Term
| Define neoplasm and contrast neoplastic growth with hyperplasia, metaplasia, dysplasia, tumor |
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Definition
Hyperplasia: increase cell numbers
Metaplasia: adaptive change, mature cell type, reversible, (smokers, ciliated cells w/ goblet cells -> squamous)
Dysplasia: pre-cancer, disordered growth, architecture, pleomorphism
Tumor: swelling, mass
Neoplasm: new growth |
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Term
| Describe the dysplasia to carcinoma in situ sequence and the clinical significance of CIS |
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Definition
hyperplasia/metaplasia -> dysplasia -> carcinoma in situ (CIS) -> invasive carcinoma
CIS: pre-malignant, neoplasm has not become invasive, "curable with a scalpel," cells tend to be undifferentiated, *intact basement membrane* |
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Term
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Definition
Cystadenoma – benign epithelial neoplasms that form large, cystic masses (as in the ovary)
Papillary cystadenoma – grossly cystic, has papillary fingers growing into cyst lumen (papilla is defined as having finger-like growths with a supporting vascular core); benign
Serous papillary cystadenoma – serous refers to the type of epithelium we see in the fallopian tube; cells that have cilia
Mucinous cystadenoma - benign neoplasm that has mucus vacuoles and typically excreting mucus into lumen of cysts. Cysts in the ovary can reach extremely large proportions; weight of the neoplasm is due to the mucus
Papilloma – benign epithelial neoplasms forming microscopically or macroscopically visible finger-like projections from epithelial surfaces, may be adenomatous or squamous |
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Term
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Definition
serous papillary cystadenoma: serous refers to the type of epithelium we see in the fallopian tube; cells that have cilia
mucinous cystadenoma: benign neoplasm that has mucus vacuoles and typically excreting mucus into lumen of cysts
-Cysts in the ovary can reach extremely large proportions; weight of the neoplasm is due to the mucus |
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Term
mixed tumor of the salivary gland
(pleomorphic adenoma) |
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Definition
pleomorphic adenoma - benign
myoepithelial cell origin
One cell line divergently differentiates into another tissue of the same cell line
Salivary gland myoepithelium differentiates into other cell types of the myoepithelial lineage
*highly regenerative* - surgeon should excise normal tissue around it as well
-if left unexcised for a long time, can develop mutations, become malignant |
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Term
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Definition
may be adenomatous or squamous
does NOT have cystic morphology
can be lined by squamous epithelium or cuboidal epithelium |
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Term
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Definition
multiple germ layers present
can have several tissue types (hair, teeth, brain, eye, etc)
-gonads are most common location
-dermoid cyst: most common ovarian neoplasm
can differentiate in a number of different ways
must specify mature, immature or malignant teratoma |
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Term
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Definition
Normal tissue, wrong spot
-tissue growing in an abnormal site
-e.g. adrenal cortical tissue on the ovary |
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Term
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Definition
malformed mass of normal tissue elements
Disorganized indigenous tissue
Benign mass of the lung, NOT a neoplasm,
e.g. excision of a 3 cm lung mass with disorganized but histologically mature cartilage, ciliated epithelium, and blood vessels |
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Term
carcinoma
tissue of origin?
examples? |
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Definition
epithelial origin
May have secondary descriptors, like benign counterparts
Adenocarcinoma: glands
Squamous cell carcinoma
Cystadenocarcinoma: ovaries |
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Term
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Definition
a lesion in which the neoplastic epithelial cells grow in a glandular pattern
e.g. adenocarcinoma of the colon |
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Term
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Definition
might see in a pap smear
a cancer in which the cells resemble stratified squamous epithelium |
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Term
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Definition
| malignancy of lymphoid cells, proliferations that arise as discrete tissue masses |
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Term
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Definition
| neoplasms that present with widespread involvement of the bone marrow and/or peripheral blood |
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Term
Compare and contrast benign and malignant neoplasms:
a. demarcation from surrounding tissue (capsule, local invasiveness),
b. rate of growth,
c. degree of differentiation (definition of differentiation?),
d. distant spread (metastases) |
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Definition
BENIGN
Well differentiated, sometimes typical of tissue of origin
Little atypia
Slow growth
mitotic figures rare & normal
Usually cohesive expansile
Circumscribed or encapsulated (remember host/pseudocapsule)
Non-invasive
No metastasis
MALIGNANT
some lack of differentiation
Anaplasia; structure often atypical
Pleomorphism
Erratic and may be slow to rapid growth; mitotic figures may be numerous & abnormal
Locally invasive, infiltrating surrounding tissue; sometimes may be seemingly cohesive and expansile
Metastasis often present; the larger and more undifferentiated the primary, the more likely are metastases |
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Term
| Describe morphologic changes associated with poorly differentiated neoplasms |
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Definition
Anaplasia
Pleomorphism
Nuclear atypia
Loss of polarity
Abnormal mitosis
Tumor giant cells |
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Term
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Definition
characteristic of malignant neoplasms
"backward growth" - dedifferentiation, or not differentiated
lack of differentiation (indicating that the tissue is cancerous)
proliferating stem cells differentiating to whatever degree they are going to differentiate, resembling or not resembling their normal tissue counterparts |
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Term
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Definition
characteristic of malignant neoplasms
variation in size and shape of the nuclei and the cell
characteristic of malignant neoplasms |
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Term
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Definition
abnormality in a cell
characteristic of malignant neoplasms
characteristically the nuclei contain abundant chromatin and are dark staining
high N:C ratio
variable/irregular nuclear shape
coarsely clumped chromatin
large nucleoli |
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Term
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Definition
characteristic of malignant neoplasms
the orientation of anaplastic cells is markedly disturbed |
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Term
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Definition
characteristic of malignant neoplasms
undifferentiated tumors usually possess large numbers of mitoses, reflecting the high proliferative activity of the parenchymal cells
atypical, bizarre mitotic figures, sometimes producing tripolar, quadripolar, or multipolar spindles |
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Term
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Definition
characteristic of malignant neoplasms
some possessing only a single huge polymorphic nucleus, others having two or more large, hyperchromatic nuclei |
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Term
| What is the clinical significance of invasiveness and metastasis? |
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Definition
Metastasis unequivocally marks a tumor as malignant because benign neoplasms do not metastasize
-*major exceptions - malignant tumors that DON'T metastasize: gliomas and basal skin cell carcinomas*
post-CIS stage
malignant neoplasms
The invasiveness of cancers permits them to penetrate into blood vessels, lymphatics, and body cavities providing opportunity for spread
Approx. 30% of newly diagnosed individuals with solid tumors present with metastases. |
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Term
| Describe concepts of recessive and dominant oncogenes and list examples. Compare and contrast mechanisms of oncogene activation |
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Definition
point mutation
over-expression
gene amplification |
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Term
List some inherited syndromes associated with a genetic predisposition to cancer
-AD
-AR, defective DNA repair
-familial cancers |
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Definition
Retinoblastoma
Familial polyposis/nonpolyposis colon cancers
Multiendocrineneoplasia (MEN)
Neurofibromatosis
von Hippel-Lindau
Xeroderma pigmentosa
Ataxia-telangiectasia
Familial cancers: uncertain genetics in most, earlier age of onset, multiple/bilateral neoplasms |
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Term
| Compare and contrast clinical features of cancer in patients with inherited predisposition vs sporadic cancer |
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Definition
earlier age of onset
multiple or bilateral neoplasms
oncogene alterations |
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Term
| Understand the cellular origin of a neoplasm |
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Definition
target cell is a stem cell
monoclonal |
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Term
| Understand tumorigenesis as a multi-step process involving accumulation of genetic alterations |
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Definition
Increasing malignancy is often acquired in incremental fashion.
multiple mutations accumulate independently in different cells -> heterogeneity, generating subclones with varying abilities to grow, invade, metastasize and resist therapy
by the time malignant tumors become evident their constituent cells are extremely heterogenous
During progression, tumor cells are subjected to immune and nonimmune selection pressures
-e.g. highly antigenic cell are destroyed by host but those with reduced growth factor requirements are positively selected
Stromal microenvironment
-tumors are made of a mix of cells: tumor cells, innate and adaptive immune cells, fibroblasts, endothelial cells and others
-The ECM stores GFs that are used in paracrine fashion for tumors to grow.
-macrophages surrounding blood vessels secrete EGF, resulting in chemotactic migration of tumor cells toward the vasculature
-Altered stiffness of the matrix alone could change the aggressiveness of a tumor
Molecular basis of multistep carcinogenesis
a.Each cancer must result from the accumulation of multiple mutations
b.Tumors accumulate an average of 90 mutant genes
c.No single oncogene can fully transform nonimmortalized cells in vitro, but cells can generally be transformed by combinations of oncogenes |
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Term
| Understand the concept of tumor clonality and its usefulness in diagnosis |
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Definition
polymorphism of x-linked AR locus is common method to determine clonality b/c 90% of population has polymorphism at that site
immune cell B & T receptor gene re-arrangements can also serve as markers in lymphomas |
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Term
| Describe the colon adenoma-carcinoma sequence |
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Definition
Normal colon cells
loss of APC tumor-suppressor gene (csome 5)
-polyp forms on colon wall
-a benign, precancerous tumor grows
Activation of K-ras oncogene (csome 12)
-a class II (benign) adenoma grows
Loss of DCC tumor-suppressor gene (csome 18)
-a class III (benign) adenoma grows
Loss of p53 tumor suppressor gene (csome 17)
-a carcinoma develops
Other changes...
-cancer metastasizes
-tumor cells invade BV, permitting metastasis |
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Term
| Compare and contrast kinetics of tumor growth with kinetics of tumor cell cycle progression, and how this relates to tumor growth fraction |
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Definition
Kinetics of growth
Monoclonal origin
With growth/progression: heterogeneity
30 doublings = 1 gm. = 1 billion cells = smallest clinically detectable mass (see Fig. 7-12, P. 277)
Attaining a mass of 1 billion cells may be only a few months in some cases, but in many if not most malignancies, it probably occurs over a time span of years
1 kg. of cells = one trillion cells – generally the maximal size compatible with life
By the time a solid tumor is clinically detected, it has already completed a major portion of it’s life cycle |
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Term
| Know therapeutic implications of tumor growth fraction |
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Definition
The proportion of cells within the tumor population that are in the proliferative pool = "growth fraction"
has a profound effect on their susceptibility to cancer chemotherapy
Most anticancer agents act on cells that are in the cell cycle (not in rest phase), so a tumor that only has 5% of cells in the proliferative phase would not respond well to therapy. You can shift the cell phases by first resecting a portion of the tumor, which will trigger the resting cells to become active in the cell cycle. Then begin chemotherapy. |
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Term
| What is the relationship between tumor progression and cellular heterogeneity within a neoplasm, and what are the implications in terms of treatment and metastatic potential? |
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Definition
| Malignant neoplasms have heterogenous constituent cells by the time of dx, due to genetic instability |
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Term
| List some host factors (angiogenesis factors, hormones) that affect neoplastic cell growth and how they might be used as targets for therapeutic intervention |
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Definition
Angiogenesis (esp. VEGF, bFGF) – allows neoplasm to grow larger than 1-2mm in diameter
oncogenes - mutated proto-oncogenes, promote autonomous cell growth in cancer cells
-make oncoproteins; can function as GF, GF-R, signal transducers, TF or cell cycle components
-causes growth to become self-sufficient
Usually GF themselves aren't altered
Oncogenic GF-R are associated with constitutive dimerization & activation w/o binding to GF, deliver continuous mitogenic signals to cell (RET protein...)
Overexpression of receptors, more common than mutations in GF-R
-ERBB1: overexpressed in many squamous cell lung carcinomas, glioblastomas, head & neck tumors
-ERBB2: breast cancer, adenocarcinomas of ovary, lung, stomach, salivary glands
signal transducing proteins mimic the function of normal cytoplasmic signal trans proteins (generally located on inner leaflet of PM)
RAS oncogene
Alterations in nonreceptor tyrosine kinase: K that normally function in transduction pathways that result in cell growth
-translocation of c-ABL tk gene from csome 9->22, fuses with BCR gene, becomes constitutively active
TFs: bind DNA & activate gene transcription, if mutated growth autonomy can occur |
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Term
| Be familiar with the general principles, value, and applications of biopsy, exfoliative and aspiration cytology, and frozen section |
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Definition
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Term
| List some examples of special markers used to diagnose cancer by immuno-histochemistry and flow cytometry |
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Definition
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Term
| Define tumor grade and clinical stage |
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Definition
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Term
| Define paraneoplastic syndrome |
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Definition
when you have physical effects caused by the neoplasm
-Symptoms that are caused by the tumor or some factor from the tumor acting at a distance
-The neoplasm might make a hormone or turn on genes that make a specific hormone
May be presenting feature of occult neoplasm, may be clinically significant, may mimic metastasis |
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Term
examples, causes of neoplasms associated with:
-endocrinopathies
-nerve & muscle syndromes
-dermatologic disorders
-osseous changes
-vascular changes
-hematologic changes
-nephrotic syndrome |
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Definition
ENDOCRINOPATHIES
Cushing - ACTH - small-cell lung carcinoma, pancreatic carcinoma, neural tumors
SIADH - ADH or ANH - small-cell lung carcinoma, intracranial neoplasms
Hypercalcemia - PTH-related protein, TGF-alpha, TNF, IL-1 - squamous cell lung carcinoma, breast carcinoma, renal carcinoma, adult T-cell leukemia/lymphoma
Hypoglycemia - insulin - ovarian carcinoma, fibrosarcoma, other mesenchymal sarcomas
Carcinoid syndrome - serotonin, bardykinin - hepatocellular carcinoma, bronchial adenoma (carcinoid), pancreatic carcinoma
Polycythemia - erythropoietin - gastric carcinoma, renal carcinoma, cerebellar hemangioma, hepatocellular carcinoma
NERVE & MUSCLE - immunological cause
Myasthenia - bronchogenic carcinoma
Disorders of the CNS & peripheral NS - breast carcinoma
DERMATOLOGIC
Acanthosis nigricans - immunological; secretion of epidermal GF - gastric carcinoma, lung carcinoma, uterine carcinoma
Dermatomyositis - immunological - bronchogenic, breast carcinoma
OSSEOUS
Hypertrophic osteoarthropathy and clubbing - unknown cause - bronchogenic carcinoma
VASCULAR & HEMATOLOGIC
Venous thrombosis (Trousseau) - tumor products (mucins activate clotting) - pancreatic carcinoma, bronchogenic carcinoma, other cancers
Nonbacterial thrombotic endocarditis - hypercoagulability - advanced cancers
Red cell aplasia - unknown cause - thymic neoplasms
nephrotic syndrome - tumor antigens, immune complexes - various cancers |
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Term
| Discuss the use of the molecular analysis of immunoglobulin and T cell receptor gene rearrangements to distinguish cancer vs. reactive or other proliferative processes |
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Definition
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Term
Inappropriately-termed malignant neoplasms
malignancy of melanocytes
malignancy of lymphoid cells
malignancy of primitive germ cells
neoplasm of glia (astrocytes or others)
hepatocellular carcinoma
Wilms tumor
neurofibrosarcoma |
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Definition
Melanoma = malignancy of melanocytes
Lymphoma = malignancy of lymphoid cells
Seminoma = malignancy of primitive germ cells (same tumor in ovary is dysgerminoma)
Glioma = neoplasm of glia (astrocytes or others)
Hepatoma = hepatocellular carcinoma
“Eponymic” neoplasms (e.g. Wilms tumor)
Other types of inappropriate terminology
Malignant schwannoma = neurofibrosarcoma, not a schwannoma which became malignant |
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Term
| “Perfectly termed” neoplasms |
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Definition
Both benign
Angiomyolipoma
-blood vessels, muscle cells, fatty cells
-most often seen in kidney
-pts present with hemorrhage, can be fatal b/c exsanguinate into benign neoplasm
Fibroadenoma
-breast neoplasm, involves both fibrous stroma and glandular epith
-Epithelial cells diff toward glandular epithelium, myoepith cells
-histo: well-formed glandular structures, luminal epith cell, myoepithelial cell |
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Term
sarcoma
tissue of origin?
what kinds of tumors do these tend to be?
examples? |
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Definition
malignant neoplasm
mesodermal differentiation (origin)
"spindle cell" tumors
liposarcoma: malignancy of fat tissue
leiomyosarcoma: smooth muscle
rhabdomyosarcoma: skeletal muscle
chondrosarcoma: cartilage
osteosarcoma: bone |
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Term
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Definition
Liposarcoma
Leiomyosarcoma
Rhabdomyosarcoma
Chondrosarcoma
Osteosarcoma |
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Term
| Pathways of metastatic spread |
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Definition
Seeding of body cavities and surfaces - often with floating malignant cells in effusion
-pleural cavity, peritoneal, less often the pericardium, knee joints, CSF.
-Malignant cells can get in the fluid, can implant on the surfaces, start to grow
-floating cancer cells: i/c fluid, you can see malignant cells in the efflusion
Lymphatic spread - natural drainage route to regional lymph nodes, (versus reactive hyperplastic lymph nodes)
-first seen in melanomas; classic ex: breast cancer
-"logic to lymphatic spread"
-LN may enlarge when it's reactive/inflamed, doesn't necessarily mean it's cancerous, req's biopsy
Hematogenous spread - usually vein invasion, follows blood flow; liver and lungs most often secondarily involved
-intra-abdominal cancers first go to the liver (gastric, pancreatic, colon)
-everywhere else: right heart, then the lung |
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Term
| Benign neoplasm characteristics |
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Definition
Well-differentiated
Usually little atypia
Slow growth
Circumscribed or encapsulated
Non-invasive
*Do not metastasize* |
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Term
| Malignant neoplasm characteristics |
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Definition
Some degree of lack of differentiation
Anaplasia
Pleomorphism
Rapid growth; mitoses (often atypical)
Locally invasive
Metastatic capability |
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Term
| Acquired pre-neoplastic disorders |
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Definition
leukoplakia: white plaques seen in mucosal surfaces (dentists)
-might be a dysplasia of the squamous mucosa, with extra keratin causing whiteness on the surface
-Over time, there are some incidences that progress to invasive cancer, relatively low but it's recognized
solar keratosis: squamous cancers of the skin
-freq seen in older pale-skinned individuals
-Will often be shaved off by dermatologist, remove pre-cancers
atrophic gastritis: precursor for gastric cancers
ulcerative colitis: by itself not a genetic injury to the colon
-development of cancer in context of constant ulceration and repair increases risk of cancer |
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Term
Molecular basis of cancer
-how does cancer start?
-which regulatory gene classes are the principal targets? (4)
-carcinogenesis is what type of process? |
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Definition
Nonlethal genetic damage of a cell (hereditary or acquired): "dedifferentiated," a cell that has the potential to differentiate but undergoes genetic mutations and so proliferates in an abnormal way
Clonal expansion of that single damaged cell - monoclonal (polymorphism of X-linked AR locus)
Four regulatory gene classes are principal targets -
growth-promoting proto-oncogenes (just need one mutant; "haploinsufficiency")
growth-inhibiting tumor suppressor genes (both normal alleles must be damaged before transformation occurs)
genes regulating programmed cell death (apoptosis genes): p53
genes involved in DNA repair (e.g. XP, "mutator PT")
Carcinogenesis is a multistep process -> heterogeneity |
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Term
| essentials of malignant transformation |
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Definition
Self-sufficiency in growth signals (e.g. HER-2 in breast cancer)
Insensitivity to growth-inhibitory signals
Evasion of apoptosis (p53, Bcl-2)
Limitless replicative potential (telomere shortening doesn't take place)
Sustained angiogenesis (to grow >2 mm in diameter, req's ability to get rid of waste products/gain nutrients, O2)
Ability to invade and metastasize
-detachment of tumor cells from each other (loss of E-cadherins)
-attachment to matrix components (laminin & fibronectin R, polarity, allows cancer cells to bind to BM constituents)
-degradation of ECM (type IV collagenase - produced by cancer cells or thru co-optation of macrophages, neutrophils)
-migration of tumor cells (autocrine motility factor)
Defects in DNA repair
Escape from immune attack |
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Term
| Describe cancer stem cells |
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Definition
| limitless proliferative capacity, two types of daughter cells (self-renewal and differentiating cell), stem cells must be eliminated to cure a cancer |
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Term
Nomenclature
Tumors of mesenchymal origin - connective tissue & derivatives
benign
malignant |
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Definition
benign: fibroma, lipoma, chondroma, osteoma
malignant: fibrosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma |
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Term
Nomenclature
Endothelial & related tissues
blood vessels
lymph vessels
synovium
mesothelium
brain coverings |
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Definition
blood vessels: hemangioma, angiosarcoma*
lymph vessels: lymphangioma, lymphangiosarcoma*
synovium: synovial sarcoma*
mesothelium: mesothelioma*
brain coverings: meningioma, invasive meningioma* |
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Term
Nomenclature: tumors of blood cells & related cells
hematopoietic cells
Lymphoid tissue |
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Definition
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Term
Nomenclature: muscle tumors
smooth
striated |
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Definition
smooth: leiomyoma, leiomyosarcoma*
striated: rhabdomyoma, rhabdomyosarcoma* |
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Term
Nomenclature: Tumors of epithelial origin
stratified squamous
basal cells of skin or adnexa
epithelial lining of glands or ducts
respiratory passages
renal epithelium
liver cells
urinary tract epithelium (transitional)
placental epithelium
testicular epithelium (germ cells) |
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Definition
stratified squamous: squamous cell papilloma, squamous cell carcinoma*
basal cells of skin or adnexa: basal cell carcinoma*
epithelial lining of glands or ducts: adenoma, adenocarcinoma*, papilloma, papillary carcinomas*, cystadenoma, cystadenocarcinoma*
respiratory passages: bronchial adenoma, bronchogenic carcinoa*
renal epithelium: renal tubular adenoma, renal cell carcinoma*
liver cells: liver cell adenoma, hepatocellular carcinoma*
urinary tract epithelium (transitional): transitional-cell papilloma, transitional-cell carcinoma*
placental epithelium: hydatidiform mole, choriocarcinoma*
testicular epithelium (germ cells): seminoma*, embryonal carcinoma* |
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Term
| Nomenclature: tumors of melanocytes |
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Definition
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Term
Nomenclature
more than one neoplastic cell type - mixed tumors, usually derived from how many germ cell layers?
Salivary glands
Renal anlage |
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Definition
ONE germ cell layer
Salivary glands: pleomorphic adenoma, malignant mixed tumor of salivary gland origin*
Renal anlage: Wilms tumor* |
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Term
Tumor markers
HORMONES
Human chorionic gonadotropin
Calcitonin
Catecholamine and metabolites
Ectopic hormones
ONCOFETAL ANTIGENS
alpha-Fetoprotein
Carcinoembryonic antigen
ISOENZYMES
Prostatic acid phosphatase
Neuron-specific enolase
PROTEINS
Immunoglobulins
Prostate-specific antigen, prostate-specific membrane antigen
MUCINS, OTHER GLYCOPROTEINS
CA-125
CA-19-9
CA-15-3
NEW MOLECULAR MARKERS
P53, APC, RAS mutants in stool & serum
p53, RAS mutants in stool & serum
P53, RAS mutants in sputum & serum
P53 mutants in urine |
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Definition
HORMONES
HCG: trophoblastic tumors, nonseminomatous testicular tumors
Calcitonin: medullary thyroid carcinoma
Catecholamine and metabolites: pheochromocytoma, related tumors
Ectopic hormones: lots, e.g. ACTH & small-cell lung carcinoma
ONCOFETAL ANTIGENS
alpha-Fetoprotein: liver cell cancer, nonseminomatous germ cell tumors of testis
Carcinoembryonic antigen: carcinomas of colon, pancreas, lung, stomach, heart
ISOENZYMES
Prostatic acid phosphatase: prostate cancer
Neuron-specific enolase: small-cell cancer of lung, neuroblastoma
PROTEINS
Immunoglobulins: multiple myeloma, other gammopathies
Prostate-specific antigen, prostate-specific membrane antigen: prostate cancer
MUCINS, OTHER GLYCOPROTEINS
CA-125: ovarian cancer
CA-19-9: colon cancer, pancreatic cancer
CA-15-3: breast cancer
NEW MOLECULAR MARKERS
P53, APC, RAS mutants in stool & serum: colon cancer
p53, RAS mutants in stool & serum: pancreatic cancer
P53, RAS mutants in sputum & serum: lung cancer
P53 mutants in urine: bladder cancer |
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Term
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Definition
a malignancy of germ cells the exception to the rule of nomenclature
it is malignant
-seminoma: seminiferous tubules
-dysgerminoma: ovaries
-germinoma: ectopic form (e.g. pineal gland) |
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Term
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Definition
has a very firm, indurated texture, the cancers, on physical exam, will often feel like a firm, hard mass (scirrhous)
-This is due to the *host’s response* to the cancer
-Fibroblasts lay down collagen; the fibroblasts themselves may have quite a bit of mitotic activity
-characteristic of breast cancer cells |
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Term
| What is the most common malignancy in the liver? |
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Definition
|
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Term
| What is the most common CIS in the U.S.? (two of them) |
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Definition
uterine cervix, breast
b/c we screen for them |
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Term
| For which cancers are the death rates higher than the incidence? |
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Definition
Lung cancer, pancreatic cancer (both sexes)
Ovarian cancer |
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Term
| Which cancers are associated with cigarette smoking? |
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Definition
mouth/pharynx/larynx
esophagus
pancreas
bladder
cervical
lung |
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Term
which cancers are most commonly seen in pts under age 15?
over age 55? |
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Definition
leukemia/lymphoma
brain
endocrine
bone
soft tissue sarcoma
lung
colon/rectum
prostate
breast
pancreas |
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Term
how many cell mutations does it take to go from a single cancer cell to one gram?
from on g to one kg? |
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Definition
10 to the 9th mutations (detectable mass = 1 gm = 1 billion cells)
10 to the 12th mutations (another 10 to the 3rd mutations), 1 kg = 1 trillion cells |
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Term
| what is the only "metastatic gene" that's been discovered? |
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Definition
ezrin
necessary for metastases in rhabdomyosarcoma & osteosarcoma |
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Term
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Definition
a type of adenoma
adenomatous polyp = *tubular adenoma*, benign neoplasm of glandular epithelium in which the neoplasms are making tubules out of the glands
-histo: benign colonic neoplasm, blue, high N:C ratio, more density
-term can also be used for benign, reactive, hyperplastic processes
villous adenoma - additional mutations may occur in this population and can grow into a carcinoma; the larger a villous adenoma grows in size, the more likely you are to find a carcinoma in that mass |
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Term
|
Definition
2 hit hypothesis
one gene mutation (RB gene) that controls cell cycle
neoplasm develops in the neuron type retinal cells of the eye |
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Term
|
Definition
| genetic mutation in the p53 gene |
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Term
|
Definition
| genetic mutation in the APC gene; causes colon cancer |
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Term
| Multiple endocrine neoplasia (MEN) |
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Definition
| genetic mutation in the MEN1 gene and the RET gene |
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Term
|
Definition
| genetic mutation in the NF1 and NF2 genes |
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Term
|
Definition
| multiple neoplasms; predisposition to a variety of cancers, esp kidney, adrenal disease |
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Term
|
Definition
GF-R in glial and neuroendocrine cells; oncogenic mutations in...
-MEN-2A: EC domain, constitutive dimerization & activation -> medullary thyroid carcinomas, adrenal & parathyroid tumors
-MEN-2B: cytoplasmic catalytic domain alters the substrate specificity of the tyr K, -> thyroid and adrenal tumors
-FLT3 gene: makes tyr K-like R that leads to constitutive signaling in some myeloid leukemias
-over 90% of GI stromal tumors have mutations in R tyr K c-KIT or PDGFR, which are receptors for stem cell factor and PDGF |
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Term
|
Definition
point mutation of RAS family genes is single most common abnormality of proto-oncogenes
Plays role in signaling cascades down-stream of growth factor receptors -> mitogenesis
KRAS – colon and pancreas
HRAS – bladder
NRAS – hematopoietic
RAS proteins bind GDP, exchange for GTP activates it (neucleotide exchange) --> downstream regulator of proliferation such as mitogen-activated protein kinase cascade (MAPKs) and GRP hydrolosis converts it back to GDP form. Both of these processes are extrinsically regulated by other proteins
-GTPase-activating proteins (GAPS) function as brakes that prevent uncontrolled RAS activity
-Can have mutation in enzymatic region necessary for GTP hydrolosis or in GAPs that would cause RAS to be constantly active |
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Term
|
Definition
can be an effect of benign tumors
progressive loss of both body fat and lean body mass, an di/c basal metabolic rate (unlike starvation), with weakness, anorexia, anemia; not caused by nutritional demands of neoplasm (cytokines?, TNF, others). Common. Besides treating tumor, no Rx for cachexia |
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Term
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Definition
Grading - "under the microscope" - based on differentiation of tumor cells, architecture, and mitotic rate, correlates of the neoplasm's aggressiveness
Staging - based on size of primary lesion, extent of spread to regional LN, and presence/absence of distant metastases
-"PNM"
Stage is of more value than grade in predicting prognosis and suggesting appropriate tx
They may correlate, but don't have to |
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