February, 2020 | Pathology Review for USMLE

Questions 131-133: Hematopathology

Question 131

A 33-year-old female presents to her obstetrician and gynecologist for a yearly physical examination. She reports that over the past 6 months, her menstrual periods have been much heavier than normal. And, over the past 2 months, she has become fatigued more easily, and sometimes short of breath with relatively minimal physical exertion. Laboratory testing reveals a hemoglobin of 8.8 g/dL. In the following chart, which choice best indicates the physiologic changes her body will undergo?

Answer for Question 131

Answer: A (Increase in cardiac output, plasma volume, and red cell 2,3 diphosphoglycerate)

Explanation: The patient is anemic, most likely an iron deficiency anemia as a result of her heavy menstrual periods. In response to anemia, the body will increase cardiac output to increase oxygen delivery to the tissues; the body will increase plasma volume to allow for better mobility of blood (i.e., decrease viscosity); and the body will increase the concentration of red blood cell 2,3-diphosphoglycerate, which in turn decreases hemoglobin affinity for oxygen, which will allow for oxygen to be more easily delivered to the tissues.

Question 132

A 34-year-old female presents to her obstetrician/gynecologist. She reports that over the past 12 months, her menstrual periods have been heavier than normal. And, over the past 4 months, she has become fatigued more easily, and sometimes short of breath with relatively minimal physical exertion. Laboratory testing reveals a hemoglobin of 8.1 g/dL. Additional laboratory testing reveals a ferritin of 3 ng/mL (normal range: 20-200 ng/mL), a total iron binding capacity of 700 µg/dL (normal range of 255-450 µg/dL), and a reticulocyte production index of <2. Of the following, which term best describes her anemia?

A. Supramicrocytic
B. Microcytic
C. Normocytic
D. Macrocytic
E. Supramacrocytic

Answer for Question 132

Answer: B (Microcytic)

Explanation: The patient has clinical features consistent with an iron deficiency anemia (i.e., occurring in a younger woman with heavy menstrual cycles). Iron deficiency anemia is characterized as a microcytic anemia. Early iron deficiency anemia can be normocytic; however, given the relatively low hemoglobin (a normal female hemoglobin is 12-16 g/dL; a mild iron deficiency anemia would have a hemoglobin that is >9.0 g/dL), and with the patient being symptomatic, it would be most likely that the patient would be microcytic.

Question 133

A 48-year-old Caucasian female who uses aspirin to treat her rheumatoid arthritis presents to an acute care clinic with complaints of abdominal pain. A guaiac test was negative. A complete blood cell count revealed a hemoglobin of 11.2 g/dL, hematocrit of 33%, MCV of 83 fL, and a red blood cell distribution width of 14. The reticulocyte production index was <2. Additional laboratory testing revealed a low serum iron and elevated ferritin concentration. Of the following, what is the most likely diagnosis?

A. Iron deficiency anemia
B. α-thalassemia
C. Anemia of chronic disease
D. Autoimmune hemolytic anemia
E. Hereditary spherocytosis

Answer For Question 133

Answer: C (Anemia of chronic disease)

Explanation: Given the clinical scenario (a normocytic anemia occurring in a patient with rheumatoid arthritis) with an elevated ferritin concentration and evidence of decreased synthesis of red blood cells, the best choice is anemia of chronic disease. In iron deficiency anemia, the ferritin would be decreased. α-thalassemia most commonly occurs in African-Americans and would be much less likely in a Caucasian. In both autoimmune hemolytic anemia and hereditary spherocytosis, the reticulocyte production index should be >2, as the body is responding to the hemolysis by increasing production of red blood cells to replace those that are destroyed.

Questions 128-130: Hematopathology

Question 128

A 39-year-old female presents to her family physician with complaints of fatigue that has increased over the past 6 months. She is a runner and has had to cut back on her morning runs because of increased shortness of breath. A complete blood cell count reveals a hemoglobin of 8.3 g/dL, hematocrit of 24%, white blood cell count of 5200 cells/mm3, and platelet count of 300,000/mm3. The MCV is 70 fl. The reticulocyte production index (RPI) is <2. Of the following, what is the most likely mechanism for her presenting symptoms?

A. Splenic sequestration of red blood cells
B. Marrow infiltration by a non-neoplastic process
C. Decreased production of red blood cells
D. Antibody-mediated destruction of red blood cells
E. Decreased lifespan of red blood cells

Answer for Question 128

Answer: C (Decreased production of red blood cells)

Explanation: Given a slow developing anemia in a younger female, iron deficiency due to blood loss related to heavy menstrual or irregular menstrual bleeding is most likely. The low MCV confirms a microcytic anemia. The low reticulocyte production index indicates underproduction, such as would occur in an iron deficiency anemia, as not enough iron is available to produce red blood cells. While an antibody-mediated destruction of red blood cells could produce spherocytes, which would lead to a low MCV, the reticulocyte production index in a hemolytic anemia would be higher. With a decreased lifespan of red blood cells, such as in hereditary spherocytosis, the reticulocyte production index should be high in response to the red blood cell destruction. Marrow infiltration by a non-neoplastic process (e.g., sarcoidosis) would most likely affect all three cell lines, leading to leukopenia and thrombocytopenia as well as anemia.

Question 129

A 37-year-old female presents to her family physician with complaints of fatigue that has developed and been increasing over the past year. A review of systems indicates that she has been having heavier than normal menstrual periods for a little over a year. A complete blood cell count reveals a hemoglobin of 8.2 g/dL (normal: 12-16 g/dL), hematocrit of 24% (normal: 37-47%), a white blood cell count of 7.3 x 103 cells/mm3 (normal range: 4.5-11 x 103 cells/mm3), mean corpuscular volume of 67 fL (normal range: 80-100 fL), and platelet count of 280,000 cells/mm3 (normal range: 150-400,000/mm3). Of the following, which set of test results would confirm iron deficiency anemia?

Answer for Question 129

Answer: C (The RPI would be less than 2, both ferritin and serum iron would be decreased, and TIBC would be increased)

Explanation: Given a slow developing anemia in a younger female, iron deficiency due to blood loss related to heavy menstrual or irregular menstrual bleeding is most likely. The low MCV confirms a microcytic anemia. In iron deficiency anemia, there is underproduction of the red blood cells, which is indicated by the RPI (reticulocyte production index) of <2. As the body has a decreased amount of iron, both the serum iron and ferritin (i.e., the storage form of iron) would be decreased. Because the amount of iron in the body is decreased, the body has more capacity to bind iron, because no iron is available (i.e., the binding sites for iron are open and available for iron to deposit), and therefore the TIBC (total iron binding capacity) would be increased.

Question 130

A 43-year-old alcoholic male presents to an acute care clinic complaining of fatigue. A complete blood cell count is performed and reveals a hemoglobin of 8.3 g/dL and hematocrit of 24%. The white blood cell count and platelet count are also slightly lower than the reference range for the lab. The MCV is 120 fL. Additional laboratory testing reveals elevated concentrations of homocysteine and methylmalonic acid. A deficiency of which of the following nutrients would explain his condition?

A. Vitamin B12
B. Folate
C. Iron
D. Calcium
E. Copper

Answer for Question 130

Answer: A (vitamin B12)

Explanation: The patient has a megaloblastic anemia, characterized by a decreased concentration of hemoglobin and a markedly elevated MCV. Two causes of megaloblastic anemia are deficiency of folate or vitamin B12. A deficiency of either will result in elevated concentrations of homocysteine; however, a deficiency of B12 will also result in a deficiency of methylmalonic acid.

Questions 125-127: Hematopathology

Question 125

A 9-year-old male is brought to the emergency room by his parents because he has been sick for the past five days. He has not passed stool in two days. He has not wanted to eat, and has been vomiting anything his parents are able to get him to eat. Physical examination reveals abdominal tenderness associated with guarding and rebound tenderness. He is diagnosed with a perforation of the terminal ileum, and a resection is performed. Examining the pathologic specimen, the pathologist notes a mass. Genetic analysis of the mass would most likely reveal which of the following?

A. t(8;14)
B. t(2; 8)
C. t(15;17)
D. t(11;14)
E. t(8;21)
F. t(9;22)
G. t(14;18)

Answer for Question 125

Answer: A (t(8;14))

Explanation: The boy has a bowel obstruction. The source of the bowel obstruction is a neoplasm. Given his age and the location, Burkitt lymphoma is very likely. Burkitt lymphoma is associated with MYC (chromosome 8). The most common translocation moves MYC adjacent to the heavy chain gene on chromosome 14; thus, t(8;14). A translocation moving the MYC gene adjacent to one of the light chain genes t(2;8) or t(8;22) is also possible, but less common than t(8;14). While AML can present as a mass, this would be much less common than Burkitt lymphoma in this age group; so t(15;17) and t(8;21) are very unlikely. Mantle cell (t(11;14)) and follicular lymphoma (t(14;18)) are much more common in adults. t(9;22) would be associated with CML or ALL, which would be uncommon causes of a mass lesion, and not frequently associated with gastrointestinal manifestations.

Question 126

A 61-year-old female presents to her family physician with complaints that over the past year she has developed several bumps at places around her body. Her sister died of metastatic breast cancer and she is concerned that the same thing may happen to her. Physical examination reveals palpable lymph nodes on the right side of her neck, both axillae, and her left femoral region. A biopsy of one of the lymph node is performed. The pathologist describes a nodular neoplastic proliferation in the lymph node. The neoplastic cells express CD20 and CD10, but do not express CD5. Of the following, which set of features best describes this neoplasm.

Answer for Question 126

Answer: A (t(14;18) is present and involves BCL-2; t(11;14) is absent)

Explanation: The clinical characteristics of follicular lymphoma include generalized lymphadenopathy at presentation, the disease affects older patients (>50 years of age), and males and females are affected about equally. The staining characteristics in this case (CD20 and CD10 positive, and CD5 negative) are consistent with follicular lymphoma, which has a t(14;18) translocation involving the BCL-2 gene. Mantle cell lymphoma has a t(11;14), which involves the cyclin D1 gene, and mantle cell lymphoma is CD 5 positive.

Question 127

A 37-year-old white female who works at a local factory presents to her family physician complaining that over the past 6 months she has been more tired than normal, and when she exerts herself she will get shorter of breath than normal. A complete blood cell count reveals a hemoglobin of 8.5 g/dL, hematocrit of 24%, white blood cells count of 7200 cells/mm3, and platelet count of 250,000/mm3. Examination of the blood smear reveals red blood cells with increased central pallor. Of the following, what is the most likely diagnosis?

A. Iron deficiency anemia
B. Sarcoidosis with involvement of the bone marrow
C. Aplastic anemia due to chemical exposure at work
D. Acute leukemia
E. Parasitic infection

Answer for Question 127

Answer: A (Iron deficiency anemia)

Explanation: Given the fact that there is anemia without a decrease in any other cell line, the disorder is specific to the red blood cells and not from a generalized process involving the bone marrow, which would likely exclude sarcoidosis and acute leukemia; in addition, an acute leukemia would most likely present quicker (weeks to a few months). Aplastic anemia, such as from a chemical exposure, would affect all cell lines, and she should have thrombocytopenia and leukopenia as well. While a parasitic infection of the blood such as babesiosis or malaria could cause anemia, there is no history of travel or other associated findings to suggest this. Heavy menstrual bleeding would be a relatively common occurrence in younger females, and can lead to iron deficiency anemia.

Questions 122-124: Hematopathology

Question 122

During a yearly physical examination of a 19-year-old male, a family physician palpates cervical lymph nodes. One of the enlarged lymph nodes is biopsied. Large cells within the lymph node express CD15 and CD30. Of the following, what is the most likely diagnosis?

A. Burkitt lymphoma
B. Follicular lymphoma
C. Diffuse large B cell lymphoma
D. Lymphocyte predominant Hodgkin disease
E. Classical Hodgkin lymphoma

Answer for Question 122

Answer: E (Classical Hodgkin lymphoma)

Explanation: The CD15 and CD30 positivity are characteristic of classical Hodgkin lymphoma. Burkitt lymphoma, follicular lymphoma, and diffuse large B cell lymphoma are B cell neoplasms and do not normally express CD15 and CD30. Lymphocyte predominant Hodgkin disease does often present as cervical lymphadenopathy; however, the neoplastic cells are CD20 positive and do not normally express CD15 and CD30.

Question 123

A 55-year-old male presents to his family physician complaining of intermittent fevers and night sweats over the past 6 months. He also notes a 20 lb. weight loss in the same time frame. Physical examination reveals an enlarged spleen. A chest x-ray reveals enlarged mediastinal lymph nodes. Biopsy of a lymph node reveals large cells, some with bilobed nuclei and prominent nucleoli, surrounded by an infiltrate of lymphocytes, eosinophils, plasma cells, and macrophages. Of the following viruses, which one is most likely to be associated with his condition?

A. HTLV
B. Hepatitis B
C. CMV
D. Parvovirus
E. EBV

Answer for Question 123

Answer: E (EBV)

Explanation: The histologic findings are consistent with mixed cellularity Hodgkin disease, with the large cells with bilobed nuclei and prominent nucleoli being Reed-Sternberg cells. Mixed cellularity is the form of Hodgkin disease that is more common in older males, and can present with systemic symptoms, such as fevers, night sweats, and weight loss. Of the viruses listed, EBV is the one most commonly associated with Hodgkin disease (70% of cases of mixed cellularity), and most likely plays a role in the development of the neoplasm.

Question 124

A 53-year-old female with a history of Hashimoto’s thyroiditis diagnosed 10 years ago and treated with thyroid hormone replacement presents to her primary care physician because of painless enlargement of a mass on the right side of her neck, which has evolved over several months. Palpation of the mass during physical exam locates the mass to approximately the same location as the right lobe of the thyroid gland and to be about 1.5 cm in size. Of the following, what is the most likely diagnosis?

A. Lymphocyte predominant Hodgkin disease
B. Burkitt lymphoma
C. Extra-nodal marginal zone lymphoma
D. Metastatic breast carcinoma
E. Occult trauma

Answer for Question 124

Answer: C (Extra-nodal marginal zone lymphoma)

Explanation: Individuals with a chronic inflammatory process (such as Hashimoto thyroiditis, but also Sjogren syndrome and chronic gastritis among others) are at risk for the development of an extra-nodal marginal zone lymphoma, which is a relatively indolent neoplasm, hence the slow growth. While lymphocyte predominant Hodgkin disease can present in a cervical location, it is a rare form of Hodgkin disease and would essentially not occur within the thyroid gland itself. Burkitt lymphoma and metastatic breast carcinoma are more aggressive, and slow growth would be less likely, and they are not associated with Hashimoto thyroiditis. While occult trauma could cause a hematoma, which could present as a mass, given the time frame, this would most likely have resolved.

Questions 119-121: Hematopathology

Question 119

A 62-year-old male is scheduled for an elective cholecystectomy. Routine laboratory testing prior to the surgery reveals a hemoglobin concentration of 19.5 g/dL. Physical examination reveals an enlarged liver and an enlarged spleen. Additional laboratory testing reveals a low concentration of erythropoietin. Of the following, which is the most likely diagnosis?

A. Chronic myelogenous leukemia
B. Hairy cell leukemia
C. Epstein-Barr virus infection
D. Polycythemia rubra vera
E. Occult renal cell carcinoma

Answer for Question 119

Answer: D (Polycythemia rubra vera)

Explanation: Polycythemia rubra vera is often asymptomatic and thus could be identified during routine laboratory testing prior to surgery. Patients have an elevated hemoglobin and a low to normal erythropoietin concentration. Hepatomegaly and splenomegaly are common findings on physical examination. Renal cell carcinoma can produce erythropoietin, and thus, cause an elevated hemoglobin concentration. Chronic myelogenous leukemia, hairy cell leukemia, and EBV infection are also associated with splenomegaly, but are not causes of primary polycythemia.

Question 120

A 61-year-old male presents to his family physician. Over the past six months, he has had numerous episodes of weakness, lightheadedness, and headache, and occasionally dyspnea when he is working at his ranch. He also notes that after a bath his skin is particularly itchy. Laboratory testing reveals a hemoglobin of 20.2 g/dL. Genetic testing would most likely reveal which of the following?

A. JAK2 mutation
B. PAK2 mutation
C. RB mutation
D. p53 mutation
E. t(15;17)
F. t(9;22)
G. t(8;21)
H. inv 16

Answer for Question 120

Answer: A (JAK2 mutation)

Explanation: The clinical scenario is consistent with polycythemia rubra vera, which occurs in patients around the age of 60 years, and, while it can be asymptomatic, it can also cause weakness, fatigue, lightheadedness, and dyspnea. Male patients will have a hemoglobin of >18.5 g/dL. A mutation of JAK2, commonly V617F, is present in almost all patients with polycythemia rubra vera.

Question 121

A 53-year-old male presents to his family physician with complaints of fatigue that has developed over the past 6 months. Physical examination reveals normal lung and heart sounds. Palpation of the abdomen reveals an enlarged spleen. Laboratory testing reveals a white blood cell count of 45,000/μL. The platelet count is normal and the hemoglobin is 11.1 g/dL. A peripheral smear of the blood reveals an increased number of both mature and immature white blood cells as well as an increased number of basophils. Genetic analysis would reveal which of the following?

A. t(8;21)
B. t(15;17)
C. t(9;22)
D. t(8;14)
E. t(8;22)

Answer for Question 121

Answer: C (t(9;22)

Explanation: The clinical scenario is consistent with chronic myelogenous leukemia (CML), which most commonly presents in individuals aged 45-55 years of age, and may be asymptomatic or present with non-specific symptoms early on. The white blood cell count is elevated, and in CML, an increased number of basophils is characteristic. Splenomegaly is a common physical finding. The translocation associated with CML is t(9;22). t(8;21) and t(15:17) are associated with AML, and patients would present more precipitously and the increased white blood cell count would be dominated by blasts. t(8;14) and t(8;22) are characteristic of Burkitt lymphoma, which presents in children and young adults, and would present most commonly as a mass lesion and not a leukemia.