymph node
A 34 year old woman comes to office after her sister was diagnosed with breast
cancer. She has no nipple discharge, breast lumps or discomfort. Breast exam is
normal. Her sister was found to have a multiple base pair insertion affecting exon
11 of the BRCA1 gene that leads to a frameshift mutation. A screening test to
evaluate for a similar insertion mutation in the patient’s BRCA1 gene is
performed. The test uses polymerase chain reaction (PCR) to amplify the target
exon and gel electrophoresis to assess the size of the exon compared to the wild-
tyle allele.

Which of the following must be known in order to perform the amplification

part of this analysis?

A Restriction enzyme susceptibility sites within the target exon

B The amino acid sequence of the abnormal BRCA1 protein
C The cDNA nucleotide sequence
D The complete nucleotide sequence of the target exon
E The nucleotide sequence of the regions flanking the target exon
 Primers to flanking
sequences of region of
interest to be amplified
15 year old teen presents with SOB and has a CT scan of the chest which reveals a large
mediastinal mass and bilateral pleural effusions. CBC shows a leukocytosis with abnormal WBCs
seen on smear.
Immunophenotyping by flow cytometry on the abnormal WBCs shows that they are positive for
TDT and CD3 but negative for CD19.

Which of the following is the most likely diagnosis?

Blood smear: shown

A Acute lymphoblastic leukemia

B Acute myelogenous leukemia
C Burkitt’s Lymphoma
D Hodgkin Lymphoma
E Mantle Cell Lymphoma
A 63 year old man presents with fatigue.
Exam: bruising; no adenopathy or hepatosplenomegaly

CBC: WBC 20,500/ul

Hgb 8 g/dL
Platelets 40,000/ul
Blood smear: shown

Which disease does this patient have?

A Acute lymphoblastic leukemia
B Acute myelogenous leukemia
C Chronic lymphocytic leukemia
D Chronic myelogenous leukemia
E Hairy cell leukemia
F Hodgkin lymphoma
G Mononucleosis
A 42 year old man presents to the ED ill-appearing with fever and sore throat.

Exam: fever; bruises on trunk and blood oozing from IV site and venipuncture
site.
Labs: Fibrinogen 110 mg/dL
A bone marrow is performed and shows immature myeloid cells with azurophilic
needle-shaped cytoplasmic granules.

Chromosomal analysis of these immature cells is most likely to show which

abnormality?

A t(8;14)
B t(9;22)
C t(14;18)
D t(15;17)
E inv 16
A 43 year old man presents with fatigue, recurrent fever and sore throat. He is
treated with antibiotics without improvement. His wife notes that he has been
bruising easily and has gum bleeding.

Exam: low grade temp; pallor; red throat; bruises on arms and thighs
Blood smear: shown

Which chromosome abnormality will likely be found?

A t(8;14)
B t(9;22)
C t(11;14)
D t(15;17)
E 13q- (deletion 13 q)
A 32 year old man is seen in his doctor’s office with progressive fatigue, easy
bruising and recurrent episodes of gum bleeding.

Exam: several ecchymoses on legs

Labs: WBC 3,000/ul
Hgb 7.8 g/dL
Platelets 65,000/ul
Coagulation studies: PT 22 seconds PTT 53 seconds
Fibrinogen 134 mg/dL D-Dimer 4.1 ug/dL
A bone marrow is done and fluorescence in situ hybridization shows a balanced
translocation between the long arms of chromosomes 15 and 17.

Which of the following proteins is most likely to be abnormal in the

hematopoietic cells of this patient?

A Epidermal growth factor receptor

B GTP binding protein
C PDGF receptor
D Retinoblastoma gene product
E Retinoic acid receptor
A 36 year old with woman presents to her physician with persistent fever,
bleeding gums and a sore throat.

Blood smear: shown

These cells contain structures that would stain positive for which of the
following?

A Major basic protein

B Myeloperoxidase
C Platelet derived growth factor
D Tartrate resistant acid phosphatase
E Terminal deoxynucleotidyl transferase
A 35 year old woman and her husband have been trying to conceive for more
than a year and are followed by an infertility specialist. The woman is found to
have significant scarring and fibrosis of the fallopian tubes secondary to pelvic
inflammatory disease that she had at a young age. After a long struggle, she
becomes pregnant, gives birth to a boy who is evaluated by a pediatrician and
found to have a flat nasal bridge, small mouth and low set ears. The pediatrician
orders a karyotype analysis on the infant (shown).

The infant is most likely to be diagnosed with which of the following

conditions?

A Acute lymphoblastic leukemia

B Chronic myelogenous leukemia
C Immotile cilia
D Macroorchidism
E RBC sickling
F Rickets
A 12 year old boy is brought to his pediatrician because of fever, fatigue and easy
brusing.

Exam: pallor; generalized lymphadenopathy; bone tenderness

Labs show anemia, thrombocytopenia and leukocytosis, with atypical lymphoblasts
A bone marrow is consistent with acute lymphoblastic leukemia
The patient is treated with combination chemotherapy and 6 mercaptopurine is
given to maintain remission.

Which of the following enzymes inactivates this drug?

A Adenosine deaminase
B Dihydrofolate reductase
C Hypoxanthine-guanine phosphoribosyl transferase
C Monoamine oxidase
D P450 mixed-function oxidase
E Topoisomerase II
F Xanthine oxidase
Purine catabolism (break down of
nucleotides from DNA from nucleus of killed
cells) involves xanthine oxidase, which
converts hypoxanthine to xanthine and
xanthine to uric acid.

6 MP is a purine analogue anti-metabolite

chemotherapy drug that competes with
hypoxanthine and guanine; unclear (to me)
how it leads to cell death.
It is metabolized by xanthine oxidase.

Allopurinol, a med we use in patients getting

chemotherapy to prevent accumulation of
uric acid when tumor cells are being lysed
(and their DNA nucleotides are being rapidly
broken down to uric acid) INHIBITS xanthine
oxidase. This helps decrease the uric acid.
High levels of uric acid that can result from
tumor lysis syndrome hurt the kidney.
HOWEVER, if allopurinol is being used in a
patient who is getting 6MP, the dose of 6MP
must be adjusted (downward) as its
catabolism (by XO) will be blocked by the
allopurinol.
A 53 year old man presents with headaches and dizziness. His medical includes
hypertension and peptic ulcer disease (GERD).

Medications: chlorthalidone and antacids.

Exam: Plethora; Afebrile, B/P 146/92 Pulse 89/min RR 16/min BMI 26 kg/M2
Spleen is palpated 5 cm below the left costal margin
Labs: WBC 15,500/ul
Hgb 21.5 g/dL Hct 64% RBC 7.6 x 106 /ul
MCV 90 fl MCH 31 pg MCHC 33 g/dL RDW 14%
Platelets 545,000/ul

This patient most likely has a mutation in which of the following types of proteins?

A Cytoplasmic tyrosine kinase

B Growth-stimulating transcription factor
C Intrinsic receptor tyrosine kinase
D Tumor suppressor protein
E Vascular growth factor
A 65 year old woman presents with a several month history of fatigue, abdominal fullness, early satiety
and weight loss. She has no fevers, night sweats or cough. She does not smoke cigarettes, drink alcohol
or use recreational drugs. She is a retired chemical engineer. She is reading Ann Patchett’s
Commonwealth.

Exam: pale, anicteric. Mild hepatogmegaly and a palpable spleen tip.

CBC shows pancytopenia.
Blood smear shows immature granulocytes, nucleated erythrocytes and tear drop RBCs.
A bone marrow is inaspirable

Which histopathologic changes are likely to be present in the spleen?

A Accumulation of macrophages with fibrillary cytoplasm

B Diffuse neutrophilic infiltration and follicular necrosis
C Dilated sinusoids and fibrous nodules with hemosiderin
D Large islands of hematopoietic progenitor cells
E Numerous noncaseating epitheliod granulomas
A 52 year old man presents with dizziness, headaches and pruritus after he showers.
He smokes a pack of cigarettes/day for the past 15 years and drinks socially.

Exam: reddish face, mild splenomegaly

CBC: WBC 15,600/ul
Hgb 19 g/dL Hct 59% RBC 7.5 x 106/ul million
Platelets 550,000/ul

Which is most likely cause of patient’s findings?

A Decreased plasma volume

B Decreased blood oxygen saturation
C Increased bone marrow sensitivity to growth factors
D Increased RBC life span
E Increased serum EPO level
Some patients with non-small cell lung cancer develop constitutive tumor kinase
activity due to production of echinoderm microtubule-associated protein-like 4
anaplastic lymphoma kinase (EML4-ALK) a fusion protein that contributes to
carcinogenesis.

This is most similar to the molecular pathophysiology of which of the following

disorders?

A Burkitt’s lymphoma
B Chronic myelogenous leukemia
C Follicular lymphoma
D Li-Fraumeni syndrome
E Mantle cell lymphoma
A 66 year old man with hypertension and stage IV chronic kidney disease comes to office for
follow up for worsening fatigue and low energy for the past several months. He has no chest
pain or shortness of breath. He was previously nonadherent with antihypertensive therapy, but
now is taking his medications since renal dysfunction was diagnosed 2 years ago. He is a former
smoker (20 packs/year). He does not drink alcohol or use recreational drugs.

Exam: B/P 126/78 Pulse 68/min Cards: S4 heart sound

Labs show a normocytic, normochromic anemia with a low reticiculocyte count.
Iron studies are normal.
Treatment with a recombinant glycoprotein hormone is begun and repeat lab testing several
weeks later shows improvement in Hgb.

The effects of the hormone prescribed for this patient are most likely mediated by which of the
following pathways?

A Adenylate cyclase/cyclic AMP

B Arachidonic acid/phospholipase A2
C Janus kinase 2/single transducers and activators of transcription
D Nuclear receptors
E Phosphatidylinositol 3-kinase
F Ras/mitogen-activated protein kinase
A 24 year old previously healthy woman is seen in the ED with 3 days of fever, dyspnea
and cough productive of yellow sputum.

Exam: Temp 38.8 B/P 110/66 Pulse 110/min; Bronchial breath sounds and crackles
in the right lower lung field
Labs: WBC 54,000/ul
Differential: PMN 68% Bands 10% Myelocytes 3% Metamyelocytes 1%
Lymphs 15%
Hgb 13 g/dL
Platelets 350,000/ul
Leukocyte alkaline phosphatase (LAP) score is elevated

Which is the most likely additional finding to be seen on her blood smear?

A Basophilic oval inclusions in mature neutrophils

B Basophilic stippling of RBCs
C Immature cells with azurophilic rods
D Neutrophils with hypersegmented nuclei
E Small lymphoid cells with cleaved nuclei
A 67 year old woman presents with fatigue and dyspnea on exertion. She has no
significant past medical history and takes no medications. She has a good diet. She
does not smoke cigarettes, drink alcohol or use recreational drugs. She just read Elena
Ferrante’s My Brilliant Friend and found it extremely disappointing.
Exam: pallor; stool is guaiac negative; no adenopathy or hepatosplenomegaly
CBC: WBC 35,000/ul
Hgb 6.7 gm/dL
Platelets 45,000/uk
Flow cytometry on peripheral blood shows CD20 positive, CD3 negative WBCs

Which of the following is the most likely diagnosis?

A Adult T cell leukemia lymphoma
B Aplastic anemia
C Chronic lymphocytic leukemia
D Chronic myelogenous leukemia
E Hodgkin lymphoma
A 68 year old woman presents with a several month history of recurrent infections including
bacterial sinusitis, pneumonia and UTIs. She has no significant past medical history and was well
up until several months ago. She does not smoke cigarettes, drink alcohol or use recreational
drugs.
Exam: normal vital signs; no hepatosplenomegaly
Labs: normochromic, normocytic anemia
Bone marrow aspirate: shown

Which of the following is the most likely cause of this patient’s increased susceptibility to
infections?
A Aberrant lysosomal transport and fusion in leukocytes
B Decreased production of functional immunoglobulins
C Defective adhesion and transmigration of leukocytes
D Impaired formation of membrane attack complex
E Impaired phagocytic ability to generate superoxide
A 23 year old man presents with a several week history of a rapidly enlarging left jaw
mass. He comes from East Africa. He has no past medical history and takes no
medications.
Exam: Afebrile. Left sided jaw mass with associated bulky cervical adenopathy; the
mass is not red or warm.
Labs HIV negative
Jaw mass biopsy shows numerous mitotic figures and apoptotic bodies.

Which genetic feature is likely to be present?

A bcl2 overexpression
B bcr-abl rearrangement
C c-myc oncogene overexpression
D n-myc oncogene overexpression
E Tyrosine kinase activation
A 42 year old previously healthy woman is seen in the office for fever and sore throat. She denies cough.
Exam: tonsillar exudate and nontender cervical adenopathy measuring 3.5 cm in diameter.
She is treated with oral antibiotics.
At follow up 1 week later her symptoms have resolved. The previously enlarged cervical lymph node has
decreased slightly in size. On several follow up visits over the ensuing year the patient remains
asymptomatic. The size of the cervical lymph node fluctuates, but does not disappear completely.
She is referred to a surgeon and an excisional bx is done.

Which of the following will most likely be seen on bx?

A Acute lymphoblastic leukemia

B Burkitt’s lymphoma
C Diffuse large B cell lymphoma
D Follicular lymphoma
E Hairy cell leukemia
F Mycosis fungoides