Exam 3/Lecture 1 Flashcards
(113 cards)
1
Q
- What is a tumor?
- What is neoplasm?
- What is cancer?
- What is benign?
- What is oncology?
A
- Tumor: A swelling of any sort but modern usage equates this term with a neoplastic mass.-> does not tell you if it is benign or mal.
- Neoplasm (from Greek “new growth”): An abnormal mass the growth of which is purposeless, autonomous
- Cancer: Synonymous with malignant neoplasm
- Benign: Not life threatening
-
Oncology (from Greek “mass or tumor”): The study of
neoplasms
2
Q
Tissue of origin: Epithelium
* What is it called when surface epithelium (non-gland) and glandular tissue is benign or malignant?
A
3
Q
A
4
Q
Label and explain
A
5
Q
Label and explain
A
6
Q
What is exophytic and endophytic growth?
A
- Exophytic: projecting above a mucosal lining (into lumen/outward)
- Endophytic: growing inward into a submucosal stroma (into tissue)
7
Q
How do polyps grow?
A
- Polyps can grow as flat or ‘sessile’ structures, single mass
- Polyps can also grow as pedunculated polyps having a stalk
8
Q
What does the stalk contain in polyps?
A
Stalk contains a ‘fibrovascular core’ (red arrow) consisting of fibrous tissue for support and vascular blood supply
9
Q
T/F: Most polyps are benign, but some can become malignant
A
True
10
Q
- What are papillomas?
- What does it consist of?
- What is not found?
A
- Papillomas are outward wart-like growths
- Consist of extensions of epithelial layer into fingerlike projections
- No fibrovascular core as found in polyps ⭐️
11
Q
Clinical-Pathological Features of Neoplasia
A
12
Q
What is the different btwn a benign tumor and malignant tumor?
A
Benign Tumor Capsule vs Malignant Tumor Edge
13
Q
What does benign tumor of salivary gland do?
A
Benign tumor of salivary gland (top) is smooth, regular. It doesn’t destroy neighboring tissue
14
Q
Malignant cancer of palate does what?
A
irregular, destroys local tissues resulting in ulceration and bleeding
15
Q
By destroying neighboring tissues, cancers cause what?
A
ulceration, bleeding and tissue death (necrosis)
16
Q
What does a benign tumor of the breast?
A
Benign tumor of breast (top, red arrow) is smooth, regular. It doesn’t destroy neighboring tissue, may just push against it.
17
Q
What does malignant cancer of breast look like?
A
Malignant cancer of breast (bottom, blue arrow) is irregular, destroys local tissues resulting in ulceration and bleeding that leads to tissue death/necrosis)
18
Q
Benign tumors are _ & _
A
Benign tumors are circumscribed & mobile
19
Q
While malignant cancers invade tissue and metastasize (travel) to distant sites, this is not what?
A
While malignant cancers invade tissue and metastasize (travel) to distant sites, this is not ‘tumor mobility’. If you tried to grab this malignant skin cancer, you would not be able to hold it and ‘wiggle’ it. Therefore, it is not mobile.
20
Q
you would be able to grab hold of this benign skin tumor (bottom) and what? Then the benign tumor is mobile
A
In contrast, you would be able to grab hold of this benign skin tumor and ‘wiggle’ it. Therefore, this benign tumor is mobile.
21
Q
Note that all benign skin moles are what?
A
well circumscribed, uniform and homogenous in appearance & color
22
Q
all malignant skin cancers (melanomas) are what?
A
are irregular in shape, heterogeneous in pattern & color
23
Q
A
24
Q
- Compared to normal cells, malignant breast cancer cells (below) are more what?
- Malignant cells often appear what?
A
- Compared to normal cells, malignant breast cancer cells (below) are more ‘atypical’ in appearance
- Malignant cells often appear heterogeneous (pleomorphic )
25
In support of their enhanced proliferative & metabolic capacities, malignant cells typically present with what?
increased numbers of nucleoli and mitotic figures (metaphase mitotic spindles – bottom right)
26
What are the microscopic features of neoplasia?
*** Nuclear-cytoplasmic ratio**, is relative size of nucleus to cytoplasm (N/C)-> Key to mal cancer cells
* As cells progress from normal to malignant morphology, N/C ratio increases because nucleus enlarges amount of cytoplasm decreases
* NC ratio is a better predictor of malignancy than increased nuclear size
27
What are morphological/proliferative changes with malignant progression
Morphological/proliferative changes with malignant progression Following physiologic stresses, pathologic stimuli or genetic changes cells undergo morphologic changes (adaptive changes):
* Hypertrophy, Atrophy, Hyperplasia, Metaplasia, Dysplasia, Anaplasia
28
What morphological and proliferative changes are reversible and nonreversible?
* Early **hyperplasia, metaplasia and dysplasi**a can be reversible, but in prolonged states can lead to malignant transformation
* **Anaplasia** is not reversible
29
* What is hyperplasia, dysplasia and anaplasia?
* What does it look like in cervical epithelium?
* **Hyperplasia** (potential precursor of dysplastic lesions): organ/tissue enlargement by increased orderly & normal cellular proliferation
* **Dysplasia**: disorderly cellular proliferation with loss of maturation, architectural orientation and polarity, with acquisition of nuclear changes of malignancy
* **Anaplasia**: Loss of structural differentiation, correlates with tumor aggressiveness
* Increased N/C ratio with disease progression
30
Label and explain
31
Label the different tissues of the respiratory tract
32
What is a grade and stage of tumors?
* Level of differentiation, or **grade** (what it looks like histo), and extent of spread of cancer within the patient, or **stage** (anatomically, how it spreads), are parameters of clinical gravity of disease
* Grading of cancer is based on degree of histologic differentiation of tumor cells and, in some cancers, number of mitoses or architectural features
* Grading (I-III) is indicative of tumor aggressiveness/patient prognosis
33
Tumor Grading (Colon Adenocarcinoma)
34
* Cancer >1-2mm3 requires what?
* What is a major player of this?
* Cancer >1-2mm3 requires blood vessel support
* Vascular endothelial growth factor (VEGF) as a major playe
35
With invasion and metastasis for cancer stages, Cell-cell connections are lost by what?
Cell-cell connections are lost by the inactivation of E-cadherin through a variety of pathways
36
What happens to the basement mebrane with Invasion and Metastasis?
Basement membrane and interstitial matrix degradation is mediated by tumor secreted proteases (Matrix metalloproteinases and cathepsin D, and urokinase plasminogen activator).
– **MMP9 Gelatinase (IV collagenase)**
37
What degrades IV collagen
– MMP9 Gelatinase (IV collagenase)
38
Proteolytic enzymes of metastasis also releases what?
Proteolytic enzymes also release growth factors into the ECM that are angiogenic, growth promoting and chemotactic
39
What are the cancer stages?
* **Stage 0**: carcinoma **in situ** (cervical epithelium)
* **Stage 1**: cancer **limited** within organ/tissue of origin (cervix)
* **Stage 2**: **regional spread** of cancer (pelvis)
* **Stage 3**: **greater than regional** anatomical cancer spread (abdomen)
* **Stage 4**: cancer spread to **distant organs** (colon, lung, brain)
40
What is dysplasia and carcinoma in situ?
* **Dysplasia**: disorderly cellular proliferation with loss of maturation, architectural orientation and polarity, with acquisition of nuclear changes of malignancy, basement membrane intact
* **Carcinoma in situ or intraepithelial neoplasia**: neoplastic cells involving the full thickness of an epithelium, **does not invade basement membrane**
41
Officially designated ‘cancer’ when malignant cells do what?
traverse (break through) basement membrane
42
What is Cancer Staging: Progression of Cervical Intraepithelial Neoplasm (CIN)?
* Growth (red) limited to basal layer of normal squamous stratified cervical epithelium
* **CIN1** – mild changes; bottom-third of epithelium, ‘low grade’, not cancer
* **CIN2** – moderate changes; 2/3 of thickness of epithelium, ‘high grade’, not cancer
* **CIN3** – more severe changes, full thickness of epithelium, ‘high grade’, not cancer
* **CIN1-3** all Cervical Intraepithelial Neoplasia (CIN) bz basement membrane intact ‘Carcinoma in situ’ or ‘Intraepithelial neoplasm’ = **Stage 0**
43
T/F: Tumor nomenclature alone is enough to predict tumor biology and behavior
FALSE: It is NOT enough
44
A patient with prostate carcinoma may live several years, but the survival of patients with pancreatic carcinomas is usually measured in what?
Months
45
Molecular defect of similar tumors may not be identical and, thus what needs to happen?
Molecular defect of similar tumors may not be identical and, thus, each tumor must be thought as a potential different disease probably both at the molecular and clinical level
46
Breast cancers begin as ‘_ _ ’ lesions, invade _ to become cancer
Breast cancers begin as **‘in situ’** lesions, invade **bm** to become cancer
47
What is a major conduit for breast cancer metastatic spread?
* Rich lymphatic environment by axillary lymph nodes is major conduit for BC metastatic spread
* Sequential sampling of lymph node chain provides prognostic clinical information about tumor progression
48
In addition to standard staging & grading metrics, what sytem was developed for breast cancer?
TNM staging system
* TNM has now been applied to many other cancer types
49
# Staging of Carcinomas by TNM System
What is staging based on, what is it extent of?
Staging is based on the size of the primary lesion, its extent of spread to regional lymph nodes, and presence or absence of metastases.
50
What is the staging of Carcinomas by TNM System for T
T for size primary tumor
* T0 undetectable tumor or can be in situ
* T1≤20mm
* T2>20mmbut<50mm
* T3>50mm
* T4 extends to chest wall or skin
51
What is the staging of Carcinomas by TNM System for N
N for regional lymph node involvement
* N0 no lymph node involvement
* N1 for ispilateral lymph node level 1
* N2 for ipsilateral lymph node > 1 (more than one)
* N3 for ipsilateral + axilliary lymph nodes (outside of immediate area)
52
What is the staging of Carcinomas by TNM System for M
M for metastases
* M0 cancer within breast tissue
* M1 presence of any metastasis
53
What is the staging system for malignant melanoma?
Given poor prognostic outcome in melanoma with minimal standard stage 1 invasion, ***Breslow score*** related to tumor depth
* < 1mm = 95-100% 5 yr survival
* 1-2 mm = 80-96% 5 yr survival
* 2.1-4mm = 60-75% 5y survival
* > 4mm = 50% 5 yr survival
54
Malignant transformation is driven by what?
by genetic instability that enhances proliferation and survival. Malignant transformation of normal cells overrides both cell cycle and lifespan constraints
* Cells growing out of control and overcome very resistant
* Upreg anything that will help them grow
55
What are some malignant transformations?
* Enhance cellular longevity via **immortalization** (reactivate telomerase activity)
* Upregulate gene expression associated with **cell proliferation** (oncogenes)
* **Abrogate cell cycle checkpoints** (loss of Rb and p53)
* Develop **resistance to apoptosis**
56
Malignant transformation & tumor progression is multi-step process is supported by what?
histologic evidence as premalignant changes with genetic parallels
57
histologic evidence as premalignant changes with genetic parallels capable of proliferating to produce
**Non-cancerous cellular lesions** capable of proliferating to produce cellular progeny which, over generations, have reasonable chance of clonal expansion with properties of malignancy
58
Preneoplastic conditions often have high rate of what?
Often have high rate of regression
59
What are Synonyms of preneoplastic conditions?
pre-cancer, premalignant lesion, intraepithelial neoplasia,
and pre-invasive cancer
60
* Preneoplastic Conditions include what?
* What do they develop from?
* dysplasia, hyperplasia, metaplasia, intraepithelial neoplasia, carcinoma in situ lesions
* Develop from **inherited** (genetic alterations) familial conditions or **acquired** conditions arising frim chronic/repeated inflammation
61
Reducing burden of pre-neoplastic lesions is important for what?
important medical goal toward reduction of cancer morbidity and mortality
62
What is Inherited Preneoplastic lesions: Hereditary Tumor Genes: Retinoblastoma (Rb)?
63
What is Hereditary predisposition: Familial Adenomatous polyposis coli (FAP)
64
What is the germ line mutation associated with in FAP?
Germ line mutation associated with FAP w/thousands of benign polyps developed by teen years-early adulthood with one or more undergoing malignant transformation after second APC mutation.
65
Familial adenomatous polyposis coli: Multistep progression to cancer
* Progression to colon cancer begins with what?
* Following mutation is?
* Patient begins to develop what?
* Progression to colon cancer begins with one inherited dysfunctional APC gene.
* Following mutation that inactivates second copy of APC
* Patient begins to develop polyps that progress with further activation of oncogenes & inactivation of tumor suppressor genes leading to cancer
66
Acquired Preneoplastic Conditions: HPV & Cervical CA
* What is the grading scale?
* CIN1: ≤1/3 thickness
* CIN2: ≥1/3 thickness
* CIN2: full thickness
67
Which HPV is Low grade CIN = CIN1
HPV 6,11, appears as genital warts (doesn’t integrate into host DNA, remains low grade)
68
Which HPV is High grade CIN = CIN2 or CIN3
HPV 16,18 (integrates into host DNA, progresses from low – high grade with additional genetic changes)
69
Officially squamous cell carcinoma (SCCA) when what happens?
basement membrane is breached
70
Acquired Preneoplastic Lesions: Barrett’s esophagus
* Esophagus is lined with _ , stomach is lined with _
* Chronic gastric reflux causes what?
* Initial esophageal adaptive response is what?
* Esophagus is lined with stratified squamous epithelium, stomach is lined with simple columnar epithelia with mucous producing Goblet cells
* **Chronic gastric reflux** causes esophageal injury & inflammation
* Initial esophageal adaptive response is **metaplastic transition** from squamous epithelium to columnar epithelium called **Barrett’s esophagus**
71
What does Barrett's esophagus look like endoscopically?
As viewed endoscopically, chronic irritation & inflammation of the esophagus leads to Barrett’s esophagus which, if left untreated, can progress from metaplasia to malignancy
72
0.5% patients with GERD develop what?
esophageal cancer with overall esophageal cancer risk 1:417 women & 1:125 men
73
Acquired Preneoplastic Conditions: Chronic Inflammation & Gastric Adenocarcinoma
* What is a bacteria that induces gastric cancers?
* What is the percentage of people that get cancer?
Helicobacter pylori-induced gastric cancers
* Immunologically mediated chronic inflammation
* Production of reactive oxygen species that damage gastric epithelial cell DNA
3% of long term infected patients
74
What is the process to gastric adenocarcinoma?
Infection->chronic gastritis->gastric atrophy->intestinal metaplasia of the lining cells->dysplasia->gastric adenocarcinoma
75
Cancer Detection/Diagnosis:
* Physical examination can do what?
* Imaging modalities can do what?
* What are other ones?
* **Physical examination** can identify palpable masses
* **Imaging** modalities can determine size, shape & construction of mass
* Tissue retrieval & **histologic examination**
* Serum & tissue **biomarkers** for cancer
76
Cancer Detection/Diagnosis is good for what?
* Early detection
* Diagnosis, staging & grading of cancer
* Assessing the effectiveness of treatment
* Checking for recurrence
77
What is the process or steps in cancer diagnosis?
* Physical examination
* Goal is early disease detection
* Check for lumps, physical changes, discharges, tenderness
* Breast examination, pelvic examination, digital rectal exam (DRE)
78
* DRE test for who?
* Allows what?
* Not all regions can be what?
* DRE test for both men and women
* Allows palpation of lower rectum, pelvis for masses/cancer including prostate cancer in men
* Not all regions of prostate can be palpated
79
* What is the PAP test?
* What is done?
* Abnormal findings are what?
* Papanicolaou test is a method of cervical screening used to detect potentially precancerous or cancerous cervical lesions
* Scraping of cervical cells examined for abnormal morphology
* Abnormal findings are followed up by biopsy collection and, if warranted, interventions that aim to prevent cancer
80
What are imaging modalities? (5)
* Radiographs
* Sonography (ultrasound)
* Computed tomography (CT)
* Magnetic resonance imaging (MRI)
* Positron emission tomography (PET)
81
What are radiographs? What is an example?
Conventional Film Images: tell dense v non-dense tissue (ex. dense tissue bone)
* Mammography uses low-energy X-rays to examine the human breast for diagnosis and screening. The goal is the early detection of breast cancer, typically through detection of characteristic masses or microcalcifications.
82
* What is sonography?
* Hyperechoic, hypoechonic, Isoechoic?
Ultrasound can distinguish between solid and hollow structures
* **Hyperechoic** – more echogenic (brighter) than normal tissue, solid mass (denser)
* **Hypoechoic** – less echogenic (darker) than normal tissue, fluid-filled (empty)
* **Isoechoic** – the same echogenicity as another tissue
| tell you hollow or solid
83
* What is a doppler ultrasound?
* What do the different colors mean?
* Uses high-frequency sound waves to measure amount of blood **flow** through arteries and veins
* Red: blood flow towards transducer
* Blue: blood flow away from transducer
* Non-invasive
84
What is Computerized Axial Tomography (CT)?
* Shows cross-sections of body that can be reconstituted into a 3D image
* Thin X-ray beam of radiation coming from different angles
* Detector system measures intensity of radiation and assigns various shades of gray ( CT numbers) to different structures
* Greater contrast between types of tissues is achieved with oral or intravenous contrast dye
| gives you degree of vol, width, depth of tumor
85
What is more sensitive for visualization of soft tissue compared to standard X-ray
CT
86
What is Magnetic Resonance Imaging (MRI)
* Magnetic forces cause hydrogen atoms in body to line up in one direction
* MRI machine emits burst of radio- frequency waves
* Waves cause hydrogen atoms to change their alignment
* When radio waves cease, hydrogen atoms return to their original position
* Positional changes are calculated & converted into 2- or 3-dimentional images
87
What is the MRI improved?
Improved resolution over CT, contrast materials can be injected through a vein to improve the quality
88
* PET images demonstrates what?
* A radiopharmaceutical glucose derivative, such as what is used?
* What is measured by PET scanner?
* PET images demonstrate **metabolic activity** of organs and other tissues such as tumors
* A radiopharmaceutical glucose derivative, such as **FDG** (18fluoro-2-deoxyglucose) is taken up by rapidly dividing cells
* Radioactive emissions are measured by a PET scanner
89
* The PET scan is Based on principle that most cancer cells are what?
* What can it visualize?
* Caveat is what?
* Based on principle that most cancer cells are rapidly dividing, highly metabolic, glucose dependent cells
* Can visualize **primary cancers, lymph node involvement**
* Caveat is highly metabolically active normal cells also take up labeled glucose
90
Laboratory Diagnosis of Cancer is used for what? What are examples?
91
What is H and E stain? What do they stain for?
* H & E = hematoxylin and eosin-> Standard histological staining method
* Hematoxylin is a basic dye, stains basophilic moieties purple
* DNA & RNA are negatively charged, have an affinity for basic dyes (basophilic)
* Eosin is an acidic dye, stains acidophilic moieties pink
* Positively-charged structures are acidophilic
* Mitochondria, many cytoplasmic constituents, proteins are acidophilic
92
* Immunohistochemical staining is a tool used in what?
* Technique is based on what?
* How does it work? Give example
* Immunohistochemical staining is a tool used in the identification of a wide variety of cell products/antigens (usually proteins)
* Technique is based on formation of antibody- antigen complexes
* **Specific antibodies** are labeled so that they can be seen after attachment to cellular antigens
* Example: testing breast cancer cells for Her2/neu receptor positivity
93
How is immunohistochemistry used to determine cancer type
Intermediate filament profile:
* Keratins = epithelia = carcinoma
* Vimentin = connective tissue (fibroblasts) = sarcoma
* Desmin = muscle
* Neurofilaments = neurons
94
Label and what are their outcomes?
95
Serum biomarkers: Prostate Specific Antigen
* Who is screened?
* PSA is secreted by?
* PSA is what?
* What are levels?
* Older men are screened for serum PSA levels for both diagnostic & prognostic outcome
* PSA is secreted by prostatic epithelial cells in small amounts into semen
* PSA is a serine protease, has a serum half life of 2-3 days
* PSA levels greater than 4.0 ng/ml are considered abnormal
* PSA levels > 10 ng/ml highly predictive of prostate cancer
96
PSA expression is limited to what?
PSA lacks what?
* PSA expression is limited to **prostate**
* PSA as a cancer biomarker **lacks specificity & sensitivity** – imperfect biomarker
* **Specificity** – is PSA elevated only in prostate cancer – leads to false positives (BPH)
* **Sensitivity** – is PSA elevated in 100% of all prostate cancers – leads to false negatives because some men are PSA-negative with prostate cancer
97
What can lead to increase PSA levels?
* BPH & prostatic infarcts can increase PSA levels
98
How do we do molecular dianosis?
* Molecular analyses by karyotyping can identify large chromosomal aberrations (insertions, deletions, translocations)
* Molecular analyses by DNA nucleotide sequencing can identify single, multiple DNA nucleotide insertions, deletions
99
* Following definitive cancer diagnosis, options include:
No further treatment
* Benign disease or excessive co-morbidities
No additional treatment other than to continue to monitor disease
* Early stage, slow-growing prostate cancer
Surgical debulking
* Reduce tumor burden, production of ascites, improve systemic function
Adjuvant chemotherapy or radiation therapy
* Presence of invasive disease
* Potential for residual disease
* Potential for (micro) metastatic disease
100
What does it mean the establish clean surgical margins?
* Goal during surgery is to remove all cancer tissue along with a rim of normal tissue around it
* During or after surgery, pathological examination of edge of tissue removed (surgical margin or margin of resection) for presence of cancer cells
101
Absence/presence cancer cells influences decisions about treatments such as what?
additional surgery and chemotherapy/radiation
102
# ```
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Surgical margins are reported as what? (3)
* **Clear** (Negative or Clean): No cancer cells are seen at edge of resected tissue. With clear margins, usually no additional surgery is needed.
* **Positive**: Cancer cells found at edge of removed tissue. More surgery is needed.
* **Close**: Cancer cells are close to the edge of the tissue, but not right at the edge. More surgery may be needed.
103
Chemotherapy:
* Therapy considered for any patient with what?
* Therapy when there can be what?
* Considerations for chemotherapy?
* Standard chemotherapy targets what?
* Therapy considered for any patient with invasive cancer on theory that there can be hematologic spread of **micro-metastatic disease**
* Therapy when there can be **disease recurrence**
* Considerations for chemotherapy: Patient age & medical history, response/toxicity to previous therapy, available regimens
* Standard chemotherapy **targets rapidly dividing (cancer) cells** (not specific)
104
Non-specifically target rapidly dividing cells in chemotherapy like?
(clinical complications include hair loss, nausea, neurotoxicity)
105
What does chemotherapy do to DNA? What does the lead to?
* Introduces lesions/mutations into DNA that stall DNA polymerase
* Sufficient DNA damage is irreparable & leads to apoptosis
106
Chemotherapy often evokes multi-mechanistic drug resistance. Explain
107
What are g lobal mechanisms of drug resistance:
108
Chemotherapy suffers from what?
Lack of target specificity:
* most chemo target all rapidly dividing cells leading to bystander death- GI epi and hair follicle epi
Drug Toxicity:
* Accumulation of drug causes toxicity in liver, nephrotoxicity, neurotoxicity
109
What are paraneoplastic syndromes?
* Are rare disorders
* Can occur in background of any cancer type, but most commonly in cancers of lung, breast, prostate, blood, thyroid and gynecological cancers
* Male and female cancer patients are affected
110
# Paraneoplastic syndromes
Malignant cells generate altered immune system producing what?
Malignant cells generate altered immune system producing autoantibodies or cancer cells directly/indirectly produce cytokines, hormones, peptides
111
* What are the two types of paraneoplastic syndromes?
* What do they produce?
* Type/degree of paraneoplastic manifestations is not directly related to what?
* Are immune & non-immune mediated (immune > non-immune)
* Produce heterogeneous clinical symptoms, affecting many organs
* Type/degree of paraneoplastic manifestations is not directly related to cancer stage, grade or prognostic outcome
112
Immune-based paraneoplastic syndromes is what?
113
Non-immune-based paraneoplastic syndromes is what?
