HEMATOLOGY MCQS

(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 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. Lymphadenopathy with malignant lymphoma is typically

nontender, as contrasted with the lymphadenopathy of infections. Follicular
lymphomas occur in adults. Follicular lymphomas may not be isolated to a
single node. Though indolent, this kind of non-Hodgkin lymphoma is difficult to
eradicate. A small percentage of them transform into diffuse large B-cell
lymphoma (DLBCL).

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

(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 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. 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 11

A 72-year-old 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,
1 promyelocyte .2 metamyelocytes, 1 myelocyte, 32 lymphs, 7 monos, and 5
nucleated RBCs/100 WBCs. He has a negative direct and indirect antiglobulin
(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

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.
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 Immune thrombocytopenic purpura

C Thrombotic thrombocytopenic purpura

D Trousseau syndrome

E Warm autoimmune hemolytic anemia

(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 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 antiglobulin (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

(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 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(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 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 Immune thrombocytopenic purpura

C Disseminated intravascular coagulation

D Drug-induced thrombocytopenia

E Thrombotic thrombocytopenic purpura

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 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, 5 lymphs and basophils 3%
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

(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 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

(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 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

(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 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

D) CORRECT. The only finding here is microcytosis, and the most common
cause is iron deficiency, and women of reproductive years are at increased
risk.

Question 20

A 20-year-old woman has had worsening fatigue for the past year. On
examination her mucus membranes are pale. No hepatosplenomegaly is
present. Her CBC shows a Hgb of 7.1 g/dL, Hct 19.9%, MCV 67 fL, platelet
count 190,000/uL, and WBC count 5,400/uL. There is no history of drug
ingestion. Which of the following is the most likely etiology for her findings?

A Cobalamin deficiency

B G6PD deficiency

C Folate deficiency

D Iron deficiency

E Von Willebrand factor deficiency

D) CORRECT. Though with ITP there are circulating antibodies to platelets

that lead to platelet destruction, the spleen itself is usually not enlarged.

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 ethanol abuse

C Myeloproliferative disorder

D Immune thrombocytopenic purpura

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

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

(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 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

(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.

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

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

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. 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 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

(B) CORRECT. Mycosis fungoides (with no relationship to fungi) is one form

of cutaneous T-cell lymphoma. The abnormal CD4 cell proliferation is
infiltrating the skin and producing erythroderma. If these neoplastic cells
circulate, it is known as Sezary syndrome.

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

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

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

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

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 erythropoiet -

(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 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

(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 (with reduced
haptoglobin). Basophilic stippling can be an indicator of toxic injury to RBCs.

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 antiglobulin test

D Decreased serum iron

E Elevated free erythrocyte protoporphyrin

(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).

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

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 36

A 73-year-old man 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 antiglobulin (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
(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 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. He has a cerebral lymphoma typical for AIDS with HIV
infection. His lymphopenia is due to a reduced CD4 T-cell count.

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 show 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

(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 39

A 28-year-old 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

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

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 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

(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 42
diffuse large B cell lymphomas arise in setting of AIDS/ post
transplantation / iatrogenic immunosuppression/elderly 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. Autosomal recessive disorders are less likely than
autosomal dominant disorders to have a family history.
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. There is no prior family history of similar
problems. 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

(D) CORRECT. There is mild macrocytosis with normal B12 (and

methlymalonic acid is a more sensitive test for B12 deficiency), 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 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 105 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 and methylmalonic acid assays are normal. His serum haptoglobin is 151
mg/dL. Direct and indirect antiglobulin (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. 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 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 show reduction in
the CD55 marker on his RBCs. Which of the following conditions is he most
likely to have?

A HIV infection

B Chronic lymphocytic leukemia

C Acute myelogenous leukemia

D Paryoxysmal nocturnal hemoglobinuria

E Langerhans cell histiocytosis

(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 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

(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 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. Infectious mononucleosis with Epstein-Barr virus (EBV)

infection is typically acquired with close personal contact. This self-limited viral
infection resolves in weeks.

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

A) CORRECT. Hereditary spherocytosis is the most common inherited

hemolytic anemia in persons of northern European descent. It has a
frequency in this population of 1 in 5000. An abnormality in the structural
membrane proteins ankyrin or spectrin accounts for the abnormality.

Question 4

A 30-year-old woman has had mild fatigue for many years. Physical
examination reveals a palpable spleen tip. Laboratory studies show Hgb 11.1
g/dL, Hct 28.8%, MCV 77 fL, platelet count 229,000/microliter, and WBC
count 7340/microliter. Her reticulocyte count is 3.9%. Examination of her
peripheral blood smear shows small RBCs that lack central pallor. Which of
the following patterns of inheritance is most likely present with her disease?

A Autosomal dominant, European ancestry

B Autosomal recessive, Asian ancestry

C X-linked recessive, Middle Eastern ancestry

D Autosomal recessive, West African ancestry

E Sporadic occurrence

(E) CORRECT. This is acute immune thrombocytopenia in a child. It is usually

self-limited. In most cases the predisposing event is a viral infection that sets
off an immune response directed specifically at platelet production.

Question 5

A 3-year-old child is noted to have small pinpoint hemorrhages on the skin,

appearing over the past 3 days. On examination the child's vital signs are
normal. There are petechae over skin of extremities and trunk. A CBC shows
Hgb 14.3 g/dL, Hct 43%, MCV 90 fL, platelet count 19,300/microliter, and
WBC count 9370/microliter. This condition resolves over the next month
without treatment. Which of the following is the most likely antecedent event
for this child's illness?

A Acetylsalicylic acid (aspirin) ingestion

B Congenital HIV infection

C Dietary cobalamin deficiency

D Repetitive trauma

E Respiratory syncytial virus infection

F Sulfonamide ingestion

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 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.
Pharyngeal tonsils are enlarged and erythematous with overlying exudate.
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

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 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. 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 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

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 21

A 25-year-old 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