Transcript Document

Hematology and Oncology
Little Old Lady in No Acute Distress
A 76 year old Caucasian female comes to her primary care
physican's office complaining of fatigue and weight loss. This
has gotten progressively worse over the past few months. She
appears cachectic and pale. Physical exam demonstrates pale
conjunctiva and nontender lymphadenopathy in the anterior
cervical chain.
Labs:
WBC 22 (N 4.5 - 11)
Iron 37 (N 50 - 170)
Hemoglobin 8.4 (N 12 - 16)
TIBC 200 (N 250 - 450)
Hematocrit 25 (N 35 - 45)
Ferritin 45 (N 10 - 120)
MCV 83 (N 80 - 100)
Saturation 35 (N 15 - 50)
Reticulocyte Count 0.5 (N 0.5 - 2.5)
Platelets 100 (N 150 - 450)
Little Old Lady in No Acute Distress
What is the most likely cause of LOL's anemia?
A. Iron deficiency
B. Lymphoma
C. Aplastic anemia
D. Folate deficiency
E. Occult GI bleed
Little Old Lady in No Acute Distress
Answer B
A - Iron deficiency anemia is associated with an increase in TIBC and
decrease in ferritin unlike LOL.
D - Folate presents with megaloblastic anemia and hypersegmented
neutrophils. Remember Vit B12 also has neurological symptoms
associated with a deficiency.
C - In aplastic anemia, the patients bone marrow isn't able to sustain
production of all cell lines and should have low blood counts for all cell
lines.
E - Occult GI bleed would appear similar to iron deficiency in terms of
lab values. Although this could be a possible cause, this patient is more
likely to have lymphoma based on lab values and physical exam
findings.
Anemia Made Easy
Anemia Trigger Words
Microcytic:
Target cells - thalassemia
Basophilic stippling - lead poising
Halo/ringed - sideroblastic
Koilonychia - iron deficiency
Normocytic:
AA male, sulfa - G6PD def
osmotic fragility test - spherocytosis
Chloramphenicol, carbamazipine, phenytoin - aplastic
Severe chest pain AA kid - sickle cell
Pigmented gall stones, elevated LDH, shistocytes - autoimmune
Macrocytic:
Diphyllobothriasis, Crohn's - Vit B12 def
Neurologic disorder - Vit B12 def
Palmar erythema, caput medusa, EtOH abuse - cirrhosis
AIDS on HAART - azidothymidine
Little Old Lady in No Acute Distress
A lymph node biopsy is performed due to a high
suspicion for malignancy. The biopsy results are
shown. The most likely diagnosis is?
A. Colon adenocarcinoma
B. Multiple myeloma
C. Chronic lymphocytic leukemia
D. Burkett's lymphoma
E. Hodgkin's lymphoma
Little Old Lady in No Acute Distress
Answer E
The biopsy results demonstrate the typical Reed-Sternberg cells of
Hodgkin's lymphoma. These cells are of B-cell origin and are CD-15
and 30 positive. Typically localized to nodes and move in a contiguous
fashion.
Multiple myeloma is a monoclonal proliferation of plasma cells
producing IgG or IgA to cause M spike on plasma electrophoresis.
Roleaux formation of RBCs. Skull has pepper pot appearance.
CLL common leukemia of older individuals with an indolent course.
Smear shows smudge cells. Typically do not treat the patients until they
have a blast crisis.
Burkett's lymphoma typically children and immunosupressed from
t(8;14). Africa has jaw lesions but sporadic has abdominal. Starry-sky
appearance.
Lymphoma at a Glance
Hodgkin's
Non-Hodgkin's
Association
EBV
HIV and immunosupression
Constitutional signs
(fever, night sweats, weight loss)
Rare - worsens prognosis
Common
Age
Bimodal distribiution
Peaks 20-40 yo
Spread
Localized to single node chain,
spreads contigously, rarely
etranodal
Diffuse periperhal nodal
involemvent, extranodal
involvement common
Types of Hodgkin's:
Nodular sclerosing (most) young adults
good prognosis
Mixed cellularity (1/4)
lots RS cells
middle prognosis
Lymphocyte dom (1/10)
young males
good prognosis
Lymphocyte dep (rare)
older males, tons RS poor prognosis
Whitney is Sick
A 2 year old African-American boy is brought to the emergency
room because of 2 hours of left-sided abdominal pain and
shortness of breath. The patient is hypotensive and
tachycardic. Physical exam demonstrated a palpable spleen 8
cm below the costal margin.
Labs:
Hemoglobin 5.1
Hematocrit 16
WBC 4500
Platelets 85000
Whitney is Sick
What is most likely causing the presenting signs and
symptoms?
A. Splenic sequestration
B. Salmonella sepsis
C. Congestive heart failure
D. Autoimmune hemolytic anemia
E. Aplastic anemia
Whitney is Sick
Answer A
With an enlarged spleen - typical of sicklers prior to autoinfarction and
involution of the spleen - blood can be sequestered cause hypovolemia
and low platelet counts.
B - Salmonella is an important bacteria to remember for sickle cell
disease. This is more likely to cause osteomyelitis. Other important
bacteria are encapsulated (H. flu, Niesseria, and Strep pneumo.)
because after splenic infarction they cannot clear these bacteria from
the blood stream.
C - The acuity of this presentation rules against CHF. This can however
cause hepatosplenomegaly and edema if right-sided.
D - Autoimmune hemolytic anemia can present similar to this however,
the slide demonstrates sickled cells.
E - Aplastic anemia would present with pancytopenia. Also this typically
occurs with drugs (see above discussion).
Hemoglobinopathies
Sickle cell: Beta-chain aa 6 G - V. Inherited on Ch 11. Fetus not
affected due to no beta-chain production. Treatment with
hydroxyurea to increase production of fetal hemoglobin. Vasoocclusive crisis - stroke, acute chest syndrome, splenic
infarction. Prolonged disease cause splenic infarction - cannot
clear encapsulated bacteria. Penicillin prophylaxis
Beta-thalasemia: Minor (one chain not produced) and major (no
beta chains). Fetal hemoglobin is produced but not adequate.
Prevalent in Mediterranean population.
Alpha-thalasemia: 4 alpha genes so can have a mix of disease
(1 to 4 with worsening symptoms). Hemoglobin bart (betatetromer). Prevalent in Asian and African population.
Oxygen Binding Curve - Questions
Shifts curve to left?
Shifts curve to right?
Fetal hemoglobin?
Amy L. at the Emergency Department
Amy L. is a 45 year old female who came to the emergency
department today because of worsening fatigue, weight loss,
and persistent urinary tract infection. She has completed a 5
day course of nitrofurantoin without any improvement. Her
vitals are stable, but her labs come back abnormal.
Labs:
WBC 36.2 (N 4.5 - 11)
Hemoglobin 10.9 (N 12 - 16)
Hematocrit 33 (N 35 - 45)
Platelets 289 (N 150 - 450)
Urine leukocytes >10
Leukocyte esterase ++
Nitrate ++
Bacteria >10,000
Blood Smear:
Amy L. at the Emergency Department
What is the best treatment option for Amy L.?
A. Imatinib
B. Cyclophosphamide, doxyrubicin, vincristine, prednisone
C. Ciprofloxacin
D. All-trans-retinoic acid
E. Trastuzumab
F. Tamoxifen
G. Doxyrubicin, bleomycin, vinblastine, dacarbazine
Amy L. at the Emergency Department
Answer D.
The pathology slide shows promyeloblasts with Auer rods. This is M3 of the CML diseases
and is treated with all-trans-retinoic acid which cases the cells to mature.
A - Imatinib is used to treat CML. This is a direct inhibitor of the bcr-abl tyrosine kinase
activity.
B - CHOP is the treatment for non-Hodgkin's lymphoma. Cyclophosphamide is an
alkylating agent acting at guanine N-7. Causes hemorrhagic cystitis (prevent with Nacetylcysteine. Doxorubicin intercalates with DNA. Causes cardiotoxicity. Vincristine binds
to tubulin to prevent polymerization of tubulin. This has neurotoxicity.
C - Although this patient is suffering from a urinary tract infection treatment of this will not
help her hematologic disorder.
E. Traztuzumab is a monoclonal antibody against the HER-2 receptor. This is used for
breast cancer.
F. Tamoxifen is a selective estrogen receptor that is used to treat breast cancer. This will
cause early menopause, and increases the risk for endometrial cancer.
G - ABVD is the treatment for Hodgkin's lymphoma. Bleomycin forms free radicals and
causes DNA breaks. Side-effect is pulmonary fibrosis. Vinblastine binds tubulin and
causes myelosupression.
Amy L. at the Emergency Department
Leukemia - increased number of leukocytes in blood and
marrow, can cause anemia and thrombocytopenia
ALL in kids, lymphoblasts with early cell markers, can spread
to CNS and sex organs.
AML in adults, trigger word is Auer rods, nine different types
but only M3 (one with Auer rods) has special treatment
CLL in older adults, indolent course with smudge cells on
slide, can have warm autoantibodies, dont treat until blast crisis
CML Philadelphia chromosome (t(9;22), bcr-abl), increased
neutrophils and metamyelocytes. Can tell differrence between
this and infection by leukocyte alkaline phosphatase
I Love Me Some Chili
A 23yo caucasian female presents to the Akron City Hospital
ED with a painful, swollen right leg. She has just returned from
none other than the Nanook Classic Chili Cook-Off in Nanook,
Alaska. Further questioning reveals that she takes a daily OCP
and smokes 1/2 PPD. Exam reveals a moderately obese
female in no apparent distress. The right lower extremity is
erythematous and moderately swollen to mid-thigh. On
palpation chords are palpated in the right calf. The most likely
diagnosis is:
a. CHF
b. DVT
c. Muskuloskeletal Strain
d. Cellulitis
Deep Vein Thrombosis
IV heparin is started as an inpatient. She is then transitioned
to warfarin for outpatient treatment. You see her in your office
in follow-up. She is doing very well. After the amazing care
she received as an inpatient, she has decided medicine really
is "just like Grey's Anatomy." She is now considering a career
in medicine. After doing a little reading about DVT and her
treatment, she has come up with a few questions.
1. Where in the clotting cascade do warfarin and
heparin
work?
2. What is the most common genetic clotting
disorder
predisposing to DVT?
Coagulation Cascade
Anticoagulation
Heparin (IV, SC)
Warfarin (PO)
-binds to antithrombin III
which catalyzes the
inactivation of thrombin (IIa),
IXa, Xa, and XIa
-inhibits the vitamin Kdependent synthesis
of clotting factors II, VII, IX
and X, as well as the
regulatory factors, protein C &
S
-Significance of inhibition of
Protein C&S?
-Monitor: PT/INR (Extrinsic)
-Teratogenic
-Monitor: PTT (Intrinsic)
-Antidote: Protamine Sulfate
-Does not cross placenta
Lipirudin & Bivalrudin- Direct
thrombin inhibitors
Test Friendly Genetic Coagulopathies
Factor V Leiden Deficiency
-Factor V is resitant to inhibitory activity of Protein C
-Most common congenital hypercoagulable state
-Heterozygotes often not effected
Hemophilia A&B
-Present with hemarthosis, deep tissue hematoma
-A, Factor VIII Deficiency
-B, Factor IX Deficiency
-Both X-linked (only affects males)
Von Willebrand
-Variable inheritance, most common Autosomal Dominant
-Inc Bleeding Time, Inc PTT (because loss of Factor VIII)
A Routine Check-Up
67yo AA male presents to your office for his annual check-up.
Today his only complaint is some mild, low back pain. He also
has a history of HTN and hyperlipidemia which are well
controlled. As part of your annual screening exam you perform
a rectal exam noting an irregular, hard 1.5cm nodule. FMH is
(+) for a brother and father with prostate cancer. You refer this
patient to a urologist for further evaluation and order a PSA.
What do you expect to see with the PSA? You have totally
blown off his back pain in lieu of the more serious findings, but
could the nodule and back pain be related?
Prostatic Adenocarcinoma
Accounts for 33% of all cancers in USA
PSA- increased total, decreased free fraction
- BPH= increased free fraction of PSA
Osteoblastic bony metastisis common in late stages
-May present with low back pain
-Increased serum alkaline phosphatase and PSA
Why didn't the patient complain of difficulty urinating or
nocturia?
-Most commonly occurs in posterior lobe (25% are in central
zone)
Prostatic Adenocarcinoma
Prostatic Adenocarcinoma
Normal
-Infiltrating glands lined by cuboidal epithelium with enlarged
nuclei, visible nucleoli, and dark cytoplasm
-Absence of outer basal layer.
Treatment
- Surgery & Radiation
- Meds
-flutamide- androgen antagonist that blocks the effect of
testosterone
-leuprolide- GnRH agonist supresses the release of
luteinizing hormone from pituitary thereby
suppressing testosterone production
Breast Cancer
A 68 year old woman presents to your office with the CC of a
lump in her breast which she noticed while performing her
monthly self exam. Being the awesome NEOUCOM student
that you are, you dive deeper into her history. She began
menses at 10 yoa and menopause at about 53 yoa. She has
never been pregnant. Her FMH also reveals a sister who
was diagnosed with breast cancer in her mid 40's. On your
exam you find an approximately 2cm firm, fixed mass in
the upper, outer quadrant of the left breast. No
lymphadenopathy is appreciated. You order a mammogram
and send her for biopsy.
Normal Breast Histology
Ductal Carcinoma In Situ
-Early malignancy- hasn't made its way through the basement membrane
-Can have solid, comedo, cribriform, papillary and clinging types
-Nuclear appearance is uniform
-Extension causes Paget disease of the nipple
-www.webpathology.com
Invasive Ductal Carcinoma
-most common (70-80%); worst and most invasive
-Generic term: AKA Carcinoma NOS
-microscopically have a diverse appearance
Invasive Lobular Carcinoma
-Signet ring cells (not always, but would be great board image)
-2nd most common
-Frequently mulitcentric and bilateral (10-20%)
Medullary Carcinoma
-Relatively rare (<1%), good prognosis
-Tumor cells grow in clusters or sheets with no evidence of
glandular differentiation
-Lymphocytic infiltrate is always present
Treatment
Surgery and Radiation
Pharmacotherapy
DNA Synthesis Inhibitors
Methotrexate- folic acid analog that inhibits dihydrofolate reductase.
- Myelosuppresion -> Rescue with leucovorin (folinic acid)
Fluouracil- pyrimidine analog bioactivated to 5F-dUMP which
complexes
with folic acid
- Myelosuppresion-> Rescue with thymidine
DNA Alkylating Agents
Cyclophosphamide- covalently x-link DNA at guanine N-7
- Hemorrhagic cystitis- partially prevented with mesna
DNA Intercalating Agents
Doxorubicin-generates free radicals and non-covalently intercalates with
DNA creating breaks in DNA strand
- Cardiotoxicity
Treatment (cont.)
Pharmacotherapy (cont.)
Mitotic Inhibitors
Docetaxel and Paclitaxel- bind to tubulin to hyperstabilize
polymerized
microtubules preventing mitotic spindles
from breaking
down (anaphase cannot occur)
Vinblastine and Vincristine- bind to tubulin and blocks polymerization
of
microtubules so that mitotic spindles cannot form
- Vincristine can be neurotoxic (arefelxia, peripheral neuritis)
and
cause paralytic ileus
- "crist" your getting on my nerves, "blast" the immune system
Hormone Antagonist
Anastrozole and Letrozole- aromatase inhibitors preventing the synthesis
of estrogen
Tamoxifen- estrogen antagonist. Decreases annual recurrence by 30%
Monoclonal Antibodies
Trastuzumab- Ab against HER-2(erb-B2)
- Cardiotoxicity
Health Maintenance
Screening- PSA and DRE offered/discussed with patients at
age 50 or age 40 if AA or have family history
Breast Cancer Screening: Yearly mammograms and breast
exam after 40. 20-39 year old breast exam every 3 years.
Mammogram and yearly breast exam 10 years prior to
diagnosis of first-degree relative.
Colon Cancer Screening: Age 50. Colonoscopy every 10 years
(if clear), Flex-sig every 5 years, Barium enema every 5 years
Cervical Cancer Screening: No screening until 21 years old,
then every year until 30. They won't ask about this because
there is a lot of fuss about the new recommendations.
Citations
"Coagulation Cascade." Centipedia. Web. 15 Apr 2011.
<http://www.centipedia.com
/images/en/a/a4/Coagulation_ cascade.png>.
"Ductal Carcinoma In Situ." WebPathology. Web. 15 Apr 2011.
<http://webpathology.com/image.asp?case=289&n=7>.
"Invasive Ductal Carcinoma." WebPathology. Web. 15 Apr
2011.
<http://webpathology.com/image.asp?case=290&n=3>.
"Invasive Lobular Carcinoma." WebPathology. Web. 15 Apr 2011.
<http://webpathology.com/image.asp?case=292&n=8>.
Lee, Margaret. "Pediatric Acute Anemia: Differential Diagnoses &
Workup."
eMedicine. Updated Apr 2009. Accessed Mar
2011.
<http://emedicine.medscape.com/article/954506-diagnosis>.
"Medullary Carcinoma." WebPathology. Web. 15 Apr 2011.
<http://webpathology.com
/image.asp?case=298&n=2>.
Citations (cont.)
"Normal Breast Histology." Duke Pathology. Web 15 Apr 2011.
<http://pathology.mc.duke.edu/research/Histo_course/breast1.jpg>.
"Normal Prostate." WebPathology. Web. 15 Apr 2011. <http://webpathology.com
/image.asp?case=14&n=2>.
"Oxygen Dissociation Curve." Animal Physiology. Web. 15 Apr 2011.
<http://www.bio.davidson.edu/Courses/anphys/1999/Dickens
/Oxygendissociation.htm>.
"Prostatic Adenocarcinoma." WebPathology. Web. 15 Apr 2011.
<http://webpathology.com/image.asp?case=20&n=2>.
"Reed-Sternberg Cell". Hematopathology. Web. 15 Apr 2011.
<http://hematopathology.stanford.edu/>.
"Sickle cell Anemia." Pathology Student. Web. 15 Apr 2011.
<http://www.pathologystudent.com/?p=310>.