Onc Exam Flashcards

Question

When might you see hypercalcemia in cancer?

Answer 1

PTHrP in non small cell lung cancer

Answer 2

ACTH in small cell lung cancer

Answer 3

small cell lung cancer

Answer 4

blood and bone marrow

Answer 5

lymph nodes

Answer 6

radiation exposure | trisomy 21

Answer 7

Acute complications of cytopenias (bleeding, infection, fatigue, dyspnea, dizziness) Fever Bone pain (bone marrow expands as leukemia grows) Lymphadenopathy is rare

Answer 8

``` Very big WBCs: Large redundant lymphocytes Open chromatin Prominent nucleoli Light purple cytoplasm No granules ```

Answer 9

``` Signs of anemia Ecchymosis, petechiae Lymphadenopathy Splenomegaly Rash ```

Answer 10

Bone marrow tests: 1. Core biopsy 2. Flow cytometry 3. Aspirate slides 4. Cytogenetics

Answer 11

Flow Cytometry: identification of cell surface proteins with fluorescence-labeled antibodies. CD19 is particularly looked for

Answer 12

mediastinal mass

Answer 13

directly toxic to lymphocytes (induce apoptosis)

Answer 14

Inhibits microtubule polymerization

Answer 15

Inhibits topoisomerase II

Answer 16

alkylating agent - induces bulky DNA lesions

Answer 17

Depletes asparagine

Answer 18

Folate antagonist

Answer 19

1. DIC (PT up, aPTT up, fibrinogen down, d-dimer up, platelets down) Treat with cryoprecipitate 2. Tumor lysis syndrome Treat with allopurinol and rasburicase

Answer 20

Being an adult, particularly 60+ years old Adverse cytogenetics B-cell phenotype Presence of minimal residual disease

Answer 21

t(9;22): Philadelphia chromosome (BAD) t(4;11): bad hyperdiploidy: good

Answer 22

Widespread acceptance in young patients with adverse cytogenetics in first remission. Standard treatment for relapsed ALL in young patients. Important factors in other scenarios: - Patient age - Presence of HLA-matched sibling

Answer 23

Molecular minimal residual disease (MRD) is the percentage of residual leukemia cells in the bone marrow, and determines risk of relapse.

Answer 24

Most common form of leukemia Only form of leukemia without increased incidence in atomic bomb survivors. A disease of the elderly.

Answer 25

``` •Small redundant lymphocytes (nucleus is about the size of an erythrocyte) •Clumped chromatin •Absent nucleoli •Light purple cytoplasm Much smaller than ALL lymphoblasts Sometimes see smudge cells ```

Answer 26

Asymptomatic lymphocytosis Lymphadenopathy is common Complications of cytopenias (recurrent sino-pulmonary infections, gradual fatigue, dyspnea, dizziness) Chronic weight loss

Answer 27

``` Stage 0: Monoclonal lymphocytosis 6,000+/μL Stage 1: Lymphadenopathy Stage 2: Hepatosplenomegaly Stage 3: Hemoglobin less than 11 g/dL Stage 4: Platelets less than 100,000 ```

Answer 28

``` Immune Thrombocytopenic Purpura (ITP) Autoimmune Hemolytic Anemia (AIHA) Hypogammaglobulinemia Pure red cell aplasia (PRCA) Other auto-immune diseases ```

Answer 29

``` Stage 3/4 CLL Rapid Lymphocyte Doubling Time Symptomatic Lymphadenopathy Fevers, Night Sweats, Weight Loss Transformation to High-grade Lymphoma ```

Answer 30

Allogeneic transplant is the only cure for CLL but carries a high mortality rate (treatment may be worse than disease in some cases).

Answer 31

``` Symptoms •Fatigue •Bruising/bleeding •Dyspnea •Fever •Bone pain Signs •Pallor •Hemorrhage •Ecchymoses, petechiae •Infection •Hepatosplenomegaly •Skin or gum infiltration ```

Answer 32

Expansion of lymph nodes - Enlargement of lymph nodes, spleen - Superior Vena Cava (SVC) syndrome (compression of VC, leading to swelling of face and lower extremities) - CSF involvement Cytopenias (infections, anemia, bleeding, petechiae)

Answer 33

fever weight loss pruritus

Answer 34

``` Excisional or Core Biopsy of hottest node –Histologic examination –Immunohistochemistry phenotype –Cytogenetics –Molecular tests (FISH, PCR) ```

Answer 35

It's kind of complicated, but ultimately it does not have a lot of prognostic value

Answer 36

``` Most common Lymphoma: Can arise anywhere in the body •Morphology –Large cell size (4-5x a normal lymphocyte) –Diffuse growth pattern •Immunohistochemistry –(+)CD19 CD20 ```

Answer 37

1. germinal center (GC) type: mutations lead to a repressed transcriptional state 2. activated b-cell (ABC) type: mutations in the b cell receptor pathway lead to unchecked activation of NFkB

Answer 38

1. enter the lymph node as naive B cell 2. upregulated in germinal center, allowing for somatic hypermutation 3. In normal B cell, factors are then downregulated; instead, EZH2 and Bcl6/2 are mutated and upregulated 4. GC-derived lymphoid neoplasm

Answer 39

``` RCHOP - Rituximab - Cytoxan - Doxorubicin - Vincristine - Prednisone + growth factor support + antibiotic prophylaxis in the elderly ```

Answer 40

- Monoclonal Antibody to CD20 - Human-Mouse Chimera - Allergic reactions can occur (especially with first dose): pretreat with Tylenol/Benadryl –Tumor Lysis when Malignant Lymphocytes 25,000+

Answer 41

1. Immuno-deficiency associated (HIV, post-allo transplant, EBV) 2. Primary effusion lymphoma (HIV, elderly, KSHV/HHV-8) 3. Double hit lymphoma (typically seen in the elderly; poor prognosis) 4. Double protein lymphoma: poor prognosis

Answer 42

``` •Probably more like Hodgkin's than DLBCL –CD30+, CD20+, nuckeal c-rel, TRAF-1 •Female Young Adults •Large mediastinal mass –SVC syndrome, thrombosis common ```

Answer 43

1. HIV associated 2. African endemic (mostly children, mass involving mandible, abdominal viscera, kidneys, ovaries, adrenals) 3. Sporadic (most common lymphoma in children; associated with t(8;14)

Answer 44

Rapid enlargement of lymphadenopathy (DAYS) All subtypes driven by c-MYC translocation Often associated with EBV all have Starry Sky appearance on histopath Aggressive, but respond well to chemo

Answer 45

"Starry Sky" –Effaced by diffuse infiltrate –Intermediate size round or oval nuclei –High mitotic index and numerous apoptotic cells –Nuclear remnants are phagocytosed by benign macrophages

Answer 46

``` Clinical Picture: •Painless, generalized lymphadenopathy •Incurable, median survival 7-9 years •Indolent waxing and waning course •Bone marrow involvement in 85% •Histologic transformation in 30-50% ``` ``` •Immunophenotype: –(+) Bcl2 –(+) CD19, CD20, CD10, Bcl6 –(-) CD5 Bcl2 ```

Answer 47

* Watch and wait * Rituxan-based therapy * CHOP or CVP * Bendamustine * Purine analogue/Alkylating Agent hybrid * Cytopenias * XRT for stage I disease

Answer 48

–nodular pattern –small cells with irregular or cleaved nuclear contours –Grade depending on # of large cells: 1-2, 3a, 3b

Answer 49

Blastic Aggressive Indolent Leukemic (indolent, behaves like CLL)

Answer 50

``` •Treatment guided by variant –Aggressive chemotherapy and transplant –Bendamustine –Bortezomib –Ibrutinib and Idelalisib in relapsed setting –Watch and Wait when indolent ```

Answer 51

``` AML •Younger patients •Extramedullary disease •Favorable prognosis •Fusion of RUNX1 and RUNX1T1 genes ```

Answer 52

Mechanism of action •Converted to its active form, aracytidine triphosphate (ara-CTP) •Incorporated into DNA, causing strand termination •Inhibits DNA and RNA polymerase. Metabolism •Metabolized in the liver to inactive uracil arabinoside •Excreted in the urine •Often administered by continuous intravenous infusion because of its short half-life

Answer 53

* Gastrointestinal: inflammation of mucous membranes, sometimes with ulceration and diarrhea * Bone marrow suppression: leukopenia, thrombocytopenia and anemia

Answer 54

Mechanism of action •Intercalation into DNA, thereby impairing transcription •Topoisomerase II inhibition •Generation of free oxygen radicals Metabolism •Metabolized in the liver •Dose must be adjusted when patients have significant hepatic dysfunction.

Answer 55

* Gastrointestinal side-effects: nausea and vomiting, inflammation of the mucous membranes, diarrhea * Bone marrow suppression * Alopecia * Cardiac toxicity

Answer 56

* Age 80+ years * ECOG 2+ (poor functional status) * Complex karyotype * Creatinine 1.3+ mg/dl

Answer 57

Acute Promyelocytic Leukemia (APL) •10% of AML •Presents with bleeding diathesis •Characterized by t(15;17), resulting in PML/RAR-alpha fusion transcript •Responds to retinoic acid and arsenic trioxide

Answer 58

•Occurs in 30% of patients during induction •Often associated with leukocytosis •Requires prompt intervention •Begin dexamethasone 10 mg intravenously twice daily ̶Continue for at least 3 days •Can be fatal if treatment is delayed Early symptoms include fever, dyspnea, and weight gain; late symptoms are pulmonary infiltrates and pleural and pericardial effusions

Answer 59

Myelodysplastic Syndrome (MDS) •Heterogeneous clonal neoplastic bone marrow disorder that results in bone marrow failure due to ineffective hematopoiesis •Associated with increased risk of progression to AML •Marked by: −Increased proliferation −Increased apoptosis

Answer 60

``` •Isolated deletion of chromosome 5q •Female predominance •Characterized mainly by anemia −Thrombocytosis is common −Neutropenia is mild •Low rate of progression to AML ```

Answer 61

EPO | or EPO+G-CSF or darbepoetin

Answer 62

If possible, allo transplant If not + dz is stable, supportive care and investigational therapy with low toxicity If not possible + dz is progressing, try lenalidomide, azacitidine, decitabine, or AML induction In 5q syndrome, use lenalidomide

Answer 63

umbilical cord blood bone marrow peripheral blood

Answer 64

Stem cells (defined by expression of CD34+) collected peripherally using apheresis (cell separator machine) •Less invasive; less discomfort; less morbidity than BM Outpatient procedure PBSCT results in more rapid hematopoietic recovery than BM No difference in treatment outcome –Using cytokine stimulation (G-CSF injections) – BM releases large number CD34 stem cells into circulation –Stem cells harvested via peripheral line

Answer 65

alterations that increase the rate of cell division (c-myc activation, inactivation of Rb) alterations that decrease genomic stability (p53, inactivation of mismatch repair genes)

Answer 66

proto-oncogene that leads to cell division | typically activated by gene translocation

Answer 67

Proto-oncogenes promote cancer when malignantly activated –An activated proto-oncogene contributes to tumorigenesis by "gain-of-function" –Thus, an activated proto-oncogene is genetically dominant at the cellular level •an activated oncogene can elicit a new phenotype (tumorigenesis) even in the presence of the corresponding wildtype allele

Answer 68

Tumor suppressor genes promote cancer when malignantly inactivated –A tumor suppressor contributes to tumorigenesis by "loss-of-function" –In most instances, an inactivated tumor suppressor gene is genetically recessive at the cellular level. •it will not promote tumorigenesis in diploid cells unless the other (wildtype) allele is also lost or inactivated •some exceptions: –dominant-negative p53 mutations –“haploinsufficient” tumor suppressor genes

Answer 69

Less than 10%

Answer 70

Heritable has earlier onset (2 years vs 6 years) | Heritable typically affects both eyes (while sporadic is often 1 tumor)

Answer 71

Mendelian dominant

Answer 72

Everyone! Heavily penetrant

Answer 73

Always develop retinoblastoma | Sometimes develop osteosarcoma (low penentrance)

Answer 74

•hypophosphorylated Rb serves to restrain the proliferation of normal cells. •regulated phosphorylation of Rb allows normal cells to proliferate at the correct time and place. Inactivation of the Rb pathway occurs in most, if not all, human tumors tumor suppressor gene

Answer 75

They are dominant negative (aka dominant tumor suppressor)

Answer 76

induces G1 arrest induces apoptosis in thymocytes replication of damaged DNA ceases inactivation of p53 occurs in most human tumors

Answer 77

Usually small well-circumscribed Closely resembles tissue of origin Does not invad

Answer 78

all different sizes poorly circumscribed range from well to poorly differentiated capable of invasion and metastasis

Answer 79

1. high N:C ratio 2. nuclear hyperchromatism 3. prominent nucleoli 4. nuclear pleomorphism 5. high mitotic rate

Answer 80

as malignant tumors grow, the neoplastic cells incite a local fibroblastic response in the primary site as it invades, as well as in the DISTANT site of metastasis. The tissue attempts to “contain” the tumor growth at these sites

Answer 81

breast, prostate, renal cell ca

Answer 82

``` Virchow's node (supraclavicular node) Krukenberg tumor (bilateral ovarian mets) ```

Answer 83

Multiple myeloma (MM) is characterized by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. These plasma cells can damage bones, kidneys and hematopoiesis.

Answer 84

B lymphocyte | Produces antibodies

Answer 85

fried egg appearance, Clock face chromatin and intracytoplasmic inclusions containing immunoglobin

Answer 86

cytoplasm filled with Russel bodies looks like a bunch of grapes Not diagnostic for multiple myeloma, but may be seen

Answer 87

Heavy chain is the bottom of the T, light chain is the top | variable region on the ends

Answer 88

IgM and IgG

Answer 89

2x more common in African American AA>white>Asian More men than women (not hugely more frequent) median age is 65 years old

Answer 90

* Anemia - 73 percent * Bone pain - 58 percent * Elevated creatinine - 48 percent * Hypercalcemia- 28 percent * Fatigue/generalized weakness - 32 percent * Weight loss - 24 percent, one-half of whom had lost 9+ kg

Answer 91

1. bone marrow histology 2. monoclonal immunoglobulins in serum and urine 3. x-ray, CT (up to 80% of patients will have bone involvement)

Answer 92

MCRAB •Anemia (hemoglobin <10 g/dL or 2 g/dL below normal) •Hypercalcemia (serum calcium >11.5 mg/dL) •Renal insufficiency (serum creatinine>2 mg/dL) •Lytic bone lesions or severe osteopenia •Extramedullary plasmacytoma

Answer 93

multiple myeloma

Answer 94

1. Proteosome inhibitors increase risk of shingles Need to prescribe acyclovir as prophylaxis along with treatment 2. Thalidomide and lenalidomide increase risk of DVTs - need thromboprophylaxis

Answer 95

Increases osteoclasts | Decreases osteoblasts

Answer 96

Osteoclast inhibition | Used in multiple myeloma

Answer 97

Less than 10% plasma cells in bone marrow No end-organ damage 1% risk per year of conversion to multiple myeloma

Answer 98

10-60% plasma cells in bone marrow No end-organ damage 10% risk of conversion to multiple myeloma

Answer 99

Extra-nodal Marginal Zone Lymphoma

Answer 100

``` •Waldenstrӧm’s macroglobulinemia –Secrete IgM •Hyperviscosity •Visual Impairment •Neurologic problems •Bleeding •Cryoglobulinemia •Morphology –Plasmacytoid –PAS staining Ig inclusions=Russell and Dutcher bodies ```

Answer 101

mantle zone | CLL/SLL

Answer 102

follicular

Answer 103

follicular | CLL/SLL

Answer 104

mantle zone

Answer 105

lymphoplasmacytic lymphoma

Answer 106

``` Median age 45-55 Symptoms: •Fatigue •Abdominal fullness •Fever, chills, sweats, weight loss Physical Findings: •Hepatosplenomegaly •Ecchymoses Common Laboratory Findings: •Increased mature and immature myeloid cells •Basophilia •Anemia •Thrombocytosis ```

Answer 107

predominance of mature myeloid cells | + some immature progenitors

Answer 108

Hypercellular (less fat) | Increased myeloid:erythroid ratio

Answer 109

BCR-ABL | Philadelphia chromosome

Answer 110

``` chronic phase (4-6 years) accelerated phase (variable) blast crisis (median survival 3-6 months) ```

Answer 111

Imatinib | allogenic stem cell transplant

Answer 112

Imatinib sits in the ATP binding site of ABL (and c-kit) and prevents the transfer of phosphate groups to other proteins, hence blocking downstream signaling. Metabolized by CYP450

Answer 113

bone marrow suppression (leukopenia, anemia, thrombocytopenia) GI (nausea, vomiting, diarrhea)

Answer 114

Development of new mutation | Increase in BCR-ABL gene copy number

Answer 115

CML Ph+ ALL c-kit disease (GIST)

Answer 116

•Elevated HGB/HCT on laboratory testing •Thrombosis •Symptoms: –Pruritus (itching)-especially after showering –Plethora (ruddy complexion) –Abdominal fullness/early satiety (splenomegaly)

Answer 117

JAK2 V617F

Answer 118

``` •Moderate to marked hypercellularity •Increased hematopoiesis –Maturation intact –Large clustered megakaryocytes •Decreased / absent iron stores •Increased reticulin fibers in minority of cases ```

Answer 119

1. Hgb 16.5+ g/dL in men or 16.0+ g/dL in women or HCT 49+% in men or 48+% in women or increased red cell mass 2. Bone marrow biopsy showing hypercellularity for age with panmyelosis with pleomorphic mature megakaryocytes 3. Presence of Jak2V617F or Jak2 exon 12 mutation Minor Criterion: Low serum erythropoietin, Endogenous erythroid colony formation in vitro Diagnosis requires either all major criteria or Major Criteria 1 and 2 and minor criterion

Answer 120

•Chronic Hypoxia (Altitude, cigarettes, sleep apnea, pulmonary disease) •Erythropoietin abuse •Familial erythrocytosis –Mutation in Epo R

Answer 121

``` Overall mortality 3% per year –Thrombosis •Increased by age 65+ and prior thrombosis –Bleeding –Transformation to AML •Influenced by duration of disease –Myelofibrosis (“Spent Phase”) •More common in age 70+ ```

Answer 122

•Therapeutic phlebotomy to maintain hct under 45, but avoiding iron deficiency •Low dose aspirin (unless contraindicated) •Aggressive management of reversible thrombotic risk factors (e.g. smoking, HTN) •Consider cytoreduction if –Patient is intolerant of phlebotomy –Thrombocytosis develops –Symptomatic or progressive splenomegaly •Choice of cytoreductive therapy –Less than age 40: interferon alfa –More than age 40: hydroxyurea

Answer 123

•Elevated platelets on laboratory testing •Thrombosis •Symptoms: –Pruritus (itching)-especially after showering –Erythromelalgia (severe pain in hands/feet) –Abdominal fullness/early satiety (splenomegaly)

Answer 124

Jak2 V617F mutation found in 50% of patients with essential thrombocytosis Allele burden may explain difference between PV and ET 5% of ET patients have mpl point mutations

Answer 125

Major Criteria 1. Sustained platelet count 450,000+/mcl for at least 2 months 2. Bone marrow showing primarily megakaryocytic proliferation and panmyelosis with very rarely minor increase in reticulin fibers (grade 1) 3. No evidence of WHO diagnosis of polycythemia vera, primary myelofibrosis, CML (bcr-abl translocation), MDS or other myeloid neoplasms 4. Jak2, CALR or MPL Minor Criterion Presence other clonal marker OR in the absence of a clonal marker, no evidence of reactive thrombocytosis All 4 major criteria need to be present or major criteria 1-3 and minor criterion for the diagnosis

Answer 126

•Uncertain if ET compromises life span •Thrombosis –Higher in patients over age 60, with a previous history of thrombosis, cardiovascular risk factors, JAK2V617F mutation •Bleeding-Higher in patients with plt 1,500,000+/mcl •Myelofibrosis (4-8% at 10 years) •AML (1% in untreated patients)

Answer 127

•All patients: Aggressive management of cardiovascular risk factors •Low risk: (Age <60, no high risk features) –Low dose aspirin •High risk (Age >60, prior thrombosis, cardiovascular risk factors) –Low dose aspirin plus hydroxyurea –Consider anagrelide or interferon alfa if hydroxyurea intolerant

Answer 128

``` •Splenomegaly –Due to extramedullary hematopoiesis –Abdominal fullness •Symptoms of anemia –Fatigue, pallor, dyspnea on exertion •Bleeding/bruising •Infection •Cachexia ```

Answer 129

``` Teardrop RBCs leukoerythroblastic features (blood looks like marrow) ```

Answer 130

•Hypercellular; Megakaryocytic hyperplasia •Pleomorphism of megakaryocytes •Granulocytic / erythroid maturation intact •Fibrotic phase - loss of hematopoiesis –Megakaryocytes spared •Osteosclerosis –Increased osteoclasts and osteoblasts

Answer 131

Variable life expectancy (months to decades) | Progression to AML in 10-15%

Answer 132

``` •Supportive Measures –Erythropoietin/transfusions –Hydroxyurea to control SBC –Splenectomy/splenic radiation •Active Therapy –Stem cell transplant –Thalidomide/Corticosteroids –Jak inhibitors ```

Answer 133

* Rare – make up 5-10% of lymphomas in US * More common in Asia * No standard treatment regimens * Range from indolent to highly aggressive * Generally worse prognosis than their B-cell counter parts

Answer 134

``` •Waste-basket diagnosis •Often present with rash •Uniformly poor prognosis •No standard treatment regimens •Morphology & Immunohistochemistry: – TCR rearrangements –Loss of T-cell surface markers –No specific cytogenetic abnormalities ```

Answer 135

type of T cell lymphoma ALK + patients are younger with better prognosis ALK - patients are older with worse prognosis Both are CD30+ and show horseshoe-shaped nuclei

Answer 136

``` Cutaneous T cell lymphoma •Indolent lymphoma –Delayed diagnosis –History of eczema •Skin lesions can progress –patch-plaque stage –Tumor –Lymph node involvement –Sezary Syndrome •Systemic involvement •Peripheral blood findings ```

Answer 137

``` –topical glucocorticoids –XRT –PUVA –Topical chemotherapy –Phototherapy –Photopheresis –Retinoids –HDAC inhibitors –Chemotherapy –Transplant ```

Answer 138

``` •Driven by HTLV-1 •Transmitted by breastfeeding, blood transfusions, needle sharing and sexual intercourse. •Long latency of 10-30 years. •Morphology: Flower Cell •Immunohistochemistry: –TAX (+) –+CD4, +CD25, occasionally +CD30 Very aggressive ```

Answer 139

flower cell

Answer 140

lymphadenopathy rash hypercalcemia CNS involvement

Answer 141

``` very potent potent antimicrotubule agent protease-cleavable linker anti-CD30 monoclonal antibody ADC binds to CD30 MMAE disrupts microtubule network ADC-CD30 complex traffics to lysosome MMAE is released Apoptosis G2/M cell cycle arrest ```

Answer 142

hodgkin lymphoma | systemic anaplastic large cell lymphoma

Answer 143

Lymphoid neoplasm defined by presence of Reed-Sternberg cells CD30+ spreads in a contiguous pattern

Answer 144

``` •Large mediastinal mass •B-symptoms: –Pruritis –Pel Ebstein fevers –Painful nodes with alcohol consumption ```

Answer 145

``` ABVD every 2 weeks •Adriamycin •Bleomycin •Vinblastine •Dacarbazine First need to evaluate Cardiac and Lung function –ECHO –PFTs with DLCO Number of cycles given depends partly on the stage and Prognosis Score –Patients may get 2-6 cycles •Highly Emetogenic •Not all patients lose their hair Radiation also used Can also use stem cell transplant in refractory cases ```

Answer 146

brentuximab | nivolumab (anti-PD1)

Onc Exam Flashcards

(175 cards)