U2-Robbins- C13: WBC, Lymph Node, Spleen, Thymus Flashcards Preview

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1

A 15-year-old boy visits his physician because of high fever of 10 days’ duration. Physical examination shows a
temperature of 38°C. He has scattered petechial hemorrhages on the trunk and extremities. There is no enlargement of
liver, spleen, or lymph nodes. The CBC shows hemoglobin, 13.2 g/dL; hematocrit, 38.9%; MCV, 93 μm3; platelet count,
175,000/mm3; and WBC count, 1850/mm3 with 1% segmented neutrophils, 98% lymphocytes, and 1% monocytes. Bone
marrow biopsy examination does not show any abnormal cells. Which of the following is the most likely diagnosis?
□ (A) Acute lymphoblastic leukemia
□ (B) Acute myelogenous leukemia
□ (C) Aplastic anemia
□ (D) Idiopathic thrombocytopenic purpura
□ (E) Overwhelming bacterial infection

 

(E) The major finding in this patient is marked granulocytopenia. All that remains on the peripheral smear are

mononuclear 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 granulocytes in this case. Overwhelming infections

cause increased peripheral use of neutrophils at sites of inflammation. Petechial hemorrhages also can occur in

overwhelming bacterial infections, such as those caused by Neisseria meningitidis. Bleeding is unlikely to be caused by

thrombocytopenia because 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

2

2 A 9-year-old boy is taken to his pediatrician because of a generalized seborrheic skin eruption and fever. He has been
diagnosed and treated for otitis media several times in the past year. On physical examination, he has mild
lymphadenopathy, hepatomegaly, and splenomegaly. The electron micrograph shown in the figure was taken from a mass
lesion involving the mastoid bone. What is the most likely diagnosis?
□ (A) Acute lymphoblastic leukemia
□ (B) Multiple myeloma
□ (C) Hodgkin lymphoma, mixed cellularity type
□ (D) Langerhans cell histiocytosis
□ (E) Disseminated tuberculosis

 

(D) Shown here are the famous rodlike tubular Birbeck granules, with the characteristic periodicity seen in Langerhans

cell proliferations. In this case, the skin eruptions, organomegaly, and lesion in the mastoid suggest infiltrates in multiple

organs. The diagnosis is multifocal Langerhans cell histiocytosis, a disease most often seen in children. In half of these

cases, exophthalmos occurs, and involvement of the hypothalamus and pituitary stalk leads to diabetes insipidus; these

findings are called Hand-Schüller-Christian disease. Acute lymphoblastic leukemia in children can involve the marrow, but

does not produce skin or bone lesions. Myeloma is a disease of adults that can produce lytic bone lesions, but not skin

lesions. Hodgkin lymphoma is seen in young adults and does not produce skin lesions or bone lesions. Tuberculosis can

produce granulomatous disease with bony destruction, but the macrophages present in the granulomas are epithelioid

macrophages that do not have Birbeck granules.

3

A 67-year-old man has had increasing weakness, fatigue, and weight loss over the past 5 months. He now has
decreasing vision in both eyes and has headaches and dizziness. His hands are sensitive to cold. On physical
examination, he has generalized lymphadenopathy and hepatosplenomegaly. Laboratory studies indicate
hyperproteinemia with a serum protein level of 15.5 g/dL and albumin concentration of 3.2 g/dL. A bone marrow biopsy is
performed, and microscopic examination of the specimen shows infiltration of small plasmacytoid lymphoid cells with
Russell bodies in the cytoplasm. Which of the following findings is most likely to be reported for this patient?
□ (A) Monoclonal IgM spike in serum
□ (B) WBC count of 255,000/mm3
Robbins & Cotran Review of Pathology Pg. 242
□ (C) Hypercalcemia
□ (D) Bence Jones proteinuria
□ (E) Karyotype with t(14;18) translocation

 

(A) This patient has symptoms of hyperviscosity syndrome, including visual disturbances, dizziness, and headaches. He

also seems to have Raynaud phenomena. His bone marrow is infiltrated with plasmacytoid lymphocytes that have stored

immunoglobulins in the cytoplasm (Russell bodies). All of these findings suggest that the patient has lymphoplasmacytic

lymphoma (Waldenström macroglobulinemia). In this disorder, neoplastic B cells differentiate to IgM-producing cells; there

is a monoclonal IgM spike in the serum. These IgM molecules aggregate and produce hyperviscosity, and some of them

agglutinate at low temperatures and produce cold agglutinin disease. There is typically no leukemic phase to Waldenström

macroglobulinemia. Myeloma, which is typically accompanied by a monoclonal gammopathy, most often does not cause

liver and spleen enlargement, and morphologically, the cells resemble plasma cells. Hypercalcemia occurs with myeloma

because of bone destruction, and punched-out lytic lesions are typical of multiple myeloma. Light chains in urine (Bence

Jones proteins) also are a feature of multiple myeloma. A t(14;18) translocation is characteristic of a follicular lymphoma.

4

A 37-year-old woman visits her physician because of a cough and fever of 1 week's duration. On physical examination,
her temperature is 38.3°C. She has diffuse crackles in all lung fields. A chest radiograph shows bilateral extensive
infiltrates. CBC shows hemoglobin, 13.9 g/dL; hematocrit, 42%; MCV, 89 μm3; platelet count, 210,000/mm3; and WBC
count, 56,000/mm3 with 63% segmented neutrophils, 15% bands, 6% metamyelocytes, 3% myelocytes, 1% blasts, 8%
lymphocytes, 2% monocytes, and 2% eosinophils. The peripheral blood leukocyte alkaline phosphatase score is
increased. Which of the following is the most likely diagnosis?
□ (A) Chronic myelogenous leukemia
□ (B) Hairy cell leukemia
□ (C) Hodgkin lymphoma, lymphocyte depletion type
□ (D) Leukemoid reaction
□ (E) Acute lymphoblastic leukemia

 

(D) Marked leukocytosis and immature myeloid cells in the peripheral blood can represent an exaggerated response to

infection (leukemoid reaction), or they can be a manifestation of chronic myelogenous leukemia (CML).The leukocyte

alkaline phosphatase score is high in the more differentiated cell population seen in reactive leukocytosis, whereas in

CML, the leukocyte alkaline phosphatase score is low. The Philadelphia chromosome (universally present in CML) is

lacking in patients with leukemoid reactions. Hairy 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. Acute

lymphoblastic leukemia is a disease of children and young adults, and the lymphoid cells do not have leukocyte alkaline

phosphatase

5

A 12-year-old boy is taken to the physician because he has had increasing abdominal distention and pain for the past 3
days. Physical examination shows lower abdominal tenderness, and the abdomen is tympanitic with reduced bowel
sounds. An abdominal CT scan shows a 7-cm mass involving the region of the ileocecal valve. Surgery is performed to
remove the mass. Histologic examination of the mass shows sheets of intermediate-sized lymphoid cells, with nuclei
having coarse chromatin, several nucleoli, and many mitoses. A bone marrow biopsy sample is negative for this cell
population. Cytogenetic analysis of the cells from the mass shows a t(8;14) karyotype. Flow cytometric analysis reveals
40% of the cells are in S phase. The tumor shrinks dramatically in size after a course of chemotherapy. Which of the
following is the most likely diagnosis?
□ (A) Diffuse large B-cell lymphoma
□ (B) Follicular lymphoma
□ (C) Acute lymphoblastic leukemia
□ (D) Plasmacytoma
□ (E) Burkitt lymphoma

 

(E) Burkitt and Burkitt-like lymphomas can be seen sporadically (in young individuals), in an endemic form in Africa (in

children), and in association with HIV infection. All forms are highly associated with translocations of the MYC gene on

chromosome 8. In the African form and in HIV-infected patients, the cells are latently infected with Epstein-Barr virus

(EBV), but sporadic cases are negative for EBV. This form of lymphoma is typically extranodal. Diffuse large cell

lymphomas are most common in adults, as are follicular lymphomas; they do not carry the t(8;14) translocation. Acute

lymphoblastic lymphomas can be seen in boys this age, but the mass is in the mediastinum, and the lymphoid cells are T

cells. Plasmacytomas appear in older adults and are unlikely to produce an abdominal mass. Because of the high growth

fraction (40% in this case), Burkitt lymphomas respond very well to chemotherapy that includes cycle acting agents. By

contrast, slow-growing tumors with a low growth fraction are more indolent and less responsive to chemotherapy.

6

A 53-year-old man comes to his physician because he felt a lump near his shoulder 1 week ago. On physical
examination, there is an enlarged, nontender, supraclavicular lymph node and enlargement of the Waldeyer ring of
oropharyngeal lymphoid tissue. There is no hepatosplenomegaly. CBC is normal except for findings of mild anemia. A
lymph node biopsy specimen shows replacement by a monomorphous population of large lymphoid cells with enlarged
nuclei and prominent nucleoli. Immunohistochemical staining and flow cytometry of the node indicates that most lymphoid
cells are CD19+, CD10+, CD3−, CD15−, and terminal deoxynucleotidyl transferase negative (TdT−). Which of the
following is the most likely diagnosis?
□ (A) Chronic lymphadenitis
□ (B) Diffuse large B-cell lymphoma
□ (C) Hodgkin lymphoma
□ (D) Lymphoblastic lymphoma
□ (E) Small lymphocytic lymphoma

(B) Diffuse large B-cell lymphoma occurs in older individuals and frequently manifests as localized disease with

extranodal involvement, particularly of the Waldeyer ring. The staining pattern indicates a B-cell proliferation (CD19+,

CD10+). T-cell (CD3) and monocytic (CD15) markers are absent. TdT can be expressed in B lineage cells at an earlier

stage of maturation. Small lymphocytic lymphoma also is a B-cell neoplasm, but it manifests with widespread

lymphadenopathy, liver and spleen enlargement, and lymphocytosis. Lymphoblastic lymphoma is a T-cell neoplasm that

occurs typically in the mediastinum of children. Hodgkin lymphoma is characterized by Reed-Sternberg cells. In chronic

lymphadenitis, the lymph node has many cell types—macrophages, lymphocytes, and plasma cells. A monomorphous

infiltrate is typical of non-Hodgkin lymphomas

7

A 50-year-old man has had headache, dizziness, and fatigue for the past 3 months. His friends have been commenting
about his increasingly ruddy complexion. He also has experienced generalized and severe pruritus, particularly when
showering. He notes that his stools are dark. On physical examination, he is afebrile, and his blood pressure is
165/90 mm Hg. 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.
The serum erythropoietin level is very low. What is the most likely diagnosis?
□ (A) Myelodysplastic syndrome
□ (B) Essential thrombocytosis
□ (C) Chronic myelogenous leukemia
□ (D) Erythroleukemia
□ (E) Polycythemia vera

 

(E) This patient has polycythemia vera, a myeloproliferative disorder characterized by an increased RBC mass, with

hematocrit concentrations typically exceeding 60%. Although the increased RBC mass is responsible for most of the

symptoms and signs, these patients also have thrombocytosis and granulocytosis. This occurs because, similar to other

myeloproliferative disorders, polycythemia vera results from transformation of a multipotent stem cell. The high hematocrit

concentration causes an increase in blood volume and distention of blood vessels. The neoplastic erythroid progenitor

cells require extremely small amounts of erythropoietin for survival and proliferation; the levels of erythropoietin are

virtually undetectable in polycythemia vera. When combined with abnormal platelet function, this condition predisposes the

patient to bleeding. Abnormal platelet function also can predispose to thrombosis. The pruritus and peptic ulceration most

Robbins & Cotran Review of Pathology Pg. 261

likely are the result of the histamine release from basophils. In some patients, the disease “burns out” to myelofibrosis. A

few patients “blast out” into acute myelogenous leukemia, and other patients develop chronic myelogenous leukemia.

Myelodysplastic syndromes and myeloproliferative disorders, such as essential thrombocytosis, are not accompanied by

such an increase in RBC mass. Erythroleukemia typically is not accompanied by such a high hematocrit concentration

because leukemic erythroid progenitors do not differentiate into mature RBCs.

8

A 50-year-old man was diagnosed with a diffuse large B-cell lymphoma. He underwent intensive chemotherapy, and a
complete remission was achieved for 7 years. He now reports fatigue and recurrent pulmonary and urinary tract infections
over the past 4 months. Physical examination shows no masses, lymphadenopathy, 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 neutrophils, 5% bands, 2% metamyelocytes, 2% myelocytes, 6% myeloblasts, 33% lymphocytes, 35%
monocytes, and 2% eosinophils. 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. Which of the following is most likely now to have occurred in this patient?
□ (A) Relapse of his previous lymphoma
□ (B) Transformation of lymphoma into myeloid leukemia
□ (C) Myelodysplasia related to therapy for the previous tumor
□ (D) De novo acute myeloblastic leukemia
□ (E) Myeloid metaplasia with myelofibrosis

(C) This patient has developed a myelodysplasia, characterized by a cellular marrow in which there are maturation

defects in multiple lineages. This diagnosis is supported by the presence of ringed sideroblasts, megaloblasts, abnormal

megakaryocytes, and myeloblasts in the marrow. Because the hematopoietic cells fail to mature normally, they are not

released into the peripheral blood. The patient has pancytopenia and is susceptible to infections. Myelodysplasias are

clonal stem cell disorders that develop de novo or after chemotherapy with alkylating agents, as in this case. The

presence of chromosomal deletions, such as 5q, is a marker of post-therapy myelodysplasia. The morphologic

abnormalities in the marrow are not seen in any of the other listed conditions.

9

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 dyspnea and right-sided chest pain. On physical examination, the
spleen and liver now appear to be enlarged. CBC shows hemoglobin, 13.3 g/dL; hematocrit, 40.1%; MCV, 91 μm3; platelet
count, 657,000/mm3; and WBC count, 17,400/mm3. The peripheral blood smear shows abnormally large platelets. Which
of the following is the most likely diagnosis?
□ (A) Essential thrombocythemia
□ (B) Chronic myelogenous leukemia
□ (C) Myelofibrosis with myeloid metaplasia
□ (D) Acute myelogenous leukemia
□ (E) Polycythemia vera

A) Essential thrombocythemia is a myeloproliferative disorder. As with all myeloproliferative diseases, the

transformation occurs in a myeloid stem cell. In this form of myeloproliferative disease, the dominant cell type affected is

the megakaryocyte, and there is thrombocytosis. Other myeloproliferative disorders, such as chronic myelogenous

leukemia, myelofibrosis, and polycythemia vera, also can be accompanied by an increased platelet count. The diagnosis

of essential thrombocytosis can be made after other causes of reactive thrombocytosis are excluded, and if the bone

marrow examination shows increased megakaryocytes with no evidence of leukemia. The throbbing, burning pain in the

extremities is caused by platelet aggregates that occlude small arterioles. The major manifestation of this disease is

thrombotic or hemorrhagic crises. The swelling in this patient's leg represents phlebothrombosis, followed by pulmonary

embolism with infarction. The peripheral blood WBC count would be high in acute myelogenous leukemia, without

thrombocytosis.

10

A 9-year-old boy living in Uganda has had increasing pain and swelling on the right side of his face over the past 8
months. On physical examination, there is a large, nontender mass involving the mandible, which deforms the right side of
his face. There is no lymphadenopathy and no splenomegaly, and he is afebrile. A biopsy of the mass is performed.
Microscopically, the specimen is composed of intermediate-sized lymphocytes with a high mitotic rate. A chromosome
analysis shows a 46,XY,t(8;14) karyotype in these cells. The hemoglobin concentration is 13.2 g/dL, platelet count is
272,000/mm3, and WBC count is 5820/mm3. Infection with which of the following is most likely to be causally related to the
development of these findings?
□ (A) Cytomegalovirus
□ (B) Epstein-Barr virus
Robbins & Cotran Review of Pathology Pg. 244
□ (C) Hepatitis B virus
□ (D) HIV
□ (E) Human papillomavirus
□ (F) Respiratory syncytial virus

(B) This patient has the endemic African variety of Burkitt lymphoma, a B-cell lymphoma that typically appears in the

maxilla or mandible of the jaw. This particular neoplasm is related to Epstein-Barr virus infection. Cytomegalovirus

infection occurs in immunocompromised patients and can be a congenital infection, but it is not a direct cause of

neoplasia. Hepatitis B virus infection can be a risk factor for hepatocellular carcinoma. HIV infection can be a risk factor for

the development of non-Hodgkin lymphomas, but most of these are either diffuse large B-cell lymphomas or small

noncleaved Burkitt-like lymphomas. Human papillomavirus infection is related to the formation of squamous dysplasias and

carcinomas, most commonly those involving the cervix. Respiratory syncytial virus infection produces pneumonia in infants

and young children, but is not related to development of neoplasms

11

A 23-year-old man undergoing chemotherapy for acute lymphoblastic leukemia has developed a fever and abdominal
pain within the past week. He now has a severe cough. On physical examination, his temperature is 38.4°C. On
auscultation, crackles are heard over all lung fields. Laboratory studies show hemoglobin, 12.8 g/dL; hematocrit, 39%;
MCV, 90 μm3; platelet count, 221,000/mm3; and WBC count, 16,475/mm3 with 51% segmented neutrophils, 5% bands,
18% lymphocytes, 8% monocytes, and 18% eosinophils. Infection with which of the following organisms is most likely to be
complicating the course of this patient's disease?
□ (A) Cryptococcus neoformans
□ (B) Cytomegalovirus
□ (C) Helicobacter pylori
□ (D) Hepatitis C virus
□ (E) Pseudomonas aeruginosa
□ (F) Strongyloides stercoralis
□ (G) Toxoplasma gondii
□ (H) Varicella-zoster virus

(F) The eosinophilia suggests a parasitic infestation. Immunocompromised individuals can have superinfection and

dissemination with strongyloidiasis. The other organisms listed are not known to be associated with eosinophilia

12

A 61-year-old man reports a history of back pain for 5 months. He has recently developed a cough that is productive of
yellow sputum. On physical examination, he is febrile, and diffuse rales are heard on auscultation of the lungs. He has no
lymphadenopathy or splenomegaly. Laboratory studies include a sputum culture that grew Streptococcus pneumoniae.
The serum creatinine level is 3.7 mg/dL, and the urea nitrogen level is 35 mg/dL. The figure shows a skull radiograph.
During his hospitalization, a bone marrow biopsy is performed. Which of the following is the biopsy specimen most likely to
show?
□ (A) Scattered small granulomas
□ (B) Numerous plasma cells
□ (C) Nodules of small mature lymphocytes
□ (D) Occasional Reed-Sternberg cells
□ (E) Hypercellularity with many blasts

 

(B) Multiple myeloma produces mass lesions of plasma cells in bone that lead to lysis and pain. The skull radiograph

shows typical punched-out lytic lesions, produced by expanding masses of plasma cells. The Ig genes in myeloma cells

always show evidence of somatic hypermutation. Bence Jones proteinuria can damage the tubules and give rise to renal

failure. Multiple myeloma can be complicated by AL amyloid, which also can lead to renal failure. Patients with myeloma

often have infections with encapsulated bacteria because of decreased production of IgG, required for opsonization.

Granulomatous disease (which is not produced by pneumococcus) can involve the marrow, but usually it does not produce

such sharply demarcated lytic lesions. Nodules of small lymphocytes suggest a small-cell lymphocytic leukemia/lymphoma,

which is not likely to produce lytic lesions. Reed-Sternberg cells suggest Hodgkin lymphoma. Blasts suggest a leukemic

process

13

A 26-year-old man has noted lumps in his neck that have been enlarging for the past 6 months. On physical
examination, he has a group of enlarged, nontender right cervical lymph nodes. A biopsy of one of the lymph nodes shows
Robbins & Cotran Review of Pathology Pg. 245
scattered Reed-Sternberg cells, macrophages, lymphocytes, neutrophils, eosinophils, and a few plasma cells. Which of
the following factors elaborated by the Reed-Sternberg cells has led to the appearance of the eosinophils within this
lesion?
□ (A) Platelet-derived growth factor
□ (B) Cyclin D1
□ (C) Interleukin-5
□ (D) Trans-retinoic acid
□ (E) Erythropoietin

 

(C) Interleukin-5 acts as an eosinophilic chemotactic factor to form an eosinophilic cellular component of the mixed

cellularity and nodular sclerosis types of Hodgkin lymphoma. In contrast, transforming growth factor-β secreted by eosinophils promotes the fibrosis that is part of nodular sclerosing Hodgkin lymphoma. Platelet-derived growth factor does

not play a major role in Hodgkin lymphoma, although it may be elaborated by cells in some carcinomas and gliomas. Cyclin

D1 is involved in the cell cycle and proliferation. Trans-retinoic acid is used in treating acute promyelocytic leukemia, in

which the abnormal gene fusion product of the t(15;17) blocks myeloid maturation at the promyelocyte stage.

Erythropoietin drives erythroid cell line proliferation.

14

A 53-year-old woman has experienced nausea with vomiting and early satiety for the past 7 months. On physical
examination, she is afebrile and has no lymphadenopathy or hepatosplenomegaly. CBC shows hemoglobin, 12.9 g/dL;
hematocrit, 41.9%; platelet count, 263,000/mm3; and WBC count, 8430/mm3. An upper gastrointestinal endoscopy shows
loss of the rugal folds of the stomach over a 4 × 8 cm area of the fundus. Gastric biopsy specimens reveal the presence of
Helicobacter pylori organisms in the mucus overlying superficial epithelial cells. There are mucosal and submucosal
monomorphous infiltrates of small lymphocytes, which are CD19+ and CD20+, but CD3−. After treatment of the H. pylori
infection, her condition improves. What is the most likely diagnosis?
□ (A) Acute lymphoblastic leukemia
□ (B) Chronic lymphocytic leukemia
□ (C) Diffuse large B-cell lymphoma
□ (D) Follicular lymphoma
□ (E) Hodgkin lymphoma, mixed cellularity type
□ (F) MALT (marginal zone) lymphoma
□ (G) Waldenström macroglobulinemia

(F) These lymphomas arise in middle-aged adults at sites of autoimmune or infectious stimulation. If the lesion is

associated with lymphoid tissue, it is sometimes called a mucosa-associated lymphoid tissue tumor (MALT lymphoma, or

MALToma). The most common sites are the thyroid (in Hashimoto thyroiditis), the salivary glands (in Sjögren syndrome),

or the stomach (in Helicobacter pylori infection). Although monoclonal (similar to a neoplasm), these MALT lesions can

regress with antibiotic therapy for H. pylori. A MALT lesion can transform to diffuse large B-cell lymphoma. The cells

correspond to the marginal B-cells found at the periphery of stimulated lymphoid follicles. The other conditions listed are

neoplastic conditions that are not related to H. pylori, and that require chemotherapy to control.

15

An 18-month-old girl has developed seborrheic skin eruptions over the past 3 months. She has had recurrent upper
respiratory 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
□ (C) Plasma cells with Russell bodies
□ (D) Reed-Sternberg cells
□ (E) Ringed sideroblasts
□ (F) Sézary cells

 

The child has Letterer-Siwe disease, a form of Langerhans cell histiocytosis. The Birbeck granules are a distinctive

feature, identified by electron microscopy, which are found in the cytoplasm of the Langerhans cells. Lymphoblasts that

mark as T cells are seen in anterior mediastinal (thymic) masses in children with acute lymphoblastic leukemia/lymphoma.

Plasma cells are seen in multiple myeloma, a disease of older adults accompanied by a monoclonal gammopathy. Reed-

Sternberg cells are seen in Hodgkin lymphoma, which is an unlikely disease in children. Ringed sideroblasts can be seen

in myelodysplastic syndromes. Sézary cells can be seen in peripheral T-cell lymphoma/leukemias, which often involve the

skin.

16

A 20-year-old man is left at the door of the emergency department by his “friends” after they spent an evening at a local
pub. On examination, his vital signs are temperature, 37°C; pulse, 110/min; respirations, 20/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 etiology for this man's findings?
□ (A) Amyloidosis
□ (B) Cirrhosis
□ (C) Gaucher disease
□ (D) Myeloproliferative disorder
□ (E) Nonbacterial thrombotic endocarditis
□ (F) Salmonella typhi infection
□ (G) Trauma

 

(G) This patient has a splenic rupture with hematoma formation in a normal-sized spleen. The likelihood of acute

alcohol ingestion favors trauma from falls, fights, and vehicular accidents. A “spontaneous” rupture of the spleen in the

absence of trauma may occur when there is splenic enlargement from infections and neoplasms. Other causes of splenic

enlargement include amyloid deposition, congestive splenomegaly from portal hypertension with cirrhosis, storage

diseases such as Gaucher disease, and myeloproliferative disorders. Embolic events from endocarditis are most likely to

occur with infective endocarditis and nonbacterial thrombotic endocarditis

17

A 34-year-old man has experienced multiple nosebleeds along with bleeding gums for the past month. On examination,
his temperature is 37.3°C. He has multiple cutaneous ecchymoses. Laboratory studies show hemoglobin, 8.5 g/dL;
hematocrit, 25.7%; platelet count, 13,000/mm3; and WBC count, 52,100/mm3 with 5% segmented neutrophils, 5% bands,
2% myelocytes, 83% blasts, 3% lymphocytes, and 2% monocytes. Examination of his peripheral blood smear shows the
blasts have delicate nuclear chromatin along with fine cytoplasmic azurophilic granules. These blasts are CD33+. Which
of the following morphologic findings is most likely to be present on his peripheral blood smear?
□ (A) Auer rods
□ (B) Döhle bodies
□ (C) Hairy projections
□ (D) Heinz bodies
□ (E) Sickle cells
□ (F) Toxic granulations

 

(A) This patient has acute myelogenous leukemia, which infiltrates the marrow and reduces normal hematopoiesis to

account for anemia and marked thrombocytopenia. The initial presentation may be acute. The Auer rods are

condensations of the azurophilic granules. Döhle bodies, which are patches of dilated endoplasmic reticulum, and toxic

granulations, which are coarse and dark primary granules, are reactive changes in mature neutrophils most indicative of

marked inflammation, such as bacterial sepsis. Hairy projections are seen on the circulating B cells of hairy-cell leukemia.

Heinz bodies are seen in G6PD deficiency and are precipitates of denatured globin. Sickling of RBCs is a feature of sickle

cell anemia, which is not related to leukemia

18

A 41-year-old man has had fevers with chills and rigors for the past 2 weeks. On physical examination, his temperature
is 39.2°C. CBC shows hemoglobin, 13.9 g/dL; hematocrit, 40.5%; MCV, 93 μm3; platelet count, 210,000/mm3; and WBC
count, 13,750/mm3 with 75% segmented neutrophils, 10% bands, 10% lymphocytes, and 5% monocytes. A bone marrow
biopsy specimen shows hypercellularity with a marked increase in myeloid precursors at all stages of maturation and in
band neutrophils. These findings are most likely caused by which of the following conditions?
□ (A) Acute viral hepatitis
□ (B) Glucocorticoid therapy
□ (C) Lung abscess
□ (D) Vigorous exercise
□ (E) Acute myelogenous leukemia

 

(C) Chronic infections and chronic inflammatory conditions, such as lung abscesses, can lead to an expansion of the

myeloid precursor pool in the bone marrow; this manifests as neutrophilic leukocytosis. Acute viral hepatitis, in contrast to

acute bacterial infections, does not cause neutrophilic leukocytosis. Glucocorticoids can increase the release of marrow

storage pool cells and diminish extravasation of neutrophils into tissues. Vigorous exercise can produce neutrophilia

transiently from demargination of neutrophils. In acute myelogenous leukemia, the marrow is filled with blasts, not maturing

myeloid elements.

19

A 37-year-old man known to have been infected with HIV for the past 10 years is admitted to the hospital with
abdominal pain of 3 days’ duration. Physical examination shows abdominal distention and absent bowel sounds. An
abdominal CT scan shows a mass lesion involving the ileum. He undergoes surgery to remove an area of bowel
obstruction in the ileum. Gross examination of the specimen shows a firm, white mass, 10 cm long and 3 cm at its greatest
depth. The mass has infiltrated through the wall of the ileum. Histologic studies show a mitotically active population of
CD19+ lymphoid cells with prominent nuclei and nucleoli. Molecular analysis is most likely to show which of the following
viral genomes in the lymphoid cells?
□ (A) Epstein-Barr virus
□ (B) HIV
□ (C) Human herpesvirus type 8
□ (D) Human T-cell leukemia/lymphoma virus type 1
□ (E) Cytomegalovirus

 

(A) This HIV-positive patient has an extranodal infiltrative mass, composed of B cells (CD19+), in the ileum. This is a

diffuse large cell lymphoma of B cells. These tumors contain the Epstein-Barr virus (EBV) genome, and it is thought that

immunosuppression allows unregulated proliferation and neoplastic transformation of EBV-infected B cells. HIV is not seen

in normal or neoplastic B cells. Human herpesvirus type 8 (also called Kaposi sarcoma herpesvirus) is found in the spindle

cells of Kaposi sarcoma and in body cavity B-cell lymphomas in patients with AIDS. Human T-cell leukemia/lymphoma

Robbins & Cotran Review of Pathology Pg. 263

virus type 1 is related to HIV-1, and it causes adult T-cell leukemia/lymphoma. Cytomegalovirus is not known to cause any

tumors

20

A 70-year-old man has experienced increasing fatigue for the past 6 months. On physical examination, he has
nontender axillary and cervical lymphadenopathy, but there is no hepatosplenomegaly. The hematologic work-up shows
hemoglobin, 9.5 g/dL; hematocrit, 28%; MCV, 90 μm3; platelet count, 120,000/mm3; and WBC count, 42,000/mm3. The
peripheral blood smear shows a monotonous population of small, round, mature-looking lymphocytes. Flow cytometry
shows these cells to be CD19+, CD5+, and TdT−. Which of the following is most likely to be seen with cytogenetic and
molecular analysis of the cells in the patient's blood?
□ (A) t(9;22) leading to BCR-ABL rearrangement
□ (B) Clonal rearrangement of immunoglobulin genes
□ (C) Clonal rearrangement of T-cell receptor genes
□ (D) t(8;14) leading to C-MYC overexpression
□ (E) t(14;18) leading to BCL2 overexpression

 

(B) The clinical history, the peripheral blood smear, and the phenotypic markers are characteristic of chronic

lymphocytic leukemia, a clonal B-cell neoplasm in which immunoglobulin genes are rearranged, and T-cell receptor genes

are in germline configuration. The t(9;22) is a feature of chronic myeloid leukemia. The t(8;14) translocation is typical of

Burkitt lymphoma; this lymphoma occurs in children at extranodal sites. 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

21

A 69-year-old woman complains of increasing back pain for 1 month. On physical examination, there is tenderness over
the lower back, but no kyphosis or scoliosis. A radiograph of the spine shows a partial collapse of T11 and several 0.5- to
1.5-cm lytic lesions with a rounded “soap-bubble” appearance in the thoracic and lumbar vertebrae. A bone marrow biopsy
is performed, and a smear of the aspirate is shown in the figure. Which of the following is the most likely laboratory finding
in this patient?
□ (A) Bence Jones proteins in the urine
□ (B) t(9;22) in the karyotype of marrow
□ (C) Elevated leukocyte alkaline phosphatase score
□ (D) Decreased serum alkaline phosphatase level
□ (E) Platelet count of 750,000/mm3
□ (F) WBC count of 394,000/mm3

(A) The characteristic “punched-out” bone lesions of multiple myeloma seen on radiographs result from bone

destruction mediated by RANKL, a cytokine produced by the myeloma cells that activates osteoclasts. Several cytokines,

most notably IL-6, are important growth factors for plasma cells. They are produced by tumor cells and resident marrow

stromal cells. High serum levels of IL-6 correlate with active disease and poor prognosis. The monoclonal population of

plasma cells often produces a monoclonal serum “spike” seen in serum or urine protein electrophoresis. Patients can have

hypercalcemia and an increased serum alkaline phosphatase level. The neoplastic cells are generally well differentiated,

with features such as a perinuclear hof, similar to normal plasma cells. The t(9;22) translocation is the Philadelphia

chromosome seen in chronic myelogenous leukemia (CML). CML and other myeloproliferative disorders sometimes are

accompanied by a thrombocytosis, but are unlikely to produce mass lesions or bony destruction. Leukemias also can fill

the marrow space, but generally do not destroy bone.

22

A 33-year-old woman reports having generalized fatigue and night sweats for 3 months. Physical examination shows
nontender right cervical lymphadenopathy. Biopsy of one lymph node shows a microscopic pattern of thick bands of
fibrous connective tissue with intervening lymphocytes, plasma cells, eosinophils, macrophages, and occasional Reed-
Sternberg cells. An abdominal CT scan and bone marrow biopsy specimen show no abnormalities. Which of the following
is the most likely subtype and stage of this patient's disease?
□ (A) Lymphocyte predominance, stage I
□ (B) Lymphocyte predominance, stage II
□ (C) Nodular sclerosis, stage I
□ (D) Mixed cellularity, stage II
□ (E) Lymphocyte depletion, stage III

C) The bands of fibrosis are typical of the nodular sclerosis type of Hodgkin lymphoma, which is most commonly seen

in young adults, particularly women. Involvement of one group of lymph nodes places this in stage I. Mediastinal

involvement is common. Most of such cases are stage I or II, and the prognosis of such early-stage cases is good

23

A 7-year-old boy has complained of worsening pain in the right side of his groin region for the past week. Physical
examination shows painful, swollen lymph nodes in the right inguinal region. An inguinal lymph node biopsy is performed.
Histologically, the node has large, variably sized, germinal centers containing tingible-body macrophages and numerous
mitotic figures. There are numerous parafollicular and sinusoidal neutrophils. What is the most likely cause of these
histologic changes?
□ (A) Acute lymphoblastic leukemia
□ (B) Sarcoidosis
□ (C) Follicular lymphoma
□ (D) Cat-scratch disease
□ (E) Acute lymphadenitis
□ (F) Toxoplasmosis

 

(E) 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 quite active and acquire plenty of cuts and scrapes

on extremities, which can become infected. Sarcoidosis is a chronic granulomatous process typically seen in adults and

characterized by the formation of noncaseating granulomas. Follicular lymphomas are B-cell neoplasms that efface the

normal architecture of the lymph nodes; these tumors do not occur in children. Cat-scratch disease can produce sarcoidlike

granulomas with stellate abscesses. Toxoplasmosis can be a congenital infection or can be seen in

immunocompromised individuals; it produces a pattern of follicular hyperplasia.

24

A 15-year-old boy has developed a cough and a high fever over the past 4 days. On physical examination, he has a
temperature of 39.2°C. Diffuse rales are heard over all lung fields. Laboratory studies show hemoglobin, 14.8 g/dL;
hematocrit, 44.4%; platelet count, 496,000/mm3; and WBC count, 15,600/mm3. Examination of the peripheral blood smear
shows RBCs with marked anisocytosis and Howell-Jolly bodies. A sputum culture grows Haemophilus influenzae. Which
of the following is the most likely diagnosis?
□ (A) DiGeorge syndrome
□ (B) Galactosemia
□ (C) Gaucher disease
□ (D) Myeloproliferative disorder
□ (E) Prior splenectomy
□ (F) Trisomy 21

 

(E) Splenectomy in childhood reduces immunity to encapsulated bacterial organisms. The spleen recycles old RBCs

and removes inclusions such as Howell-Jolly bodies (similar to getting the cherry pits out without damaging the cherry).

About one third of all circulating platelets are pooled in the spleen, and granulocytes are marginated in splenic sinusoids,

so that when the spleen is absent, the WBC and platelet counts increase. DiGeorge syndrome leads to cell-mediated

immunodeficiency and increased viral, fungal, and parasitic diseases. Galactosemia results from an inborn error of

metabolism, leading to liver disease and fibrosis that can cause splenomegaly. Gaucher disease leads to splenomegaly

without significant immunodeficiency. Myeloproliferative disorders increase the size of the spleen. The thymus, but not the

spleen, is sometimes involved in patients with Down syndrome (trisomy 21).

25

A 4-year-old boy has appeared listless for about 1 week. He now complains of pain when he is picked up by his
mother, and he exhibits irritability when his arms or legs are touched. In the past 2 days, several large ecchymoses have
appeared on the right thigh and left shoulder. CBC shows hemoglobin, 10.2 g/dL; hematocrit, 30.5%; MCV, 96 μm3;
platelet count, 45,000/mm3; and WBC count, 13,990/mm3. Examination of the peripheral blood smear shows blasts that
lack peroxidase-positive granules, but contain PAS-positive aggregates and stain positively for TdT. Flow cytometry
shows the phenotype of blasts to be CD19+, CD3−, and sIg−. Which of the following is the most likely diagnosis?
□ (A) Chronic myelogenous leukemia
□ (B) Idiopathic thrombocytopenic purpura
□ (C) Acute myelogenous leukemia
□ (D) Chronic lymphocytic leukemia
□ (E) Acute lymphoblastic leukemia

 

(E) These findings are characteristic of a childhood acute lymphoblastic leukemia of the precursor-B cell type. The

rapid 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 lymphoid cells. Chronic myelogenous leukemia is a disease of adults, and the 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. 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.

26

A 49-year-old woman has experienced increasing weakness and chest pain over the past 6 months. On physical
examination, she is afebrile and normotensive. Motor strength is 5/5 in all extremities, but diminishes to 4/5 with repetitive
movement. There is no muscle pain or tenderness. Laboratory studies show hemoglobin, 14 g/dL; hematocrit, 42%;
platelet count, 246,000/mm3; and WBC count, 6480/mm3. A chest CT scan shows an irregular 10 × 12 cm anterior
mediastinal mass. The surgeon has difficulty removing the mass because it infiltrates surrounding structures.
Microscopically, the mass is composed of large, spindled, atypical epithelial cells mixed with lymphoid cells. Which of the
following is the most likely diagnosis of this lesion?
□ (A) Granulomatous inflammation
□ (B) Hodgkin lymphoma
□ (C) Lymphoblastic lymphoma
□ (D) Malignant thymoma
□ (E) Metastatic breast carcinoma
□ (F) Organizing abscess

(D) Thymomas are rare neoplasms that can be benign or malignant. In one third to one half of cases, thymomas

produce myasthenia gravis as an initial presentation (as in this case). Benign thymomas have a mixed population of

lymphocytes and epithelial cells and are circumscribed, whereas malignant thymomas are invasive and have atypical cells.

Thymic carcinomas resemble squamous cell carcinomas. Granulomas can have epithelioid macrophages and

lymphocytes, but the thymus is an unusual location. Hodgkin lymphoma involves lymph nodes in the middle or posterior

mediastinum. Lymphoblastic lymphoma of the T cell variety is seen in the thymus in children, and it has no epithelial

component. Metastases to the thymus are quite unusual. An organizing abscess could have granulation tissue at its edge,

with a mixture of inflammatory cell types, but not atypical cells.

27

A 69-year-old man notices the presence of “lumps” in the right side of his neck that have been enlarging over the past
year. Physical examination shows firm, nontender posterior cervical lymph nodes 1 to 2 cm in diameter. The overlying skin
is intact and not erythematous. A lymph node is biopsied. Which of the following histologic features provides the best
evidence for malignant lymphoma in this node?
□ (A) Presence of lymphoid cells positive for kappa, but not lambda, light chains
□ (B) Absence of a pattern of follicles with germinal centers
□ (C) Proliferation of small capillaries in the medullary and paracortical regions
□ (D) Presence of cells that stain with monoclonal antibody to the CD30 antigen
□ (E) Absence of plasma cells and immunoblasts in sinusoidal spaces

 

(A) All lymphoid neoplasms are derived from a single transformed cell and are monoclonal. Monoclonality in B-cell

neoplasms, which comprise 80% to 85% of all lymphoid neoplasms, often can be shown by staining for light chains.

Populations of normal or reactive (polyclonal) B cells contain a mixture of B cells expressing 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 inflammatory conditions or in immunosuppression. A proliferation of capillaries is typically a benign,

reactive process. 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.

28

A 62-year-old man visits his physician because of prolonged fever and a 4-kg weight loss over the past 6 months. On
physical examination, his temperature is 38.6°C. He has generalized nontender lymphadenopathy, and the spleen tip is
palpable. Laboratory studies show hemoglobin, 10.1 g/dL; hematocrit, 30.3%; platelet count, 140,000/mm3; and WBC
count, 24,500/mm3 with 10% segmented neutrophils, 1% bands, 86% lymphocytes, and 3% monocytes. A cervical lymph
node biopsy specimen shows a nodular pattern of small lymphoid cells. A bone marrow specimen shows infiltrates of
similar small cells having surface immunoglobulin that are CD5+, but CD10−. Cytogenetic analysis indicates t(11;14) in
these cells. What is the most likely diagnosis?
□ (A) Mantle cell lymphoma
□ (B) Follicular lymphoma
□ (C) Acute lymphoblastic leukemia
□ (D) Burkitt lymphoma
□ (E) Small lymphocytic lymphoma

(A) The immunophenotype is characteristic for mantle cell lymphoma. Of the lesions listed, lymphoblastic lymphoma

and Burkitt lymphoma occur in a much younger age group. Burkitt lymphoma has a t(8;14) translocation. The remaining

three lesions occur in an older age group. Of these, small lymphocytic lymphoma manifests with absolute lymphocytosis

and the peripheral blood picture of chronic lymphocytic leukemia. Follicular lymphoma has a distinct and characteristic

translocation t(14;18) involving the BCL2 gene. In contrast, mantle cell lymphoma, seen in older men, has the t(11;14)

translocation, which activates the cyclin D1 (BCL1) gene; these tumors do not respond well to chemotherapy

29

A 45-year-old man has experienced recurrent fevers and a 6-kg weight loss over the past 5 months. On physical
examination, his temperature is 37.5°C, and he has cervical lymphadenopathy. The patient reports that the adenopathy
becomes very tender after he drinks a six-pack of beer. A lymph node biopsy specimen shows effacement of the nodal
architecture by a population of small lymphocytes, plasma cells, eosinophils, and macrophages. Which of the following additional cell types, which stains positively for CD15, is most likely to be found in this disease?
□ (A) Reed-Sternberg cell
□ (B) Immunoblast
□ (C) Epithelioid cell
□ (D) Neutrophils
□ (E) Mast cell

 

(A) The features suggest Hodgkin lymphoma (HL), mixed cellularity type, which tends to affect older men. As in all

other forms of HL but lympocyte predominance, the Reed-Sternberg cells and variants stain with CD15. These cells also

express CD30, an activation marker on T cells, B cells, and monocytes. Clinical symptoms are common in the mixed

cellularity type of HL, and this histologic type tends to manifest in advanced stages. The pain associated with alcohol

consumption is a paraneoplastic phenomenon peculiar to HL. The Reed-Sternberg cells make up a relatively small

percentage of the tumor mass, with most of the cell population consisting of reactive cells such as lymphocytes, plasma

cells, macrophages, and eosinophils. Immunoblasts suggest a B-cell proliferation. Epithelioid cells are seen in

granulomatous inflammatory reactions. Neutrophils accumulate at sites of acute inflammation. Mast cells are not numerous

in HL; they participate in type I hypersensitivity responses.

30

A 23-year-old woman has noticed that she develops a skin rash if she spends prolonged periods outdoors. She has a
malar skin rash on physical examination. Laboratory studies include a positive ANA test result with a titer of 1 : 1024 and a
“rim” pattern. An anti–double-stranded DNA test result also is positive. The hemoglobin concentration is 12.1 g/dL,
hematocrit is 35.5%, MCV is 89 μm3, platelet count is 109,000/mm3, and WBC count is 4500/mm3. Which of the following
findings is most likely to be shown by a WBC differential count?
□ (A) Eosinophilia
□ (B) Thrombocytosis
□ (C) Monocytosis
□ (D) Neutrophilia
□ (E) Basophilia

This patient has evidence of an autoimmune disease, most likely systemic lupus erythematosus (SLE). SLE can be

accompanied by monocytosis. (Cytopenias also can occur in SLE because of autoantibodies against blood elements, a

form of type II hypersensitivity.) Eosinophilia is a feature more often seen in allergic conditions, parasitic infestations, and

chronic myelogenous leukemia (CML). Thrombocytosis usually occurs in neoplastic disorders of myeloid stem cells, such

as the myeloproliferative disorders that include CML. Neutrophilia is seen in acute infectious and inflammatory conditions.

Basophilia occurs infrequently, but also can be seen in CML.