Chapter 7 Flashcards
Migratory thrombophlebitis (trousseau syndrome) is associated with which cancers
Deep seated cancer, most often pancreas or lungs
What is the state of the antigenic markers of B cell lymphoma in immunosuppressed patients
Express LMP-1, EBNA-2 (both would be killed by CTL in immunocompetent pts) and lack MYC
Which conditions are fine needle aspirations used
Assessment of readily palpable lesions in sites such as breast, thyroid, and lymph nodes
How many layers are the majority of tumors composed of
Majority of neoplasms, even mixed, are composed of a single germ layer
Where do cancers of the inner quadrants of breast first disseminate
LN salong the internal mammary arteries
What is the common pattern see in the formation of ovarian cystic teratomas, aka Dermoid cysts
Along ectodermal lines composed of hair, teeth, and sebaceous glands)
What is the general nuclear morphology seen in tumor cells
Large nuclei compared to the size of the cytoplasm, and can approach a ratio of 1:1, rather than the normal 1:4 of 1:6
What is ATLL dues to HTLV-1 endemic
Japan, Caribbean basin, South America, and Africa
Why are biopsies of testicular masses never done
Iatrogenic spread on surgical equipment may occur
What is a pseudoencapsulated mass
In slow growing malignant tumors, masses develop rows of cells penetrating the margin and infiltrating
What is the definition of initiation with regards to a a neoplasm
Exposure of cells to a sufficient dose of carcinogenic agent, which alters the cell to have the potential to give rise to a tumor
When is a tumor said the be invasive
When it breaches the basement membrane
What Increases the risk of breast and endometrial cancers
Estrogen exposure, particularly if unopposed by progesterone
What areas is Burkitt’s lymphoma the most common childhood tumor
New Guinea and central Africa
What is seeding of body cavities
When a malignant neoplasm penetrates into a natural open cavity lacking barriers (most commonly the peritoneal, but includes, pleural, pericardial, subarachnoid, and joints)
How does LMP-1 in EBV work to allow cell proliferation
Acts as an activated CD40 receptor, leading to B cell lymphomas
What type of tumors are less likely to have specialized functional activity
Rapidly growing anaplastic tumors
Where do breast carcinomas preferably spread
To bone
How does the classification TNM system work
T for primary tumor (1-4, with 0 being in situ)
N for regional LN (1-3, 0 being no LN involvement)
M for metastasis (1-2, with 0 being no distant metastasis)
What is the effect of having a highly inducible CYP1A1
7 times increased risk of lung cancer in smokers than those without
Pathogenic strains of H. Pylori are known to contain which product and what is its function
-CagA (cytotoxin-associated A), which penetrates the gastric epithelium and can cause ulcers and other effects
Body cavity seeding is characteristic of which condition
Carcinomas of ovarian origin, which spread to peritoneal cavities.
What is a scirrhous tumor
Stony hard tumor, like in the breast
How is susceptibility to certain carcinogens polymorphic
Most are activated metabolically via CYP450s, which are polymorphic. So having a certain type may predispose to some carcinogens
Which strains of HPV are associated with genital warts
6,11
What is the only human retrovirus that is a carcinogen
Human T-cell leukemia virus 1 (HTLV-1)
What is the relationship between promoters and neoplasms
Promoters themselves are not carcinogenic and can not cause a tumor, as their effects do not change DNA and are reversible.They must follow an initiation event in order to cause a cancer
What are the most common cancers in adults and how does this compare to children
- Carcinomas are most common in adults
- Lymphomas and leukemias most common in children
What is pseudomyxoma peritonei and what causes them
The peritoneal cavity is filled with a gelatinous neoplastic mass via a music secreting carcinoma, usually appendicular or ovarian in origin
Increased UV rays from the sun are associated with which conditions
Squamous cell carcinoma, basal cell carcinoma, melanoma of the skin
What is the antigenic levels in Burkitt lymphoma
Does not express LMP-1, EBNA-2 or other EBV proteins that drive proliferation
What is an ultimate carcinogen
The final product of an indirect carcinogen after it has been metabolized into its active form
What is the most common lung neoplasia associated with hypercalcemia
Squamous cell carcinoma
What is the strength of direct carcinogens
Very weak, but are used as cancer chemotherapy
What is the target of HTLV-1 and what is the result
Targets CD4 T cells, which is the major target of neoplasia
What is the potential result from a benign pancreatic islet tumor
production of insulin in an amount to produce hypoglycemia
Antibodies against which general cell structures are good for solid tumors
Abs against intermediate filaments
What is the example of neoplastic precursor lesion
Colonic villous adenoma, which will lead to cancer in 50% or patients
Where do virtually a precursor lesions arise
Epithelial surfaces
What are endocrinopathies
Paraneoplastic syndromes in which nonendocrine origin develop secretory activity known as ectopic hormone production
What is the result of tax in HTLV-1
- increased pro growth signaling
- Increased genomic instability (increase aneuploid leukemias)
What is the most important substance in the case of malignant paraneoplasia causing hypercalcemia
Parathyroid hormone related protein (PTHRP), which is similar to PTH, but released from all tissues
What is the effect of E7 and HPV infections with cancer
All contribute to spending through the G1-S cycle checkpoint.
- Binds to Rb-E2F and releases E2F to progress cell cycle
- Binds and inhibits p21 and p27, which normally inhibit CDKs
- activate cyclins A and E
What is cachectin
Aka TNF
Disseminated intravascular coagulation is associated with which cancers
Acute promyelocytic leukemia and prostatic adenocarcinoma
What are the characteristics of all carcinogenic and what are the properties of the substrates they bind to
All chemical carcinogenics are electrophiles and bind to nucleophilic sites in the cell
What are mitoses indicative in tumors
High proliferative activity of parenchymal cells
What is the path of hepatocellular carcinomas
Penetrate the portal and hepatic radicals then inotthe main venous channels
Where do bronchogenic carcinomas spread
Adrenals and the brain
Which conditions bode well for patients with oligodendrogliomas
Loss of chromosome 1p and 19q without EGF receptor amplification
Where do neuroblastomas spread
Liver and bones
What is the most common noninflammatory precursor lesions
Endometrial hyperplasia in response to sustained estrogen exposure
What is anaplasia
Lack of differentiation in tumor cells
What cancers are associated with H. Pylori
Gastric adenocarcinomas and gastric lymphomas
What percentage of newly diagnosed solid tumors present with metastasis
30%
How can you differentiate between Cushing syndrome caused by excess production of pituitary and endocrinopathies
Endocrinopathies from lung cancer will have pro-opiomelanocortin, while pituitary excess will not
What is a Choristoma
Heterotopic rest of cells (pancreatic neoplasm located in the stomach)
What is a hamartoma
Disorganized by benign mass composed of cells indigenous to the involved site
What is associated with intense intermittent UV exposure
Melanomas
What type of germ cells do teratomas originate from
Totipotent germ cells (normally found in ovaries and testis)
What is the risk in children with CT scans
2-3 CT scans have 3x risk of leukemia
5-10 CT scans have 3x risk of brain cancer
What is the most common pathway of initial dissemination of carcinomas
Transportation through lymphatics
B cell lymphomas due to H. Pylori can be cleared by what, and what is the reasoning
Cleared due to antibiotics, which kill the bacteria. This removes the antigen for T cells, which are required for the activation of the B cells
What is the long term effect of initiation process
It is permanent change to DNA and is irreversible
When and what are inducers of the change brought on by initiators
When there are promoters, such as phorbol esters, hormones, phenols, and drugs
How would brain cancers be targeted
PI3K
What is the process of HPV DNA integrating into the host
- Integrations interrupts viral DNA writhing the E1/E2 reading frame
- loss of viral E2 repressor
- overexpression of E6 and E7 oncogenes
How would breast cancers be targeted
HER2
How would lung cancers be molecularly targeted
Mutated KIT
What is the relationship between chronic inflammation and cancer
Chronic inflammation increases the risk of cancer
What are the sources for aromatic and all dyes
Analine dye and rubber industries
What are the most common cancers associated with EBV
Tumors derived from B cells and nasopharyngeal carcinomas
Gastric lymphomas associated with H. Pylori are of what origin
B cell origin from normal Peyer’s patches and MALT structures
What strains of HPV are high risk
16,18
What is a immunohistochemical stain for ALK trying to identify
Lung cancers and lymphomas
What is leukoplakia
Thinking of squamous epithelium on the vulva or penis or oral cavity that can give rise to squamous carcinoma
How does tax in HTLV increase pro-growth signaling
- Interacts with PI3K and AKT for cell survival
- up regulates cyclin D2, and repressed the inhibitors
- Upregulates NF-KB, which is activator for lymphocytes
Which form of breast cancers have a better prognosis
Receptor positive breast cancers
Where are the most common locations of cancer in US women
Lung, breast, colon/rectum
What is the most common cancer that evolves from the precancerous stage “cancer in situ”
Carcinoma of the uterus (best illustrated), cancers of skin, breast
What is the active product in many hydrocarbons and what is their effect
Forms epoxides, which form covalent adducts with Primarily DNA and RNA
What type of tumor secrete the hormones characteristics of their origin
Benign tumors and carcinomas because they are still very well differentiated back to the tissue or origin
What bodes poorly for patients with neuroblastoma
Amplification of NMYC and deletions of 1p
What is the characteristic of benign tumors with regards to differentiation
Well differentiated, mitosis are rare, and are of normal configuration
What are the common sites for neoplastic hypercalcemia
Breast, lung, kidney, ovary
What condition is hypertrophic osteoarthropathy associated with
Cancer, as it is rarely seen in noncancer patients. 1-10% of lung carcinomas shows this condition
What is the pathways used by LMP-1 in B lymphomas following EBV infection
- Activated Jak-Stat and NF-kB (proliferation)
- activated BCL-2 (survival)
What is the mutation in TP53 that is common in hepatocellular carcinoma (which can be induced by aflaxonB1)
G:C —> T:A tranversion at codon 249 (AA change from arginine to serine)
What are the malignant cancers that regularly do not metastasize
Gliomas (malignant neoplasms of glial cells) and basal cell carcinomas
What is a carcinoma in situ
Dysplasia changes are noted. And involve the full thickness of the epithelium, but the lesion does not penetrate the basement membrane
What is the function of EBNA-2 in EBV
Encodes a nuclear protein that acts as a Notch receptor
What condition is highly associated with developing EBV positive B cell tumors, and where do they develope
Immunosuppressive and in the CNS and gut
What is desmoplasia
Formation of collagenous stroma
What gives the measure of leukemia cells in treated patients with CML
BCR-ABL transcripts
What are the three proteins carried by HTLV-1 that is common in all retroviruses, and what it the unique protein
All retrovirus: pol, gag, env
HTLV-1: tax
What is the result of the Overexpression of E6 in HPV
- Binds to p53 and mediates destruction
- stimulates TERT, which increases telomerase activity
How is HTLV-1 transmitted
Sex, breast feeding, blood products
What does HTLV-1 cause
Adult T cell leukemia/lymphoma (ATLL)
What is the type of cancer associated with Cushing syndrome
50% have small cell lung cancer
What is the rule of thumb for naming malignant tumors
Tissue of origin, followed by -sarcoma (ex:fibrosarcoma, chondrosarcoma
What is the general rule of thumb for naming benign tumors
The type of tissue, followed by -oma. (Ex: Fibroma, chondroma,)
What type of tumor is characteristic of anaplasia as its hallmark
Malignant tumors are anaplastic, aka not well differentiated
What are the two basic components of all tumors
- Neoplastic cells that constitute the tumor parenchyma
- Reactive stroma made up of connective tissues, blood vessels, and immune cells
Virtually all of Burkitt lymphomas are associated with what
Translocation that activate the MYC oncogene.
-In particular, the translocation (8;14)
What is associated with the total cumulative exposure to UV radios
Nonmelanoma skin cancers
What is the most common endocrinopathy
Cushing syndrome
Antibodies found on a tumor against cytokeratins would be indicative of which cell origin
Epithelial origin
Lung cancer patients with Cushing syndrome have elevated levels of what
-pro-opiomelanocortin and corticotropin
Where are the most common cancers in women worldwide
Breast, cervix, and lung
What are the characteristics of acanthosis nigricans
Grey black patches of thickened hyperkeratic skin with a velvety appearance
Miners of radioactive elements of Europe and Mocky mountains have an increased risk of what
10x increased risk for lung cancer
Where do cancers of the vertebral column disseminate and which cancers are they associated with
Through the paravertebral plexus involved frequently with metastasis of thyroid and prostate
What is the percentage of hepatocellular carcinomas caused by hep B and C
70-85%
What are the 5 DNA viruses that have been identified to cause cancer in humans
-HPV, EBV, Hep BV, Markle cell polyoma virus, HHV-8
What is a pleomorphic adenoma
A mixed tumor, in which the original clone is able to produce both epithelial and myoepithelial cells (contains cartilage/bone and epithelial components)
What percentage of cancers worldwide are due to infectious agents
15%
What is paraneoplastic syndrome
Distribution and elaboration of hormones that are indigenous to the tissue of origin
What is the leading cancer killer in both men and women
Lung (28 and 26%)
What is the large majority of cervical carcinomas and head/neck cancers caused by
HPV
What are sources for polycyclic hydrocarbons
Burning animal fats, fossil fuels and tobacco combustion
What tumors are characteristic of hematogenous spread, and which vessels are commonly involved
Typical of sarcomas, penetrate veins more commonly than arteries
Where do breast carcinomas usually arise and where do they disseminate to
Commonly arise in the upper outer quadrant, so they disseminate first to the axillary LN
How are most chemical carcinogens activated
Most are indirect, meaning they are activated metabolically via CYP-450
What is the most common paraneoplastic syndrome
Hypercalcemia (more often related to cancer than hyperPTHism
How does polymorphism play into the susceptibility of HPV infections and cancer
TP53 polymorphic at codon 72 (proline or arginine). Arg72 is more susceptible to degradation via E6
What is the path of renal cell carcinoma
Invades the renal vein branches, then the renal vein, then up the IVC to the heart
What is a common effect of using direct carcinogens as chemotherapy
Development of a secondary cancer, commonly acute myeloid leukemia
What is acanthosis nigracans associated with
Cancer in 50% of patients, especially those over 40
What do well differentiated squamous cells carcinomas secrete
Keratin
Cancer cachexia is associated with which 3 things
- Equal fat and muscle loss
- Elevated BMR
- Systemic inflammation and cytokines
What are the characteristics of dysplasia
Disordered growth, principally in the epithelia with the loss of uniformity of individual cells and architectural orientation (pleomorphic, large nuclei)
What do well differentiated hepatocellular carcinomas secrete
Bile
Where are the most common sites of tumors in US men
Prostate, lung, colon/rectum
What are papillomas
Benign epithelial neoplasms producing visible fingerlike projections, aka polyps
What is the first bacteria classified as a carcinogen
H. pylori
What are the two conditions commonly associated with hypercalcemia
- osteolysis induced by cancer
- calcemic humoral substances by extraosseous neoplasms
How would colon cancers be targeted
BRAF
What do a high percentage of leukemias due to HTLV-1 express
FOXP3, which leads to immunosuppression and death
What percent of which population has an highly inducible CYP1A1 and is more susceptible to benzo[a]pyrene
10% of the white population
What is the source of aflatoxin B1
Certain strains of aspergillis
What strains of HPV cause warts
1,2,4,7 cause benign squamous papillomas (aka warts)
What occurs in osteolysis induced by cancer
Not considered a paraneoplastic condition
-primary in bone, such as myeloma, or metastatic to bone from a primary lesion
What is Cushing syndrome caused by
Excess production of corticotropin and corticotropin like peptides
How does cancer rank on the leading cause of death in the US
Second only to CV
What is the correlation between EBV and nasopharyngeal carcinoma
100% of nasopharyngeal cancers contain EBV
What is gene required for the metabolism of the polycyclic aromatic hydrocarbon benzo[a]pyrene
CYP1A1
What is the titer levels in patients with nasopharyngeal cancer
Viral capsid antibodies are elevated, and appearance of IgA abs before the tumor ever shows
When does arterial hematogenous spread occur
Tumor cells pass through the pulmonary capillary beds or pulmonary arteriovenous shunts
What is a tumor capsule
IN benign tumors, there is a rim of compressed fibrous tissue that separates from the host tissue
What is the tumor capsule compared of and what deposits it
Extracellular matrix that is deposited by stromal cells, which are activated by hypoxic conditions due to compression via the tumor
What populations commonly develop nasopharyngeal cancers
Inuit people, southern China, Africa
Which UV is responsible for cutaneous cancers
UVB
What are the commonly hit locations first hit by hematogenous spread
Liver (via portal system) and lungs (caval system)
What is dietary consumption of aflaxon B1 strongly correlated with
Hepatocellular carcinoma in Africa
Where do carcinomas of the lung arising in the major respiratory passages metastasize first
Perihilar tracheobronchial and mediastinal LN
Where are the most common cancers in men worldwide
Lung, stomach, and liver
What is the most at risk location to radiation
Myeloid leukemias
How would prostate cancers be targeted
EGFR
What is the PCR product that is indicative of Ewing sarcoma
(11;22)(q24;q12) translocation
What is the correlation between Burkitt lymphoma and EBV infections
- 90% of Africans with Burkitt’s have EBV
- 100% have Abs against viral capsid proteins
What is the prognosis of HER2 positive breast cancer and what is some treatment options
HER2 breast cancers have poor prognosis, but can be targets by Ab against HER2
What is UVC not associated with cancer
It is blocked out by the ozone
What is run to assess the presence or absence of metastatic lesion in lymph nodes during tumors
Biopsy of sentinel nodes (aka first node in the regional lymphatic basin that receives flow from the primary tumor)
After initial dissemination, where do breast carcinomas spread
Supra and infraclavicular LN
What do Direct carcinogens need to become carcinogenic
Nothing, they do not require metabolic conversion
