WebPath Hematopathology

Question 25 A 19-year-old primigravida of Southeast Asian ancestry gives birth at 35 weeks gestation a male infant. On physical examination the infant is markedly hydropic. Laboratory studies show his hematocrit is 17% and the peripheral blood smear reveals numerous nucleated red blood cells and even a few erythroblasts. The red blood cells display marked anisocytosis and poikilocytosis. Which of the following diseases is most likely to be present in this infant? A Sickle cell anemia B Alpha-thalassemia C Hemoglobin E disease D G6PD deficiency E Hereditary elliptocytosis

(B) CORRECT. The form of alpha-thalassemia seen in Southeast Asia has two abnormal alpha globin genes on the same chromosome, so it is possible to inherit two bad sets, leading to a complete lack of alpha globin chain formation, so that fetal hemoglobin (two alpha and two gamma chains) cannot be made, and there is a severe anemia.

Question 23 A 51-year-old man has become increasingly fatigued for the past 10 months. On physical examination there are no abnormal findings. Laboratory studies show his Hgb is 9.2, Hct 27.9%, MCV 132 fL, platelet count 242,000/microliter, and WBC count 7590/microliter. Which of the following morphologic findings is most likely to be present on examination of his peripheral blood smear? A Hypersegmented neutrophils B Nucleated red blood cells C Blasts with Auer rods D Hypochromic, microcytic RBC's E Schistocytes

(A) CORRECT. The increased MCV points to a macrocytic anemia such as a megaloblastic anemia that can also have hypersegmented PMN's from delayed maturation and reduced numbers of nuclear divisions.

Question 31 A 38-year-old woman has become increasingly fatigued for the past 3 months. During the past week she has noted purple blotches on her skin. On physical examination there are purpuric areas of skin on her trunk and extremities. She has no hepatosplenomegaly and no lymphadenopathy. Laboratory studies show Hgb 6.8 g/dL, Hct 20.7%, MCV 91 fL, platelet count 28,760/microliter, and WBC count 1940/microliter. Which of the following is the most likely diagnosis? A Aplastic anemia B Myeloproliferative disorder C Immune thrombocytopenic purpura D Large B cell lymphoma E Hereditary spherocytosis

(A) CORRECT. There is evidence from the peripheral cytopenias for marked hypocellularity of the bone marrow with aplastic anemia. The spleen is of normal size with aplastic anemia. The 'aplasia' here refers to the three major cell lines: myeloid, and megakaryocytic as well as erythroid.

Question 7 A 30-year-old man has had a progressively worsening productive cough for one month. On physical examination, a few small non-tender lymph nodes are palpable in the axillae, and the tip of the spleen is palpable. Laboratory studies show Hgb 10.2 g/dL, Hct 31.1%, MCV 90 fL, WBC count 67,000/microliter, and platelet count 36,000/microliter. Microscopic examination of his peripheral blood smear shows many blasts with Auer rods. Which of the following is the most likely diagnosis? A Leukemoid reaction B Acute myelogenous leukemia C Chronic lymphocytic leukemia D Lymphoblastic leukemia E Leukoerythroblastosis

(B) CORRECT. The high WBC count with the blasts and Auer rods are very characteristic for an acute myelogenous leukemia (AML) that can occur in young adults.

Question 3 A 17-year-old adolescent has had malaise for the past 3 weeks. He has a mild pharyngitis on physical examination, as well as tender axillary and inguinal lymphadenopathy. The spleen is palpable. A CBC shows Hgb 14.0 g/dL, Hct 42.2%, MCV 90 fL, platelet count 301,300/microliter, and WBC count 8120/microliter with 'atypical lymphocytes' on the peripheral blood smear. His illness is most likely to be acquired via which of the following mechanisms? A Congenital genetic abnormality B From close contact on a date C As a result of an insect bite D Through an environmental exposure at work E Without any known etiology

(B) CORRECT. Infectious mononucleosis with Epstein-Barr virus (EBV) infection is typically acquired with close personal contact. This self-limited viral infection resolves in weeks.

Question 9 A 69-year-old man has noted the presence of several lumps on the right side of his neck for the past 5 months. On physical examination he has firm, non-tender, movable lymph nodes palpable in right posterior cervical region. He does not have splenomegaly or hepatomegaly. Laboratory studies show Hgb 11.3 g/dL, Hct 40%, MCV 87 fL, platelet count 256,000/microliter, and WBC count 7230/microliter. A cervical lymph node biopsy is performed and on microscopic examination shows numerous crowded nodules of small, monomorphic lymphocytes. Which of the following is the most likely diagnosis? A Chronic lymphocytic leukemia B Follicular lymphoma C Infectious mononucleosis D Hodgkin lymphoma, lymphocyte predominance type E Reactive hyperplasia

(B) CORRECT. Lymphadenopathy with malignant lymphoma is typically nontender, as contrasted with the lymphadenopathy of infections. Follicular lymphomas occur in adults.

Question 32 A 44-year-old man has noted a change in the appearance of his face over the past 7 months. On physical examination his facial skin is thickened and reddened. A punch biopsy of skin is performed and on microscopic examination shows infiltration by neoplastic T lymphocytes that are CD4 positive. Which of the following is the most likely diagnosis? A Hodgkin lymphoma B Mycosis fungoides C Burkitt lymphoma D Acute lymphocytic leukemia E Hairy cell leukemia

(B) CORRECT. Mycosis fungoides (with no relationship to fungi) is one form of cutaneous T-cell lymphoma. The abnormal CD4 cell proliferation is infiltrting the skin and producing erythroderma. If these neoplastic cells circulate, it is known as Sezary syndrome.

Question 14 A 16-year-old boy has had a low energy level for as long as he can remember. On physical examination he has a palpable spleen tip. A CBC shows Hgb of 8.8 g/dL, Hct 24.1%, MCV 65 fL, platelet count 187,000/microliter, and WBC count 7400/microliter. His serum ferritin is 3740 ng/mL. A bone marrow biopsy is performed and on microscopic examination reveals a myeloid:erythroid ratio of 1:4, and there is 4+ stainable iron. Which of the following is the most likely diagnosis? A G6PD deficiency B Beta-thalassemia C Sickle cell anemia D Hereditary spherocytosis E Malaria

(B) CORRECT. Reduced beta-globin chain synthesis from beta-thalassemia leads to RBC microcytosis, hypochromia, ineffective erythropoiesis, and excessive iron absorption. There is chronic anemia, because the major hemoglobin A1 is produced insufficiently. The nature of the mutation, typically affecting RNA transcript production, determines the severity of the disease.

Question 2 A 33-year-old woman has experienced low grade fevers, night sweats, and generalized malaise for the past 2 months. On physical examination she has non-tender cervical and supraclavicular lymphadenopathy. A cervical lymph node biopsy is performed. On microscopic examination at high magnification there are occasional CD15+ and CD30+ Reed-Sternberg cells along with large and small lymphocytes and bands of fibrosis. Which of the following is the most likely diagnosis? A Burkitt lymphoma B Hodgkin lymphoma C Cat scratch disease D Mycosis fungoides E Multiple myeloma

(B) CORRECT. Reed-Sternberg cells are multinucleated with large nucleoli. Variants of them called lacunar cells are also seen with some forms of Hodgkin lymphoma. Her 2 lymph node groups on one side of the diaphragm put this at stage II, but the prognosis is still good.

Question 17 A 29-year-old woman has the sudden onset of fever, abdominal pain, tachycardia, and nausea. On physical examination her vital signs include T 37.6°C, P 90/minute, RR 18/minute, and BP 100/60 mm Hg. Her conjunctivae are icteric. The spleen tip is palpable. Laboratory studies shows Hgb 9.0 g/dL, Hct 27.3%, MCV 99 fL, platelet count 209,500/microliter, and WBC count 6840/microliter. Her reticulocyte count is 0.1%. On microscopic examination of her peripheral blood smear, the RBC's are small and lack central pallor. Which of the following most likely initiated this woman's acute illness? A Quinacrine use B Parvovirus infection C Decreased oxygen tension D Exposure to cold E Transfusion therapy

(B) CORRECT. The findings point to hereditary spherocytosis. Parvovirus B19 infects erythroid precursors and can lead to an aplastic crisis in persons with hemoglobinopathies. The hemoglobinopathy impairs the marrow ability to respond to the stress of the acute infection.

Question 28 A 5-year-old boy has become increasingly lethargic for the past 2 months. On physical examination his temperature is 37.3°C. There are ecchymoses noted on the skin of his lower legs. Laboratory studies show Hgb 9.2 g/dL, Hct 27.8%, MCV 91 fL, platelet count 101,000/microliter, and WBC count 12,128/microliter. A bone marrow biopsy is performed and on microscopic examination shows nearly 100% cellularity with replacement by primitive cells that have large nuclei with delicate chromatin and indistinct nucleoli with scanty cytoplasm. These cells mark for CD10 (CALLA) antigen. Which of the following is the most likely diagnosis? A Acute myeloid leukemia B Hodgkin lymphoma C Acute lymphoblastic leukemia D Epstein-Barr virus infection E Chronic myelogenous leukemia F Chronic lymphocytic leukemia

(C) CORRECT. He has ALL, which typically occurs in children. The CALLA variety is common and responds well to therapy.

Question 11 A 72-year-old Caucasian man has had increasing fatigue for the past year. On physical examination there are no abnormal findings. Laboratory studies show a Hgb of 9.1 gm/dL, Hct 27.9%, MCV 96 fL, WBC count 3700/microliter, and platelet count 125,000/microliter. The WBC differential count shows 53 segs, 5 bands, 2 metamyelocytes, 1 myelocyte, 32 lymphs, 7 monos, and 5 nucleated RBCs/100 WBCs. He has a negative direct and indirect Coombs test. Which of the following diseases is he most likely to have? A Metastatic carcinoma B Chronic alcoholism C Malabsorption D Hemoglobinopathy E Chronic blood loss F Systemic lupus erythematosus

(A) CORRECT. Metastatic tumor involving marrow, or marrow fibrosis, is a 'myelophthisic' process that reduces normal hematopoiesis and leads to a peripheral 'leukoerythroblastic' picture with immature RBC's and WBC's in the peripheral blood, as seen here with nucleated RBCs and white cells even more immature than bands (metamyelocytes, myelocytes) on the smear.

Question 10 A 45-year-old man has had increasing abdominal discomfort with abdominal enlargement for the past two years. On physical examination, the spleen can be felt below the left costal margin. There is no fluid wave. An abdominal CT scan reveals massive (estimated 3000 gm size) splenomegaly. Laboratory data include Hgb 9 g/dL, WBC count 5,000/microliter, and platelet count 50,000/microliter. Which of the following underlying conditions is he most likely to have? A Myelofibrosis B Sickle cell anemia C Portal hypertension D Infectious mononucleosis E Hemochromatosis

(A) CORRECT. Myeloproliferative disorders, and myelofibrosis in particular, are known to cause massive splenomegaly. As hematopoiesis is reduced in the marrow, it moves elsewhere (extramedullary hematopoiesis) such as the spleen.

Question 36 A 73-year-old woman has had increasing fatigue with a 3 kg weight loss over the past 7 months. Her hands become purple and painful upon exposure to cold. On physical examination she has a palpable spleen tip. Laboratory studies show Hgb 10.5 g/dL, Hct 31.7%, MCV 99 fL, platelet count 193,600/microliter, and WBC count 5390/microliter. The direct Coombs test is positive at 4°C and negative at 37°C. Which of the following underlying diseases is this woman most likely to have? A Non-Hodgkin lymphoma B Systemic lupus erythematosus C Pernicious anemia D Scleroderma E Thalassemia minor

(A) CORRECT. She has a cold autoimmune hemolytic anemia. Though this may be idiopathic or due to an infection (Epstein-Barr virus; Mycoplasma) a malignant lymphoma must be considered. Since the RBC's are being sequestered in the spleen with extravascular hemolysis, there is splenomegaly. A warm autoimmune hemolytic anemia will often produce intravascular hemolysis with hemoglobinemia that will more often lead to renal failure. There will more often be jaundice with intravascular hemolysis. Intravascular hemolysis will decrease haptoglobin more.

Question 27 A 52-year-old man has had a fever with cough for a month. On physical examination his temperature is 37.5°C. There are crackles auscultated in upper lung fields. A chest radiograph shows a reticulonodular pattern with upper lobe cavitary lesions. His sputum is positive for acid fast bacilli. A CBC shows: Hgb 14.2 g/dL, Hct 42.5%, MCV 92 fL, platelet count 225,000/uL, and WBC count 44,500/uL with differential count of 59 segs, 20 bands, 8 metas, 4 myelos, 2 promyelos, 5 lymphs, and 2 monos. Which of the following laboratory test findings is most likely to be present in this man? A High leukocyte alkaline phosphatase B Karyotype with 46, XY, t(9;22) C Monoclonal gammopathy D Elevated D-dimer E Positive TdT assay

(A) CORRECT. The findings point to a leukemoid reaction that can be seen with infections such as tuberculosis.

Question 5 A clinical study is conducted involving adults from 18 to 80 years of age who underwent splenectomy for blunt force abdominal trauma. An age-matched control group of patients consists of patients who have congestive splenomegaly. The laboratory findings from these subjects are analyzed. Which of the following laboratory test findings is most likely to be observed only in the study group following splenectomy? A Thrombocytopenia B RBC Howell-Jolly bodies C Decreased RBC distribution width D Leukopenia E Nucleated RBCs

(B) CORRECT. Increased numbers of red blood cell inclusions such as nuclear fragments (Howell-Jolly bodies) and degenerated hemoglobin (Heinz bodies) appear following splenectomy. The other listed foils require a spleen.

Question 8 A 68-year-old man has had malaise for the past year. On physical examination, there are no abnormal findings. His Hgb is 10.5 g/dL, Hct 31.5%, MCV 88 fL, platelet count 211,000/microliter, and WBC count 6980/microliter. His total serum iron is 130 microgm/dL total iron binding capacity (TIBC) 230 microgm/dL, and soluble serum transferrin receptor is normal. A bone marrow biopsy is performed and microscopic examination shows that maturation is occurring in all cell lines and there are no abnormal cells seen. Stainable iron in the bone marrow is increased. Which of the following underlying diseases is he most likely to have? A Diverticulosis B Hepatitis C infection C Systemic lupus erythematosus D Atrophic gastritis E Fanconi anemia

(B) CORRECT. He has findings of anemia of chronic disease, with a high (or normal) % iron saturation, increased iron stores, and normal soluble serum transferrin receptor. In iron deficiency, iron stores are diminished, % saturation decreased, and soluble serum transferrin receptor increased. Hepatitis C viral infection is a chronic disease.

Question 19 A 42-year-old woman has noticed during the past month that even minor bumps produce major bruises over her body. On physical examination she has areas of purpura on the skin of her arms and legs. She is afebrile. Laboratory studies shows her prothrombin time is 12.9 seconds (control 13 sec) and partial thromboplastin time 26.2 seconds (control 25 sec). Her CBC shows a Hgb of 11.1 g/dL, Hct 33.1%, MCV 84 fL, platelet count 790,000/uL, and WBC count 45,400/uL. A bone marrow biopsy is performed and on microscopic examination shows hypercellularity with myeloid and megakaryocytic hyperplasia. Which of the following is the most likely diagnosis? A Epstein-Barr virus infection B Myeloproliferative disorder C Drug reaction to recent antibiotic therapy D Wiskott-Aldrich syndrome E Megaloblastic anemia

(B) CORRECT. There is an increase in numbers of more than one cell line in the marrow. Paradoxically, there is bleeding because the platelets are functionally abnormal, even though there are lots of them.

Question 39 A 28-year-old African-American woman has had worsening fatigue for the past 2 months. On physical examination she has an erythematous macular rash on her upper chest, forearms, and face. Laboratory studies show Hgb 9.2 g/dL, Hct 27.9%, MCV 101 fL, platelet count 179,000/microliter, and WBC count 5850/microliter. The red blood cell distribution width is markedly increased. Her peripheral blood smear shows polychromasia. Her reticulocyte count is 4.2%. The serum haptoglobin is 3 mg/dL. Serum chemistries show total protein 7.9 g/dL, albumin 3.8 g/dL, alkaline phosphatase 49 U/L, AST 81 U/L, ALT 27 U/L, total bilirubin 3.3 mg/dL, and direct bilirubin 0.8 mg/dL. Hemoglobinuria is detected on urinalysis. Which of the following underlying conditions is she most likely to have? A Multiple myeloma B Systemic lupus erythematosus C Hepatitis C infection D Hereditary spherocytosis E Vitamin B12 deficiency

(B) CORRECT. These findings all point to intravascular hemolysis that can be seen with warm autoimmune hemolytic anemia that can complicate autoimmune diseases such as SLE. Her reticulocytosis is the response to the hemolysis and accounts for the mild increase in MCV.

Question 43 Two teenage siblings in the same family are noted to have frequent nosebleeds and easy bruising from even minor trauma. Both have had menorrhagia since menarche. One girl's CBC shows Hgb 14 g/dL, Hct 42.3%, MCV 90 fL, platelet count 242,000/microliter, and WBC count 7720/microliter. Her prothrombin time is 12 seconds and partial thromboplastin time 25 seconds. Platelet function studies show decreased aggregation in response to ADP, collagen, epinephrine, and thrombin. Which of the following disorders are these siblings most likely to have? A Hemophilia A B Antithrombin III deficiency C Glanzmann thrombasthenia D Systemic lupus erythematosus E Von Willebrand disease

(C) CORRECT. Glanzmann thrombasthenia is an autosomal recessive disorder from abnormalities in platelet glycoprotein IIb or IIIa, which form a receptor that is required for platelet aggregation, for uptake of fibrinogen into platelets, and clot retraction. This is a qualitative platelet defect; there are normal numbers of circulating platelets.

Question 20 A clinical study is performed with subjects who are adults found to have anemia. Their clinical histories and laboratory findings are reviewed. It is observed that ingestion of a drug preceded development of the anemia in some of the subjects, but not in others. Which of the following conditions is most likely to be found in persons without a history of drug ingestion? A G6PD deficiency B Autoimmune hemolytic anemia C Macrocytic anemia D Aplastic anemia E Microcytic anemia

(E) CORRECT. Microcytic anemia is usually the result of an iron deficient state not associated with drug usage.

Question 42 A 10-year-old girl is noted to have increasing facial distortion for the past 8 months from a lesion involving her jaw. On physical examination she has a right mandibular mass. A biopsy is performed and on microscopic examination reveals a monotonous pattern of small non-cleaved lymphocytes. Cytogenetic analysis of these cells shows t(8;14). Infection with which of the following organisms is most likely to be associated with development of this girl's mass lesion? A Adenovirus B Cytomegalovirus C Epstein-Barr virus D Hepatitis C virus E Herpes simplex virus F HIV G HTLV-1

(C) CORRECT. Burkitt lymphoma is endemic in Africa, mainly seen in children and young adults, and EBV infection is implicated in the pathogenesis of this B-cell lymphoma. Although Burkitt lymphoma is one of the fastest growing neoplasms, half of cases do respond to chemotherapy with long-term survival.

Question 16 A 48-year-old man has experienced increasing malaise and difficulty concentrating at work for the past 6 months. On physical examination he has splenomegaly but no lymphadenopathy. He is afebrile. Laboratory studies show Hgb 12.0 g/dL, Hct 35.8%, MCV 92 fL, platelet count 390,000/uL, and WBC count 190,000/uL with differential count 73 segs, 12 bands, 6 metamyelocytes, 2 myelocytes, 2 myeloblasts, and 5 lymphs. The leukocyte alkaline phosphatase (LAP) score is very low. A bone marrow biopsy is performed. Which of the following microscopic findings is most likely to be found in this biopsy? A Sheets of plasma cells B Atypical cytokeratin positive glands C Numerous mature and immature myeloid cells D Predominance of adipocytes E Granulomas that have many acid fast bacilli

(C) CORRECT. He has chronic myelogenous leukemia (CML) which is a form of chronic myeloproliferative process in which one or more cell lines (myeloid, erythroid, megakaryocytic) becomes increased. This is usually driven by an acquired cytogenetic abnormality in a stem cell line, a t(9;22) that forms a BCR-ABL fusion gene with tyrosine kinase activation. Unlike acute myelogenous leukemia, blasts are uncommon in CML.

Question 40 A 37-year-old man known to be infected with HIV for the past 10 years has had abdominal pain for the past 3 days. Physical examination reveals abdominal distension with diffuse tenderness and absent bowel sounds. An abdominal CT scan reveals a mass lesion involving the small intestine. He is taken to surgery, and an area of bowel obstruction in the ileum is removed. Gross examination of the specimen shows a near-encircling firm white mass 10 cm long and 3 cm in greatest depth that infiltrates through the wall of the bowel. Which of the following neoplasms is this man most likely to have? A Plasmacytoma B Hodgkin lymphoma, lymphocyte predominant type C High-grade B cell lymphoma D Metastatic adenocarcinoma E Myeloproliferative disorder F Adenocarcinoma

(C) CORRECT. Such lymphomas are typical for, as well as diagnostic of, AIDS in the setting of HIV infection. Extranodal involvement is common.

Question 24 A 72-year-old man has been feeling tired for the past 8 months. On physical examination there are no abnormal findings. Laboratory studies show Hgb 10.4 g/dL, Hct 30.3%, MCV 72 fL, platelet count 239,000/uL, and WBC count 7500/uL with automated differential count of 70.1% grans, 18.8% lymphs, and 11.1% monos. His total bilirubin is 1.0 mg/dL. Which of the following morphologic findings is most likely to be seen on his peripheral blood smear? A Fragmentation B Many nucleated forms C Hypochromasia D Spherocytosis E Howell-Jolly bodies

(C) CORRECT. The most probable cause of a hypochromic, microcytic anemia in an older man is iron deficiency anemia.

Question 33 A 49-year-old man has had increasing fatigue for the past 4 months. On physical examination he has massive splenomegaly but no lymphadenopathy. Laboratory studies show a Hgb of 10.1 g/dL, Hct 30.3%, MCV 90 fL, WBC count 1600/microliter, and platelet count 48,000/microliter. Examination of his peripheral blood smear shows increased numbers of peripheral blood lymphocytes containing tartrate-resistant acid phosphatase. Which of the following is the most likely diagnosis? A Chronic lymphocytic leukemia B HTLV-1 infection with leukemia C Hairy cell leukemia D Gaucher disease E Myelodysplasia

(C) CORRECT. The name comes from characteristic cytoplasmic projections on the abnormal cells seen on the peripheral blood smear. This proliferation of B-lymphocytes involves peripheral blood, bone marrow, and spleen. Splenomegaly is often present, but hepatomegaly is not common, and lymphadenopathy is rare with hairy cell leukemia.

Question 12 A 40-year-old woman has had a week long course of fever and mental confusion. Physical examination shows T 38.2°C, P 100/minute, RR 22/minute, and BP 100/60 mm Hg. She has widespread petechiae of skin and mucosal surfaces. Laboratory studies show her serum urea nitrogen is 52 mg/dL with creatinine 5.3 mg/dL. She has a hemoglobin of 12.2 g/dL, hematocrit 36.8%, MCV 93 fL, platelet count 19,000/microliter, and WBC count 8180/microliter. Schistocytes are seen on her peripheral blood smear. Her prothrombin time, partial thromboplastin time, and D-dimer are not elevated. Which of the following is the most likely diagnosis? A Disseminated intravascular coagulopathy B Idiopathic thrombocytopenic purpura C Thrombotic thrombocytopenic purpura D Trousseau syndrome E Warm autoimmune hemolytic anemia

(C) CORRECT. The pentad of fever, mental changes, renal failure, thrombocytopenia, and microangiopathic hemolytic anemia is characteristic of TTP. Platelets are activated directly, and not the coagulation system as a whole, so that the prothrombin time, partial thromboplastin time, and D-dimer are either not elevated or minimally elevated. The platelet activation leads to formation of hyaline thrombi in small arteries that promotes tissue ischemia in organs such as brain, with consequent neurologic impairment. Platelet transfusion is contraindicated.

6) A 30-year-old man has had a sore throat with fever for 5 days. On physical examination he has mildly tender generalized cervical lymphadenopathy. Laboratory findings include Hgb 13 g/dL, platelet count 277,000/microliter, and WBC count 12,670/microliter with differential count of 75 segs, 10 bands, and 15 lymphs Which of the following is the most likely diagnosis? A Lymphocytic lymphoma B Hodgkin lymphoma C Group A Streptococcus infection D Human immunodeficiency virus infection E Brucellosis

(C) CORRECT. This is a typical history for infection with reactive lymphadenopathy. The microscopic findings in the node would include prominent germinal centers in follicles with a diffuse polyclonal hyperplasia composed of lymphocytes, plasma cells, and macrophages. The leukocytosis with left shift suggest bacterial infection.

Question 38 A 32-year-old man has had worsening headaches for the past 2 months. On physical examination he is afebrile. He has no lymphadenopathy or hepatosplenomegaly. Laboratory studies shows Hgb 12 g/dL, platelet count 250,000/microliter, and WBC count 6000/microliter with differential count of 80% granulocytes, 10% lymphocytes, and 10% monocytes. A head CT scan reveals a 3 cm mass lesion to the right of midline next to the lateral ventricle. A stereotaxic brain biopsy is performed and microscopic examination shows diffuse large B cell lymphoma. Which of the following laboratory test findings is this patient most likely to have? A Elevated terminal deoxyribonucleodidyl transferase B Bence-Jones proteinuria C Elevated serum IgM D HIV-1 RNA of 80,000 copies/mL E Lymphoma positive for tartrate-resistant acid phosphatase

(D) CORRECT. He has a cerebral lymphoma typical for AIDS with HIV infection. His lymphopenia is due to a reduced CD4 T-cell count.

Question 45 A 42-year-old man has had multiple episodes of painful red nodules on his skin from dermal venous thrombosis, as well as abdominal pain from mesenteric vein thrombosis over the past year. He notes passing darker urine. Laboratory studies show Hgb 9.4 g/dL, Hct 29.2%, MCV 100 fL, platelet count 215,000/microliter, and WBC count of 8800/microliter. His RBCs show increased sensitivity to complement lysis. Flow cytometry is most likely to show reduction in which of the following markers on his RBCs? A CD4 B CD19 C CD33 D CD55 E CD68

(D) CORRECT. He has paroxysmal nocturnal hemoglobinuria (PNH) an acquired stem cell disorder from mutation in the PIGA gene that renders RBCs very sensitive to complement lysis, as well as thrombosis in unusual veins. There is also risk for leukemia. The RBC markers CD55 and CD59 are reduced with PNH.

Question 37 A 12-year-old girl has the sudden onset of severe abdominal pain and back pain. On physical examination her abdomen is diffusely tender, but there are no masses. She is afebrile. A CBC shows Hgb 6.5 g/dL, Hct 19.0%, MCV 99 fL, platelet count 149,000/microliter, and WBC count 11,200/microliter. Examination of her peripheral blood smear shows nucleated RBCs and sickled RBCs. Which of the following types of gene mutation is she most likely to have? A Deletion B Duplication C Insertion D Missense E Nonsense F Splice site G Tandem repeat

(D) CORRECT. Missense mutations involve a change in a single base pair for a amino acid. The defect in sickle cell anemia is a single amino acid substitution (valine for glutamic acid), but the beta globin chain is still made. The gene mutation originated in places such as West Africa where selection pressure from falciparum malaria gave heterozygotes a selective advantage. The gene frequency may less commonly be present in some Mediterranean and eastern Arabian populations. There is enough fetal hemoglobin at birth and through infancy to prevent significant sickling with sickle cell disease.

Question 15 An 83-year-old woman fell and broke her left wrist. She underwent open reduction with internal fixation of the radial head fracture. Postoperatively she received heparin prophylaxis for thromboembolism and diuretics to treat pulmonary edema. Laboratory studies showed: On admission: Hgb 13.2 g/dL, Hct 39.1%, MCV 85 fL, platelet count 209,000/microliter, WBC count 5720/microliter, prothrombin time 13 seconds, partial thromboplastin time 28 seconds 1 week later: Hgb 13 g/dL, Hct 38.8%, MCV 86 fL, platelet count 101,000/microliter, WBC count 6310/microliter, prothrombin time 12 seconds, partial thromboplastin time 27 seconds She suddenly developed difficulty in moving her right arm. What is the most likely cause for her findings? A Hypersplenism B Idiopathic thrombocytopenic purpura C Disseminated intravascular coagulation D Drug-induced thrombocytopenia E Thrombotic-thrombocytopenic purpura

(D) CORRECT. She has heparin-induced thrombocytopenia. In about 5% of patients receiving heparin, antibodies develop to a complex of platelet factor 4 with heparin, and in 5 to 14 days there is a marked drop in platelet count. The feared complication is thrombosis ('white clot' syndrome), which can be arterial or venous, and in this patient a thrombotic stroke is likely to have occurred. Low molecular weight heparins are less likely to have this complication.

Question 35 A 2-year-old boy has had a seborrheic eruption over the scalp and trunk over the past month. He then develops a right ear ache. On physical examination the right tympanic membrane is erythematous and bulging. He has hepatosplenomegaly and generalized lymphadenopathy. Laboratory studies show Hgb 9.5 g/dL, Hct 28.7%, MCV 90 fL, platelet count 58,000/microliter, and WBC count 3540/microliter. A bone marrow biopsy is performed and on microscopic examination shows 100% cellularity with extensive infiltration by cells resembling macrophages that express CD1a antigen and, by electron microscopy, have prominent HX bodies (Birbeck granules). Which of the following conditions is most likely to produce this boy's findings? A Myeloproliferative disorder B Plasmodium vivax infection C Hodgkin lymphoma, lymphocyte depletion type D Langerhans cell histiocytosis E AIDS

(D) CORRECT. The Langerhans cell histiocytoses include Letterer-Siwe disease (as in this case, it is typically a disseminated disease of children), and localized eosinophilic granuloma (often involving bone).

1) A 62-year-old man has had dull, constant back pain for 3 months. He recently developed a cough productive of yellowish sputum. On physical examination there are crackles at the right lung base. A plain film radiograph of the spine reveals several 1 to 2 cm lytic lesions of the vertebral bodies. Laboratory studies show glucose 78 mg/dL, urea nitrogen 49 mg/dL, creatinine 5 mg/dL, total protein 8.3 g/dL, albumin 3.7 g/dL, alkaline phosphatase 176 U/L, AST 45 U/L, ALT 22 U/L, and total bilirubin 1.2 mg/dL. A sputum culture grows Streptococcus pneumoniae. Which of the following pathologic findings is most likely to be seen in a bone marrow biopsy from this man? A Scattered small granulomas B Nodules of small mature lymphocytes C Occasional Reed-Sternberg cells D Numerous plasma cells E Hypercellularity with many blasts

(D) CORRECT. The findings suggest multiple myeloma. He has a markedly increased level of serum globulins. The renal failure from light chains deposited in the kidneys, and the increased risk for encapsulated bacterial infections is typical. The lytic bone lesions are collections of plasma cells.

Question 44 A 47-year-old man has been chronically fatigued for the past year. A physical examination yields no abnormal findings. A CBC shows: Hgb 10.8 g/dL, Hct 33.1%, MCV 104 fL, platelet count 239,000/microliter, and WBC count 7720/microliter. His peripheral blood smear shows normal WBC morphology and RBCs with mild poikilocytosis and a few target cells. His serum vitamin B12 is 512 pg/mL and folate 4.7 ng/mL. His serum haptoglobin is 151 mg/dL. Direct and indirect Coombs tests are negative. Which of the following underlying conditions is most likely to explain his findings? A Chronic lymphocytic leukemia B Peptic ulcer disease C Lead poisoning D Chronic alcohol abuse E Hereditary spherocytosis

(D) CORRECT. There is mild macrocytosis with normal B12 and folate, without evidence for significant hemolysis. Liver disease can lead to RBC membrane abnormalities, with the presence of a few target cells on the peripheral blood smear as well as macrocytes. Alcohol can also directly affect RBC maturation. Chronic alcohol abusers may also have poor diets lacking in folate. An MCV >105 fL is much more likely to result from megaloblastic anemia (B12 or folate deficiency).

Question 22 A study is conducted to determine what changes in the size of the spleen take place with hematologic disorders. The spleen sizes are estimated from CT scans for adult patients who developed complications of their hematologic disease. For which of the following diseases is the spleen most likely to remain normal in size? A Autoimmune hemolytic anemia B Chronic alcohol abuse C Myeloproliferative disorder D Idiopathic thrombocytopenic purpura E Sickle cell anemia

(D) CORRECT. Though with ITP there are circulating antibodies to platelets that lead to platelet destruction, the spleen itself is usually not enlarged.

Question 41 A 20-year-old healthy man incurs blunt force trauma to the abdomen in a motor vehicle accident. On physical examination he has upper abdominal tenderness. An abdominal CT scan reveals a splenic hematoma. At laparotomy a splenectomy is performed. Following splenectomy, which of the following peripheral blood morphologic findings is most likely to be present? A Tear drop cells B Elliptocytes C Target cells D Macro-ovalocytes E RBC inclusions

(E) CORRECT. Howell-Jolly bodies and Pappenheimer bodies are seen within RBC's in splenectomized patients. A functioning spleen would normally remove such inclusions.

Question 18 A 55-year-old man has had fatigue, fever, and episodes of epistaxis for the past 3 months. On physical examination his temperature is 37.4°C. Laboratory studies show Hgb 12.5 g/dL, Hct 37.6%, MCV 89 fL, platelet count 170,000/microliter, and WBC count 52,000/microliter. Examination of his peripheral blood smear shows large blasts with Auer rods. Which of the following risk factors most likely preceded development of his current illness? A Malaria B Infectious mononucleosis C Diabetes mellitus D Beta-thalassemia E Myelodysplasia

(E) CORRECT. Auer rods are formed of the cytoplasmic granules of the myeloid blasts of acute myelogenous leukemia (AML) and are a typical finding with AML. Myelodysplastic syndromes can precede development of AML, as can some cases of myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, and chemotherapeutic regimens.

Question 30 A 53-year-old man has had constant dull pain in his lower right back for the past 4 months. On physical examination there is tenderness on percussion of his right costovertebral angle. An abdominal CT scan reveals a 6 cm mass in the upper pole of the right kidney. A CBC shows: Hgb 21.3 g/dL, Hct 64.0%, MCV 96 fL, platelet count 199,000/microliter, and WBC count 8230/microliter. Serum chemistries include glucose 77 mg/dL, urea nitrogen 17 mg/dL, and creatinine 1.1 mg/dL. Which of the following is the most likely cause for his findings? A Polycythemia rubra vera B Erythroleukemia C Hemophilia A D Diabetes insipidus E Increased erythropoietin

(E) CORRECT. He has a secondary form of polycythemia. Renal cell carcinomas are known to secrete erythropoietin and lead to this paraneoplastic effect with polycythemia.

Question 21 A 25-year-old African-American man is given anti-malarial prophylaxis for a trip to West Africa. Over the next week he develops increasing fatigue. On physical examination there are no abnormal findings. Laboratory studies show a hematocrit of 30%. Examination of his peripheral blood smear shows red blood cells with numerous Heinz bodies. There is a family history of this disorder, with males, but not females, affected. Which of the following is the most likely diagnosis? A Beta-thalassemia B Sickle cell anemia C Alpha-thalassemia D Hereditary spherocytosis E G6PD deficiency

(E) CORRECT. He has glucose-6-phosphate dehydrogenase (G6PD) deficiency, which can result in a hemolytic anemia on exposure to oxidizing agents including certain drugs such as antimalarials. This is an X-linked disorder. The Heinz bodies within the RBCs are formed from denatured hemoglobin.

Question 13 For the past 4 months, a 62-year-old previously healthy man has noted increasing fatigue and shortness of breath with minimal exercise. He has felt some abdominal discomfort over the past month. On physical examination he has non-tender cervical lymphadenopathy. The liver span is 15 cm in the right mid-clavicular line; the edge is smooth and palpable just below right costal margin. The spleen is palpated 3 cm below left costal margin on inspiration. A CBC shows WBC count 23,100/microliter with 16 segs, 2 bands, 78 lymphs, and 4 monos, Hgb 11.9 g/dL, Hct 36%, MCV 90, and platelet count 277,300/microliter. The direct Coombs test is positive. Which of the following is the most likely diagnosis? A Leukemoid reaction B Chronic myelogenous leukemia C Acute myelogenous leukemia D Acute lymphocytic leukemia E Chronic lymphocytic leukemia F Systemic lupus erythematosus

(E) CORRECT. Most of the circulating cells are small, mature lymphocytes with CLL. Most persons with CLL are older adults. CLL can have a tissue component called small lymphocytic lymphoma (SLL) with the same small lymphocytes infiltrating organs such as liver and spleen.

Question 34 A 10-year-old girl has exhibited increasing sluggishness with poorer performance in school over the past year. She has not had increased numbers of infections. The child now complains of headaches. A physical examination shows no hepatosplenomegaly or lymphadenopathy. A CBC shows: Hgb 11.8 g/dL, Hct 33.9%, MCV 71 fL, platelet count 293,000/microliter, and WBC count 8160/microliter. Examination of her peripheral blood smear shows basophilic stippling of erythrocytes. The serum haptoglobin is 5 mg/dL. Which of the following laboratory test findings is most likely to be present in this girl A Hemoglobin S on electrophoresis B Increased osmotic fragility C Positive direct Coombs test D Decreased serum iron E Elevated free erythrocyte protoporphyrin

(E) CORRECT. She has lead poisoning. Lead inhibits incorporation of iron into heme, leading to elevated zinc protoporphyrin and free erythrocyte protoporphyrin. The diminished heme synthesis leads to a hypochromic, microcytic anemia, and there may be mild hemolysis. Basophilic stippling can be an indicator of toxic injury to RBCs.

Question 29 A 78-year-old woman has developed increasing dyspnea for the past 2 weeks. On physical examination she has diffuse rales in all lung fields. Scleral icterus is noted. A CBC shows Hgb 7.1, Hct 22.2, MCV 93 fL, platelet count 205,000/microliter, and WBC count 6500/microliter with differential count of 60 segs, 4 bands, 25 lymphs, 9 monos, and 2 eos with 10 nucleated RBCs/100 WBCs. Which of the following is the most likely diagnosis? A Iron deficiency anemia B Pernicious anemia C Anemia of chronic disease D Sickle cell anemia E Hemolytic anemia

(E) CORRECT. She may have an autoimmune hemolytic anemia, and may have an underlying malignancy such as lymphoma. The icterus is consistent with hyperbilirubinemia from hemolysis. Nucleated RBCs are consistent with high marrow output of erythroid cells. The marked anemia has led to high output congestive heart failure with pulmonary edema.

Question 4 A 42-year-old man has had fevers for the past 4 weeks. On physical examination his temperature is 37.8°C. Laboratory studies show a Hgb of 12.2 g/dL, Hct 37.1%, MCV 92 fL, platelet count 243,000/uL, and WBC count 75,000/uL. The WBC differential count shows 82 segs, 8 bands, 3 metamyelocytes, 1 myelocyte, 4 lymphocytes, and 1 monocyte. The leukocyte alkaline phosphatase (LAP) score is high at 130. Which of the following laboratory test findings is most likely to be present in this man? A Bone marrow karyotype of 46, XY, t(9;22) B Serologic titer of 1:1024 for anti-double stranded DNA C Serum vitamin B12 level of 100 pg/mL D 4+ ketonuria and 4+ proteinuria E Blood culture positive for Streptococcus, viridans group

(E) CORRECT. The high WBC count with left shift (but no blasts) and the high LAP score are consistent with a leukemoid reaction. The term 'leukemoid' is used because there is a markedly increased WBC count, with immature forms of WBCs, similar to leukemia. In his case, the infection is driving the leukocytosis.

Question 26 A 46-year-old man has had worsening arthritis and swelling of his feet for the past year. On physical examination he has rales audible in all lung fields. A chest radiograph shows cardiomegaly and pulmonary edema. Laboratory studies show Hgb 13.0 g/dL, Hct 39.1%, MCV 86 fL, platelet count 255,500/uL, and WBC count 5920/uL. His serum iron is 406 microgram/mL with iron binding capacity 440 microgram/mL and ferritin 830 ng/mL. Which of the following is the most likely diagnosis? A Beta-thalassemia B Autoimmune hemolytic anemia C Anemia of chronic disease D Polycythemia vera E Pernicious anemia F Hereditary hemochromatosis

(F) CORRECT. Hereditary hemochromatosis results from increased iron absorbtion with markedly increased iron stores. The iron accumulation in tissues results in manifestations such as hepatomegaly, skin pigmentation, diabetes mellitus, heart disease, arthritis, and hypogonadism.