Heme-Onc Flashcards
Multiple Myeloma presentation, dx
~60
Bone pain, usually back
Renal failure
Constipation & fatigue 2/2 hypercalcemia
Normocytic anemia Renal dysfunction Hypercalcemia Urine: bence jones proteins XR: punched out, osteoporotic lesions
Soft tissue sarcoma locations w/ mets, presentation, dx, staging, tx
Extremities, trunk, retroperitoneal
Pulmonary mets
Younger, healthy patients
Unexplained mass…literally just a big lump
Non-tender
No surrounding skin changes (hematoma, erythema)
No systemic symptoms
Core biopsy…not excisional!!
CT for lung mets if higher stage
Stage 1-3: based on size, depth, grade…no mets
Stage 4: mets
Excision with 2cm margin…not amputation
+/- chemo depending on stage
GI stromal tumor (GIST) path, presentation, tx
KIT oncogene CD117 overexpression ==> proliferation of interstitial cells of cajal ==> stomach/small bowel tumor
Often asymptomatic or bleeding
Resection + imitinab
Breast cancer staging, dx workup, tx by stage
Stage I 3cm –node
Stage III 5 + 1 node
Stage IV: any metastasis
FNA ⇒ core biopsy for staging ⇒ bilateral mammography
Staging: CBC, LFT, CXR always ⇒ CT, bone scan, brain MRI if suspicious for metastases
Sentinel LN biopsy for staging
Stage I: lumpectomy + radiation
Stage II+: surgery + chemo
ER/PR positive: estrogen (aromatase) inhibitors
Her-2 positive: trastuzamab
Inherited hypercoagulable disorders ddx, path w/ commonality*, presentation, dx, tx
- Factor V leiden (most common) ==> Factor V becomes resistant to inactivation by protein C
- Protein C / S deficiency
- Antithrombin 3 deficiency
PE, MI, stroke, miscarriage
Heparin ==> warfarin (6 months for first event, 12 months for second, lifelong for 3+)
Retinoblastoma path, presentation*, dx, tx
Failed Rb suppressor inactivation ==> rapid metastasis to liver and brain
LEUKOCORIA ==> immediate ophthalmology referral*
Eye pain
CT or US
Surgical removal
Clotting cascade described
- Fibrin clot formation
INTRINSIC: 12 ==> 11 ==> 9 ==> 8 ==> 10
EXTRINSIC: Tissue Factor (3, produced by vessels) ==> 7 ==> 10
BOTH: 10 ==> 5 ==> 10-5 complex ==> prothrombin (f2) ==> thrombin (f2a) ==> fibrinogen to fibrin ==> fibrin polymer forms clot - Platelet plug formation:
vWF carries factor VIII and forms “glue” between collagen (exposed @ damaged vessel) & platelet
Thrombin activates platelets ==> activated platelets bind fibrinogen ==> fibrinogen links activated platelets
In-vivo clot inhibitors
Antithrombin: inactivates thrombin & f7, 9, 10, 11
Protein C & S: thrombin activated ==> inactivates 5 and 8
Heparin mechanism, lab effects, s/e, reversal, alternative drugs
Activates antithrombin 3 ==> inactivates thrombin & f7, 9, 10, 11
Increases PTT (intrinsic pathway)
Heparin-induced thrombocytopenia (HIT) 2/2 autoantibodies against platelets ==> bleeding & thrombosis
Protamine sulfate
Argatroban (thrombin inhibitor)
Enoxaparin (f10 inhibitor)
Warfarin mechanism, lab effects, s/e, reversal
Vitamin K antagonist: inhibits vitamin-K dependent factors (7, 9, 10, prothrombin)
Affects PT (extrinsic pathway)
Initially depletes protein C & S ==> causing hypercoagulability…thus heparin bridge required
Vitamin K reversal
PTT measures
Intrinsic pathway: 12, 11, 9, 8, 10, 5, prothrombin, thrombin
PT measures
Extrinsic pathway: 7, 10, 5, prothrombin, thrombin
Hemophilia path, types, dx, severities, tx
X-linked clotting factor deficiency
A: factor 8 deficiency (90% of cases)
B: factor 9 deficiency (9% of cases)
Prolonged PTT only! (normal bleeding time?)
Obtain specific factor assay to determine type
Mild > 5% normal factor levels
Severe <1% normal factor levels
Clotting factor transfusion or cryoprecipitate
Von Willebrand’s disease path, presentation, dx, tx
Autosomal dominant deficient/dysfunctional vWF ==> dysfunctional factor 8 (carried by vWF)
Less severe bleeding than hemophilia
Prolonged PTT & bleeding time
Ristocetin assay
DDAVP (releases more factor 8)
Disseminated intravascular coagulation (DIC) path, presentation, dx, tx
Underlying disorder (obstetric, infection, neoplasm, shock etc.) causing fibrin deposition in small vessels ==> end organ damage & bleeding 2/2 thrombocytopenia and clotting factor deficiency
Bleeding & organ damage
Increased PT & PTT, D-dimer, fibrin split products
Decreased clotting factors, platelets, fibrinogen
+Microangiopathic hemolytic anemia
Basically, nothing normal
Reverse underlying cause
Thrombotic thrombocytopenic purpura (TTP) path, dx, tx
Underlying disorder causing platelet microthrombi occlusion of small vessels ==> end organ damage
Often kids... 5+ Low platelets Microangiopathic hemolytic anemia Neurologic sx (seizure, delirium) Fever Renal failure (Cr elevation) Smear: schistocytes 2/2 hemolytic anemia NORMAL: PT, PTT, fibrinogen
Steroids
Plasma replacement
NOT: platelet replacement (worsens)
Hemolytic uremic syndrome (HUS) dx, tx
Renal failure (more severe than TTP)
Microangiopathic hemolytic anemia
Thrombocytopenia
Steroids
Plasma replacement
NOT: platelet replacement (worsens)
Idiopathic thrombocytopenic purpura (ITP) path, presentation, dx, tx
IgG autoantibodies to platelets
Less severe bleeding than HUS, TTP, DIC
Exclusion
Steroids
Anemia general categories, ddx***
- Decreased production: low reticulocyte count (100)
2/2 DNA synthesis problem: B12 (cobalamin) deficiency, folate deficiency, chemotherapy - Increased destruction: elevated reticulocyte count (>2.5), EPO, and indirect bilirubin
- Blood loss
Iron deficiency anemia vs anemia of chronic disease dx
Fe deficiency: Low serum Fe High TIBC & transferrin (Fe transporter) Low Fe/TIBC Low ferritin (Fe storage) High RDW
Chronic disease:
Low serum Fe
Low TIBC & transferrin
High ferritin
Megaloblastic anemia path, presentation, dx, tx
B12/cobalamin deficiency 2/2 malabsorption (pernicious anemia, tapeworm)
Folate deficiency 2/2 malabsorption, alcoholism, drugs
Fatigue, pallor, diarrhea etc.
B12: demyelination ==> neuropsychiatric and motor/sensory dysfunction
MCV > 100
Hypersegmented neutrophils
Schilling test: saturate liver stores with IM unlabeled B12 ==> ingest radiolabeled B12 ==> if absorbed, radiolabeled will be in urine
Hereditary spherocytosis path, presentation, dx, tx
RBC membrane fragility ==> hemolytic anemia
Pallor, fatigue, jaundice
Hemoglobinuria (dark urine) LDH elevation Elevated indirect bilirubin Smear: spherocytes lacking central pallor \+ osmotic fragility test
Steroids
G6PD deficiency path, presentation, dx, tx
X-linked recessive RBC sensitivity to oxidative stressors (fava beans, sulfonamides, antimalarials)
Pallor, fatigue, jaundice
Hemoglobinuria (dark urine)
LDH elevation
Elevated indirect bilirubin
Steroids
Fanconi’s anemia presentation
Short stature
Thumb aplasia
Cafe-au-lait spots
Sickle cell anemia path, complications, dx, tx*
Autosomal recessive glu==>val replacement on beta-subunit of Hgb ==> anemia and vasoocclusion
Splenic infarction (pneumococcal infection) Acute chest Cholecystitis Aplastic crisis 2/2 parvo Osteomyelitis (s. aureus, salmonella) Stroke
Smear: sickle and target cells
Dx: quantitative hemoglobin electrophoresis
Hydroxyurea (stimulates fetal hemoglobin)
Exchange transfusion*
Acute chest: incentive spirometry
Alpha thalassemia types w/ presentations, dx, tx
Hydrops: 0/4 alpha genes present ==> death in utero
H-disease: 1/4 alpha genes present
Hypochromic microcytic anemia
Chronic hemolysis ==> splenomegaly, jaundice, cholelithiasis, extramedullary hematopoiesis bone changes
Transfusions with deferoxamine iron chelation
Trait: 2/4 genes present
Hypochromic microcytic anemia
Asymptomatic
Carrier: 3/4 genes present
Beta thalassemia types w/ presentations, dx, tx
Major: 0/2 beta genes present
Hypochromic microcytic anemia
Requires transfusions + deferoxamine
Minor: 1/2 beta genes present
Hypochromic microcytic anemia
Asymptomatic
Polycythemia vera path, presentation, dx, tx
JAK-2 mutation ==> universal marrow proliferation, but predominantly erythrocytosis
Elderly
CHF 2/2 hyperviscosity
Hepatosplenomegaly
Low EPO (unlike most other polycythemias)
Hydroxyurea
Transfusion reactions w/ path, presentation, tx
Non-hemolytic febrile:
IL-6 elevation
Fever, chills, rigor hours-post transfusion
Stop transfusion + tylenol
Minor allergic:
Antibody formation against donor RBC
Hives
Stop transfusion + benadryl / epinephrine
Hemolytic transfusion reaction:
Hypotension 2/2 anaphylaxis
Acute lymphoblastic leukemia path (ALL), presentation, dx*, tx, prognosis
B or T cell proliferation ==> pancytopenia
Most common pediatric cancer Occurs in adults too Hepatosplenomegaly B-ALL: fatigue, anemia, bone pain T-ALL: mediastinal thymus lymphoma causing local sx
Pancytopenia
Smear: lymphoblasts (minimal cytoplasm, granules or nucleoli. negative myeloperoxidase)
Dx: bone marrow biopsy >25% lymphoblasts
Chemo + allopurinol (prevents tumor lysis syndrome)
Children: excellent
Acute myelogenous leukemia (AML) path, presentation, dx, tx, prognosis
Myeloid lineage proliferation in bone marrow==> pancytopenia
Adults & kids
Benzene exposure
Sludging: pulmonary, CNS symptoms
Rarely hepatosplenomegaly
Smear: myeloblasts (more cytoplasm, granular, prominent nucleoli, + myeloperoxidase, + AUER RODS)
Chemo + allopurinol (prevents tumor lysis syndrome)
Poor prognosis
Chronic lymphocytic leukemia path, presentation, dx*, tx
Mature lymphocyte proliferation
Elderly, often asymptomatic
Fatigue, malaise
Infection
Hepatosplenomegaly & lymphadenopathy
Lymphocyte > 5000
Granulocytosis, anemia, thrombocytopenia
Smear: lymphocytosis with smudge cells**
Treat only once symptomatic ==> palliative but slowly progressing
Chronic myelogenous leukemia (CML) path, presentation, dx, tx
BCR-ABL (9,22) translocation ==> granulocytosis
Spectrum of types: chronic to acute blast crisis
Middle-aged adult
Usually asymptomatic
Hepatosplenomegaly
Constitutional
PCR: BCR-ABL translocation
Massive neutrophilia
Low leukocyte alkaline phosphatase
High LDH, uric acid
Imatinib (gleevec) inhibits BCR-ABL tyrosine kinase
Bone marrow transplant
Hairy cell leukemia path, presentation, dx, tx
Adult B-cells proliferation
Constitutional
Infection and bleeding 2/2 marrow infiltration
Rarely leukocytosis
Tartrate-resistant acid phosphatase (TRAP) stain showing hairy cells
Non-hodgkin’s lymphoma path, presentation, dx, tx
t14,18 translocation, EBV, H. pylori ==> B & T cell proliferation in lymphoid tissue
Usually adults, sometimes children
Lymphadenopathy and hepatosplenomegaly
Constitutional symptoms
Mass formation & extranodal manifestations when severe
Excisional lymph node biopsy
Hodgkin’s lymphoma path, presentation, dx, tx
B-cell proliferation
Bimodal ages: 30’s and 60’s
Above diaphragm adenopathy
Oscillating weeks of fevers
Hepatosplenomegaly
Excisional lymph node biopsy: reed-sternberg binucleated B-cells with “owl-eye” appearance
Multiple myeloma path, presentation, dx, tx
B-cell proliferation with excessive IgA, IgM, and/or kappa/lambda light chains. MGUS precursor.
Elderly w/ Bone pain Renal failure Anemia Constipation 2/2 hypercalcemia
Triad: M-proteins, B-cell proliferation, lytic bone lesions
Melphalan
Waldenstrom’s macroglobulinemia path, presentation, dx, tx
IgM hyperproliferation ==> hyperviscosity, cold agglutinin disease, amyloid. MGUS precursor.
Raynaud’s
Neurologic problems
?
?
Amyloidosis dx
Congo red stain showing apple-green birefringence under polarized light
Neutropenia pathogens, tx
S. aureus, pseudomonas, E. coli, Proteus, Klebsiella
G-CSF
If febrile: broad spectrum abx
Transplant types, rejection types
Autologous: to self
Allogenic: another person
Syngeneic: twin-twin
Hyperacute: hours post-transplant 2/2 preformed antibodies ==> vascular thrombi ==> cytotoxic treatment
Acute: days to 3 months 2/2 T-cell mediation ==> steroid treatment
Chronic: months to years ==> no tx
Graft-versus-host: donated T-cells attack host skin, GI
Angiofibroma path, presentation*, dx, tx
Tumor
Bleeding w/ mass
Clinical
Surgery
