Hematology/Oncology

1. Hematology/Oncology AOA USMLE Step 1 Review Ashley Smith

2. Outline • RBC Questions • Platelet Abnormalities • WBC Questions • Oncology Questions • Extra time for your Questions

3. 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

4. Answer • A is the correct answerG6PD 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.

5. 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

6. Answer • A is the correct answerHemoglobinopathies (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

7. 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

8. Answer • C is the correct answerThe 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.

9. 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

10. Answer • C is the correct answerThis 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.

11. RBC5 • What process do erythrocytes obtain their energy primarily from under normal physiological conditions?A. GlycolysisB. Lipid metabolismC. Oxidative phosphorylationD. PhotosynthesisE. Pyruvate metabolism

12. 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.

13. Anemia Classification

14. Iron Deficiency vs Chronic Disease

15. Hemolytic Anemia • Hereditary Spherocytosis: Lab test? • G6PD – Inheritance? • Autoimmune • Warm – IgG • Cold – IgM Associated with what bacteria?

16. 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

17. Answer • C is the correct answerMyeloblasts 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.

18. 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

19. Answer • A is the correct answerThis 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.

20. 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)

21. 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.

22. 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

23. 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.

24. 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

25. Leukemia Review

26. Lymphoma Review

27. 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

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

29. 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

30. Answer • A is the correct answerThe 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.

31. 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 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

32. Answer • D is the correct answerThis 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.

33. Lung Cancer Review

34. 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. EsophagusB. Large intestineC. PharynxD. Small IntestineE. Stomach

35. Answer • B is the correct answerThe 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

36. 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

37. 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.

38. Colon Cancer Review Polyp Syndromes FAP, Lynch, Peutz-Jeghers Screening? Symptoms? Ascending vs Descending Treatment? Prognostic factor? Metastasis?

39. 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

40. 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.

41. Breast Cancer Review • Risk Factors? • Screening? • Most Common Type? • Common location/presentation? • Diagnosis? • Metastasis? • Prognostic indicator?

42. Questions?

43. References • www.wikitestprep.org • Deja ReviewUSMLE Step 1 Essentials • USMLE Step 1: Lange Q&A • My Email: afrey@neoucom.edu