Path: Epidemiology and Classification of Neoplasia Flashcards
What is heterotopia?
congenital anomaly characterized by normal tissue in an abnormal location
What is metaplasia?
replacement of one cell type with another cell type.
What is dysplasia?
abnormal growth- pre-neoplastic change seen in the epithelia
What is a benign neoplasia?
localized neoplasm that cannot spread to other sites
What is a malignant neoplasia?
cancer. Can invade locally and spread to distant sites
What is anaplasia?
A lack of differentiation within a tumor.
What terminology surrounds benign neoplasms?
typically end in -oma.
What terminology is used to describe malignant mesenchymal neoplasms?
end in -sarcoma
mesenchymal refers to connective tissue
What terminology is used to describe malignant epithelial neoplasms?
carcinoma
What is lymphoma?
malignant neoplasm of lymphocytes
What is melanoma?
malignant neoplasm of melanocytes
What is mesothelioma?
malignant neoplasm of mesothelium
What is seminoma?
malignant neoplasm of the seminiferous tubules
What is choristoma?
heterotopia- normal tissues found in abnormal locations
What is hepatoma?
old term for hepatocellular carcinoma
What are four features typically used to help distinguish between benign and malignant neoplasms?
differentiation and anaplasia
rate of growth
local invasion
metastasis
What are some features associated with lack of differentiation?
- pleomorphism- variation in size and shape; lack of uniformity
- abnormal nuclear morphology: hyperchromasia, increased N:C ratio, irrecular nuclear contours, course chromatin; large nucleoli
- mitosis/atypical mitosis
- loss of polarity
- tumor giant cell formation
- necrosis
What are three pathways for metastatic dissemination?
- direct seeding (ie. colon cancer grows through serosa and seeds peritoneal cavity)
- lymphatic
- hematogenous
How much of cancer risk is thought to be attributable to the environment?
2/3
What are three genetic sources for cancer risk?
- autosomal dominant cancer syndromes: mutations in tumor suppressor genes
- defective DNA repair
- familial cancer: high freq. of cancer in a family w/o a clearly defined tansmission pattern. potentially due to multiple low penetrance alleles
What are three examples of chronic inflammation as a non-hereditary predisposing condition for cancer?
H. pylori, chronic viral hepatitis C infection, and ulcerative colitis
What kinds of genes are usually mutated in cancer?
- oncogenes
- tumor suppressor genes
- genes that regulate apoptosis
- DNA repair genes
What are 7 changes that happen with malignancy?
- self-sufficiency in growth signals
- insensitivity to growth inhibitory signals
- evasion of apoptosis
- limitless replicative potential
- sustained angiogenesis
- ability to invade and metastasize
- defective DNA repair
What are some ways in which a cell might acquire self-sufficiency in growth signals?
overproduction of growth factor and a switch from paracrine to autocrine
mutations or overexpressions of growth factor receptors that allow them to dimerize and activate in the absence of growth factor binding. HER2 receptor gene amplification in breast/gastric cancers is an example.
What are examples of activation of signal transducers?
RAS genes are an example. point mutations most common abnormality of proto-oncogenes
How do tumor suppressor genes contribute to growth?
tumor suppressor mutations lead to an insensitivity to growth inhibition
What are some of the steps required for metastasis?
get through the ECM get through the serosa survive interactions with lymphocytes extravasation angiogenesis in new site growth
What mutation is involved in HNPCC?
(hereditary nonpolyposis colorectal cancer) aka lynch syndrome.
mutation in DNA mismatch repair enzymes.
How might epigenetic changes lead to cancer?
hypermethylation might silence critical tumor suppressor genes
How might immune cells promote cancer?
- pro-survival and pro-proliferation cytokines
- may promote switch from vascular quiescence to angiogenesis
- tumor infiltrating macrophages may promote metastasis, potentially by chemotactic migration of tumor toward the vasculature.
To what does immuno-editing refer?
immune system may play a role in selecting tumor variants that have reduced immunogenicity
Why do we think the immune system might combat cancer (the evidence- 4 reasons)
lymphocytic infiltrates are seen around cancer, transplanted tumors don’t always survive well, incr. incidence of cancer in the immunocompromised, tumor-specific T cells and antibodies
What are some potential tumor antigens? (5)
mutated gene products, overly expressed proteins, oncogenic virus proteins, fetal proteins expressed in an adult, alter glycolipids/proteins
What are 4 antitumor mechanisms?
- cytotoxic T cells
- natural killer cells
- macrophages (ROSs)
- antibodies (in therapy)
What are 6 ways that tumor cells evade the immune system?
- antigen-neg variants
- reduced MHC expression
- lack of costimulation leading to T cell apoptosis
- immunosuppression (TGF-beta)
- antigen masking
- induction of apoptosis of T cells
What is one example of a therapeutic anti-tumor vaccine? How does it work?
provenge for metastatic prostate cancer
stimulates an immune response to prostatic acid phosphatase (PAP). must be customized to each patient. APCs are cultured with PAP and reinfused into patient.
How might benign neoplasms have catastrophic effects (4)?
location (ie. in the brain)
hormone synthesis
bleeding
infection
What is cachexia? Why is it important?
cachexia: loss of body fat and lean body mass associated with profound weakness, anorexia, and anemia. unexplained by nutritional demands of the tumor, but may be related to cytokine production. May limit therapeutic options.
What is paraneoplastic syndrome?
symptom complex not explained by local or distant spread of tumor or elaboration of hormones. May be lethal; may be earliest manifestation of the tumor.
What are some examples of paraneoplastic syndromes?
pancreatic cancer that promotes venous thrombosis; gastric and bronchogenic cancers that promote overly robust immunloogic responses.
What is tumor grade?
degree of differentiation- specific for each cancer type. usually 2-4 tiers.
What is tumor stage? What is it used for?
used to predict prognosis and make treatment decisions.
In what ways are tumor markers useful?
generally useful for detecting recurrence but not for definitive diagnosis.
What are four sampling techniques?
- excisional biopsy (cut all the way around the lesion and send to path)
- incisional biopsy
- fine needle aspiration
- exfoliative smear (pap smear)
