Cancer Flashcards
smallest clinically detectable tumor?
1g, 109 cells, had already undergone 30 population doublings
what is the max size of a tumor compatible with life?
1kg (10 additional doublings from a 1g tumor)
what is the clinical significance of the size of a clinically detectable tumor?
by the time the 1g tumor is detected, it has already competed a major portion of its lifespan
what determines the growth rate of a tumor?
- the doubling time of the tumor cells
- the fraction of tumor cells that are in the replicative pool
- the rate at which cells are shed or die
relationship of effectiveness of chemotherapeutic drugs and replicative pool size?
tumors with a large percentage of cells in the replicative pool will respond better to chemo than those with a low percentage of replicating cells (chemo targets actively cycling cells)
difference between malignant and benign tumors with regard to level of differentiation
malignant tumors tend to be LESS differentiated than benign tumors, so they grow more rapidly than benign tumors
what does multistep carcinogenesis mean
the cancer results from the accumulation of multiple mutations over time, ex. colorectal cancer
mechanism of CRC development
- first hit is a mutation (germ line or somatic) in APC
- second hit is the inactivation of other APC allele via abnormal methylation
- proto-oncogene K-RAS converts to oncogenic form of K-RAS
COULD LEAD TO CELLS SENESCE WITH JUST ADENOMA POLYPS, IF P53 MUTATES, TELOMERASE AFFECTED AT THE END
what is hyperplasia
accumulation of excessive numbers of normal appearing cells within normal appearing tissue
what is dysplasia
disordered growth resulting in disordered architecture of the tissue
what is anaplasia
tissue and cellular architecture lacking the differentiated characteristics of an identifiable tissue of origin
what is pleomorphism
variation in size and shape of both cells and nuclei of the cells
what is abnormal nuclear morphology
atypical mitosis which leads to tripolar, multipolar mitotic spindles (cell trying to divide into three cells or more)
what could be an effect of abnormal nuclear morphology?
chromosomes not split up correctly, loss of function/tumor suppressor genes in one daughter cell
characteristic of anaplasia
- pleomorphism
- abnormal cell morphology
- disorganized tissue structure
- tumor giant cells present
what is a tumor giant cell
large cell with either one large polymorphic nucleus or multiple nuclei
characteristic of benign tumor
mass of cells lacks ability to metastasize, cells within this mass resemble their parent tissue, surrounded by a fibrous capsule
characteristic of malignant tumors
tumor invades surrounding tissues, capable of producing metastases that may recur after attempted removal, cells within this mass diverge significantly from the parent tissue in morphology
how are cancers named
for the site of the body where they first develop
what are carcinomas
cancers of epithelial origin (ex. adeno)
what are sarcomas
cancers of connective tissue origin (ex. osteo, chondro, myo, lympho)
what is the most common type of cancer in adults
carcinoma, 90%
what is a lymphoma
solid tumor of lymphoid cells, 4% of cancer in adults, 8% of cancer in children
what is leukemia
tumor comprised of any of a variety of hematopoietic cell types dispersed through circulation, 4% of cancer in adults, 30% of cancer in children (ALL)
what are sarcomas
a rare type of cancer in adults, 1% in adults, 7% of cancers in children, originates from mesenchymal cells
what is retinoblastoma
cancer of retina, 2% of childhood cancers
what is wilms tumor
cancer of the kidney, 5% of childhood cancers
what is neuroblastoma
adrenal gland tumors, 6% of pediatric cancers
most common sarcomas in children
rhabdomyosarcoma, osteosarcoma, Ewing’s sarcoma
most common brain and CNS tumors in children
astrocytomas, medulloblastoma, ependymoma, 25% of childhood cancers
most common cancer in the US
melanoma and non-melanoma skin cancer
most common cancer in the world
lung cancer
4 types of lung cancer
adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma
2 subtypes of non-melanoma skin cancer
- squamous cell carcinoma
2. basal cell carcinoma
what does short periods of intense UV exposure increase the risk of
melanoma
what does chronic sun exposure increase risk of
non-carcinoma skin cancer
what is melanoma
aggressive form of skin cancer with poor prognosis and multiple sites of metastasis
median survival for metastaic melanoma
6-12 months
common sites of metastasis for melanoma
lung, brain, bone, liver
where does melanoma develop?
melanocytes, which are pigmented cells found in the basal layer of epidermis
what is familial melanoma
melanoma associated with mutations in CDKN2A locus
what does CDKN2A encode
p16Ink4a and p15Ink4b CDK inhibitors and p14Arf p53 activator
what does mutation in the CDKN2A locus infer
CDK will not be inhibited and p53 will not be activated, leading to cell survival and proliferation
what is sporadic melanoma
melanoma arising from sun-exposed sun due to mutations in B-Raf, Ras and p16, sometimes epigenetic silencing of PTEN
what sporadic melanoma is associated with non-sun exposed skin
mutations in RTKinase c-Kit, sometimes epigenetic silencing of PTEN
what is the most common form of skin cancer
basal cell carcinoma
characteristics of basal cell carcinoma
originates from cells in basal layer of skin, rarely metastasize, good prognosis, can be removed surgically
characteristics of squamous cell carcinoma
arises from keratinocytes in epidermis, can become metastatic, can be removed surgically if NOT metastatic
risk factors for squamous cell carcinoma versus basal cell and melanomas
squamous cell carcinoma can develop due to industrial chemical exposure and tobacco chewing in addition to sun exposure
what mutations cause basal cell carcinoma
inactivating mutations (LOF, tumor suppressor) in PTCH and activating mutations (GOF, oncogene) in SMO
what would mutation in PTCH and SMO lead to
increased GLI1-mediated gene transcription and increased expression of cyclinD, leading to increased gene expression and unregulated cell division and abnormal growth
what is Gorlin syndrome
inherited form of basal cell carcinoma, inherited mutations in PTCH (mutation in PTCH where it does not inhibit SMO)
drugs to treat basal cell carcinoma
cyclopamine, vismodegib, both inhibit SMO
pathology of squamous cell carcinoma
inactivating (loss of function, tumor suppressor) mutation in p53, also oncogenic mutation in RAS (Ras activated)
- UV damage to DNA, but absence of functional p53 does not initiate cell cycle arrest (via binding to p21, which inhibits Cdk)
- lack of cell cycle arrest allows proliferation of cells that have undergone UV induced mutations
how is early stage squamous cell carcinoma treated
5-fluorouracil cream
what is SCLC
small cell carcinoma lung cancer, is a central, aggressive, (early) metastatic cancer but is sensitive to chemo
what is NSCLC
non-small cell carcinoma lung cancer, not metastatic, resistant to chemo
what are included in NSCLC
adenocarcinoma, squamous cell carcinoma, large cell carcinoma
risk factors for SCLC
smoking
common sites of metastasis for SCLC
liver, bone marrow, brain, adrenal glands
mutations found in SCLC
p53 and Rb found in 80% of cases (cannot initiate cell death or stop CDK, cannot halt proliferation)
characteristic of cells in SCLC
the cells can secrete ACTH and form cushing’s disease
what is cushing’s disease
hypercortisolism, increased ACTH, fatty deposits around face and upper back, weight gain in midsection but NOT the limbs
what is the most common form of NSCLC
squamous cell carcinoma
usual presentation of squamous cell carcinoma
bronchial obstruction
what is the most common form of lung cancer found in non-smokers
adenocarcinoma of the lung
characteristics of adenocarcinoma of the lung
mucosal glands in the bronchi, is more peripheral and can be mistaken for metastatic lesions
characteristics of large cell carcinoma
large peripheral masses, poorly differentiated, grow rapidly, can produce hormones that result in paraneoplastic syndromes
what is paraneoplastic syndromes
system complexes in cancer-bearing individuals that cannot be explained by the spread of the tumor or by hormones indigenous to tissue from which the tumor arose
cell type of acute lymphoblastic leukemia (ALL)
immature pre-B or B cells
characteristics of ALL
rare, affects younger people, aggressive disease that replaces bone marrow and invades tissues
diagnosis of ALL
characteristic cells on examination of blood or bone marrow, flow cytometry may be required to distinguish from acute myeloid leukemia (AML)
cell type affected in CLL (chronic lymphoblastic leukemia)
mature B cells
characteristics of CLL
common in elderly, may be nonagressive
diagnosis of CLL
lymphocytosis on blood film, CLL lymphocytes express characteristic surface molecules detected by flow cytometry
cells affected in lymphoma
mature B-cells
characteristics of lymphona
frequently associated with EBV or infection and chromosomal translocation, cause solid lesions beginning in lymph nodes or mucosa associated lymphoid tissue
diagnosis of lymphoma
bx of affected tissue, heavy chain rearrangement, chromosomal analysis
cells affected in multiple myeloma
plasma cells
characteristics of MM
common in elderly
diagnosis of MM
detection of monoclonal immunoglobulin in blood or light chains in urine, presence of plasma cells in marrow and osteolytic lesion on radiograph
cells affected in T-cell malignancy
T-cells
characteristics of T-cell malignancy
is rare, may be caused by HTLVI infection
diagnosis of T-cell malignancy
can behave either as leukemia (blood involvement) or lymphoma (solid tissue involvement)
what is cancer cachexia
progressive loss of body fat and lean body mass accompanied with profound weakness, anorexia, and anemia, that is NOT caused by nutritional demands of the tumor
what causes cancer cachexia
possibly production of cytokines by the tumor, which results in mobilization of fats from tissue stores and appetite suppression
what are the paraneoplastic syndromes?
- hypercalcemia
- cushing syndrome
- acanthosis nigricans
- clubbing of fingers
what causes finger clubbing
cardiopulmonary disorders, commonly lung cancer
most common paraneoplastic syndrome?
hypercalcemia
what causes hypercalcemia
- osteolysis induced by the cancer
2. production of calcemic humoral substances by extraosseous neoplasms
what is cushing’s disease associated with
small cell carcinoma lung cancer (SCLC)
what is acanthosis nigricans
gray-black patches in skin folds of neck, groin, and anogenital regions, usually associated with gastrointestinal adenocarcinoma