Transcript Hematology/Oncology Review

Hematology/Oncology Review
November 23, 2009
Topics to Review
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Leukemias
Lymphomas
Plasma Cell Dyscrasias
Myeloproliferative Disorders
Myelodysplastic Disorders
Platelet disorders
Topics in medical oncology
Question 1
• 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
hemoglogin of 13.9 g/dL, hematocrit 42%, MCV 89, platelet count
210,000, and WBC count 56,000 with 63% seg. Neutrophils, 15%
bands, 6% metamyelocytes, 3% myelocytes, and 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?
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A) Chronic myelogenous leukemia
B) Hairy cell leukemia
C) Hodgkin disease, lymphocyte depletion type
D) Leukemoid reaction
E) Acute Lymphoblastic Leukemia
Answer 1
• The answer is D, leukemoid reaction. 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 tartrateresistant acid phosphatase. Hodgkin disease 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.
Question 2
• A 50 year old man has had headache and dizziness for the past 3
months. He has also experienced generalized and severe pruritis,
particularly when showering. He notes that his stools are dark. On
physical examination, he is afebrile, and his blood pressure is
165/90 mmHg. There is no hepatosplenomegaly or
lymphadenopathy. A stool sample is positive for occult blood. CBC
shows hemoglobin of 22.3 g/dL, hematocrit 67.1%, MCV 94, platelet
count 453,000, and WBC count 7800. Which of the following is the
most likely diagnosis?
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A) Myelodysplastic syndrome
B) Essential thrombocytosis
C) Chronic Myelogenous Leukemia
D) Erythroleukemia
E) Polycythemia Vera
Answer 2
• 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, like 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. When combined with abnormal platelet
function, this condition presdisposes the patient to bleeding. The
abnormal platelet function can also presdispose to thrombosis. The
pruritis and peptic ulceration most likely are the result of the
histamine release from basophils. In some patients, the disease
“burns out” to myelofibrosis. A few patients “blast out” to AML.
Myelodysplastic syndromes and other myeloproliferative disorders,
such as essential thrombocytosis, are not accompanied by such an
increase in RBC mass. Erythroleukemia is not typically
accompanied by such a high hematocrit concentration, because
leukemic erythroid progenitors do not differentiate into mature RBC’s
Question 3
• A 46 year old man notices that his friends have been commenting
about his increasingly ruddy complexion over the past 4 months. He
has also been experiencing increasing fatigue. On physical
examination, he is afebrile, and his spleen tip is palpable.
Laboratory studies show hemoglobin of 21.3 g/dL, hematocrit
63.9%, platelet count 376,000, and WBC 9210. The serum
erythropoietin level is very low. Which of the following is most likely
to produce these findings?
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A) Dehydration
B) Renal cell carcinoma
C) Polycythemia Vera
D) Cyanotic Heart Disease
E) Living at high altitude
Answer 3
• Polycythemia Vera, one of the myeloproliferative disorders, is a
neoplastic disorder of myeloid stem cells, which tend to differentiate
predominantly along the erythroid lineage, giving rise to
polycythemia. The neoplastic erythroid progenitor cells require
extremely small amounts of erythropoietin for survival and
proliferation; hence, the levels of erythropoietin are virtually
undetectable in polycythemia vera. In patients with chronic
hypoxemia, erythropoietin levels are elevated, producing excess
RBC’s. Erythropoietin secretion is triggered by anoxia in high
altitude dwellers and in patients with chronic lung disease or
cyanotic heart disease. Renal cell carcinomas can produce
erythropoietin and trigger a paraneoplastic erythrocytosis. In
dehydration, hemoconcentration can cause transient polycythemia,
but this does not affect normal erythropoietin secretion.
Question 4
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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 seven 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 of 8.7, hematocrit 25.2%, MCV 88, platelets 67,000, and WBC
2300 with 15% seg 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 to have now
occurred in this patient?
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A) Relapse of his previous lymphoma
B) Transformation of the lymphoma into myeloid leukemia
C) Myelodysplasia related to therapy for the previous tumor
D) De novo acute myeloblastic leukemia
E) Myeloid metaplasia with myelofibrosis
Answer 4
• The answer is 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.
Question 5
• 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.
and the urea nitrogen level is 35 mg/dL. A skull radiograph is
shown. During the course of hospitalization, a bone marrow biopsy
is performed. Which of the following is the biopsy specimen most
likely to show?
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A) Scattered small granulomas
B) Numerous Plasma Cells
C) Nodules of small, mature lymphocytes
D) Occasional Reed Sternberg cells
E) Hypercellularity with many blasts
Multiple Myeloma
Answer 5
• The answer is 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. Bence Jones proteinuria can
damage the tubules and give rise to renal failure. Multiple myeloma
can be complicated by AL amyloid, which can also 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 disease. Blasts suggest a
leukemic process.
Question 6
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A 53 year old woman has experienced nausea with vomiting and early
satiety for the past 7 months. On physical exam, she is afebrile and has no
lymphadenopathy or hepatosplenomegaly. CBC shows hemoglobin of 12.9,
hematocrite 41.9%, platelet count 263,000, and WBC count 8430. An upper
GI endoscopy shows loss of the rugal folds of the stomach over a 4x8 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. Which of the following is
the most likely diagnosis?
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A) Acute lymphoblastic leukemia
B) Chronic lymphocytic leukemia
C) Diffuse Large B cell lymphoma
D) Follicular Lymphoma
E) Hodgkin disease, mixed cellularity subtype
F) MALT (marginal zone) lymphoma
G) Waldenstrom macroglobulinemia
Answer 6
• The answer is F, MALT (marginal zone) lymphoma. These
lympomas 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. The most common sites are the thyroid (Hashimoto
throiditis), the salivary glands (in Sjogren syndrome), or the stomach
(in H. Pylori associated chronic gastritis. Although monoclonal (like
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 lesions are
neoplastic conditions that are not related to H. Pylori and require
chemotherapy to control.
Question 7
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A 50 year old woman sees her physician because of a 3 month history of
fatigue and dizziness. She has recently experienced syncopal episodes.
On physical examination, she is afebrile, with a pulse of 88, respirations 19,
and blood pressure 115/75. She exhibits marked pallor but no
hepatosplenomegaly or lymphadenopathy. Laboratory findings show
hemoglobin of 6.6, hematocrit 19.9%, platelet count 199,800, WBC 4780,
and reticulocyte count 0.1%. The MCV, MCHC, and serum ferritin level are
normal. A bone marrow biopsy specimen of aspirate shows normal
cellularity, but the cells of the erythroid series, such as pronormoblasts,
normoblasts, and later stages, are greatly reduced. Other elements are
normal in number and differentiation. Which of the following is the most
likely diagnosis?
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A) Breast carcinoma
B) Hairy cell leukemia
C) Hodgkin disease, mixed cellularity subtype
D) Multiple myeloma
E) Mycosis fungoides
F) Thymoma
G) Waldenstrom macroglobulinemia
Answer 7
• The answer is F, thymoma. The patient has a rare disorder called
pure red cell aplasia, which is characterized by selective
suppression of the erythroid lineage in the bone marrow. This
curious entity is sometimes associated with a thymic tumor. In about
one half of such cases, removal of the thymic tumor relieves the
RBC aplasia, suggesting some autoimmune mechanism as the
cause of the aplasia. Carcinomas can infiltrate the marrow space, a
myelophthisic process, and reduce hematopoiesis, but not the
erythroid line selectively. Hodgkin disease, multiple myeloma, and
Waldenstrom macroglobulinemia can do the same. Patients with
leukemias tend to have an elevated peripheral blood WBC count,
and when the leukemic cells fill the marrow, all other cell lines are
reduced. Mycosis fungoides is a T cell neoplasm involving the skin.
Question 8
• A 70 year old man has experienced increasing fatigue for the past 6
months. On physical exam, he has nontender axillary and cervical
lymphadenopathy, but there is no hepatosplenomegaly. The
hematologic workup shows hemoglobin of 9.5, hematocrit 28%,
MCV 90, platelet count 120,000, and WBC 42,000. 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?
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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
CLL/SLL
Answer 8
• The answer is B, clonal rearrangement of immunoglobulin genes.
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.
Question 9
• 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?
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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
Hodgkin disease- Reed Sternberg
cell
Answer 9
• The answer is C, nodular sclerosis stage I. The bands of fibrosis
are typical of the nodular sclerosis type, which is most commonly
seen in young adults, particularly female patients. 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.
Question 10
• A 4 year old child has appeared listless for about 1 week. He now
complains of pain when he is picked up by his mother, and he
demonstrates 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 of 10.2, hematocrit
30.5%, MCV 96, platelet count 45,000, and WBC 13,990.
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?
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A) Chronic myelogenous leukemia
B) Idiopathic thrombocytopenic purpura
C) Acute myelogenous leukemia
D) Chronic lymphocytic leukemia
E) Acute lymphoblastic leukemia
Answer 10
• These findings are characteristic of a childhood acute lymphoblastic
leukemia of the pre-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 and B cell type lymphoid cells.
Chronic myelogenous leukemia is a disease of adults, and the WBC
is quite high; the peripheral blood contains some myeloblasts, but
other stages of myeloid differentiation are also detected. In ITP, only
the platelet count is reduced, because of antibody mediated
destruction of platelets. An AML is a disease of young to middle
aged adults, and there would be peroxidase positive myeloblasts
and phenotypic features of myeloid cells. CLL is a disease of older
adults; patients have many small circulating mature B lymphocytes.
Question 11
• A 39 year old man experiences sudden onset of a severe headache.
Physical examination shows no localizing neurologic 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, hematocrit 28.9%, platelet count 26,400,
and WBC 75,000. The peripheral blood smear has the appearance
shown, and shistocytes are also seen. The plasma D dimer level
(fibrin degradation products), prothrombin time, and partial
thromboplastin time are all elevated. Cytogenetic analysis of cells
from a bone marrow biopsy specimen is most likely to yield which of
the following karyotypic abnormalities?
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A) t(8;21)
B) t(9;22)
C) t(14;18)
D) t(15;17)
E) t(8;14)
Auer rods- acute promyelocytic
leukemia
Answer 11
• The answer is D, t(15;17). This peripheral blood smear is
characteristic of acute promyelocytic leukemia (M3 class of AML),
with many promyelocytes containing prominent azurophilic granules
and short, red, cytoplasmic, rodlike inclusion called Auer rods.
Release of the granules can trigger the coagulation cascade,
leading to disseminated intravascular coagulation (DIC). As in this
case, many patients develop DIC. The t(15;17) translocation is
characteristic of this disease; it results in the fusion of the retinoic
acid receptor gene on chromosome 17 with the promyelocytic
leukemia gene on chromosome 15. The fusion gene results in
elaboration of an abnormal retinoic acid receptor that blocks myeloid
differentiation. Therapy with retinoic acid (Vitamin A) can alleviate
the block and induce remission in many patients. The t(8;21)
abnormality is seen in the M2 variant of acute myelogenous
leukemia.
Question 12
A 20 y/o female presents with anemia secondary to a
history of heavy menstrual periods since menarche.
On further questioning, her mother also has a history
of heavy periods and “some kind of clotting disorder.”
Given the mostly likely diagnosis, evaluation of
platelets, bleeding time and coagulation would likely
show which of the following?
A. Increased bleeding time, decreased platelets
B. Increased PT, PTT, bleeding time, dec platelets
C. Increased bleeding time and PTT, normal platelets
D. No abnormality
E. Increased PTT only
Answer 12
• The correct answer is C. The patient likely
has von Willebrand Disease. See chart
Disease PLTs
ITP/TTP/
HUS
vWD
Nml
Hemophilia
Nml
DIC
Bleed
Time
PT
PTT
Nml
Nml
Nml
Nml
Nml
Question 13
• A 44 year-old female reports a waxing and waning cough, dyspnea
and vague chest discomfort for the past five years. She also has
intermittent fevers over the same time period with a six pound
weight loss. On exam, red, tender subcutaneous swelling is found
on both lower limbs, and decreased breath sounds and rales are
found bilaterally. A biopsy of one of the skin lesions shows
noncaseating granulomas. A chest X-ray shows mediastinal
lymphadenopathy. Which of the following electrolyte abnormalities is
most likely evident in this patient's plasma?
A. Hypercalcemia
B. Hyperkalemia
C. Hypernatremia
D. Hypocholermia
E. Hyponatremia
Answer 13
• A is the correct answer
The likely diagnosis is pulmonary sarcoidosis.
The noncaseating granulomas are evident in the
skin lesions of erythema nodosum and the chest
X-ray shows hilar adenopathy. An increase in
serum vitamin D levels are a result of
hypersecretion by pulmonary macrophages,
resulting in the body retaining calcium.
Hypercalcemia and hypercalciuria are apparent
on laboratory examination.
Question 14
• A patient comes to you for counseling about his
risk for colon cancer. Which of the following risk
factors in this patient is thought to be associated
with colon cancer?
• A. Hx of colon CA in a 2nd cousin
• B. Obesity
• C. Irritable Bowel Syndrome
• D. Diet rich in fruit and vegetables
• E. Smoking
Answer 14
• The answer is B, obesity
• Colon cancer is thought to be associated
with obesity, history of cancer in a 1st
degree relative, inflammatory bowel
disease, and diets rich in red meat.
• Diets rich in fruits, veggies and fiber can
be colon protective. Regular exercise may
also be of benefit
Question 15
• A firm, irregular prostatic nodule is discovered
during annual physical examination of a 66y/o
patient. Biopsy reveals the presence of prostate
cancer. Which of the following factors has the
greatest prognostic impact?
• A. Degree of cellular atypia
• B. Histological grading
• C. Initial PSA level
• D. Pathological staging
• E. Presence of mitotic figures
Answer 15
• The answer is D, Pathological Staging
Stage is determined by extent of tumor
infiltration and metastasis. TNM is a
common method. Survival has been more
closely correlated with staging vs grading
of tumor. PSA is not a reliable prognostic
indicator but can be useful in monitoring
disease recurrence.
Breast Cancer facts
• Fibrocystic changes- Most common cause of “breast lump”
(lumpy/bumpy breast)—irregular and not a discrete mass, ductal
proliferation/dilation and fibrosis, cyclic changes
• Fibroadenoma- discrete, firm breast mass in young woman
(20’s/30’s), fibrous proliferation with compressed ductules, enlarge
during pregnancy or with menstrual cycle
• Intraductal papilloma- small mass lesion in lactiferous sinuses, most
common reason for bloody nipple discharge
• Fat necrosis- can present as a discrete painless breast mass with
irregular borders (mimicking cancer), often associated with trauma,
microscopically see macrophages and neutrophils around necrotic
adipocytes
• Mastitis- Red, hot, tender breast lesions, often found in lactating
women, most common cause= Staphylococcus Aureus
Breast Cancer Facts
• Fibrocystic change may be assossiated with proliferative changes
that increase chance for breast cancer (epithelial hyperplasia,
atypical hyperplasia)
• DCIS- At least half of mammographically detectable breast cancers
(trt. = surgical excision and radiotherapy), cribriform lesions,
calcification due to necrosis of neoplastic cells, necrotic cells
exuding into ducts= comedocarcinoma
• Paget disease of nipple- extension of malignant cells of DCIS to
nipple and areola, causing a skin lesion resembling seborrheic
dermatitis
• Colloid carcinoma- mucin, medullary carcinoma- large, lymphocytes
• LCIS- lesion most likely to be bilateral, invasive lobular- “indian
filing”
• Invasive cancer- Painless, firm, enlarging lesion with irregular
borders, possible axillary lymphadenopathy, can infiltrate lymphatics
and cause “inflammatory carcinoma”- peau d’orange skin
• ER/PR + = good marker (trt. with tamoxifen), HER 2 neu + trt. With
trastuzumab
Sources
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Questions:
Klatt, Edward C, M.D. and Kumar, Vinay, M.D. Robbins and Kotran Review
of Pathology: Second Edition. 2005
www.wikitestprep.org
Deja Review USMLE Step 1 Essentials
USMLE Step 1: Lange Q&A
Images:
www.path.sunysb.edu/labs/test%20web/stains.html
http://www.bindingsite.com/news-5.asp?id=226&view=archive
http://www.wadsworth.org/chemheme/heme/glass/slide_002_smudge_cells.
htm
http://www.lmp.ualberta.ca/resources/pathoimages/PC-R.htm
• http://wjso.com/content/figures/1477-7819-6-34-5-l.jpg