Eugene Heme Oncology Flashcards by X x

Cell Cycle Cancer examples

Hereditary Melanoma, Retinoblastoma, Li-Fraumeni Syndrome Catergory

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point mutation in cyclin-dependent kinase (cdk4) inhibitor on Chr9; insensitive to p16 inhibition

Hereditary Melanoma: Pathophysiology

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Loss of RB (cell cycle control protein)

Retinoblastoma: Pathophysiology/Diagnosis

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tumor suppresor: when NOT phosphorylated, binds E2F to block transcription and cell division (inactive in most human cancers)

Rb pathway: Rb

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onco, TFs required for cell cycle progression, blocked by Rb binding

Rb pathway: E2F

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onco, phosphorylate (inactivate) Rb

Rb pathway: Cdk4/Cyclin D

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tumor suppressor, downregulate Cdk4/Cyclin D activity

Rb pathway: p16

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Lots of cancers (breast, colon, etc.)

Li-Fraumeni Syndrome: Signs/Symptoms

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Inherited p53 mutation

Li-Fraumeni Syndrome: Pathophysiology/Diagnosis

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tumor suppressor, activates p53

p53 pathway: ATM (Li-Fraumeni)

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oncoprotein, inhibits p53

p53 pathway: Mdm2 (Li-Fraumeni)

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tumor suppressor, G1 cycle arrest allows for DNA repair in fibroblasts, some epithelial cells, apoptosis in thymocytes

p53 pathway: p53 (Li-Fraumeni)

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tumor suppressor, downstream of p53

p53 pathway: p21 (Li-Fraumeni)

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trisomy 21, Fanconi’s anemia, Li-Fraumeni

Acute Myloid Leukemia (AML): Inherited

Downs also ALL

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Age (>60 yo = poor outcomes), rad exposure, MDS, myeloproliferative neoplasms (CML, PV, ET), prior chemo (alkylating agents for lymphoma, breast cancer; topoisomerase inhibitors for testicular cancer via 11q23 MLL gene deletion)

Acute Myeloid Leukemia (AML): Epi/Risk Factors

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large, very granular cells with bilobed nuclei

Acute Myloid Leukemia: APL subtype

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blasts w/lots of cytoplasm, prominent nucleoli, granules and some maturing cells

Acute Myloid Leukemia: M2 subtype Histology

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Sx: Anemia, infections, bleeding. Hemorrhage, skin or gum infiltration, no mediastinal masses, LAD and hepatosplenomegaly less likely

Acute Myeloid Leukemia (AML): Signs/Symptoms

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Generally poor (<60% @ 5yr); t(8;21)(15;17), inv(16) good, 5q, chemo or complex karyotype bad

Acute Myeloid Leukemia (AML): Prognosis

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If good prognosis: 7+3: cytarabine x7d, doxorubicin x3d

Acute Myeloid Leukemia (AML): Treatment/Notes

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AML by day 14 of cyta/doxo 7+3

hopefully shows aplastic marrow

if not salvage/clinical trial/palliation

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Sx: Anemia, infections, high risk for hemorrhage; differentiation syndrome: fever, dyspnea, weight gain, pulmonary infiltrates, pleural and pericardial infusions

Acute Promyelocytic Leukemia (APL)(AML M3 Subtype)

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Myeloblast/lymphoblast progenitor cell overgrowth; t(15;17) PML/RAR-alpha fusion transcript

Acute Promyelocytic Leukemia (APL)(AML M3 Subtype): Pathophysiology/Diagnosis

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Acute Promyelocytic Leukemia (APL)(AML M3 Subtype): Prognosis

80-90% at five years

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Sensitive to ATRA, may cause differentiation syndrome. Tx: dexamethasone, arsenic trioxide (ATO)

Acute Promyelocytic Leukemia (APL)(AML M3 Subtype): Treatment/Notes

myeloblast/lymphoblast progenitor cell overgrowth

Acute Leukemias (AML, APL, ALL): pathophysiology

iliac crest bone biopsy, blood tests

Acute Leukemias (AML, APL, ALL): diagnosis

leukostasis (AML>ALL, tx: leukaphoresis, hydroxyurea), DIC, tumor lysis syndrome

Acute Leukemias (AML, APL, ALL): complications

Rare. Extremes of age, radiation, downs

Acute Lymphoblastic Leukemia (ALL): Epi/Risk Factors

Sx: Anemia, infections, bleeding, ant. mediastinal mass, DIC, bone pain; rarely lymphadenopathy and hepatosplenomegaly

Acute Lymphoblastic Leukemia (ALL): Signs/Symptoms/Findings

Mediastinal mass, especially

T-ALL common presentation

way high lymphocytes, large cells, high N:C ratio, prominent nucleoli, no granules, open chromatin, lack of PMNs and platelets

Acute Lymphoblastic Leukemia histology

TdT+, Ig+, CD10+

B-cell ALL surface markers

TdT+, CD2+, CD3+

T-cell ALL surface markers

peds: 10; adults >60

ALL adverse prognostic factors: age

>30k (B), or >100k (T)

ALL adverse prognostic factors: WBC

philedelphia: t(9;22), found in adults >60; t(4;11), found in peds <1

ALL adverse prognostic factors: cytogenetics

Acute Lymphoblastic Leukemia (ALL): Prognosis

>90% five year survival. Philadelphia chromosome bad

Induction w/ CHOP; CNS prophylaxis, stem cell xplant, maintenance (prednisone, mercaptopurine, MTX)

Acute Lymphoblastic Leukemia (ALL): Treatment/Notes

myelodysplasia 5 ways

Mylodystplastic syndrome, 5q, Polycythemia Vera, Essential thrombocythemia, primary myelofibrosis

Risk of transformation to AML

Myelodysplastic Syndrome (MDS)

High blasts, proliferation, apoptosis; low WBC, RBC, plts. anemia

Myelodysplastic Syndrome (MDS): Signs/Symptoms/Findings

Stem cell disorder: bad hematopoesis leads to defects in all non lymphoid lined, cytopenia due to TNF-mediated apoptosis. De novo or exposure: chemo, radiation, benzenes

Myelodysplastic Syndrome MDS

Low risk: Lenalidomide if 5q del, growth factor therapy if not High risk or EPOdecitabine if no Sx stem cell transplant curative

Myelodysplastic Syndrome (MDS): Treatment/Notes

Deletion leads to Anemia with increased PLT (megakaryocytes slow-growing)

5q Syndrome, MDS subtype

Del(5q31) leads to del(RPS14) leads to death of rapidly dividing cells (erythroid). Low AML conversion

5q Syndrome

MPN: expansion of RBC lineage

Polycythemia Vera: Findings

itching, ruddy complexion, splenomegaly, early saiety, DVT or PE

Polycythemia Vera: Symptoms

JAK2V617F in 92% of cases leads to increase in all cell types (mainly RBC lineage)

Polycythemia Vera: Pathophysiology/Diagnosis

MPN w/Good prognosis. 3% yearly mortality

Polycythemia Vera: Prognosis

Platelet lineage expansion. increased PLT, normal Hgb

Essential Thrombocytosis (Primary Thrombocythemia): Findings

megokaryocytes in bone marrow, exclusion, JAK2 mut in 42%

Essential Thrombocytosis (Primary Thrombocythemia): Pathophysiology/Diagnosis

low risk: low dose aspirin; high risk (>60, past thrombosis, CV risk): low dose aspirin, hydroxyurea

Essential Thrombocytosis (Primary Thrombocythemia): Treatment/Notes

teardrop RBCs (dacrocytes), increased LDH

Primary Myelofibrosis (Idiopathic Myelofibrosis): Findings

bleeding, anemia, infxn, cachexia, fullness, splenomagaly

Primary Myelofibrosis (Idiopathic Myelofibrosis): Signs/Symptoms

Marrow fibrosis, extra-medullary hematopoiesis

Primary Myelofibrosis (Idiopathic Myelofibrosis): Pathophysiology/Diagnosis

5 year survival, CALR better than JAK2

Primary Myelofibrosis: Prognosis

epo/transfusion, hydroxyurea, thalidomide/steroids, SC transplant (cure!), JAK inhibitors

Primary Myelofibrosis (Idiopathic Myelofibrosis): Treatment/Notes

increased mature and immature myeloid cells, basophilia, decreased hgb/hct, increased platelets (thrombocytosis)

Chronic Myelogenous Leukemia (CML): Findings

fatigue, fullness, hepatosplenomagaly, weight loss, ecchymoses, anemia

Chronic Myelogenous Leukemia (CML): Signs/Symptoms

abl is oncogene, MR3 (major) = >3log bcr-abl reduction, MR4.5 (complete) = 4.5 log reduction

chronic myelogenous leukemia (CML): genetics

t(9;22) leads to Bcr/Abl fusion gene on Philadelphia chromosome (22q-) leads to increased tyrosine kinase activity

Chronic Myelogenous Leukemia (CML): Pathophysiology/Diagnosis

slow-growing Ca harder to kill. Chronic phase of high blood counts (4-6 years) leads to accelerated phase (`1y) leads to blast crisis, AML (3-6 mos to death)

Chronic Myelogenous Leukemia (CML): Prognosis

Tx: Imatinib (Gleevec) ± xplant Progresses from chronic (splenomegaly or asymptomatic) leads to accelerated (anemia, decreased PLT) leads to blast crisis (~AML)

Chronic Myelogenous Leukemia (CML): Treatment

most common leukemia, >60 yo, not radiation!

Chronic Lymphocytic Leukemia (CLL): Epi/Risk Factors

Sx: Asymptomatic increased WBC, lymphadenopathy, splenomegaly, sino-pulmonary infxns, gradual onset fatigue, dyspnea, dizziness, weight loss

Chronic Lymphocytic Leukemia (CLL): Signs/Symptoms

lymphocytosis (small w/clumped chromatin), smudge cells

Chronic Lymphocytic Leukemia (CLL): findings

CD20+***, CD5+

Chronic Lymphocytic Leukemia (CLL): Diagnosis (flow cytometry)

Dx: CBC, peripheral blood smear/FACS, no marrow biopsy

Chronic Lymphocytic Leukemia (CLL): Pathophysiology/Diagnosis

Largely incurable except in rare cases with bone marrow xplant (slow-growing Ca harder to kill); Prognosis: 13q- good, 11q- & 17p- bad

Chronic Lymphocytic Leukemia (CLL): Prognosis

Tx: FCR (fludarabine, cyclo-phosphamide, rituximab), alemtuzumab, idelalisib, ibrutinib, allogenic xplant (only cure, but 20% fatal)

Chronic Lymphocytic Leukemia (CLL): Treatment

AIHA, ITP, pure red cell aplasia ( decreased RBCs, severe anemia), decreased Ig's (chronic infxn)

Chronic Lymphocytic Leukemia (CLL): Complications

Aberrant lymphocytes in blood or marrow, <5000 lymphocytes, not considered malignancy but can be risk for one

Monoclonal B-Lymphocytosis

Most common lymphoma, 25K/yr

Diffuse Large B-Cell Lymphoma (DLBCL): Epi/Risk Factors

Large lymphocytes (4-5x normal), diffuse growth

Diffuse Large B-Cell Lymphoma (DLBCL): Findings

germinal center markers (CD19, 20, 10; BC16)

Diffuse Large B-Cell Lymphoma (DLBCL): IHC markers

lymphadenopathy, night sweats, fatigue

Diffuse Large B-Cell Lymphoma (DLBCL): Signs/Symptoms

BCL6 overexpression (GC type), NFkB addition (non-GC), or Type 3 (primary mediastinal) subtypes

Diffuse Large B-Cell Lymphoma (DLBCL): Pathophysiology/Diagnosis

Not great (50% 10 yr in germinal-center-like, less good in ABC, PMBL)

Diffuse Large B-Cell Lymphoma (DLBCL): Prognosis

Tx: R-CHOP (Rituximab, Cyclophosphamide, Hdoxorubin, Ovincristine, Prednisone immunodeficiency-associated, primary effusion lymphoma

Diffuse Large B-Cell Lymphoma (DLBCL): Treatment/Notes

All respond better to infusional chemo and etoposide

Special situational and subtype DLBCL

burkitts or DLBCL of germinal center origin + HIV

HIV DLBCL (well controlled)

primary effusion lymphoma, post-germainal center immunoblastic lymphoma, plasmoblastic lymphoma, bad prognosis

HIV DLBCL (not controlled)

hodgkin's-like, lymphoid or plasmacytic proliferations in immunosuppressed pt

post-transplant DLBCL

CD30 mutation (like Hodgkin's), YA female; mass, thrombosis, SVC syndrome

Type 3 aka Primary Mediastinal BCL

Elderly, aggressive CNS disease, treat with intrathecal chemo

Double Hit Lymphoma (MYC +/- BCL2 or 6 mutations)

EBV infection (especially African)

Burkitt's Lymphoma: Epi/Risk Factors

Starry-sky appearance (normal macrophages eat nuclear remnants)

Burkitt's Lymphoma: Histo

IgM+, germinal center markers (CD19, 20, 10, Bc16); never express Bcl12

Burkitt's Lymphoma: IHC

aggressive chemo, CODOX-M-IVAC (McGrath protocol); very curable

Burkitt's Lymphoma: treatment

c-myc translocation from t(8;14), t(8;22), or t(2;8), EBV

Burkitt's Lymphoma: Pathophysiology

3 types: HIV-associated, African endemic (mass in mandible), sporadic

Burkitt's Lymphoma: Notes

Painless nodes, nodular pattern with small cells

Follicular BCL: Signs/Symptoms/Findings

CD10(+), t(14;18) common (Bcl2)

Follicular BCL: Pathophysiology/Diagnosis

Follicular BCL: Prognosis

7-9 yrs (BCL subtype)

Incurable but can treat with Rituximab, XRT for stage I

Follicular: Treatment/Notes

Nodular to diffuse, small lymphocytes

Mantle Zone: Signs/Symptoms/Findings

older males, CD5(+), Cyclin D1(+)

Mantle Zone BCL epi

translocation of cyclin D1 (11) and heavy-chain Ig(14)

Mantle Zone: Pathophysiology/Diagnosis

Based on Ki67 levels; high to low: blastic, aggressive, indolent, leukemic)

Mantle Zone: Prognosis

Bortezomib, aggressive chemo and auto-SC transplant v. watch & wait (depending on variant)

Mantle Zone: Treatment/Notes

Causes: Sjogren's, Hashimoto's (thyroiditis), H. pylori (gastritis), HCV (splenomegaly), c. psittaci (ocular adnexa), borrelia, c. jejuni

Extra-Nodal Marginal Zone (MALT): Epi/Risk Factors AND Signs/Symptoms/Findings AND Picture

CD20, 19 but no germinal center trademark CD10

Extra-Nodal Marginal Zone (MALT): Pathophysiology/Diagnosis

Treat antigenic stimulation to cure

Extra-Nodal Marginal Zone (MALT): Treatment/Notes

Polymorphous small lymphocytes

Marginal Zone: Signs/Symptoms/Findings AND Picture

increased NFkB via translocations

Marginal Zone: Pathophysiology/Diagnosis

Look like hybrid of plasma cells and lymphocytes

Lymphoplasmacytic Lymphoma: Signs/Symptoms/Findings

Igm(+), leads to increased viscosity, neuro/visual problems

Lymphoplasmacytic Lymphoma: Pathophysiology/Diagnosis

IgM causes Waldenstrom's macroglobulinemia

Lymphoplasmacytic Lymphoma: Treatment/Notes

Rare, 5-10% of NHL in US, more in Asia (secondary to Ebv)

Peripheral T-Cell Lymphomas (PTCL): Epi/Risk Factors

General features: infiltration of plasma cells, B-cells, usually have T-cell markers, TCR rearrangements common

Peripheral T-Cell Lymphomas (PTCL): Signs/Symptoms/Findings AND Picture

Types: angioimmunoblastic, extranodal NK/T-cell (nasal type), hepatosplenic, subQ, enteropathy-associated

Peripheral T-Cell Lymphomas (PTCL): Pathophysiology/Diagnosis

Peripheral T-Cell Lymphomas (PTCL): Prognosis

Worse than B-cell; median survival is 1-3y, except ALK+ ALCL (5y surivial is 65-90%)

Horseshoe-shaped nuclei, CD30+, ugly anaplastic-cells

Anaplastic Large Cell: Signs/Symptoms/Findings

Brentuximab (anti CD30)

Anaplastic Large Cell: Treatment/Notes

younger, better prognosis, t(2;5) mutation

Anaplastic Large Cell T-Cell lymphoma, ALK+

Rash, poor prognosis, no standard Tx

Peripheral TCL NOS: Signs/Symptoms/Findings

AI syndromes, hemolytic anemia, TCP, rash

Angioblastic T-cell lymphoma (AILT) presentation

arborized vessels, polymorphous infiltrate, Bc16, CD10; lacking normal CD2, 3, 5, 7

Angioblastic T-cell lymphoma (AILT), smear and IHC

lymphoma treated with gemcitabine

Angioblastic T-cell lymphoma (AILT) treatment

Always EBV+, often Asian; large blue granules, CD56+ NK cells, (-) TCR rearrangment

Extranodal NK/T-cell lymphoma (nasal type): epi, findings and IHC

high dose radiation and chemo; dismal prognosis

Extranodal NK/T-cell lymphoma (nasal type): tx and prognosis

heptosplenomegaly, coombs (-) hemolytic anemia, purpura/rash, RBCs engulfed by phagocytes, smear is small to medium cells with (=) TCR rearrangment (usually gamma/delta)

hepatosplenic t-cell lymphoma

progressing skin lesions, history of eczema, plaque leads to tumor leads to LN involvement

Mycosis Fungoides: Signs/Symptoms/Findings

steroids, topical radiation, phototherapy, topical chemo (early), chemo and transplant (late)

Mycosis Fungoides: tx

subcutaneous infiltrate, hemaphagocytic syndrome

subcutaneous panniculitis-like lymphoma

(+) TCR rearrangment (alpha/beta), CD3&8+, no NK cells (CD56-)

subcutaneous panniculitis-like lymphoma

carribean

Adult T-Cell Leukemia/Lymphoma: Epi/Risk Factors

long latency (10-30y), rash, hypercalcemia, CNS sx (confusion)

Adult T-Cell Leukemia/Lymphoma: Signs/Symptoms/Findings

Flower cells

Adult T-Cell Leukemia/Lymphoma: Signs/Symptoms/Findings

Driven by HTLV-1 via breast milk, blood, sex; TAX(+), CD4(+), CD25(+)

Adult T-Cell Leukemia/Lymphoma: Pathophysiology/Diagnosis

Adult T-Cell Leukemia/Lymphoma: Prognosis

19 weeks! | :(

EPOCH or novel therapies

Adult T-Cell Leukemia/Lymphoma: Treatment/Notes

Young adults w/Slarge mediastinal mass, B-symptoms (pruritus, Pel Ebstein (periodic) fevers, painful nodes upon boozing)

Hodgkin's Lymphoma: Epi/Risk Factors

Histo: Reed-Sternberg, owl's eye nuclei, eosinophils and macs, fibrotic bands

Hodgkin's Lymphoma: Histo

10k/year, bimodal (15-35, >50)

Hodgkin's Lymphoma: Epi

B-cell origin, but no B- or T-cell markers; CD30(+), CD15(+), PAX(+)

Hodgkin's Lymphoma: Pathophysiology/Diagnosis

Based on IPS score, generally good (1% fatal)

Hodgkin's Lymphoma: Prognosis

90% cured with ABVD combo chemotherapy (pulmonary toxicity possible)

Hodgkin's Lymphoma: Treatment/Notes

Salvage with xplant or Brentuximab

Hodgkin's Lymphoma: Treatment/Notes

Rare, 5% of HL, young males, Nodular infiltrates, small lymphocytes, no Reed-Sternberg cells

Lymphocyte-Predominant Hodgkin's Lymphoma: Epi/Risk Factors

CD20(+), CD30(=); cervical LAD

Lymphocyte-Predominant Hodgkin's Lymphoma: Pathophysiology/Diagnosis

Tx: ABVD (A/Doxorubicin, Bleomycin, Vincristine, Dacarbazine); salvage after PET dx relapse

Lymphocyte-Predominant Hodgkin's Lymphoma: Treatment/Notes

most common HL, thick fibrous bands on smear

nodular sclerosis HL

HIV associated HL

mixed cellularity HL

mass > 1/3 thoracic cavity, B symptoms or high ESR (inflammation), older (>40-50y)

poor prognosis for early HL

older than 45, male, albumin under 40, hgb under 105, stage IV, leukocytosis>15k/mm3, lymphs ,600 or <8% WBC count

poor prognosis in advanced HL (IPS score)

2nd most common heme malignancy; black>W>asian M>F (1.4:1)

Multiple Myeloma: Epi/Risk Factors

Sx: Calcium is high, renal insufficiency (Cr>2), Anemia (Hgb<10), Bone pain;XR: lucencies = lytic lesions

Multiple Myeloma: Signs/Symptoms/Findings

Histo: Mott cells, Dutcher bodies, CD38+ (kappa or gamma restricted)

Multiple Myeloma: Signs/Symptoms/Findings

Dx: monoclonal protein spike in SPEP or UPEP, >10% monoclonal plasma in BM, >1 CRAB

Multiple Myeloma: Pathophysiology/Diagnosis

MM prognosis

38.2% 5yr OS if treated, 6mo if not; Chromosome abnormality in 90% of pts

t(4;14)(p16;q32), t(14;16)(q32;q23) and -17p13 (aka p53)

bad prognosis in MM

deletion of 13q14

intermediate prognosis in MM

no cytogenic abnormalities in MM

good prognosis

chemo and biphosphonates

tx for MM bone disease complications

lenalidomide, bortezomib

Multiple Myeloma: Treatment/Notes

before day 100

acute GVHD timing

inflammatory attack by donor T-cells on host organs (gut, liver, skin)

acute GVHD pathogenesis

erythematous maculopaular rash, increased bilirubin, diarrhea

acute GVHD presentation

prevent with cyclosporine +/- MTX, treat with prednisone

acute GVHD tx

after day 100

chronic GVHD timing

defect in immune reconstitution leads to dysregulation, impaired organ function, decreased survival

chronic GVHD pathogenesis

AI symptoms in skin, eyes, gut, mouth, liver, MSK, lungs, GU; scleroderma, skin and deep sclerosis

chronic GVHD presentation

risk of rejection is proportional to

MHC/HLA mismatch

Eugene Heme Oncology Flashcards

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