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oncology Flashcards

1
Q

What are the 4 main cellular processes that are dysregulated in a cancer?

A
  1. Innappropriate proliferation
  2. Resistance to differentiation and apoptosis
  3. Genomic instability
  4. Ability to grow there it shouldn’t
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2
Q

What is a protooncogene?

A

A highly conserved eukaryotic gene, important in cellular growth and development. (Can become oncogene by over/under expression or by mutation)

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3
Q

What are 2 subtypes of protooncogenes?

A
  • Cancer oncogenes- cellular genes involved in development/maintenance of malignant phenotype
  • Viral oncogenes- viral genes which are able to transform genes
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4
Q

What are the 4 main oncogenic mechanisms?

A
  1. Growth factors
  2. Signal transduction
  3. Cell cycle control
  4. Regulation of gene expression
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5
Q

What are tumor suppressor mechanisms (and two important genes!)?

A
  • Genes that are dispensable for normal development, but serve only to prevent transformation (aka malignancy)
  • Two most important are p16 and p53
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6
Q

What is Li-Fraumeni Syndrome?

A
  • A hereditary predisposition to cancer
  • Are born with an abnormal copy of p53 protein (tumors have mutations at both alleles)
  • Often leads to glioblastomas, leukemias, breast, lung, and pancreatic cancers (or Wilm, sarcomas)
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7
Q

Explain the picture below:

A
  • RB block progression into the cell cycle
  • Cyclins clock RB (and allow cell cycle progression)
  • p16 blocks cyclins (and allows RB to block cell cycle)
  • p53 turns on RB and blocks cell cycle progression
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8
Q

Explain the picture below:

A
  • p53 turns on Nova/Bax and causes apoptosis
  • AKT blocks apoptosis
  • PTEN blocks AKT (causes apoptosis)
  • Bcl2 blocks apoptosis
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9
Q

What two things are essential for neoplastic cells to form cancer?

A
  • Maintain ability to “self-renew”
  • Malignant cells cannot die
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10
Q

Can a p53 mutation ever be good?

A

No, this is always associated with bad prognosis of cancer

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11
Q

In order to cause harm, a tumor cell must: (6 steps)

A
  1. Locally invade
  2. Grow into lymphatics or blood vessel
  3. Spread to distant site
  4. Attach to endothelium and leave blood/lymphatic
  5. Grow in new place, destroy normal stroma
  6. Induce new blood vessels
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12
Q

Which two forms of abnormal growth are always pathologic?

A

Dysplasia and neoplasia (can still be benign or malignant however)

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13
Q

What are some causes of physiologic hyperplasia?

A
  • Hormonal (glandular epithelium in breast during puberty)
  • Compensatory (contralateral kidney after nephrectomy)
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14
Q

What is an example of physiologic hypertrophy?

A

Skeletal muscle growth

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15
Q

What are two components of physiologic metaplasia?

A
  • Usually an adaptive response
  • Usually reversible
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16
Q

What are some histological characteristics of dysplasia?

A
  • Variation in size and shape (pleomorphism)
  • Nuclear enlargement
  • Nuclear irregularity
  • Dark staining of nuclei (hyperchromasia)
  • Loss of polarity
  • Loss of maturation
  • Abnormal location of mitotic figures
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17
Q

What is the difference between well and poor differentiation in neoplasia?

A
  • Well= can still tell where the cells came from
  • Poor= can no longer tell where cells came from
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18
Q

What are some histological characteristics of benign neoplasms?

A
  • Usually resembles normal counterpart
  • Well differentiated
  • Low mitotic rate
  • Well circumscribed
  • Do not metastasize
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19
Q

What is a paraneoplastic syndrome?

A

Local tumor secretes factors that give systemic effects

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20
Q

What is the difference between carcinoma and carcinoma in situ neoplasms?

A
  • Carcinoma- invade surrounding tissue, atypical morphology, extend beyond basement membrane
  • Carcinoma in situ- dysplastic changes involving full thickness of epithelium, do not extend beyond basement membrane
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21
Q

What is the difference between sarcoma and carcinoma?

A
  • Sarcoma- arise in mesenchyme (more common in children/teens)
  • Carcinoma- Malignancy of epithelial origin (most common of the solid tumors)
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22
Q

What are some histological characteristics of malignant neoplasms?

A
  • Atypia/ anaplasia/ pleomorphism
  • Poorly circumscribed and invasive border
  • High mitotic rate
  • Metastatases
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23
Q

What is the difference between grade and stage of a tumor?

A
  • Grade= level of differentiation under a microscope (low grade is better prognosis and well differentiated)
  • Stage= extent of the spread (usually on scale of 4, systems are tumor specific)
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24
Q

What are the 6 main hallmarks of cancer (tumor focused)?

A
  • Sustaining proliferative signal
  • Evading growth suppressors
  • Activating invasion and metastasis
  • Enabling replicative immortality
  • Inducing angiogensis
  • Resisting cell death
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25
What are the 4 hallmarks of cancer (related to patient's body)?
* Avoiding immune destruction * Deregulating cellular energetics * Tumor-promoting inflammation * Genome instability and mutation
26
How do people acutally die from cancer?
* **Local effects** (organ failure, hemorrhage) * **Infection** (chemo and surgery) * **VTE** (hypercolaguable state and increase bleeding) * **Systemic effects** (anorexia, cachexia, sarcopenia)
27
When should fine needle aspiration be used (and not be used) for diagnosis of cancer?
* Good for carcinoma * Bad for cancers with complicated structure (lymphoma)
28
How do we decide to treat cancer?
Based on the cell of origin (today)
29
What is the difference between normal, early tumor, and late tumor for cell growth?
* **Normal:** most non-cycling cells (low growth) * **Early:** mostly cycling cells (high growth) * **Late:** necrotic center, many non-cycling (lower growth)
30
What are the most common sites for meastasis of cancers?
* Lung * Liver * Brain * Bone
31
What is the "gompertzian" growth of tumors?
32
What is log cell kill?
Only kill proportion of cells with treatment, not numbers!
33
# Define the following: * Neoadjuvant * Adjuvant * Induction
* **Neoadjuvant**- therapy prior to primary therapy * **Adjuvant**- therapy in addition to primary therapy * **Induction-** initial treatment to cancer, followed by consolidation and maintenance
34
What is an ECOG score?
* A score of the patient's performance * Looks at the effect of cancer vs. comorbidities * Low= fully active (0) * High= near death (4)
35
Which cancers are associated with tumor lysis syndrome?
* Burkitt Lymphoma * T-cell Acute Lymphoblastic Lymphoma * Leads to acute renal failure
36
Which leukemia is associated with the following emergency risks? * Hyperleukocytosis * DIC * Neutropenic fever * SVC syndrome * Respiratory compromise * Tumor lysis syndrome
Acute Lymphoblastic Lymphoma (ALL)
37
What is the difference between good and bad prognosis in ALL?
* **Good:** t(12;21) and hyperdiploidy * **Bad**: t(9;22) and hypodiploidy, age less than 1 or over 10, high WBC (\>50)
38
Which leukemia is most associated with DIC?
* Acute promyelocyte Leukemia (APL, subset of AML) * Due to PML/RARa t(15;17) and HLA-DR negative * Treat with ATRA/arsenic
39
Which leukemia has the presence of Auer Rods?
AML, due to increased myeloperoxidase
40
What is the difference between good and bad prognosis in AML?
* **Good:** t(15;17), t(18;21), inv(16) * **Bad:** deletion of chromosome 5 or 7, prior MDS, MPD, radiation, or chemotherapy
41
Which leukemia is associated with smudge cells, AIHA, and exaggerated response to bug bites?
Chronic Lymphocytic Leukemia (CLL)
42
What are some of the increased risks with CLL?
* Can transform into DLBCL (richter transformation) * Risk of herpes virus and VZV reaction * Leukostasis if WBC \>400 (rare) * AIHA
43
What is the main treatment used for CML and why?
* Abl tyrsoine kinase inhibitor (**imatinib**) * Used to inhibit the tyrosine kinase that is constitutively expressed as a result of BCR/ABL translocation (causing too much proliferation)
44
Which immune markers are associated with: * T cells * Myelocytes * B cells * Stem Cells * Myeloid Cells
* **T cells**- CD 1, 2, 3, 4, 5, 7, 8 * **Myelocytes**- CD13, 14, 15 * **B cells**- CD19, 20, 21, 22, 23 * **Stem Cells**- CD34 * **Myeloid Cells**- CD33
45
Which cancer has a large increase in basophils?
CML
46
Which leukemia often presents as lymphoma due to lymphadenopathy?
CLL (SLL)
47
What are some mutation in AML with normal cytogenetics?
* FLT3 (most frequent and poor prognosis) * NPM1 * RAS * CEBPA
48
What are some unique clinical manifestations in ALL?
* Lymphnode involvement * Mediastinal mass (T-ALL) * CNS involvment * Testicular involvment
49
What does hypodiploid and hyperdiploid mean?
* **Hyperdiploid-** ***more*** than the diploid number of chromosomes (***good*** prognosis in ALL) * **Hypodiploid**- ***less*** than the diploid number of chromosomes (***bad*** prognosis in ALL)
50
What kind of translocation is the Philadelphia chromosome?
* A somatic translocation (during mitosis) * It only causes abnormalities in affected cell line (not all cells of offspring)
51
What are the 3 main causes of lymphadenopathy (differential)?
* Reactive (benign) * Lymphoma (Hodgkin or Non) * Metastatic Disease
52
What causes follicular hyperplasia of lymphnode?
* Proliferation of B lymphocytes * Increased need for antibody production * Causes enlargement of GC (macrophages and mitotic activity) * *Example is strep throat*
53
What causes paracortical hyperplasia of a lymphnode?
* Proliferation of T lymphocytes * Increased need for cell-mediated immunity * Expansion of paracortical regions (increased mitosis and activated lymphocytes) * *Example is infectious mononucleosis*
54
What causes sinus histocytosis in a lymph node?
* Proliferation of macrophages * Stimulation of APC * Expansion of subcapsular/medullary sinuses * *Example is LN draining a carcinoma*
55
What are some of the big Non-Hodgkin lymphoma risk factors?
* Infections (viral) * Medical conditions that compromise immune system * Toxic chemicals * Age * *\*Most patients have no risk factor\**
56
What is the working formulation of Non-Hodgkin's lymphomas?
* **Low grade** (SLL and Follicular lymphoma) * **Intermediate grade** (Diffuse large B cell lymphoma) * **High grade** (Burkitt and lymphoblastic lymphoma)
57
What is the key histological marker of lymphoma in a lymph node?
Loss of architecture!
58
What is the differerence between A and B clinical presentation of lymphoma?
* **_A symptoms_** are due to growth of malignant lymphocytes forming a mass or LAD * **_B symptoms_** are **fevers** (\>38), drenching night **sweats,** or **weight loss** (10% over 6 months)
59
What is the staging of lymphoma?
1. **Single nodal** region or extranodal site 2. **Two or more** nodal regions or extranodal site and regional nodal involvement on same side of diaphragm 3. Lymphatic involvement on **both sides of diaphragm** 4. **Liver or bone marrow** involvement or extensive extralymphatic organ involvement
60
What kind of biopsy should be used for lymph nodes?
* **NEVER** fine need aspirate * Core needle biopsy (okay) * Surgical Excision (**best**)
61
What are the Non-Hodgkin Lymphoma Treatment Principles?
* **Indolent**= observe until symptomatic * **Aggressive**= often curable with chemotherapy
62
What are plasma cell dyscrasias (PCD)?
Diseases associated with monoclonal proliferation of immunoglobulin producing plasma cells (adults) * Multiple Myeloma * Smodering Multiple Myeloma * Monoclonal Gammopathy of Uncertain Significance * Waldenstrom's Macroglobulinemia * Amyloidosis
63
Why does multiple myeloma lead to lytic bone disease?
The plasma cells activate osteoclasts and suppress osteoblasts
64
What are some of the commonly involved bones in MM bone pain?
* Vertebral column * Ribs * Skull * Pelvis * Femurs * Clavicles * Scapulae
65
Which immunoglobulin abnormalities are common in MM?
* **IgG (60%)** * **IgA (25%)** * **Light chains only (10%)**
66
What does CRAB stand for?
* Myleoma Defining Event: * Hyper**c**alcemia * **R**enal Disease * **A**nemia * **B**one Disease
67
What is the classic case presentation of Waldenstrom Macroglobulinemia?
* Headache and blurred vision * Hyperviscosity * Will show IgM monoclonal spike!
68
What organs can be involved in amyloidosis?
* Kidney (most often) * Liver and spleen * GI tract * Heart * Skin * Nervous System * Respiratory System * Blood
69
When should surgery be used for cancer?
For accessible sites (skin, peripheral lung, colon, breast)
70
When should radiation therapy be used for cancer?
* **Organ sparing**: skin, larynx, oropharynx, limbs * **Accessible sites:** skin, peripheral lung, colon, breast
71
What are the benefits of surgery + RT?
* Surgery is used as a local excision to remove gross disease * RT is used for microscopic disease (spares normal/tissue function and less reliant on pathologist)
72
When should RT be used alone, instead of surgery (for cancer)?
* Early head and neck cancer * Cervix cancer * Prostate cancer
73
What therapies should be used for hematologic malignancies?
* Chemo + RT (not surgery) * These are very sensitive to RT!
74
What causes early satiety in cancer?
Splenomegaly! (blocks stomach expansion)
75
What is the main difference between Hodgkin and Non-Hodgkin lymphoma?
* Hodgkin- most spread from LN to LN (lymph) * Non-Hodgkin- Can go anywhere (blood)
76
What can lead to a mediastinal mass (4 Ts)?
* Ectopic **_T_**hyroid * Tumor of **_T_**hymus * **_T_**aratoma (germ cell) * **_T_**errible Lymphoma
77
What are some classic characteristics of enlarged lymphodes (LAD)?
* Not growing and history of infection (post-reactive, **residual**) * Rock hard and fixed (**metastatic** cancer) * Mobile and rubbery (**lymphoma**) * Tender (**infection**) * Supraclavicular nodes are **abnormal** (biopsy)
78
Why are the CNS and testes known as sanctuary sites in ALL?
Because chemotherapy doesn't get here
79
What is associated with a t(14;18) translocation?
* Follicular lymphooma * Heavy chain and BCL2 translocation * Leads to the blockage of apoptosis in germinal center cells (increased BCL2)
80
What is associated with t(11;14) translocation?
* Mantle Cell Lymphoma * Heavy chain and Cyclin D1 translocation * Leads to increased G1/S transition (increased CyclinD)
81
What is associated with chromosome 8 translocations?
* Burkitt's Lymphoma * Heavy chain and c-myc translocation * C-myc promotes cell growth
82
What is associated with TdT+ cells?
* Lymphoblastic Lymphoma (Immature T cells) * Acute Lymphoblastic Leukemia (Immature B cells)
83
What is associated with a t(15;17) translocation?
* Acute Promyelocyte Leukemia (APL) * PML/RARa translocation * Cells stuck as promyelocytes * Treat with ATRA
84
What is associated with t(9;22) translocation?
* CML (and really bad ALL) * Translocation of ABL to consituitively activate tyrosine kinase * Treat with imatinib (TKI)
85
Which cancer has bad prognosis associated with deletion of chromosome 5 or 7?
* Acute Myeloid Leukemia

Hematology Block (4 decks)

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