SAS/Review Flashcards
What do pathologist look at when they are grading a lymphoma?
What do they look at for staging?
-
Grading
- Look at the cell morphology
- Cell size, atypia, mitosis
-
Staging
- Bone marrow biopsy
- Look at tumor and clinical features
How long does it take for Warfarin to have an anticoagulant effect?
At least 5 days (may be longer)
Warfarin affects the synthesis of clotting factors, so need to wait for existing ones to die off before there is an effect
What is the difference between a proto-ocogene and an oncogene?
-
Proto-oncogene
- A gene that promotes normal cell growth, that is under regulatory control
-
Oncogene
- Promotes cell growth in cancer cells - NOT under regulatory control
- Proto-oncogenes that lose their regulation (ex: by being translocated to a different spot) become oncogenes
A patient with 3 months of fatigue, fever, night sweats, and painless cervical lymphadenopathy has her lymph node biopsied.
What is the histological finding and cell of origin indicated by the arrow?
Reed-Sternberg cell
Cell of origin = B cell
Seen in Hodgkin Lymphoma
List 2 things that caues hepcidin levels to increase
List 1 thing that causes hepcidin levels to decrease
Increases with infection, inflammation
Decreases with iron deficiency
Hepcidin decreases iron absorption from the gut
What is the next diagnostic step for any abnormal finding on breast imaging (mammogram)?
Biopsy
Even if no other concerns for malignancy, need to biopsy
What kind of cell is this?
Neutrophil
But abnromal because too many lobes
List 2 things that increase a patient’s risk of delayed hemolytic transfusion reaction
- Previous pregnancies
- Previous blood transfusion
Basically, exposure to another person’s blood (even if the same type)
What cell has the following immunohistochemical markers?
CD3+
CD45+
T cell
Which type of cancer is most strongly associated with environmental exposures like aniline dyes?
Transitional cell carcinoma of the bladder
Vs. squamous cell, which is more associated with inflammation
How will hemolysis affect reticulocyte count?
Hemolysis will increase reticulocyte count
- The body will try to make more cells to replace the ones that are dying -> increased reticulocytes*
- If reticulocyte count is inappropriately low, indicates there is a problem with erythropoiesis*
- Will be low in aplastic anemia, megaloblastic anemia, iron deficiency, ALL*
List 4 conditions that would result in schistocyte formation
DIC
TTP
Cardiac valve dysfunction
HELLP
- All have microangiopathic hemolytic anemia -> schistocytes*
- Note: autoimmune hemolytic anemia -> spherocytes*
What are the symptoms of SVC syndrome?
- Facial plethora
- Dilated collateral veins along the chest
- Extremity edema
- Headaches due to vascular congestion
Which hematologic malignancy has the best prognosis?
Childhood ALL
Which malignancy is associated with HTLV1?
Adult T-lymphocyte leukemia
Which subdividion of AML is the most curable?
Acute Promyelocytic Leukemia
Which translocation results in expression of BCL2?
Which hematologic malignancy is this associated with?
t(14;18)
Follicular lymphoma
Overexpression of BCL-2 = resistance to apoptosis in germinal centers
List the 3 stages (and their characteristics) of the natural history of CML
-
Chronic phase
- Leukocytosis
- Left shift
- Basophilia
-
Accelerated phase
- Progressive splenomegaly
- Basophilia
- Thromobcytosis/thrombocytopenia
- More blasts
-
Blast phase
- Acute leukemia (myeloid, lymphoid, or bi-phenotpyic)
The platelet glycoprotein 1b receptor binds to…
Von Willebrand Factor
Describe the general treatment approach for a patient with stage III (muscle invasive) gastric cancer
-
Neoadjuvant chemo
- Goal is to downstage the tumor
- Surgical resection
-
Adjuvant chemo if any lymph nodes are involved
- Goal is to serilize the surgical field, decrease local recurrence
Note: in this scenario, radiation can be given after surgery WITH chemo, if pt did not have chemo before; radiation is only used alone for palliative sx control
What is the reversal agent for heparin?
Protamine sulfate
Also works for unfractionated heparin
What are the two malignancies associated with this histological finding?
(Just the picture)
Which one is most likely, given that schistocytes are present?
Auer Rods
-
Acute mylogenous leukemia
- Especially Acute promylocytic leukemia - most likely dx with schistocytes
- APL is a subtype of AML
- Chronic mylogenous leukemia (sometimes)
Auer rods are only seein in cells of myloid origin, and they are always malignant
What labs will help you distinguish between a clotting factor deficiency vs. inhibitor?
Mixing study
Mix pt blood with normal plasma
- If PT/PTT improves, pt is deficient
- If PT/PTT do not improve, pt has an inhibitor
- The inhibitor/antibody/whatever in the pts blood binds to the normal factors in the plasma, thus inactivating them
What is the appropriate managment for a patient with hemochromatosis who also has low hemoglobin?
Iron chelator
If normal hemoglobin, do phlebotomy
How does hepcidin affect iron metabolism…
- In the gut?
- In the body?
Hepcidin…
- Decreases iron absorption from the gut
- Slows iron transport out of hepatocytes and macrophages
More hepcidin = less usable iron
What hematopologic malignancy is associated with the following immunohistochemical markers?
CD19+
TdT+
B-Cell Lymphoid Leukeimia (B-ALL)
What treatment should you give for a patient wtih a Factor VIII inhibitor who is actively bleeding?
Activated prothrombin complex concentration
- Bypasses need for other clotting factors*
- Plasmapheresis or clotting factor concentrates won’t work bc the inhibitor will inactivate them*
What is the disease-defining translocation of acute promyelocytic leukemia?
t(15;17)
How do anti-PD-1 antibodies work to treat cancer?
If a tumor expresses PDL-1, it can bind to PD-1 (the receptor) on a T-cells, thus inactivating the T cell
- An anti-PDL-1 antibody will bind to PD-L1, preventing it from binding to its receptor on the T cell
- This allows the T-cell to become activated against the tumor cell
- Signal to activate the T cell: MCH on tumor binds T-cell receptor AND tumor B7 binds CD23*
- Note: CTLA-4 can get in the way of co-stimulation, so blocking this -> even more T cell activation*
Which virus is associated with nasopharyngeal carcinoma?
Ebstein Barr Virus
EBV also associated with: Burkitt’s Lymphoma, lymphoproliferative disese in post-transplant setting
Describe the presentation of acute promyelocytic leukemia
- Young patinet
- Low blood counts
- Bleeding/bruising (could be intracranial bleed)
- DIC
- Elevated D-dimer, PT, PTT
- t(15;17) translocation is diagnostic*
- Treat emergently with all-trans retinoid acid (don’t wait for cytology)*
For breast cancer, is more aggressive surgery (ex: mastectomy instead of lumpectomy) associated with better outcomes?
No!
Standard of care now is to do lumpectomy with sentinal LN dissection; only do full axillary LN dissection if there is evidence of spread
In general, there are just more side effects (but not better outcomes) with more aggressive surgery
List 2 patient populations that are at an increased risk of aplastic crisis after a parvovirus B-19 infection
People with chronic hemolytic anemias (Sickle cell)
People who are immunosuppressed (HIV)
What is the mechanism of transfusion related lung injury?
Antibodies in the transfused blood attack the pt’s white blood cells (especially in the lung)
-> Fever, chills, shortness of breath, hypoxia
What is the normal percentage of cells in bone marrow?
100 - pt age
The rest should be fat
- Ex: a 20 year old pt will have 80% cells in their bone marrow*
- Less is concerning for aplastic anemia*
In a patient with newly diagnosed breast cancer, what are the indications for genetic testing?
Pt is young (≤ 50)
Extensive family hx of breast cancer (especially dx at a young age)
But always test tumor markers (ex: ER, PR, HER2)
What is the most significant toxicity associated with doxorubicin?
Cardiomyopathy
What kind of lymphoma is this?
Follicular lymphoma
Describe the diagnostic criteria for antiphospholipid antibody syndrome
At least 1 clinical criteria and 1 laboratory criteria
- Clinical
- Vascular thormbosis
- Pregnancy morbidity
- Laboratory
- (must be present on 2+ occasions, at least 12 weeks apart)*
- Lupus anticoagulant
- Anticardiolipin antibody (IgG or IgM, med-high titer)
- Anti-Beta2-Glycoprotein I antibody (IgG or IgM, high titer)
Which ancillary studies require fresh tissue?
Cytogenetics
Flow cytometry
If fresh tisuse is not available, can still do FISH, Molecular analysis, immunohistochemistry
In follicular lymphoma, which of the following is more concerning?
- A singular, small, high-grade lesion
- Several diffuse low-grade lesions
a. A singular, small, high-grade lesion
Tumor grade is more importnat than spread in evaluating follicular lymphoma
High grade = bad :(
A patient with small cell lung cancer complains of weight gain and facial puffiness.
What paraneoplastic syndrome does she most likely have?
Excess ACTH
Expect poor wound healing, thin skin, easy bruising, striae, other signs of too much cortisol
After chemotherapy, when do you expect white counts to be the lowest?
7 days after chemo
What cell has the following immunohistochemical markers?
CD 138+
Cytoplasmic Ig
Plasma cell
Which lymph nodes are most commonly involved in Classic Hodgkin Lymphoma?
Cervical
Mediastinal also common
List 4 malignancies associated with EBV
- Hodgkin’s lymphoma
- Burkitt’s Lymphoma (non-Hodgkin)
- Nasopharyngeal carcinoma
- Lymphoproliferative disease in post-transplant setting
Which type of lung cancer is most likely to occur in nonsmokers?
Adenocarcinoma
Bronchogenic and bronchioalveolar?
Can occur in smokers and nonsmokers
Squamous, small cell, and large cell are all strongly assoicated with smoking
What is the treatment for a patinet with DVT who also has heparin-induced thrombocytopenia?
Direct thrombin inhibitor (IV administration)
- Normal tx for DVT is heparin (or LMWH)*
- If pt has HIT, heparin will not help - use direct thrombin inhibitor*
What pathogen is associated with gastric carcinoma?
H. Pylori
What is the next diagnostic step in an adult patient who present with anemia and occult blood in the stool?
Colonoscopy
Note: at this point it would be a dianostic test (not a screening test) since there are sx of something wrong
Reed-Sternberg cells:
- Histological markers (3):
- Associated malignancy:
- Histological markers: CD30+, CD15+
- CD30 and CD15 are specific
- Associated malignancy: Hodgkin Lymphoma
- Hodgkin Lymphoma is a B cell lymphoma, but mising some B cell markers (CD20-, CD45-)*
- Note: Most common nodular sclerosing type is CD20-, but less common nodular lymphocytic type is CD20+*
- Thank you @Will Schwartz!*
What is the most likely diagnosis for this patient?
Most likely clinical manifestation?
Hereditary eliptocytosis
-> intermittent hemolysis
What blood type should be given to patients with unknown blood type requiring emergent transfustion?
O negative
What is the most common symptom of a pancoast tumor in its early stages?
Sharp shoulder pain
As the tumor grows, can radiate toward the armpit, shoulder blade, and scapula, cause Horner’s syndrome
Invades the thoracic inlet
What is the next diagnostic step for a patient with symptoms of nerve impingement in the left arm, chronic cough, Horner’s syndrome, and a 40 pack/year smoking history?
MRI of the neck
Will be able to see the specific nerve impingement
Chronic Myeloid Leukemia can progress to which two other malignanies?
B-cell Lymphoblastic Leukemia* (aka ALL of the B cell)
Acute Mylogenous Leukemia
*Strange that it can go from myeloid -> lymphoid malignancy but apparently it happens
How do you reverse Warfarin?
Vitamin K
And maybe
Fresh frozen plasma or Clotting factor concentrate
- Vitamin K stops warfarin for inhibiting VKOR; but takes time to work*
- If pt is actively bleeding, give FFP or clotting factors in addition*
Are these lymphoid or myeloid cells?
Lymphoid
A patient presents with the following:
- Fever
- Confusion
- Severe thrombocytopenia
- Mild anemia
- Schistocytes on peripheral blood smear
- Normal D-dimer
What is the most likely diagnosis?
Appropriate treatment?
TTP
Treat emergently with plasmapheresis
Which viruses (2) are associated with HCC?
HBV, HCV
What is the difference in presentation between febrile nonhemolytic transfusion reaction and transfusion-related acute lung injury?
Transfusion-related acute lung injury will have shortness of breath and hypoxia
- Febrile nonhemolytic transfusion reaction will not have hypoxia
Which chemotherapy agent (that we’ve talked about) is most likely to cause heart issues?
Doxorubicin (an anthracycline)
Also trastuzumab
List 3 chromosomal abnromalities that may be present in patinet with therapy-related MDS (t-MDS)
- Loss of a portion of chromosome 5
- Loss of a portion of chromosome 7
- 11q23 translocation
- Associatied with topoisomerase inhibiors specifically
t-MDS can be seen in pts who have received chemotherapy or radiation
Which malignancies (3) are associated with EBV?
- Hodgkin lymphoma
- Burkitt lymphoma (type of NHL)
- Nasophryngeal carcinoma
What is the next diagnostic step for any patient with a low platelet count?
Review the peripheral blood smear
Which hematopoietic malignancy would show these markers:
- CD10+
- CD19+
- CD3-
B-cell ALL (B-cell lymphoblastic leukemia)
Which hemolytic anemia results spherocyte formation (vs. schistocytes)?
Autoimmune hemolytic anemia
What is the mechanism that causes heparin-induced thrombocytopenia?
Immune response to heparin
- Body forms immune complex
- Results in platelet activation
Note - not all antibodies will result in platelet activation and HIT
In general, what is the treatment approach to non-metasatic gastric cancer?
Goal = cure
- Neoadjuvant chemo
- Goal is to downstage the tumor
- Then surgery
- Goal is to remove all or as much as possible
- Then more chemo
- Goal is to eliminate micro-metastatic disease
What is the (pathophysiologic) cause of idiopathic TTP?
ADAMTS13 deficiency
- Supposed to cleave and inactivate vWF
- Without ADAMTS13, vWF goes nuts, causing thrombi everywehre
- Fever, CNS confusion, low platelets, schistocytes present, normal D-dimer*
- Treat emergently with plasmapheresis*
What B-cell lineage is associatd with classic Hodgkin Lymphoma?
PAX5+
In which phase(s) of the cell cycle does doxorubicin work?
Any!
Doxorubicin is not cell-cycle specific
Doxorubicin is an anthracycline - it keeps coming up that it causes cardiotoxicity
Are these lymphoid or myeloid cells?
Myeloid
Which marker will always be present in AML?
MPO+
May also have CD13+, CD33+
Will never have B cell markers like CD19
What might cause a patinet with G6PD deficiency to have normal G6PD levels?
Acute attack
- If a pt is presenting with hemolysis after TMP-SMX anda peripheral smear with bite cells, but normal G6PD levels, they still most likely have G6PD*
- Confirm by testing G6PD levels after the acute attack is over*
Will somebody with Vitamin B12 deficiency have an increased LDH?
Yes
(Not sure why, suggest an edit if you can explain!)
How does Factor V Leiden mutation affect the coagulation cascade?
(Effect and mechanism)
Increased risk of venous thrombosis
- Factor V Leiden mutation makes Factor Va resistant to inactivation by Protein C
- It also sucks at helping Protein C inactivate Factor VIIIa
- Result is increased coagulability, which manifests as increased risk of DVT
Some increased risk of arterial thrombosis in some cases (CAD), but DVT is more important to remember
What conditions are associated with hypersegmented neutrophils?
Megaloblastic anemias
(more than 4 lobes)
