C H A P T E R 1 3   Hematopathology of White Blood Cells
43 A 38-year-old man experiences sudden onset of a severe
headache. Physical examination shows no localizing neuro-
logic signs and no organomegaly. A stool sample is positive
for occult blood. Areas of purpura appear on the skin of his
extremities. Laboratory studies show hemoglobin of 9.6 g/dL,
hematocrit of 28.9%, platelet count of 16,400/mm3, and
WBC count of 75,000/mm3. The peripheral blood smear
has the appearance shown in the figure; schistocytes also
are seen. The plasma D-dimer level (fibrin degradation pro­
ducts), prothrombin time, and partial thromboplastin time
all are elevated. Cytogenetic analysis of cells from a bone mar-
row biopsy specimen is most likely to yield what karyotypic
abnormality?
t(8;14)
A Chronic myelogenous leukemia
t(8;21)
B Hodgkin lymphoma
t(9;22)
C
t(14;18)
D 46 A 50-year-old man with a diffuse large B-cell lymphoma
t(15;17)
E underwent intensive chemotherapy, and a complete remis-
44 A 38-year-old woman has had bleeding gums for the
past 3 weeks. Physical examination shows that her gingivae
are thickened and friable. She has hepatosplenomegaly and
generalized nontender lymphadenopathy. CBC shows hemo-
globin, 11.2 g/dL; hematocrit, 33.9%; MCV, 89 μm3; platelet
count, 95,000/mm3; and WBC count, 4500/mm3 with 25%
segmented neutrophils, 10% bands, 2% metamyelocytes, 55%
lymphocytes, 8% monocytes, and 1 nucleated RBC per 100
WBCs. A bone marrow biopsy specimen shows 100% cellularity,
with many large blasts that are peroxidase negative, nonspecific
esterase positive, and CD13 and CD14 positive. What is the
most likely diagnosis?
A Acute erythroleukemia
B Acute lymphoblastic leukemia
C Acute megakaryocytic leukemia
D Acute monocytic leukemia
E Acute promyelocytic leukemia
  
191
45 A 22-year-old university student reports easy fatigability
of 2 months’ duration. On physical examination, she has no
hepatosplenomegaly or lymphadenopathy. Mucosal gingival
hemorrhages are noted. CBC shows hemoglobin, 9.5 g/dL;
hematocrit, 28.2%; MCV, 94 μm3; platelet count, 20,000/mm3;
and WBC count, 107,000/mm3. Her peripheral blood smear is
shown in the figure, and these cells contain peroxidase posi-
tive granules. A bone marrow biopsy specimen shows 100%
cellularity with few residual normal hematopoietic cells.
Which of the following is the most likely diagnosis?
Acute lymphoblastic leukemia
A
Acute myelogenous leukemia
B
Chronic lymphocytic leukemia
C
D
E
sion was achieved for 7 years. He now reports fatigue and re-
current pulmonary and urinary tract infections over the past
4 months. Physical examination shows no masses, lymphade-
nopathy, or hepatosplenomegaly. CBC shows hemoglobin, 8.7
g/dL; hematocrit, 25.2%; MCV, 88 μm3; platelet count, 67,000/
mm3; and WBC count, 2300/mm3 with 15% segmented neu-
trophils, 5% bands, 2% metamyelocytes, 2% myelocytes, 6%
myeloblasts, 33% lymphocytes, 35% monocytes, and 2% eosino-
phils. A bone marrow biopsy specimen shows 90% cellularity
with many immature cells, including ringed sideroblasts,
megaloblasts, hypolobated megakaryocytes, and myeloblasts.
Karyotypic analysis shows 5q deletions in many cells. This
clinical picture is most consistent with which of the following
conditions?
De novo acute myeloblastic leukemia
A
Myeloid metaplasia with myelofibrosis
B
Myelodysplasia related to therapy
C
Relapse of his previous lymphoma
D
Transformation into myeloid leukemia
E
192 U N I T I I   Diseases of Organ Systems

47 In an experiment, cell samples are collected from the

bone marrow aspirates of patients who were diagnosed with
lymphoproliferative disorders. Cytogenetic analyses are per-
formed on these cells, and a subset of the cases is found to have
the BCR-ABL fusion gene from the reciprocal translocation
t(9;22)(q34;11). The presence of this gene results in increased
tyrosine kinase activity. Patients with which of the following
conditions are most likely to have this gene?
Acute promyelocytic leukemia
A
Chronic myelogenous leukemia
B
Follicular lymphoma
C
Hodgkin lymphoma, lymphocyte depletion type
D
Multiple myeloma
E

48 A 63-year-old woman experiences a burning sensation

in her hands and feet. Two months ago, she had an episode
of swelling with tenderness in the right leg, followed by dys- 50 A 45-year-old man has experienced a gradual weight
pnea and right-sided chest pain. On physical examination, the loss and weakness, anorexia, and easy fatigability for 9
spleen and liver now appear to be enlarged. CBC shows hemo- months. Physical examination shows marked splenomegaly.
globin, 13.3 g/dL; hematocrit, 40.1%; MCV, 91 μm3; platelet CBC shows hemoglobin, 12.9 g/dL; hematocrit, 38.1%;
count, 657,000/mm3; and WBC count, 17,400/mm3. The peri­ MCV, 92 μm3; platelet count, 410,000/mm3; and WBC count,
pheral blood smear shows abnormally large platelets. Which 168,000/mm3. The peripheral blood smear is depicted in the
of the following is the most likely diagnosis? figure. Karyotypic analysis shows the Ph1 chromosome. The
Acute myelogenous leukemia
A patient undergoes chemotherapy with imatinib mesylate (ty-
Chronic myelogenous leukemia
B rosine kinase inhibitor). He remains in remission for 3 years
Essential thrombocytosis
C and then begins to experience fatigue and an 8-kg weight loss.
Myelofibrosis with myeloid metaplasia
D CBC shows hemoglobin, 10.5 g/dL; hematocrit, 30%; platelet
Polycythemia vera
E count, 60,000/μL; and WBC count, 40,000/μL. Karyotypic
analysis shows two Ph1 chromosomes and aneuploidy. Flow
49 A 60-year-old woman has had headaches and dizziness for cytometric analysis of the peripheral blood shows CD19+,
the past 5 weeks. She has been taking omeprazole for ulcers. On CD10+, sIg−, and CD3− cells. Which of the following
physical examination, she is afebrile and normotensive, and her complications of the initial disease did this patient develop
face has a plethoric to cyanotic appearance. There is mild sple- after therapy?
nomegaly, but no other abnormal findings. Laboratory studies Acute myeloblastic leukemia
A
show hemoglobin, 21.7 g/dL; hematocrit, 65%; platelet count, B-cell lymphoblastic leukemia
B
400,000/mm3; and WBC count, 30,000/mm3 with 85% polymor- Hairy cell leukemia
C
phonuclear leukocytes, 10% lymphocytes, and 5% monocytes. Myelodysplastic syndrome
D
The peripheral blood smear shows abnormally large platelets Sézary syndrome
E
and nucleated RBCs. Which of the following is most characteris-
tic of the natural history of this patient’s disease? 51 A 50-year-old man has had headache, dizziness, and
A Development of a gastric non-Hodgkin lymphoma fatigue for the past 3 months. His friends have been comment-
B Increase in monoclonal serum immunoglobulin ing about his increasingly ruddy complexion. He also has experi­
C Marrow fibrosis with extramedullary hematopoiesis enced generalized and severe pruritus, particularly when
Spontaneous remissions and relapses without
D  showering. He notes that his stools are dark. On physical exami-
treatment nation, he is afebrile, and his blood pressure is 165/95 mm Hg.
E Transformation into acute B-lymphoblastic leukemia There is no hepatosplenomegaly or lymphadenopathy. A stool
   sample is positive for occult blood. CBC shows hemoglobin,
22.3 g/dL; hematocrit, 67.1%; MCV, 94 μm3; platelet count,
453,000/mm3; and WBC count, 7800/mm3. What is the most
likely diagnosis?
Chronic myelogenous leukemia
A
Erythroleukemia
B
Essential thrombocytosis
C
Myelodysplastic syndrome
D
Polycythemia vera
E
 C H A P T E R 1 3   Hematopathology of White Blood Cells
52 A 66-year-old man has experienced fatigue, a 5-kg weight
loss, night sweats, and abdominal discomfort for 10 months. On
physical examination, he has marked splenomegaly; there is no
lymphadenopathy. Laboratory studies show hemoglobin, 10.1
g/dL; hematocrit, 30.5%; MCV, 89 μm3; platelet count, 94,000/
mm3; and WBC count, 14,750/mm3 with 55% segmented neutro-
phils, 9% bands, 20% lymphocytes, 8% monocytes, 4% metamye­
locytes, 3% myelocytes, 1% eosinophils, and 2 nucleated RBCs
per 100 WBCs. The peripheral blood smear also shows teardrop
cells. The serum uric acid level is 12 mg/dL. A bone marrow
biopsy specimen shows extensive marrow fibrosis and clusters
of atypical megakaryocytes. Which of the following is most likely
to account for the enlargement in this patient’s spleen?
A Extramedullary hematopoiesis
B Granulomas with Histoplasma capsulatum
C Hodgkin lymphoma
D Metastatic adenocarcinoma
E Portal hypertension
53 A 9-year-old boy has developed a fever over the past
15 days. He has been diagnosed and treated for otitis media
multiple times in the past year. On physical examination, he
has mild lymphadenopathy, hepatomegaly, and splenomegaly.
There are extensive crusted papules on his skin. A CT scan of
his head shows a 4-cm osteolytic mass in the mastoid bone. A
biopsy of the mass is performed, with the electron micrograph
shown in the figure. What is the most likely diagnosis?
Acute lymphoblastic leukemia
A
Disseminated tuberculosis
B
Hodgkin lymphoma, mixed cellularity type
C
Langerhans cell histiocytosis
D
Multiple myeloma
E
193
54 An 18-month-old girl has developed seborrheic skin erup-
tions over the past 3 months. She has had recurrent upper respi-
ratory and middle ear infections with Streptococcus pneumoniae
for the past year. Physical examination indicates that she also has
hepatosplenomegaly and generalized lymphadenopathy. Her
hearing is reduced in the right ear. A skull radiograph shows
an expansile, 2-cm lytic lesion involving the right temporal
bone. Laboratory studies show no anemia, ­thrombocytopenia,
or ­leukopenia. The mass is curetted. Which of the following is
most likely to be seen on microscopic examination of this mass?
A Histiocytes with Birbeck granules
B Lymphoblasts marking with CD3
C Plasma cells with Russell bodies
D Reed-Sternberg cells and variants
E Ring sideroblasts with perinuclear granules
F Sézary cells with cerebriform nuclei
  
55 A 20-year-old man is left at the door of the emergency
department by “friends” after they spent an evening at a local
pub. On examination, his vital signs are temperature, 37° C;
pulse, 110/min; respirations, 26/min; and blood pressure,
75/40 mm Hg. He has left upper quadrant tenderness on
palpation. An abdominal CT scan was obtained and is shown
in the figure. What is the most likely underlying cause of this
clinical picture?
Cirrhosis
A
Gaucher disease
B
Malaria
C
Myeloproliferative disorder
D
Nonbacterial thrombotic endocarditis
E
Salmonella typhi infection
F
Trauma
G
194 U N I T I I   Diseases of Organ Systems

56 A 60-year-old man with a history of chronic alcohol 58 A 14-year-old boy has developed a cough and a high fever
abuse has had increasing abdominal discomfort and fatigue over the past 4 days. On physical examination, he has a tem-
for the past 9 months. He has noted easy bruising of his skin perature of 39.2° C. Diffuse rales are heard over all lung fields.
with minor trauma for the past month. On examination, he Laboratory studies show hemoglobin, 14.8 g/dL; hematocrit,
is afebrile, but his spleen is enlarged and tender. Laboratory 44.4%; platelet count, 496,000/mm3; and WBC count, 15,600/
studies show hemoglobin, 7.7 g/dL; hematocrit, 23%; platelet mm3. Examination of the peripheral blood smear shows RBCs
count, 30,000/mm3; and WBC count, 2300/mm3 with 45% with marked anisocytosis and Howell-Jolly bodies. A sputum
polymorphonuclear leukocytes, 50% lymphocytes, and 5% culture grows Haemophilus influenzae. Which of the following
monocytes. What is the most likely diagnosis? is the most likely diagnosis?
A Acute myelogenous leukemia DiGeorge syndrome
A
B Infectious mononucleosis Galactosemia
B
C Micronodular cirrhosis Gaucher disease
C
D Niemann-Pick disease Myeloproliferative disorder
D
E Metastatic adenocarcinoma Prior splenectomy
E
F Systemic lupus erythematosus Trisomy 21
F
  
59 A clinical study is performed in which the subjects are
children 1 to 4 years old who have had multiple infections
with viral, fungal, and parasitic diseases. Compared with a
normal control group, these children do not have thymic cells
that bear markers of cortical lymphocytes. Which of the follow-
ing karyotypic abnormalities is most likely to be seen in the
children in this study?
+21
A
22q11.2
B
t(9;22)
C
t(15;17)
D
X(fra)
E
XXY
F

60 A 49-year-old woman has experienced increasing weak-

ness and chest pain over the past 6 months. On physical
57 A 27-year-old man has had a fever with chills and rigors ­examination, she is afebrile and normotensive. Motor strength
for the past 10 days. On physical examination, his temperature is 5/5 in all extremities, but diminishes to 4/5 with repetitive
is 37.9° C, pulse is 87/min, respirations are 21/min, and blood movement. There is no muscle pain or tenderness. Laboratory
pressure is 100/55 mm Hg. A diastolic murmur is heard on studies show hemoglobin, 14 g/dL; hematocrit, 42%; platelet
auscultation of the chest. There is a tender, palpable spleen count, 246,000/mm3; and WBC count, 6480/mm3. A chest CT
tip. Laboratory studies show hemoglobin, 12.8 g/dL; hema- scan shows an irregular 10 × 12 cm anterior mediastinal mass.
tocrit, 38.4%; platelet count, 231,000/mm3; and WBC count, The surgeon has difficulty removing the mass because it in-
12,980/mm3 with 69% segmented neutrophils, 8% bands, 1% filtrates surrounding structures. Microscopically, the mass is
metamyelocytes, 18% lymphocytes, and 4% monocytes. The composed of large, spindled, atypical epithelial cells mixed
representative gross appearance of the spleen is shown in the with lymphoid cells. Which of the following is the most likely
figure. What is the most likely underlying condition respon- cause of this mass lesion?
sible for the changes in the spleen? Extrapulmonary tuberculosis
A
Acute myelogenous leukemia
A Hodgkin lymphoma
B
Disseminated histoplasmosis
B Lymphoblastic lymphoma
C
Hodgkin lymphoma
C Malignant thymoma
D
Infective endocarditis
D Metastatic breast carcinoma
E
Metastatic carcinoma
E Organizing abscess
F
Micronodular cirrhosis
F
Rheumatic heart disease
G
 C H A P T E R 1 3   Hematopathology of White Blood Cells
ANSWERS
1  E  The major finding in this patient is marked granulocy-
topenia. All that remains on the peripheral smear are mono-
nuclear cells (remember to multiply the percentages in the
differential by the total WBC count to get the absolute values;
rather than one cell line being overrepresented, another may
be nearly missing). Accelerated removal or destruction of
neutrophils could account for the selective absence of granu-
locytes in this case. Overwhelming acute infections or other
causes for widespread innate immune response can lead to
increased peripheral use of neutrophils at sites of inflamma-
tion. Petechial hemorrhages also can occur in overwhelming
bacterial infections, such as those caused by Neisseria menin-
gitidis. Bleeding is unlikely to be caused by thrombocytopenia
because in this case the platelet count is normal. Normal bone
marrow findings exclude acute lymphoid or mye­loid leukemia.
In aplastic anemia, the marrow is poorly cellular, and there is
a reduction in RBCs, WBCs, and platelet production.
PBD9 582–583  BP9 425–426  PBD8 592–593  BP8 441–442
2  A  Her severe pancytopenia resulted from drug toxicity.
This predisposed her to subsequent sepsis, with aspergillosis
as the cause of pulmonary nodules, and neutropenia the
signi­ficant risk factor. These fungal organisms often invade
blood vessels, producing hemorrhagic lesions. Bartonellosis
can produce bacillary angiomatosis, which is more likely to
involve the skin. Mycobacterium avium complex is more likely
to involve organs of the mononuclear phagocyte system and
unlikely to produce large nodules. Escherichia coli, similar to
many bacterial infections, can occur in HIV infection, but it
has a pattern of acute neutrophilic infiltrates. Herpes simplex
virus (type 1 or 2) is an unlikely disseminated infection in
HIV. Pneumocystis pneumonia rarely produces nodular lesions.
Toxoplasmosis is uncommon in the lung, even in immuno-
compromised individuals.
PBD9 582–583  BP9 425–426  PBD8 593  BP8 441–442
3  D  The figures shows a neutrophilic leukocytosis, and
there can also be a “left shift” from increased band neutro-
phils. Chronic infections and ongoing inflammatory condi-
tions, such as lung abscesses, can lead to an expansion of
the myeloid precursor pool in the bone marrow with myeloid
hyperplasia. Acute viral hepatitis, in contrast to acute bacte-
rial infections, does not cause neutrophilic leukocytosis. In
chronic myelogenous leukemia, the marrow is filled with
myeloid cells throughout the spectrum of maturation, and
more immature forms in the peripheral blood, including
metamyelocytes, myelocytes, and even a few blasts, along
with increased eosino­phils and basophils. Glucocorticoids
can increase the release of marrow storage pool cells and
diminish extravasation of neutrophils into tissues. Vigorous
exercise can produce neutrophilia transiently from demar-
gination of neutrophils. A large spleen tends to sequester
peripheral blood cells, reducing their circulating numbers.
PBD9 583–584  BP9 426  PBD8 593–594  BP8 442–443
4  C  An autoimmune disease, most likely systemic lupus
erythematosus (SLE) in this patient, can be accompanied by
195
monocytosis. Cytopenias also can occur in SLE because of au-
toantibodies against blood elements, a form of type II hypersen-
sitivity. Basophilia occurs infrequently, but also can be seen in
chronic myelogenous leukemia (CML). Eosinophilia is a feature
more often seen in allergic conditions, tissue parasitic infestations,
and CML. Neutrophilia is seen in acute infectious and inflam-
matory conditions. Thrombocytosis usually occurs in neoplastic
disorders of myeloid stem cells, such as the myeloproliferative
disorders that include CML and essential thrombocytosis.
PBD9 584  BP9 426  PBD8 594  BP8 442
5  D  The eosinophilia suggests a parasitic infestation.
Immunocompromised individuals can have superinfection
and dissemination with strongyloidiasis. Type 1 hypersen-
sitivity with allergic reactions may also be accompanied by
eosinophilia. The other organisms listed are not known to be
associated with eosinophilia.
PBD9 584  BP9 426  PBD8 594  BP8 442
6  E  Toxic granulations, which are coarse and dark primary
granules, and Döhle bodies, which are patches of dilated en-
doplasmic reticulum, represent reactive changes of neutro-
phils that are most indicative of overwhelming inflammatory
conditions, such as bacterial sepsis. The route of infection in
this case is injection drug use. Infectious mononucleosis is
accompanied by an increase in “atypical” lymphocytes. Leu-
kemia, granulomatous infections, or viral infections do not
cause toxic changes in neutrophils.
PBD9 583-584  BP9 426  PBD8 594  BP8 441–442
7  C  This granulomatous infection has led to leukocytosis
with lymphocytosis and monocytosis. Blood monocytes be-
come tissue macrophages that evolve into ­epithelioid cells
and giant cells of granulomatous inflammation. The most
consistent form of leukocytosis from infection is neutrophilia
with acute bacterial infections, such as Staphylococcus aureus
infection. Viral, mycobacterial, and fungal infections produce
less consistent peripheral blood findings. An acute lympho-
blastic leukemia is likely to be accompanied by a higher WBC
count with circulating lymphoblasts. Hodgkin lymphomas
have no consistent peripheral blood findings and are not
likely to produce solitary lung nodules. Myelodysplastic
syndromes are marked by the presence of immature myeloid
cells and cytopenias in the peripheral blood.
PBD9 584  BP9 426  PBD8 594  BP8 442
8  D  Marked leukocytosis and immature myeloid cells in
the peripheral blood can represent an exaggerated response
to infection (leukemoid reaction), or it can be a manifestation
of chronic myelogenous leukemia (CML). Normal matura-
tion of myeloid cells in the marrow rules out CML. Although
not provided in this case, a leukocyte alkaline phosphatase
(LAP) score is high in the more differentiated cell population
of reactive leukocytosis, whereas in CML, the LAP score is
low. The Philadelphia chromosome (present in most CML
cases) is lacking in patients with leukemoid reactions. Hairy
196 U N I T I I   Diseases of Organ Systems
cell leukemia is accompanied by peripheral blood leukocytes
that mark with tartrate-resistant acid phosphatase. Hodgkin
lymphoma is not characterized by an increased WBC count.
A myelodysplastic syndrome is a stem cell maturation disor-
der involving all nonlymphoid cell lineages, not just granu-
locytes.
PBD9 584  BP9 426–427  PBD8 593–595  BP8 442
9  A  The smear shows large “atypical” lymphocytes with
abundant cytoplasm indented by red cells, and these are
present most often in patients with infectious mononucleosis,
and sometimes other viral infections, such as cytomegalovirus.
These atypical cells are large lymphocytes with abundant
cytoplasm and a large nucleus with fine chromatin. Infec-
tious mononucleosis is caused by Epstein-Barr virus (EBV)
and transmitted by close personal contact. In patients with
infectious mononucleosis, the EBV genes cause proliferation
and activation of multiple clones of B cells, and there is poly-
clonal B-cell expansion. These B cells secrete antibodies with
several specificities, including antibodies that cross-react
with sheep RBCs. These heterophil antibodies produce a
positive monospot test result. The atypical lymphocytes are
CD8+ T cells that are activated by EBV-infected B cells. There
is no increase in basophils, eosinophils, or monocytes in in-
fectious mononucleosis. Eating raw oysters is a risk factor
for hepatitis A because oysters that filter polluted seawater
concentrate the virus in their tissues. Disorders of globin
chain synthesis affect RBCs, as in the thalassemias. Infectious
mononucleosis is not known as a transfusion-associated dis-
ease. Likewise, intravenous drug use is typically not a risk
factor for infectious mononucleosis, but individuals sharing
infected needles are at risk for bacterial infections, HIV
infection, and viral hepatitis.
PBD9 361–362, 584  BP9 426–427  PBD8 356, 595  BP8 442–443
10  A  Painful and acute enlarged nodes suggest a reactive
condition and not a neoplastic process such as a lymphoma
or a leukemia. In children, enlarged tender nodes and acute
lymphadenitis are common. Many infectious processes can
give rise to these findings, particularly bacterial infections.
Children are “antigen sponges” when exposed to the usual
minor infections; they are quite active and acquire plenty of
cuts and scrapes on extremities, which can become infected,
with reactive hyperplasia of regional nodes. Cat-scratch disease
can produce sarcoidlike granulomas with stellate abscesses.
Follicular lymphomas are B-cell neoplasms that efface the
normal architecture of the lymph nodes; these tumors do
not occur in children. Sarcoidosis is a chronic granulomatous
process typically seen in adults and characterized by the for-
mation of noncaseating granulomas. Toxoplasmosis can be a
congenital infection or can be seen in immunocompromised
individuals; it produces a pattern of follicular hyperplasia.
PBD9 584–585  BP9 427–428  PBD8 595  BP8 443–444
11  F  Lymph nodes draining from a cancer often show a
reactive pattern, with dilated sinusoids that have endothelial
hypertrophy and are filled with histiocytes (i.e., macro-
phages). Sinus histiocytosis represents an immunologic
response to cancer antigens. Thus not all enlarged nodes
are caused by metastatic disease in cancer patients. CD3 is a
T-cell marker, CD19 and CD20 are B-cell markers, and CD68
is a macrophage (histiocyte) marker. Polyclonal prolif-
erations are typically benign reactive processes, whereas a
monoclonal proliferation suggests a neoplasm. Aneuploidy
and high S phase are characteristics of malignant neoplasms;
a high S phase mostly occurs in rapidly growing tumors, such
as diffuse large B-cell lymphomas, and in a few carcinomas,
such as small-cell anaplastic carcinoma. Inflammation would
produce pain and tenderness, and the patient may be febrile.
Generalized inflammatory diseases or chronic infections can
increase the number of plasma cells in lymph nodes.
PBD9 584–585  BP9 428  PBD8 595–596  BP8 443–444
12  A  Cat-scratch disease is a form of self-limited infec-
tious lymphadenitis that most often is seen in children, typi-
cally “downstream” of lymphatic drainage from the site of
an injury on a distal extremity. Hence axillary and cervical
lymph node regions are most often involved. Cytomegalo-
virus infection is typically seen in immunocompromised in-
dividuals and is not a common cause of lymphadenopathy.
Epstein-Barr virus (EBV) infection at this age is most often
associated with infectious mononucleosis and pharyngitis,
and the lymphadenopathy is nonspecific. Staphylococcus
aureus can produce suppurative inflammation with sepsis.
Yersinia pestis, the agent that causes bubonic plague, produc-
es lymphadenopathy that can ulcerate and a hemorrhagic
necrotizing lymphadenitis; it has a high mortality rate.
PBD9 584–585  BP9 428  PBD8 595–596  BP8 444
13  E  Both primary and acquired immune deficiencies
produce immune dysregulation from which malignancies
may arise. These malignancies are most often neoplastic
proliferations of white cells: lymphomas, leukemias, and
Hodgkin lymphoma, but carcinomas may also occur. Of the
primary immune deficiencies, Wiskott-Aldrich syndrome
has the highest percentage of lymphomas among malignan-
cies that develop. Epstein-Barr virus infection may be an ad-
ditional triggering event. Conversely, persons with lymphoid
malignancies may develop secondary immunodeficiency,
with increased risk for opportunistic infection. The other
listed options are not specifically linked to development of
malignancies.
PBD9 586–587  BP9 429  PBD8 600  BP8 445
14  D  His age and the mediastinal location are typical of a
lymphoblastic lymphoma involving the thymus. This lesion
is within the spectrum of acute lymphoblastic leukemia or
lymphoma (ALL). Most cases of ALL with lymphomatous
presentation are of the pre–T-cell type, supported by the ex-
pression of the T-cell markers CD2 and CD7. The NOTCH1
gene encodes a transmembrane receptor required for T-cell
development, and more than half of pre–T-cell tumors have
activating point mutations. TdT is a marker of pre–T cells
and pre–B cells. A Burkitt lymphoma is a B-cell lymphoma
that also can be seen in adolescents, but usually is present in
the jaw or abdomen. Nodular sclerosing follicular lymphomas
 C H A P T E R 1 3   Hematopathology of White Blood Cells
and mantle cell lymphomas are B-cell tumors usually seen in
older patients, and they do not involve the thymus. Hodgkin
lymphoma does occur in the mediastinum, but it involves
mediastinal nodes, not thymus. The histologic features of
Hodgkin lymphoma include the presence of Reed-Sternberg
cells, and this variant has fibrous bands intersecting the lym-
phoid cells. Small lymphocytic lymphoma is the tissue phase
of chronic lymphocytic leukemia seen in older adults.
PBD9 588–591  BP9 430–431  PBD8 602–603  BP8 446–449
15  A  The clinical history, the peripheral blood smear, and
the phenotypic markers are characteristic of chronic lympho-
cytic leukemia (CLL), a clonal B-cell neoplasm in which
immunoglobulin genes are rearranged, and T-cell receptor
genes are in germline configuration. There is typically a tis-
sue component of small lymphocytic lymphoma (SLL). The
t(8;14) translocation is typical of Burkitt lymphoma; this lym-
phoma occurs in children at extranodal sites. The t(9;22) is a
feature of chronic myeloid leukemia. The t(14;18) translocation
is a feature of follicular lymphomas, which are distinctive
B-cell tumors that involve the nodes and produce a follicular
pattern. The lymphoma cells can be present in blood, but
they do not look like mature lymphocytes.
PBD9 593–594  BP9 433–434  PBD8 603–605  BP8 450–451
16  D  The figure shows a follicular non-Hodgkin lympho-
ma. All lymphoid neoplasms are derived from a single trans-
formed cell and are monoclonal. B-cell neoplasms comprise
80% to 85% of all lymphoid neoplasms, and their monoclonality
can often be shown by immunostaining that reveals one light
chain in the neoplastic cells. Populations of normal or reactive
(polyclonal) B cells contain a mixture of B cells expressing both
kappa and lambda light chains. Some lymphoid neoplasms
have a follicular pattern. A normal pattern of follicles is
sometimes absent if the node is involved, as in some in-
flammatory conditions or in immunosuppression. The CD30
antigen is a marker for activated T and B cells. Plasma cells
are variably present in reactive conditions, but their absence
does not indicate malignancy. A proliferation of capillaries is
typically a benign, reactive process.
PBD9 594–595  BP9 429–431  PBD8 599  BP8 445
7  A  These findings are characteristic of a childhood acute
1
lymphoblastic leukemia of the precursor–B-cell type. The rap-
id expansion of the marrow caused by proliferation of blasts
can lead to bone pain and tenderness. Features supporting
an acute leukemia are anemia, thrombocytopenia, and the
presence of blasts in the peripheral blood and bone marrow.
Anemia and thrombocytopenia result from suppression of
normal hematopoiesis by the leukemic clone in the marrow.
The phenotype of CD19+, CD3−, and sIg− is typical of pre–B
cells. TdT is a marker of early T-cell–type and B-cell–type lym-
phoid cells. An acute myelogenous leukemia is a disease of
young to middle-aged adults, and there would be peroxidase-
positive myeloblasts and phenotypic features of myeloid cells.
Chronic lymphocytic leukemia is a disease of older adults;
patients have many small circulating mature B lymphocytes.
Chronic mye­logenous leukemia is a disease of adults, and the
197
WBC count is quite high; the peripheral blood contains some
myeloblasts, but other stages of myeloid differentiation also
are detected. In idiopathic thrombocytopenic purpura, only
the platelet count is reduced because of antibody-mediated
destruction of platelets.
PBD9 588–591  BP9 429–433  PBD8 602–603  BP8 446–447
18  A  These markers strongly favor a very good progno-
sis for acute lymphoblastic leukemia (ALL), the most com-
mon malignancy in children: early precursor–B-cell type,
hyperdiploidy, and patient age between 2 and 10 years,
chromosomal trisomy, and t(12;21). Marrow infiltration by
the leukemic cells leads to pancytopenia. Poor prognostic
markers for acute lymphoblastic leukemia/lymphoma are
T-cell phenotype, patient age younger than 2 years, WBC
count >100,000, presence of t(9;22) MLL gene mutations, and
presentation in adolescence and adulthood. In most T-cell ALL
cases in adolescents, a media­stinal mass arises in the thymus,
and lymphoid infiltrates appear in tissues of the mononuclear
phagocyte system. The success of a treatment plan is also
aided by a caring and supportive family.
PBD9 590–593  BP9 430–433  PBD8 601–603  BP8 447–449
19  C  Follicular lymphoma is the most common form of
non-Hodgkin lymphoma among adults in Europe and North
America. Men and women are equally affected. The neoplastic
B cells mimic a population of follicular center cells and pro-
duce a nodular or follicular pattern. Nodal involvement is often
generalized, but extranodal involvement is uncommon. The
t(14;18) translocation, which is characteristic, causes over-
expression of the BCL2 gene by juxtaposing it with the IgH
locus; the cells are resistant to apoptosis. In keeping with
this, follicular lymphomas are indolent tumors that continue
to accumulate cells for 7 to 9 years. The lymphoid popula-
tion in acute lymphadenitis is reactive, and there is no bone
marrow involvement. In Hodgkin lymphoma, there are few
Reed-Sternberg cells, surrounded by a reactive lymphoid
population. Mantle cell lymphoma also is a B-cell tumor; it is
more aggressive than follicular lymphoma and is typified by
the t(11;14) translocation, in which the cyclin D1 gene (BCL2)
is overexpressed. In toxoplasmosis, there would be a mixed
population of inflammatory cells and some necrosis.
PBD9 594–595  BP9 434–435  PBD8 605–606  BP8 451
20  B  Sonja Henie died from complications of chronic lym-
phocytic leukemia (CLL). The figure shows increased numbers
of circulating small, round, mature lymphocytes with scant cy-
toplasm in the peripheral blood smear. The CLL cells express
the CD5 marker and the pan B-cell markers CD19 and CD20.
Most patients have a disease course of 4 to 6 years before death,
and symptoms appear as the leukemic cells begin to fill the
marrow. In some patients, the same small lymphocytes appear
in tissues; the condition is then known as small lymphocytic lym-
phoma. Acute lymphoblastic leukemia is a disease of children
and young adults, characterized by proliferation of lympho-
blasts. These cells are much larger than the cells in CLL and
have nucleoli. The lymphocytes seen in infectious mononu-
cleosis are atypical lymphocytes, which have abundant, pale