Hematology/Oncology

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Hematology/Oncology

• AOA USMLE Step 1 Review
• Ashley Smith

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Outline

• RBC Questions
• Platelet Abnormalities
• WBC Questions
• Oncology Questions
• Extra time for your Questions

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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 bodiesB.
  Howell-Jolly bodiesC. Basophilic stipplingD.
  Auer rodsE. Reed-Sternberg cells

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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,
  Middle-Eastern, 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 "owl-eyes"
  pathognomonic for Hodgkin's lymphoma.

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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 hemoglobinopathyB. Iron-deficiency
  anemiaC. Prothrombotic stateD. PorphyriaE.
  Thalassemia

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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

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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 spherocytosisB.
  Iron-deficiency anemiaC. Vitamin B12 deficiency
  anemiaD. Sickle cell anemiaE. Thalassemia

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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.

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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
  protoporphyrinB. Serum ferritinC. Serum ironD.
  Soluble transferrin receptor levelsE. Total iron
  binding capacity

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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 followsabsent iron
  storesdecreased serum ferritindecreased 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.

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RBC5

• What process do erythrocytes obtain their energy
  primarily from under normal physiological
  conditions?A. GlycolysisB. Lipid metabolismC.
  Oxidative phosphorylationD. PhotosynthesisE.
  Pyruvate metabolism

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Answer

• A is the correct answer
• Erythrocytes do not have any membrane-bound
  organelles (such as mitochondria). Therefore,
  they can only obtain their energy through
  glycolysis.

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Anemia Classification
Microcytic (lt 80) Normocytic (80-100) Macrocytic (gt 100)
Iron deficiency Chronic Disease Folate deficiency
Chronic Disease Others B12 deficiency
Sickle Cell Hemolytic often Liver disease
Thalassemia Aplastic Hypothyroidism
Lead Poisoning EtOH
Sideroblastic

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Iron Deficiency vs Chronic Disease
Type Serum Iron TIBC Ferritin Marrow Iron
Iron Def
Chronic Disease
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Hemolytic Anemia

• Hereditary Spherocytosis Lab test?
• G6PD Inheritance?
• Autoimmune
• Warm IgG
• Cold IgM Associated with what bacteria?

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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. ErythrocyteB. LymphocyteC.
  NeutrophilD. MonocyteE. Platelet

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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.

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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 VirusB. Hepatitis B
  VirusC. Human Immunodefiency VirusD. Human
  Papilloma VirusE. Human T-cell Lymphoma Virus-1

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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.

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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)       bcr-c-abl
• (B)       bcl-2 activation
• (C)       c-myc activation
• (D)       t(8, 14)
• (E)       t(9, 22)
•  
•  

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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-ablPhiladelphia
  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.

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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

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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.

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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
  

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Leukemia Review
ALL Kids, fever, HSM, LAD
AML Auer rods, t(15,17) assoc with which type? Tx?
CLL Elderly, smudge cells
CML Philadelphia Cr, what translocation? Tx?
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Lymphoma Review
Hodgkins Reed Sternberg, young men, B symptoms, contiguous
Burkitt EBV, starry sky, jaw mass, t(8,14)
Follicular Most common, translocation?
Lympho-blastic T-cell, mediastinal mass in kids
Mycosis Fungoides Skin manifestations
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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?
• Increased bleeding time, decreased platelets
• Increased PT, PTT, bleeding time, dec platelets
• Increased bleeding time and PTT, normal platelets
• No abnormality
• Increased PTT only

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Answer

• The correct answer is C. The patient likely has
  von Willebrand Disease. See chart

Disease PLTs Bleed Time PT PTT
ITP/TTP/HUS Nml Nml
vWD Nml Nml
Hemophilia Nml Nml Nml
DIC
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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.
  HypercalcemiaB. HyperkalemiaC. HypernatremiaD.
  HypocholermiaE. Hyponatremia

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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.

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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 patients most likely prognosis?A. Benign
  courseB. Good prognosis with surgeryC. Good
  prognosis due to low incidence of metastatic
  spreadD. Poor prognosis due to likely metastatic
  spread to distant sitesE. Prognosis comparable
  to squamous cell carcinoma of the lung

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Answer

• D is the correct answer This patients
  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.

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Lung Cancer Review
Type Key Words Paraneoplastic?
Squamous Best prognosis, smoking, hilar PTH
Adeno Most common, scar, peripheral
Large Cell/Oat Cell Peripheral lung, poor prognosis HCG, gynecomastia
Small Cell Distant mets, poor prognosis ACTH, ADH
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Oncology3

• A pathologist receives a normal specimen resected
  from a patients 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. EsophagusB. Large intestineC.
  PharynxD. Small IntestineE. Stomach

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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

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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

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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.

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Colon Cancer Review

• Polyp Syndromes
• FAP, Lynch, Peutz-Jeghers
• Screening?
• Symptoms? Ascending vs Descending
• Treatment?
• Prognostic factor?
• Metastasis?

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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

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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.

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Breast Cancer Review

• Risk Factors?
• Screening?
• Most Common Type?
• Common location/presentation?
• Diagnosis?
• Metastasis?
• Prognostic indicator?

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Questions?
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References

• www.wikitestprep.org
• Deja Review USMLE Step 1 Essentials
• USMLE Step 1 Lange QA
• My Email afrey_at_neoucom.edu