USMLE Heme Onc Flashcards
Acute leukemia
Thrombocytopenia
AL amyloidosis dx
In patients with suspected AL amyloidosis, the combination of bone marrow biopsy and abdominal fat pad aspiration has a sensitivity of approximately 90%.
classic features of AL amyloidosis, including macroglossia, hepatomegaly, nephrotic syndrome, peripheral neuropathy, and the presence of an IgG lambda M-protein
Acute Lymphocytic Leukemia
Prognostic factors:
- Age — the young fare better (< 30)
- Blast count > 30,000 do poorly
- Cytogenetics — hyperdiploidy is a good finding, whereas a Philadelphia chromosome t(9,22) is a poor prognostic finding
Acute Lymphocytic Leukemia
Tx
- Supportive care with transfusions
- Leukophoresis is not usually necessary since the blasts are smaller and less likely to cause sludging
- Combination chemotherapy
- Induction chemotherapy using multi-drug regimens
- Consolidation chemotherapy with multi-drug regimens for multiple cycles
- Maintenance (different from Myeloid)
- CNS prophylasxis intrathecal / radiation
Alpha Thalassemia
- aaa- -a-a- -a— —
- (Hgb H) (Hgb Barts)
- Should have a low MCV
- Should have an elevated reticulocyte count if anemic
- Normal electrophoresis
- Diagnosis can be made by a chain gene analysis
AML M3
- Cytogenetics = t(15,17)
- Tx:
**_AML /// M3 /// DIC _ **
- Translocation involving the retinoic acid receptor gene
- Good prognosis category
- Prominent Auer rods
- Commonly associated with DIC
- Tx: All Trans Retinoic Acid (ATRA) + chemotherapy with at least an anthracycline
AML Treatment
- Induction
- Consolidation Chemo
- Supportive care with transfusions
- Leukophoresis if blast count > 100,000 or for symptoms of hyperviscosity
- Combination chemotherapy
- Bone marrow transplant
- Induction chemotherapy — designed to take a patient to aplasia with recovery of “normal” hematopoiesis and a remission state
- Consolidation chemotherapy — designed to reinforce the remission obtained; usually multiple cycles given
Anal cancer treatment?
- Anal cancer is treated initially with combined radiation therapy and chemotherapy.
- Mitomycin plus 5-fluorouracil is the standard chemotherapy regimen used in conjunction with radiation therapy in the treatment of anal cancer.
Anemia Of Inflamation
- Iron Low
- TIBC Low
- % sat Low/Normal
- Ferritin High ( > 100)
Usually normochromic normocytic RBCs - Decreased reticulocyte count
Gold standard - Bone Bx
Anemia Of Inflamation Tx
Exogenous erythropoietin • Transfusion support • Optimize associated medical illness
Antiphospholipid antibody
PT / PTT effect
PTT prolonged
Antiphospholipid Antibody Syndrome
• Prolonged PTT (kinda odd eventhough its a hypercoagulable dz)
- Treatment options
- Anticoagulation
- Warfarin
- Heparin/LMWH
- ASA
- Anticoagulation
Antithrombin III Deficiency
Tx:
- It Inactivates activated IX, X, XI, XII
- Should always measure p_rior to the institution of heparin therapy but may be decreased secondary to thrombosis_
- Tx: Heparin (resistant) / Warfarin long term / AT III recombinant for surgery
(activated Protein C)
APC Resistance
Tx:
- Mutation in Factor V, resulting in resistance to activated protein C
- Most common inherited hypercoagulable defect
- Found in up to 25% of patients with recurrent thrombosis
- Additive to other risk factors (OCRs, pregnancy,other defects)
- Tx: Warfarin / hparin / LMWH
Aplastic Anemia / causes
- Drugs
- Sulfa drugs
- Chloramphenicol
- Radiation
- Benzenes
- Gold
- PNH
- Viral infection
DX with bone marrow
Aplastic Anemia Tx:
Immunosuppression with ATG [Anti-thymocyte globulin] /cyclosporine
- Older patients
- Younger patients with no marrow donor
Bone marrow transplant
- Younger patients with a donor
Treat a postmenopausal patient with newly diagnosed breast cancer with well-differentiated, estrogen receptor-positive/progesterone receptor-positive, HER2-negative breast cancer.
Aromatase inhibitors are the standard of care for postmenopausal women with these tumors.
Postmenopausal women with hormone receptor–positive breast cancer should take a 5-year course of an aromatase inhibitor as primary treatment or for an additional** 5 years after completing a **5-year course of tamoxifen therapy. In women who are initially treated with tamoxifen, an aromatase inhibitor may be started following 2 to 3 years of tamoxifen therapy to complete a total of 5 years of hormonal therapy.
Trastuzumab is indicated for tumors that overexpress HER2
Asymptomatic follicular lymphoma
Regardless of the stage at presentation, patients with asymptomatic follicular lymphoma can be followed without therapeutic intervention until they experience symptoms.
Auer Cells / AML
Autoimmune Hemolytic Anemia
- Macrocytic due to hight retic count / higher LDH / Higher Bilirubin indirect
- Direct Coombs Test
- Demonstrates antibody on the RBC surface / Mix patient’s blood with anti-IgG or C3 antibodies
- Indirect Coombs
- Test Demonstrates antibody in the serum
- Autoimmune hemolytic anemia
- Glucose 6 phosphate dehydrogenase def
- paroxysmal nocturnal hemoglobinuria
- Pyruvate kinase def
- Microagiopathic hemolytic anemia
AIHA - warm antibody / spherocytes and direct coombs test
PNH: Associated with pancytopenia, hemolytic anemia and thrombosis
PK def: differs from G6PD def in that erythrocytes from PK patients are not subject to hemolysis following oxidative stress and no characteristic morphologic red cell abnormalities on peripheral smear.
Microangiopathic HA have schistocytes on peripheral blood smear and low plt
G6PD def:
B12/Folate Deficiencies
- Macrocytic
- Elevated RDW
- Decreased WBC and platelet counts
- Hypersegmentation
- Decreased reticulocyte count
- *MMA** level is high in B12 Def
- *Homocysteine** is High in both
Best strategy to prevent further CVS complications in SCD
Chronic simple transfusion therapy has been shown to be more effective then hydroxyurea
Beta Thalassemia
- Decreased production of the 3 globin chain
- Should have a low MCV
- Should have an elevated reticulocyte count
- Should see elevated levels of Hgb A2 on hemoglobin electrophoresis
Bite Cells
Shistocytes (helmet cells)
Spherocytes
Target cells
Tear drop cells
Basophillic stippling
Howe Jolly
Due to phagocytes / thalassemia / G6PD def
RBC fragemnt / DIC, TTP or HUS Tramatic hemolysis
Shperoidal RBC no central palar / Autoimmune / hereditary Spherocytosis
Target cells bulls eye / thalassemia, RbC dz, postsplenectomy or liver dz
Tear drop / Meylofibrosis, major thalasemia
Basophillic stippling / blue grannules / thalassemia and iron def, ETOH abuse , lead
Howel Jolly bodies / rbc nuclear remnant / asplenia** or **splenic hypofunctions
Acute Lymphocytic Leukemia
- Primarily occurs in children
- Lymphadenopathy and splenomegaly occur in 50%
- An anterior mediastinal mass is common with the T-cell subtypes**(young male with mediastinal mass)
- CNS disease is common**
- Classification made using stains, flow cytometry, and cytogenetics
AE AE AE AE /// Toxicity
- Bleomycin
- Anthracyclines /Trastuzumab
- Methotrexate
- Cisplatin
- Cyclophosphamide
- 5 FU
- Pulmonary fibrosis
- Cardiomyopathy
- Liver toxicity /pneumonitis
- nephrotociity / ototoxicity
- hemorrhagic cystitis / bladd canc
- Sever diarrhea
Bleeding treatments in renal failure (uremic)
DDAVP
- Conjugated estrogen (second line)
- Cryoprecipitate
- Increase release of Factor VIII/VW factor polymers from endothelial storage site
- Possible increase platelet reactivity
- Enhance platelet aggregation
Bone metastases
Most common would include:
- Prostate
- Breast
- Lung
- Renal cell
- Myeloma (Lytic always)
Diagnosis should be made with:
- Bone scan (shows blastic only)
- Metastatic bone survey
- needed to see the lytic lesions
Treatment should include:
- Radiation therapy for pain control
- Evaluation for need for prophylactic rod placement
- Consideration of bisphosphonate therapy for breast cancer and myeloma
Brain Metastases
Most common tumors associated are:
- Lung
- Breast
- Melanoma
- Renal cell carcinoma
Treatment includes:
- Immediate large doses of steroids usually IV dexame thasone
- If the lesion is single, resection or stereotactic treatment may be tried
- For multiple lesions, and after any resection, whole-brain radiation therapy should be given
Breast Cancer Risk
• BRCA1
- Chromosome 17: AD
- Lifetime risk of developing breast cancer is 50% to 85%
- Also increases the lifetime risk of developing ovarian cancer to 33%
- Associated with an increase in the risk of breast and prostate cancer in men
Breast Cancer
• Prevention
- The use of tamoxifen reduces the risk of developing breast cancer in patients with increased risk
- In High risk patients
- Previous cancer
- Strong family history
- BRCA1-or BRCA2-positive
Breast Cancer
BRCA2
- Chromosome 13: AD
- Similar risk for breast cancer 50-85%
- Somewhat smaller risk for ovarian cancer (10-20%)
- Associated with increased incidence of breast cancer in men
Breast Mass:
Solid vs. cystic??
What is next?
• Solid vs. cystic??
- Can determine using ultrasound
- If cystic, can aspirate; if bloody fluid or recurs, then should biopsy
- If solid**, should do **FNA or core biopsy
• _Palpable mas_s without abnormality on mammogram
- Should biopsy
Breast Cancer Treatment
- < 1-cm tumor, node negative — NO ADDITIONAL TREATMENT
- >1 cm tumor or (anysize tumore +node positive) —ADJUVANT TREATMENT
-
Premenopausal
- chemo therapy
- +/- hormones (If ER/PR +ve then 5 yrs hormone/ Tamoxifen therapy)
-
Postmenopausal
- hormones (aromatase inhibitors) +/- chemo
- chemo +/- hormones
- TRASTUZUMAB** if **HER2/neu and node+
do not use Aromatase Inhibitors in premenopausal women.
CA 125 / how useful is it?
- 80% with ovarian cancer
also with +ve
- Cervix, breast, Endometrial, Lung, Colon
This is more like a monitoring factor while getting treatment.
- Cancer Incidence
- Cancer Death
- Male
- Female
Cancer Incidence
- Males : Prostate > Lung > Colorectal
- Females : Breast > Lung > Colorectal
Cancer Death
- Males : Lung > Prostate > Colorectal
- Females : Lung > Breast > Colorectal
Carcinoma in Situ -Lobar
Lobular
- Nonpalpable with no reliable mammographic changes
- Marker for cancer development in either breast
- Frequently is multifocal and bilateral
Treatment** varies from **observation only to tamoxifen to bilateral mastectomy
Carcinoma In Situ - Ductal
Ductal (DCIS)
- Benign
- More common than lobular
- See microcalcifications on mammogram
- High-grade has higher risk of evolving into invasive disease
Treatment is mastectomy vs. breast conservation surgery +/- XRT followed by tamoxifen
Starry Skies Burkitts
Cervical Cancer
• Treatment
- CIN I:
- CIN II:
- CIN III:
- CIN I: observation vs. cryotherapy
- CIN II: ablation or excision
- CIN III: ablation or excision
Causes of EPO resistance
- Iron def
- B12 or folate def
- Inadequate HD
- Infection
- Extensive hyperparathyroid bone dz
- Occult malignancy
- Medication (ACEi ARB)
Cervical cancer screening
- HIV/SLE/Transplant
- AGE< 21
- 21-29
- 30-65
- >65
- onset of sex Q6M X2 then yearly
- No screening
- Cytology Q3Y
- Cytology Q3Y or Cytology with HPV Q5Y
- No screening if -ve (3 paps or 2 HPV)
CLL
• Commonly associated with second malignancies
- Lung cancer
- Head and neck cancer
Chronic Lymphocytic Leukemia
Tx:
Indication
Treatment:
- Chlorambucil
- Fludarabine
- Combination chemotherapy
- Alemtuzumab
- Rituximab/ofatumumab
Indications for treatment include
- Symptomatic disease
- Rapid doubling of the WBC count < 1 yr
- Anemia
- Thrombocytopenia
Chronic Lymphocytic Leukemia
Staging
RAI staging system Survival:
- 0 Lymphocytosis >10yrs
- I. Lymphadenopathy 9 yrs
- II Splenomegaly 6-7 yrs
- III Anemia 2-3 yrs
- IV Thrombocytopenia 2-3 yrs
Clues on peripheral smear:
- Blasts =
- Auer rods =
- Mature cells =
- Mature lymphocytes =
- Maturing myeloid cells =
- Blasts = acute leukemia
- Auer rods = myeloid blasts
- Mature cells = chronic leukemia
- Mature lymphocytes = CLL
- Maturing myeloid cells = CML
Chronic Lymphocytic Leukemia [ALWAYS on Boards]
Work up
- A bone marrow aspirate and biopsy
- Flow cytometry on peripheral blood
- Cytogenetics on bone marrow
- Flow cytometry, which is usually diagnostic
- Typically a B-cell disorder with an abnormal pattern
- CD19, CD20, CD23 Positive (BCell usually +ve for CD 19/20/23)
- CD5 Positive as well
- Light chain restricted
Chronic Myeloid Leukemia
- Typical laboratory presentation
- High WBC count / “Myelocyte spike”
- Eosinophilia and basophilia
Labs :
- Low LAP (leukocyte alkaline phosphatase) (not done now a days)
- Marrow that is hypercellular
- Characteristic chromosomal abnormality / t(9,22)
Few side effects primarily fluid retention
- Imatinib (Gleevak)
- Nilotinib
- Dasatinib
Bone marrow transplantation
- Still therapy of choice for young patients with a matched available donor / Only curative therapy known to date
- Best when performed early in the disease
CML Accelerated phase:
- Increasingly difficult to control counts
- Increasing eosinophilia and basophilia
- Accumulation of additional cytogenetic abnormalities
- Treatment becomes more difficult
CML can becom AML or ALL
CML Chronic phase:
- Usually relatively asymptomatic
- Easily controlled counts
-
Disease duration
- 2 years untreated
- 3-4 years with hydroxyurea
- 4-5 years with interferon
- Unknown with imatinib **** tyrosin kinase inhibitors
Colon Cancer / staging / treatment / post survalance
- All men and women, beginning at age 50 years, should undergo screening colonoscopy.
- STAGE I (T1-2 N0) STAGE II (T3-4 N0) Stage III (N1 N2) no M — VI M+ve
- FOLFOX chemotherapy
- All patients with stage III colon cancer, regardless of age, should receive postoperative adjuvant chemotherapy unless contraindicated because of medical or psychiatric disorders.
- Patients with rectal cancers that are not full-thickness lesions and do not have obvious lymph node involvement typically are managed with primary surgical resection.
- Postoperative surveillance for stage III colon cancer includes physical examination and carcinoembryonic antigen monitoring every 3 to 6 months; chest/abdomen/pelvic CT scanning annually for 3 to 5 years; and colonoscopy 1 year after resection and then repeated at 3- to 5-year intervals.
- Cushing Syndrome
- Diagnosis is made by:
- Treatment options include:
Cushing Syndrome
- Small cell carcinoma, carcinoid tumors, and in association with MEN I syndrome / Ectopic ACTH
- Seen with hypokalemic alkalosis
- weakness, hypertension, & hyperglycemia
- buffalo hump, moon faces, hyperpigmentation, hirsutism
Diagnosis is made by:
- Elevated ACTH
- Cortisol levels that do not suppress with dexamethasone
Treatment options include:
- Treatment of the primary tumor
- Inhibitors of steroid synthesis such as ketoconazole or aminoglutethimide
Dermatomyositis
Dz
Dx
Tx
- Visceral adenocarcinomas such as stomach, breast, lung, and ovary assiciated dz
- Polymyositis associated with skin changes
- Proximal painless muscle weakness
- Violaceous rash on exposed parts, especially the eyelids
- Dysphagia is common
Diagnosis:
- Elevated CPK, aldolase, LDH, and ESR
- Abnormal EMG
- Muscle bx necrosis of muscle fibers and an inflammatory reaction
Treatments include:
- Steroids
- Treatment of the underlying malignancy
DIC Smear
- P prolonged
- PTT prolonged
- PLT Low
- Fibrinogen Low
- D-Dimer +ve
- Protamine +ve
On Smear
- Schistocytes
- Thrombocytopenia
- Retic ount Eelevation
Diagnose polycythemia vera
Identification of the JAK2 V617F mutation in patients with a hemoglobin level greater than 18.5 g/dL (185 g/L) in men or greater than 16.5 g/dL (165 g/L) in women, with concomitant leukocytosis, thrombocytosis, and hepatosplenomegaly, is diagnostic of polycythemia vera.
DIC tx
vWD tx
acquired hemophilia Tx
DIC tx resh frozen plasma and cryoprecipitate
vWD tx _Desmopressin /vW factor if avaialbe _
acquired hemophilia Tx Recombinant activated factor VIIa
DIC treatment
- Treat underlying disorder
- Support with appropriate products
- Cryoprecipitate
- FFP
- Platelets
- pRBCs
- Heparin therapy - rarely needed
Eaton-Lambert Syndrome
- Small cell lung cancer
- Variant of myasthenia gravis
Initial symptom: Weakness of the proximal muscles
- Autoimmune in nature, secondary to autoantibodies that result in **impaired release of acetylcholine **
Diagnosis
- abnormal EMG with improvement in strength upon repetitive stimulation
- EMG is usually unaffected by addition of edrophonium chloride
Treatment:
- Treatment of malignancy
- Guanidine
- Plasma exchange
- IVIG
- Immunosuppression
Elevated PT and PTT
1:1 inhibitor mixing
if corrects look for factor def
if does not correct late for coagulation factor inhibitors
WET - Warfarin Extrinsic PT (27 910) Vit K
HITT - Heparin Intrinsic PTT 89
Diabetic amyotrophy
Asymmetric focal lower Ext pain associated with muscle atrophy, areflexia, atunomic dysfunction and unintentional weight loss
Essential Thrombocytosis - Dx Need rule out:
- Thrombocytosis sustained over 6 months that is unexplained
- May be associated with splenomegaly but not usually massive
- No clear diagnostic tests exist
- Although in about 50% JAK-2 is abnormal
- R/O IDA / Malignancy / Ifection / Malignancy
Treatment options include:
- Observation
- Hydroxyurea and busulfan
- Interferon-a
- Anagrelide
EXTRINSIC Factors
7
VII
WET Warfarin Extrinsic PT
Factor VIII Inhibitors
- IgG antibodies
- Detected when the 1:1 mix does not correct
- Treat with activated IX** product, porcine VIII, Factor Vila (NovoSeven®), or **immunosuppression
first-line agent in constipation-predominant irritable bowel syndrome
Lubiprostone is not a first-line agent in constipation-predominant irritable bowel syndrome, but it is appropriate for patients whose symptoms persist despite the use of fiber and standard laxatives.
Treat a patient with advanced symptomatic follicular lymphoma.
Rituximab (2 yrs), combination chemotherapy, and prednisone followed by rituximab maintenance therapy
Germ cell
Treatment
- Fewer than 5%
- Usually large tumors
- May secrete aFP or bHCG
- Presents with early-stage disease
_Treated with surgery, followed by _
- chemotherapy with agents that include
- BEP (bleomycin, etoposide, and cisplatin)
Small intestinal bacterial overgrowth
Should be considered in patients presenting with diarrhea, bloating, or weight loss; vitamin B12 deficiency or an elevated serum folate level can be laboratory clues to the diagnosis.
Gleason Score
• Gives a grade to both the predominant and secondary growth pattern, and adds the scores
• Total will be 2-10, with higher grade correlated with higher incidence of spread and mortality
• 7 or > Gleason score is high-risk disease
Hairy Cell Leukemia
(B-Cell)
- B cell in phenotype Usual presentation is:
- TRIAD
- Pancytopenia
- Large splenomegaly
- Inaspirable bone marrow
- Bone marrow with hypercellularity and increased reticulin fibrosis “dry tap”
-
TRAP stain positivity
- Tartrate-resistant acid phosphatase stain
A single cycle of parenteral cladribine is curative in more than 80% of patients with hairy cell leukemia.
Also : “dry tap” and a biopsy shows diffuse infiltration with small lymphocytes with hair-like projections expressing CD20 but not CD5.
Hb AS
- Unable to fully concentrate urine
- Sickle Cell Trait
Hemoglobin SS
- Pain crisis
- Nonhealing leg ulcers
- AVN
- Aplastic crisis from parvovirus B19
- Functional asplenia
- Develop microinfarcts of organs, such as brain — CVA
- Develop priapism and also retinal detachment
Hemophilia A Tx:
Factor VIII Def
- Synthesized in the liver
- Need 25% activity for normal hemostasis
- Severe disease < 1% activity
- Moderate disease 1-5% activity
- Mild disease > 5% activity
-
Tx:
- Mild DAAVP /
- for mild or moderate > [Factore VIII or Cryopercipitate
Hemophilia B Tx:
Factor IX deficiency / Synthesized in the liver
- Requires vitamin K as a cofactor for modification
Tx:
- FFP
- Factor IX concentrates — monoclonal and recombinant are available
- Twice the volume of distribution to consider when calculating replacement doses
Hereditary Hemochromatosis
Dx About the Dz
- Transferrin saturation (best test for Dx) > 45% women and > 50% men
- Ferritin > 1,000 (in women it will take longer to accumulate 1000 due to bleed)
- Liver biopsy (Gold standard)
About the Dz
- Autosomal and recessive inheritance
- Frequent in Caucasians
- Mutation in C282Y or H63D genes
- Modulates absorption of iron via HFE protein (increase absorption)
bladder cancer is treated: (High-risk, early-stage )
High-risk, early-stage bladder cancer is treated with intravesicular medication, typically bacillus Calmette-Guérin immunotherapy.
Hodgkin Lymphoma Dx
- Diagnosis made by finding Reed-Sternberg cells
- WHO defines classical Hodgkin’s and NLPHL
Hypersegmented
6 lobes or many 5 lobes
macroovalucyt-b12folate
Pelger-HuetCells-Myelodysplasia
Pelger-HuetCells-Myelodysplasia
myeloma-plasmacells
Spherocytes
