Transcript Hematology/Oncology

Hematology/Oncology
AOA USMLE Step 1 Review
Ashley Smith
Outline
•
•
•
•
RBC Questions
Platelet Abnormalities
WBC Questions
Oncology Questions
• Extra time for your Questions
RBC1
• An otherwise healthy Kenyan man is prescribed
trimethoprim-sulfamethoxazole for a urinary tract
infection. She presents to the emergency department
with jaundice, fatigue, and confusion. Which of the
following might you see in the RBCs of a peripheral
smear?
A. Heinz bodies
B. Howell-Jolly bodies
C. Basophilic stippling
D. Auer rods
E. Reed-Sternberg cells
Answer
• A is the correct answer
G6PD deficiency is often asymptomatic until faced with
an oxidative challenge, such as the drug TMP-SMX. It
usually occurs in people of central African, MiddleEastern, or Western Asian origin. The classic finding in
RBCs is Heinz bodies (Answer A), which are collections
of denatured hemoglobin. Howell-Jolly bodies are
nuclear remnants in RBCs that remain due to failure of
splenic sequestration in Sickle-cell disease. Basophilic
stippling represents RNA collections that are most
classically associated with lead poisoning. Auer rods are
clumps of granular material diagnostic of acute myeloid
leukemia (AML). Reed-sternberg bodies are the "owleyes" pathognomonic for Hodgkin's lymphoma.
RBC2
• A 24-year-old, thin, African man comes to your office as
a new patient. He has recently moved to America and
speaks little English. When you ask about previous
medical history, he says that he has a problem with his
blood and has frequent pain, but cannot explain any
more. His sclerae are icteric. Upon questioning, he
reports that his family members also have the same
problem with their blood. What type of hematologic
disorder should be suspected in this patient?
A. Genetic hemoglobinopathy
B. Iron-deficiency anemia
C. Prothrombotic state
D. Porphyria
E. Thalassemia
Answer
•
A is the correct answer
Hemoglobinopathies (A) are qualitative defects in hemoglobin, typically due to genetic mutations
in globin genes. This leads to amino acid substitutions, which affects the structure, function, and
stability of the hemoglobin. The most common mutation is that of beta-globin, leading to the HbS
of sickle cell disease. This patient's appearance, ancestry, and family history make a
hemoglobinopathy most likely.
Iron-deficiency anemia (B) can be caused by many disease processes such as blood loss or
inadequate dietary intake, but would be unlikely to cause systemic disease as this patient
manifests.
Prothrombotic state (C) can be genetic or acquired. This patient's presentation and appearance
are not suggestive of a prothrombotic state, and his young age also makes this relatively less
likely.
(D) Porphyrias can be inherited or acquired. They are caused by excessive production,
accumulation and excretion of porphyrins or their precursors. These are much rarer than
hemoglobinopathies, especially in Africans.
Thalassemia (E) is a quantitative deficiency of hemoglobin caused by an unbalanced synthesis of
globin chains. Typically, an entire chain is deficient, either lacking an alpha-chain or a beta-chain.
If the patient does not have a hemoglobinopathy, this diagnosis may be worth exploring.
•
Sickle Cell - salmonella osteomyelitis
RBC3
• You are examining a patient's peripheral blood smear under a light
microscope. The patient is a 35-year-old woman who complains of
increasing fatigue over the last several months. She is a strict
vegetarian and eats no animal products. As a child, she had a
portion of her terminal ileum removed.
• The smear is notable for considerable enlargement of the RBCs and
hypersegmented neutrophils. You don't notice any schistocytes.
From these observations, what is the most likely condition the
patient has?
A. Heriditary spherocytosis
B. Iron-deficiency anemia
C. Vitamin B12 deficiency anemia
D. Sickle cell anemia
E. Thalassemia
Answer
• C is the correct answer
The smear is consistent with megaloblastic anemia which usually
results from folate or Vitamin B12 deficiency. In this case the history
is most consistent with B12 deficiency (lack of red meat, terminal
ileum resection, pernicious anemia).
• Iron deficiency anemia would result in a microcytic anemia and be
more consistent in a woman with heavy menstrual periods.
Thalassemia is also microcytic but would usually present earlier an
is characterized by uniform small RBCs. Sickle cell anemia would
show evidence of sickling. Hereditary spherocytosis would
demonstrate round RBCs on peripheral smear and also usually
presents in childhood with anemia and enlarged spleen.
RBC4
• A 75-year-old man with a history of rheumatoid arthritis
presents complaining of progressively worsening fatigue
and weight loss. He has lost 30 lbs over the past two
months and is losing his appetite. A stool guaiac is
positive and his hematocrit is 32%. Considering the most
likely cause of this patient's anemia, which value is most
likely to be decreased?
A. RBC protoporphyrin
B. Serum ferritin
C. Serum iron
D. Soluble transferrin receptor levels
E. Total iron binding capacity
Answer
•
C is the correct answer
This patient likely has an iron-deficiency anemia secondary to occult blood
loss (possibly due to colon cancer given the positive stool guiac). The
stages of iron deficiency in sequence are as follows:absent iron
stores;decreased serum ferritin;decreased serum iron; increased TIBC;
decreased iron saturation(%); normochromic normocytic anemia; microcytic
hypochromic anemia. The total iron binding capacity will be elevated as
there are relatively "more" binding sites for iron on transferrin receptors.
Increased transferrin levels will also increase the soluble receptor levels.
RBC protoporphyrin will rise as iron is needed to proceed from this
intermediate in heme synthesis.
Serum ferritin in iron-deficiency anemia is generally low, as it reflects the
iron "stores" in the bone marrow (which will be depleted). However, in
patients with concomitant inflammatory states such as cancer (possible
colon cancer in this patient) or autoimmune disease (rheumatoid arthritis in
this patient), ferritin levels may not be decreased as it is also an acute
phase reactant.
RBC5
• What process do erythrocytes obtain their
energy primarily from under normal physiological
conditions?
A. Glycolysis
B. Lipid metabolism
C. Oxidative phosphorylation
D. Photosynthesis
E. Pyruvate metabolism
Answer
• A is the correct answer
•
Erythrocytes do not have any membranebound organelles (such as mitochondria).
Therefore, they can only obtain their
energy through glycolysis.
Anemia Classification
Microcytic (< 80)
Normocytic (80-100)
Macrocytic (> 100)
Iron deficiency
Chronic Disease
Folate deficiency
Chronic Disease
* Others
B12 deficiency
Sickle Cell
Hemolytic often
Liver disease
Thalassemia
Aplastic
Hypothyroidism
Lead Poisoning
Sideroblastic
EtOH
Iron Deficiency vs Chronic Disease
Type
Iron Def
Chronic
Disease
Serum
Iron
TIBC
Ferritin
Marrow
Iron
Hemolytic Anemia
• Hereditary Spherocytosis: Lab test?
• G6PD – Inheritance?
• Autoimmune
– Warm – IgG
– Cold – IgM Associated with what bacteria?
WBC1
• In young infants as well as geriatrics patients,
"bandemia" (increased band cells) is a sign of acute
bacterial infection. When a band cells differentiates,
which of the following types of cells is a possible mature
cell type it can become?
A. Erythrocyte
B. Lymphocyte
C. Neutrophil
D. Monocyte
E. Platelet
Answer
• C is the correct answer
Myeloblasts differentiate into promyelocytes,
myelocytes, metamyelocytes, then band cells,
and finally branch into neutrophils, eosinophils
and basophils. These types of cells are all
known as granulocytes. Lymphoblasts
differentiate into B cell and T cell lymphocytes,
as well as natural killer cells. Monoblasts
differentiate into monocytes. Megakaryoblasts
turn into megakaryocytes, which produce
platelets.
WBC2
• A 35 year-old male presents with fever and abdominal
swelling. He reports weight loss and night sweats over
the past month. Physical exam reveals enlarged
abdominal lymph nodes; a lymph node biopsy
demonstrates a "starry sky" appearance.
Which virus is most likely associated with the condition
described above?
A. Epstein Barr Virus
B. Hepatitis B Virus
C. Human Immunodefiency Virus
D. Human Papilloma Virus
E. Human T-cell Lymphoma Virus-1
Answer
• A is the correct answer
This patient classically presents with Burkitt's lymphoma.
This neoplasm has been linked to infection with Epstein
Barr Virus (EBV, (A)).
(B) HBV is associated with hepatocellular carcinoma.
(C) HIV is associated with Kaposi's sarcoma.
(D) HPV is linked to cancers of the cervix and vulva, as
well as laryngeal papillomas.
(E) HTLV-1 is linked to adult T cell leukemia and
lymphoma.
WBC3
• A patient presents with cervical lymphadenopathy.
Biopsy demonstrates a nodular lymphoma with follicle
formation. This lesion would most likely be associated
with which of the following?
(A)
(B)
(C)
(D)
(E)
bcr-c-abl
bcl-2 activation
c-myc activation
t(8, 14)
t(9, 22)
Answer
• The correct answer is B. Nodular lymphomas of all
types are derived from the B-cell line. The translocation
t(14, 18), with bcl-2 activation, is associated with these
lymphomas.
• An abl-bcr hybrid (bcr-c-abl;Philadelphia chromosome
choice A) and t(9, 22) translocation (choice E) are
associated with chronic myeloid leukemia (CML).
• c-myc activation (choice C) and t(8, 14) (choice D) are
associated with Burkitt lymphoma.
WBC4
• 60 y/o African American male presents with
constipation and generalized bone pain is found
to have hypercalcemia. Skull x-ray shows lytic
bone lesions. What abnormality is likely on
urinalysis?
• A. Increased leukocyte esterase
• B. Decreased specific gravity
• C. Glucose
• D. Increased protein
• E. No abnormality
Answer
• The answer is D, Increased protein
The patient in this case presents with symptoms of
hypercalcemia secondary to multiple myeloma.
In addition to lytic bone lesions, it is
characterized by Bence Jones protein (Ig kappa
light chain) in the urine, anemia and rouleaux
formation of rbcs, and increased infections.
The other U/A findings are associated with UTI, DI,
DM respectively.
WBC5 Diagnosis?
• 4 y/o m w/ 1 wk h/o fever, pallor, ha, and bone
tenderness. PE: fever, HSM, and generalized LAD. Bld
Smear reveals absolute lymphocytosis with abundant
TdT+ lymphoblasts
• 17 y/o m w/ 2mo h/o fever, night sweats and wt loss. PE:
cervical LAD and HSM, CBC: leukocytosis, CXR: bil hilar
LAD, node biopsy: Reed-Sternberg cells
• 60 y/o m w/ fatigue and anorexia. PE: gen LAD and
HSM, WBC: 250,000, pos direct Coombs, smear shows
numerous small round lymphocytes and smudge cells
Leukemia Review
ALL
Kids, fever, HSM, LAD
AML
Auer rods, t(15,17)
assoc with which
type? Tx?
Elderly, smudge cells
CLL
CML
Philadelphia Cr, what
translocation? Tx?
Lymphoma Review
Hodgkins
Burkitt
Reed Sternberg,
young men, B
symptoms, contiguous
EBV, starry sky, jaw
mass, t(8,14)
Follicular
Most common,
translocation?
Lymphoblastic
T-cell, mediastinal
mass in kids
Mycosis
Skin manifestations
Fungoides
Platelets
A 20 y/o female presents with anemia secondary to a
history of heavy menstrual periods since menarche. On
further questioning, her mother also has a history of
heavy periods and “some kind of clotting disorder.”
Given the mostly likely diagnosis, evaluation of
platelets, bleeding time and coagulation would likely
show which of the following?
A. Increased bleeding time, decreased platelets
B. Increased PT, PTT, bleeding time, dec platelets
C. Increased bleeding time and PTT, normal platelets
D. No abnormality
E. Increased PTT only
Answer
• The correct answer is C. The patient likely has
von Willebrand Disease. See chart:
Disease PLTs
Bleed
Time
ITP/TTP/
HUS
vWD
Nml
Hemophilia Nml
DIC
PT
PTT
Nml
Nml
Nml
Nml
Nml
Oncology1
• A 44 year-old female reports a waxing and waning cough, dyspnea
and vague chest discomfort for the past five years. She also has
intermittent fevers over the same time period with a six pound
weight loss. On exam, red, tender subcutaneous swelling is found
on both lower limbs, and decreased breath sounds and rales are
found bilaterally. A biopsy of one of the skin lesions shows
noncaseating granulomas. A chest X-ray shows mediastinal
lymphadenopathy. Which of the following electrolyte abnormalities is
most likely evident in this patient's plasma?
A. Hypercalcemia
B. Hyperkalemia
C. Hypernatremia
D. Hypocholermia
E. Hyponatremia
Answer
• A is the correct answer
The likely diagnosis is pulmonary sarcoidosis.
The noncaseating granulomas are evident in the
skin lesions of erythema nodosum and the chest
X-ray shows hilar adenopathy. An increase in
serum vitamin D levels are a result of
hypersecretion by pulmonary macrophages,
resulting in the body retaining calcium.
Hypercalcemia and hypercalciuria are apparent
on laboratory examination.
Oncology2
• A 66-year-old man presents with new-onset weight gain, excessive
sweating, and increased fatigue. His only significant past medical
history is a bout of uncomplicated pneumonia several years ago. On
physical examination, his voice sounds hoarse, which he attributes
to his 2-packs per day smoking habit for the last 25 years, and there
are purple markings over his abdomen. Corticotrophin releasing
hormone (CRH) challenge and dexamethasone suppression test are
within normal limits, and bilateral adrenal CT scan is negative. Chest
X-ray reveals a left lung mass adjacent to the hilum. Assuming that a
lung neoplasm is responsible for his symptoms, what is this patient’s
most likely prognosis?
A. Benign course
B. Good prognosis with surgery
C. Good prognosis due to low incidence of metastatic spread
D. Poor prognosis due to likely metastatic spread to distant sites
E. Prognosis comparable to squamous cell carcinoma of the lung
Answer
• D is the correct answer
This patient’s 50-pack-year history of smoking puts him at risk for
carcinoma of the lung. His signs and symptoms are consistent with
paraneoplastic syndrome, commonly seen in the setting of small cell
lung cancer. Small cell lung cancer carries the worst prognosis of all
lung carcinomas due to its early metastatic spread to distant sites,
including the brain, liver, bone, and adrenal glands. For this reason,
surgery is not generally considered as effective treatment. Small cell
lung cancer frequently involves hilar and mediastinal lymph nodes,
which can be demonstrated on chest X-ray and manifest as
hoarseness due to invasion or compression of the left recurrent
laryngeal nerve by the expanding lymph nodes.
Choices A, B, and C are incorrect. Squamous cell carcinoma
(Choice E) carries the best prognosis of all lung cancer for potential
5-year survival.
Lung Cancer Review
Type
Key Words
Squamous
Best prognosis, PTH
smoking, hilar
Most common,
scar, peripheral
Peripheral lung, HCG,
poor prognosis gynecomastia
Adeno
Large Cell/Oat
Cell
Small Cell
Distant mets,
poor prognosis
Paraneoplastic?
ACTH, ADH
Oncology3
• A pathologist receives a normal specimen resected from
a patient’s gastrointestinal tract. Under the microscope,
she sees that the mucosa contains columnar cells
lacking villi. There are many straight and long tubular
glands. This specimen most likely originates from which
portion of the GI tract?
A. Esophagus
B. Large intestine
C. Pharynx
D. Small Intestine
E. Stomach
Answer
• B is the correct answer
The large intestine (choice B) contains the cecum and the colon. Its
mucosa is composed of columnar cells lacking villi, and contains
openings which give way to tubular glands known as the crypts of
Lieberkuhn.
The mucosa of the esophagus (choice A) is composed of thick,
stratified, squamous, nonkeratinized epithelium.
The pharynx (choice C) contains stratified, squamous epithelium, as
well as ciliated, pseudostratified, columnar epithelium.
Intestinal villi are the hallmark of the small intestine (choice D). They
are composed of outgrowths of the mucous membrane into the
lumen. Crypts of Lieberkuhn are also found in the small intestine.
The stomach (choice E) mucosa contain simple, columnar cells, but
lacks the crypts of Lieberkuhn
Oncology4
• A patient comes to you for counseling about his
risk for colon cancer. Which of the following risk
factors in this patient is thought to be associated
with colon cancer?
• A. Hx of colon CA in a 2nd cousin
• B. Obesity
• C. Irritable Bowel Syndrome
• D. Diet rich in fruit and vegetables
• E. Smoking
Answer
• The answer is B, obesity
• Colon cancer is thought to be associated
with obesity, history of cancer in a 1st
degree relative, inflammatory bowel
disease, and diets rich in red meat.
• Diets rich in fruits, veggies and fiber can
be colon protective. Regular exercise may
also be of benefit.
Colon Cancer Review
Polyp Syndromes
FAP, Lynch, Peutz-Jeghers
Screening?
Symptoms? Ascending vs Descending
Treatment?
Prognostic factor?
Metastasis?
Oncology5
• A firm, irregular prostatic nodule is discovered
during annual physical examination of a 66y/o
patient. Biopsy reveals the presence of prostate
cancer. Which of the following factors has the
greatest prognostic impact?
• A. Degree of cellular atypia
• B. Histological grading
• C. Initial PSA level
• D. Pathological staging
• E. Presence of mitotic figures
Answer
• The answer is D, Pathological Staging
Stage is determined by extent of tumor
infiltration and metastasis. TNM is a
common method. Survival has been more
closely correlated with staging vs grading
of tumor. PSA is not a reliable prognostic
indicator but can be useful in monitoring
disease recurrence.
Breast Cancer Review
•
•
•
•
•
•
•
Risk Factors?
Screening?
Most Common Type?
Common location/presentation?
Diagnosis?
Metastasis?
Prognostic indicator?
Questions?
References
• www.wikitestprep.org
• Deja Review USMLE Step 1 Essentials
• USMLE Step 1: Lange Q&A
• My Email: [email protected]