Gen Path Exam 2 - Neoplasia Flashcards
New growth
Neoplasia
Loss of normal growth control; cells start doing their own thing, “transformed”
Neoplasia
Parasitic and autonomous qualities
Neoplasia
Study of neoplasms (tumors)
Oncology
What is the spectrum of neoplasia?
Benign -> locally aggressive -> intermediate malignant -> malignant
What are the 2 anatomic components of tumors?
Parenchyma
Stroma
Neoplastic cells; determines how a tumor is named
Parenchyma
Supporting CT and vasculature
Stroma
Degree of resemblance of tumor cells to parent cells
Differentiation
More resemblance between tumor cells and parent cells
Well differentiated (“low grade”)
Little resemblance between tumor cells and parent cells
Poorly differentiated (“high grade”)
Dedifferentiated or undifferentiated
Anaplasia
What does increased/abnormal DNA replication lead to (“poorly differentiated”)? (6)
Pleomorphism
Nuclear hyperchromatism
Increased nuclear/cytoplasmic ratio
Atypical nuclei
Numerous and atypical mitoses
Prominent nucleoli
A microscopic, potentially reversible, altered growth or maturation pattern
Dysplasia
In epithelial tissues (cervix, oral mucosa), it is precancerous and may progress to malignancy
Dysplasia
What is seen under the microscope in precancerous epithelial tissues undergoing dysplasia?
Disorderly:
Maturation
Pleomorphism
Mitotic activity
In bone lesions, it does NOT imply a precancerous state, just altered growth
Dysplasia
Dysplastic changes involving the full-
thickness of the epithelium
Carcinoma in-situ
Known as the most advanced stage of dysplasia
Carcinoma in-situ
Still a pre-invasive (precancerous) state, so
not cancer
Carcinoma in-situ
Clinical appearance, anatomic site, or
cell type (root word) + “oma”
Benign epithelial tumors
Named for appearance- finger-like epithelial
projections overlying cores of vascular fibrous CT
Papilloma
Arises from surface epithelium (Squamous-
skin, larynx, tongue; Transitional- bladder,
ureter, renal pelvis)
Papilloma
Benign tumor of glandular epithelium; can have many variants
Adenoma
Characterized by adenomatous papillary processes that extend into cystic spaces, as in cystadenoma of the ovary
Papillary cystadenoma
Most often named by tissue of origin
Benign mesenchymal
Fibrous tissue (benign mesenchymal)
Fibroma
Cartilaginous (benign mesenchymal)
Chondroma
Smooth muscle (benign mesenchymal)
Leiomyoma
Skeletal muscle (benign mesenchymal)
Rhabdomyoma
Fat (benign mesenchymal)
Lipoma
Bone (benign mesenchymal)
Osteoma
Vessels (benign mesenchymal)
Angioma
Pleomorphic adenoma (salivary), fibroadenoma (breast)- only fibrous portion is neoplastic
Benign mixed tumors
Neoplasm with cells derived from more than 1 germ layer, totipotent cells
Teratoma
Disorganized tissue native to the site (non-neoplastic generally)
Hamartoma
Disorganized tissue at unexpected site (non-neoplastic)
Choristoma
A mass that projects above a mucosal surface
Polyp
What are the notable malignant -oma exceptions? (6)
Lymphoma
Melanoma
Mesothelioma
Seminoma
Glioblastoma
Hepatoma
What are the notable non-neoplastic -oma exceptions?
Granuloma (group of macrophages)
Hematoma (bruise)
Root word anatomically or cellularly + “Carcinoma”
Malignant epithelial
Synonym of malignant
Cancer
From squamous epithelium (skin, mouth, esophagus, vagina) or areas of squamous metaplasia (bronchi or cervix)
Squamous cell carcinoma
Marked by production of keratin
Squamous cell carcinoma
From urinary tract epithelium
Transitional cell carcinoma
Glandular origin; includes tumors of GI, mucosa, endometrium, pancreas
Adenocarcinoma
Often shows desmoplasia
Adenocarcinoma
The root word anatomically/cellularly +
“Sarcoma
Malignant mesenchymal
Fibrous (malignant mesenchymal)
Fibrosarcoma
Cartilaginous (malignant mesenchymal)
Chondrosarcoma
Bone (malignant mesenchymal)
Osteosarcoma
Skeletal muscle (malignant mesenchymal)
Rhabdomyosarcoma
Smooth muscle (malignant mesenchymal)
Leiomyosarcoma
Fat (malignant mesenchymal)
Liposarcoma
Vessels (malignant mesenchymal)
Angiosarcoma
Burkitt lymphoma
Hodgkin disease/lymphoma
Wilm’s tumor
Eponyms
Which one is correctly matched?
a. chondroma, non-neoplastic collection of tissue not native to the site
b. angioma, malignant tumor of blood vessels
c. pleomorphic adenoma, a high-grade malignancy of glandular epithelium
d. rhabdomyoma, benign tumor of skeletal muscle
d. rhabdomyoma, benign tumor of skeletal muscle
Name some words often added to describe variants of a tumor’s appearance under the microscope
Cystic, papillary, tubular, solid, etc
Benign or malignant?
Clinical presentation:
Non-cancerous
Slow growing
Local, does not spread, may cause local damage
Surgically removable
Survivable - good prognosis
Benign
Benign or malignant?
Clinical presentation:
Cancerous
Rapid growth
Invade and destroy adjacent tissue
Metastasis = defining feature
Can cause death - poor prognosis
Malignant
Benign or malignant?
Microscopic:
Well-differentiated
Normal mitoses
Encapsulation
Benign
Benign or malignant?
Microscopic:
Well to poorly differentiated (or anaplastic)
Atypical mitoses
Non-encapsulated
Malignant
Benign or malignant?
Rate of growth is slow (months to years)
Benign
Benign or malignant?
Rate of growth affected by hormones, blood supply, pressure constraints
Benign
Benign or malignant?
Rate of growth is variable, may be rapid
Malignant
Benign or malignant?
Rate of growth may outgrow blood supply, leading to necrosis
Malignant
Benign or malignant?
Local invasion capsule at periphery
Benign
Benign or malignant?
Local invasion beyond anatomic tissue boundaries
Malignant
Benign or malignant?
Local invasion is destructive and no capsule
Malignant
Benign or malignant?
Crosses over anatomical boundaries (ex: nose up to brain)
Malignant
What is the hallmark of malignancy?
Metastasis
What does the capacity of metastasis depend on?
Tumor type
What percentage of newly diagnosed malignant tumors have clinically evident
metastases?
30% (early detection is important!)
More anaplastic, larger tumor = _______ likely to spread
more
In what ways does malignancy spread?
Seeding in body cavities
Lymphatic spread
Hematogenous (blood) spread
Paths of least resistance
What type of malignancy spread?
Ovarian cancer
Seeding in body cavities
What type of malignancy spread?
Carcinomas
Lymphatic spread
What type of malignancy spread?
Sarcomas
Hematogenous (blood) spread
What type of malignancy spread?
Lung and liver are common vsecondary sites
Hematogenous (blood) spread
What type of malignancy spread?
Neural spread
Path of least resistance
What type of malignancy spread?
Batson’s venous plexus - along vertebral column, potential spread to jaw
Path of least resistance
Cancer is a _________ disorder- mostly from acquired random mutations during regular ______ ___________ (Bad luck!) or from environmental exposure
genetic; cell division
Genetic changes are heritable with the
accumulation of mutations leading to
characteristic features of cancer; however,
actual inherited cancers are ____________
infrequent
Cancer is a _____________ process. It does not just happen from one time of “bad luck”
multi-step
What are the steps of neoplasm formation?
Initiation
Promotion
Progression
What step of neoplasm formation?
Carcinogen exposure causing genetic damage and single cell (“monoclonal”) growth
Initiation
What step of neoplasm formation?
Additional genetic damage over time leads to heterogenous population of cells (visible clinically)
Promotion
What step of neoplasm formation?
Evolution and selection of more aggressive tumors capable of metastasis that are less responsive to treatment
Progression
Name 3 carcinogens that can cause a neoplasm to form
Chemicals
Radiant energy
Microbial agents (ex: viruses like HPV, EBV)
What are the 4 major classes of cancer genes that control growth?
Proto-oncogenes
Tumor suppressor genes
Apoptosis regulation genes
Tumor cell/host cell interaction genes
Which major class of cancer genes that control growth?
Increase growth
Proto-oncogenes
Which major class of cancer genes that control growth?
Stop cell growth and help in DNA repair
Tumor suppressor genes
What is the classic example of a tumor suppressor gene?
TP53 (aka p53)
Which major class of cancer genes that control growth?
Determine cell death
Apoptosis regulation genes
Which major class of cancer genes that control growth?
Cytotoxic T lymphocytes kill cells with unrepaired genetic damage
Tumor cell/host cell interaction genes
Name the 4 hallmarks of cancer highlighted in class
- Self-sufficiency in growth signals (oncogenes)
- Insensitivity to growth inhibition (tumor suppressor genes)
- Evasion of apoptosis (apoptosis regulation genes)
- Evasion of immune system (tumor cell/host interaction genes)
The immune system (cell-mediated) helps prevent what?
Tumor formation/progression
What is the evidence that the immune system helps prevent tumor formation and progression?
Increased frequency of cancer in immunocompromised (ex: congenital, transplant, AIDS)
Uses endogenous or synthetic substances to improve or restore immune system function to fight cancer
Immunotherapy
What is the target and indication of Rituximab?
Target = CD20
Indication = B-NHL
What is the target and indication of Herceptin?
Target = HER2/neu
Indication = breast cancer
What is the target and indication of Certuximab?
Target = EGFR
Indication = Head, neck, oral cancer
The majority of cancers are inherited.
About 1/3 of newly diagnosed malignancies have already metastasized.
a. Both statements are true
b. Both statements are false
c. The first statement is true, the second statement is false
d. The first statement is false, the second statement is true
d. The first statement is false, the second statement is true
The branch of medicine which deals with the incidence, distribution, and possible control of diseases and other factors relating to health
Epidemiology
Studying who (Age, gender) gets a tumor,
where they live (environmental risk
factors) and their family (genetic factors,
acquired predisposing conditions) helps identify etiology and pathogenesis
Epidemiology
What helps with the following?
Preventing and reducing disease burden
Improving tx
Reducing cost
Predicting needs for resource allocation
Epidemiology
Has the overall death rate increased or decreased?
Decreased (less smoking, earlier detection, better tx)
Has the overall incidence rate increased or decreased for women and men?
Increased for women
Stable for men
Which state has the highest incidence of new cancer cases and deaths in the US?
KY
Name environmental exposures that are associated with increased cancer risk
Occupational
Chronic sun exposure
Smoking
Alcohol
Obesity
Oncogenic viruses (HPV)
T/F: Older people are more likely to get cancer
True
What kind of cancers do children usually get?
Leukemia, lymphoma, sarcoma, CNS tumor
What should you closely follow for early cancer detection?
Precursor (precancer/premalignant) lesions
Risk for?
Smoking induced squamous metaplasia
Dysplasia of bronchial mucosa
Bronchogenic carcinoma
Risk for?
Endometrial hyperplasia and dysplasia
Endometrial carcinoma
Risk for?
Oral, vulvar, and penile leukoplakia
Squamous cell carcinoma
Risk for?
Villous adenoma of colon
Colorectal carcinoma
Are benign tumors premalignant?
Generally no
Name the tumor effects on host
Location is crucial
Hormone production
Bleeding + infedction
Intestinal complications
Symptoms not related to tumor spread or hormone production
Paraneoplastic syndromes
Affects 10-15% of cancer patients
Paraneoplastic syndromes
May indicate underlying neoplasm
Paraneoplastic syndromes
Can be lethal and can mimic metastatic disease
Paraneoplastic syndromes
Diverse and associated with many tumors
Paraneoplastic syndromes
Name the 4 Paraneoplastic syndromes
Cachexia
Hypercalcemia
Cushing syndrome
Hypercoagulability
Which Paraneoplastic syndrome?
Progressive loss of body fat and lead body mass with weakness, anorexia, and anemia
Cachexia
Which Paraneoplastic syndrome?
High metabolic rate
Cachexia
Which Paraneoplastic syndrome?
Caused by tumor and host cytokines, not due to tumor’s nutritional demands
Cachexia
Which Paraneoplastic syndrome?
Due to release of PTHrP, TGF-a (activates osteoclasts and active vitamin D)
Hypercalcemia
Which Paraneoplastic syndrome?
Ectopic ACTH production
Cushing syndrome
Which Paraneoplastic syndrome?
Venous thrombosis and nonbacterial thrombotic endocarditis
Hypercoagulability
Estimates aggressiveness based on cytologic differentiation
Grading
Goes from I - IV in order of increasing anaplasia
Grading
Which has greater clinical value, grading or staging?
Staging
Size of primary tumor and extent of regional and distant spread
Staging
TNM system
Staging
What does TNM system measure/stand for?
T = tumor size (1-4)
N = regional nodal involvement (0-3)
M = metastasis (0,1)
AJC system (0-IV)
Staging
What is required for a lab diagnosis of cancer?
Detailed clinical findings
Adequate, representative, properly preserved biopsy
What do you put biopsied samples in?
Formalin
What are the sampling approaches?
Cytologic smear
Biopsy
What are the 2 types of cytologic smears?
Direct scraping
Fine needle aspiration
Which type of cytologic smear?
Good for superficial fungal and herpes infections
Direct scraping
Which type of cytologic smear?
Good for readily palpable lesions (breast, thyroid, lymph node, salivary gland)
Fine needle aspiration
Which sampling approach?
Incisional (part of the tissue) or excisional (all abnormal tissue)
Biopsy
____________ assistance ensures accurate sampling for internal lesions. Name a few examples
Radiologic
Ex: mammogram-guided, CT-guided, ultrasound-guided
Routine samples are _________ fixed and embedded in paraffin wax (FFPE) for routine H&E staining.
This same tissue block can later be used for additional ______-based molecular tests (FISH, IHC, PCR etc.)
formalin; DNA
Useful to determine the cellular differentiation of poorly differentiated tumor cells
Immunohistochemistry
Useful in diagnosis of lymphomas to determine lineage (B or T cell) and differentiation stage and in treatment of B-cell lymphomas
Immunohistochemistry
Requires fresh tissue (no formalin!)
Flow cytometry
Helps classify leukemia and lymphoma
Flow cytometry
What are the serologic markers for tumors?
PSA
Carcinoembryonic antigen (CEA)
Alpha-fetoprotein
Which serologic marker for tumors?
Low sensitivity and low specificity
PSA
Which serologic marker for tumors?
Cancers of colon, pancreas, stomach, and breast
Carcinoembryonic antigen (CEA)
Which serologic marker for tumors?
Hepatocellular carcinomas, yolk sac remnants
Alpha-fetoprotein
Which serologic marker for tumors?
Not good for early detection, but GREAT for detecting reccurrences
PSA, CEA, and alpha-fetoprotein
Uses body fluids that contain tumor cells or their products for screening, detecting, and monitoring cancer
Liquid biopsy
Can detect monoclonality in lymphoid malignancies
PCR
Translocations and gene amplification
FISH/PCR
Which molecular technique?
Tumors from different sites with similar mutations can be given similar drugs
Targeted therapy
Rapid sequencing on entire genome
Genomics
Can identify driver and passenger mutations that help target treatment
Genomics
Epigenetic modifications genome-wide
Epigenomics
Microarray quantifies all RNAs expressed
Transcriptomics
Measure all proteins simultaneously
Proteomics
Test all of the cell’s metabolites
Metabolomics
T/F: RNA is easier to work with than DNA
FALSE, DNA is easier to work with
Currently developing methods to sequence several hundred _____ _________ to detect mutations in as few as 5% of tumor cells
key genes
Used to identify changes in DNA copy number
DNA arrays
In the future, may be used to predict drug efficacy
Epigenomics
In the future of cancer diagnostics, there will be a paradigm shift to classify tumors based on _____________ and associated therapeutic _________, rather than on morphology or cell origin
mutation; targets
Optimal diagnosis and management combines what?
Histopathology + molecular diagnostic techniques
