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85 Cards in this Set

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What are they general characteristics of Neoplasia?
Uncontrolled, disorderly proliferation of cells, resulting in a benign or malignant tumor or neoplasm.
What is dysplasia?
1) Reversible change
2) Often precedes malignancy
3) Morphologically manifests by disorderly amturation and spatial arrangement of cells, marked variability in nuclear size and shape and increased, often abnormal mitosis.
4) Exemplified by dysplasia of squamous epithelium of the cervix, which is often a precursor of malignancy.
What are neoplasms?
1) Resemblance to tissue of origin is close, the neoplasm is termed WELL DIFFERENTIATED; if little resemblance to teh tissue of origin is seen , it is POORLY DIFFERENTIATED.
2) Neoplasms grow at the expense of finction and vitality of normal tissue without benefit to the host and are largely independent of host control mechanism.
What is a malignant tumor?
1) Capable of invasion (spread of the neoplasm into adjacent structures) adn metastasis ( implantation of the neoplasm into noncontiguous sites); this is the most important defining characteristic of malignancy, although there are some malignant tumors, such as basal cell carcinoma of the skin, that rarely metastasize.
2) Usually less differentiated than benign tumors.
3)Marked by anaplasia, in whih timor cells are very poorly differentiated and exhibit pleomorphism, hyperchromatism, and increased nuclear-cytoplasmic ratio, abnormal mitoses, cellular dyspolarity, and often prominent nucleoli.
4) In general, highly anaplastic tumors are very aggressive, and well-differentiated tumors are less aggressive. Paradoxically, the most aggressive tumors often respond well to chemotherapy and radiotherapy, because these modalities are most effective with rapidly dividing cells.
What is Carcinoma?
Malignant tumor of epithelial origin
What is Squamous cell carcinoma?
1) Originates from stratified squamous epithelium of, for example, the skin, mouth, esophagus, and vagina, as well as from areas of squamous metaplasia, as in teh bronchi or the squamocolumnar junction of the uterine cervix.
2) marked by the production of keratin.
What is transitional cell carcinoma?
Arises from the transitional cell epithelium of the urinary tract.
What is adenocarcinoma?
Carcinoma of the glandular epithelium and includes amlignant tumors of the GI mucosa, endometrium, and pancreas.
2) Often associated with desmoplasia, tumor-induced proliferation of non-neoplastic fibrous CT, particularly in adenocarcinoma of the breast, pancreas, and prostate.
Wht is sarcoma?
1) malignant tumor of mesenchymal origin.
2) Often used with a prefi that denotes the tissue of origin of the timor, as in osteosarcomaa, rhabdomyocarcoma, leiomyosarcoma, and liposarcoma.
What are eponymically named tumors?
1) Burkitt lymphoma
2) Hodgkin disease
3) Wilms tumor
What is a teratoma?
1) neoplasm derived from all three germ cell layers, which may contain structures such as skin, bone, cartilage, teeth, and intestinal epithelium.
2) May be either malignant or benign
3) Usually arises in the ovaries or testes.
Describe Benign Tumors.
1) Usually well differentiated and closely resemble teh tissue of origin
2) Do not metastasize and grow slowly. They can be harmful if their growth compresses adjacent tissues. For example, benign intracranial tumors can be more lethal than some malignant skin tumors.
3) Tend to become encapsulated.
4) Denoted by the suffix -oma, as in lipoma and fibroma.
5) Don't confuse this with some malignant neoplams, as hepatoma, melanoma, lymphoma, and mesotheliuma, as well as several non-neoplastic swelings, including granuloma and hematoma.
What is a papilloma?
1) Papilloma is a benign neoplasm most often arrising form surface epithelium such as squamous epithelium of the skin, larynx, or tongue.
2) Consists of delicate finger-like epithelial processes overlyig a core of connective tissue stroma that contains blood vessels.
3) May also develop from transitional epithelium of the urinary bladder, ureter, or renal pelvis.
What is an adenoma?
Benign neoplasm of glandular epithelium that occurs in several variants like papillary cystadenoma and fibroadenoma.
What is papillary cystadenoma?
Characterized by adenomatous papillary processes that extend into cystic spaces, as in cystadenoma of the ovary.
What is a fibroadenoma?
Marked by proliferation of CT surrounding neoplastic glandular epithelium; for example fibroadenoma of the breast.
What are benign tumors of mesenchymal origin?
1) Most often named by the tissue of origin; for example leiomyoma, rhabdomoma, lipoma, fibroma, and chondroma.
2) Include the most common neoplasm of women, the uterine leiomyoma, or fibroid tumor.
What is Choristoma?
Small non-neoplastic area of normal tissue misplaced within another organ, sucha as pancreatic tissue within the wall of the stomach.
What is a Hamartoma?
Non-neoplastic, disorganized, tumor-like overgrowth of cell types that are regularly found within the affected organ; hemangioma, an irregular accumulatoin of blood vessels is an example.
What is monoclonality?
1) Denotes origin from a single precursor cell
2) Characteristic of most neoplasms; in contrast, polyclonal proliferations are almost always non-neoplastic.
3) Assessed by a variety of approaches.
What do Glucose-6-phosphate dehydrogenase isoenzyme studies do?
1) Offering compelling evidence for monoclonality of tumors; because of X inactivation in early embryonic life, tissues of females heterozygous for G6PD isoenzymes consist of a mosaic of cell types with random cells expressing one or the other of the two isoenzymes.
2) monoclonal tumors express only one of the isoenzymes
3) Polyclonal cellular proliferations exhibit both isoenzymes.
How are immunoglobulins involved as indicators of monoclonality in malignancies of B cell origin?
1) Produced by B cell malignant tumors and are demonstrable as cytoplasmic or surface immunoglobulin or, in the case of multiple myeloma, are secreted and are demonstrable in the serum.
2) Monoclonal, the resultant mixture of immunoglobulin molecules will exhibit either kappa or lambda chain specificity, but not both, a characteristic finding in neoplastic B cell proliferations.
3) B cell or plasma cell proliferations are polyclonal, they result in the production of heterogeneous immunoglobulin molecules, some of which express kappa specificity and others that express lambda specificity.
What is immunoglobulin gene rearrangement in regards to being an indicator of monoclonality in malignancies of B cell origin?
1) Characteristic of B cell maturation. The number of possible combinations achieved by rearrangement is almost countless; it can be assumed that each normal B cell is marked by a unique rearrangement pattern. Neoplastic proliferation results in large numbers of cells, all demonstrating the same pattern of immunoglobulin gene rearrangement denoting their common origin form a single cell.
3) Assessed by molecular diagnostic techniques
4) Because immunoglobulin heavy chain rearrangement is limited to B cells, this approach also demonstrates teh B cell origin of a tumor.
How are surface antigens idicators of monoclonality in malignancies of T cell origin?
1) demonstrable as T cells mature; they may be characteristic of either the stage of maturation or functional subclass. Cellular proliferations in which large numbers of T cells share surface markers in common are suggestive of monoclonality.
2) In addition to many others, include the CD4 antigen marking T helper cells and the CD8 antigen marking T suppressor and cytotoxic cells.
What is T cell receptor gene arrangement and how is it involved as an indicator of monoclonality in malignancies of T cell origin?
1) Analogous to immunoglobulin gene rearrangement and is used in a similar manner to demonstrate both the T cell origin of a tuor and its monoclonality.
What is invasion of a tumor cell?
1) Aggressive infiltration of adjacent tissues by a malignant tumor.
2) Often extends into lymphatics and blood vessels, with the formation of tumor emboli that may be carried to distal sites. not all tumor emboli results in metastatic tumor implants, and the presence of tumor cells withing blood vessels or lymphatics indicates only the penetration of basement membranes and is not synonymous with metastasis.
What are the six steps of metastasis?
1) Growth and vascularization of the primary tumor
2) Invasiveness and penetration of basement membranes into lymphatics or blood vessels.
3) Transport and survival of tumor cells in the circulation.
4) Arrest of tumor emboli in the target tissue and passage again across basement membranes
5) Overcoming of target tissue defense mechanisms
6) Development of successful metastatic implants.
What are the preferential routes of metastasis?
1) Vary with specific neoplasms
2) Carconomas tent to metastasize via lymphatic spread.
3) Sarcomas tend to invade blood vessels early, resulting in widespread blood-borne dissemination.
4) Notable exceptions include renal cell and hepatocellular carcinoma, which are market by early venous invasion and hematogenous dissemination.
What are the target organs of metastasis?
1) Most commonly the liver, lungs, brain, adrenal glands, lymph nodes, and bone marrow.
2) Rarely include skeletal muscle or the spleen.
What is tumor progression in regards to metastasis?
1) Characterized by the accumulation of successive cytogenetic or molecular abnormalities.
2) Exemplified by the progression of changes from normal colonic epithelium to adenoma to carcinoma to metastasis, with parallel changes in APC, K-ras, DCC, p53, and possibly other genes.
3) Individual neoplastic cells within a tumor may have varying metastatic potential.
What is Cachexia and wasting?
1) Origin is complex; it is characterized by weakness, weight loss, anorexia, anemia, infection, and hyprmetabolism.
2) May be mediated in part by cachectin (TNF-alpha), a product of macrophages that promotes catabolism of fatty tissue.
What are the endocrine abnormalities of malignance?
1) Caused by tumors of endocrine gland origin, which may actively elaborate hormones, leading to a variety of syndromes.
2) Pituitary abnormalities
3) Adrenocortical abnormalities
4) Ovarian abnormalities
5) Trophoblastic tissue abnormalities
What are pituitary abnormalities of malignancy?
1) Prolactinoma, leading to amenorrhea, infertility, and some times galactorrhea.
2) Somatotropic (acidophilic) adenoma, leading to gigantism in children and acromegaly in adults.
3) Corticotropic (most often basophilic) adenoma, leading to Cushing disease (adrenal hypercorticism of pituitary origin)
What are the adrenocortical abnormalities of malignancy?
Include adrenogenital syndrome, Conn syndrome, and Cushing syndrome of adrenal origin, resulting from adrenal cortical tumors.
What are ovarian abnormalities of malignancy?
1) Granulosa-theca cell tumor, leading to hyperestrinism
2) Sertoli-Leydig cell tumor, leading to excess androgen production.
What are trophoblastic tissue abnormalities of malignancy?
Include hyperproduction of human chorionic gonadotropin from hydatiform mole or choriocarcinoma.
List 6 endocrinopathies.
1) Cushing syndrome
2) Inappropriate secretion of ADH
3) Hypercalcemia
4) Hypoglycemia
5) Polycythemia
6) Hyperthyroidism
What is Cushig syndrome in regards to paraneoplastic syndrome?
Caused by production of ACTH-like substances by small cell carcinoma of the lung.
What is Inappropriate secretion of ADH in regards to paraneoplastic syndrome?
Comes form a variety of tumors, most commonly small cell carcinoma of the lung.
What is hypercalcemia as a paraneoplastic syndrome?
Caused by metastatic disease in bone, secretion of a substance similar to parathormone by squamous cell bronchogenic carcinoma, or secretoin of a substance similar to osteoclast activating factor by the malignant plasma cells of multiple myeloma
What is Hypoglycemia in regards to paraneoplastic syndrome?
Caused by secretion of insulin-like substances by hepatocellular carcinomas, mesotheliomas, and some sarcomas
What is Polycythemia in regards to paraneoplastic syndrome?
Caused by elaboration of erythropoietin by renal tumors and other neoplams.
What is hyperthyroidism in regards to paraneoplastic syndrome?
Caused by production of substances like thyroid-stimulating hormone by hydatidiform moles, choriocarciomas, and some lung tumors
What are neorologic abnormalities of paraneoplastic syndromes?
1) May occur in the absence of metastatic disease
2) Include degenerative cerebral changes with dementia, cerebellar changes with resultant gait dysfunction, and peripheral neuropathies
What are skin lesions related to paraneoplastic syndromes?
1) May be associated with visceral malignancies
2) Include acanthosis nigricans and dermatomyositis.
What coagulation abnormalities are associated with paraneoplastic syndromes?
1) Include migratory thrombophlebitis associated with carcinoma of the pancreas and other visceral malignancies (Trousseau phenomenon), and disseminated intravascular coagulation associated with various neoplasms.
What are oncofetal antigens?
1) Proteins normally expressed only in fetal or embryonic life; their expression by neoplastic cells is considered a manifestation of dediffrentiation
2) The undifferentiated neoplastic cells tend to resemble their embryonic counterparts.
3) Include carcinoembryonic antigen (CEA), which is associated with colon cancer and other cancers and preneoplastic processes, and alpha-fetoprotein (AFP), which is associated with hepatocellular carcinoma and many germ cell tumors. AFP is also iincreased in fetal anencephaly and other neural tube defects.
What are direct-reacting carcinogens?
Do not need to be chemically altered to act.
What are indirect-reacting carcinogens?
Require metabolic conversion form procarcinogens to active ultimate carcinogens.
For example, a mucosal glucuronidase in the urinary bladder converts to beta-napthylamine glucuronide to the carcinogen beta-naphthylamine.
What are the stages of chemical carcinogenesis?
Initiation and Promotion
What is Initiation?
The first critical carcinogenic event, and it is usually a reaction between a carcinogen adn DNA. Two or more agents may act together as cocarcinogens
What is promotion?
Induced by a stimulator of cell proliferation and enhances the carcinogenic process. A promoter, not a corcinogenic in itself, enhances other agents' carcinogenicity.
For example, phorbol esters react with membrane receptors, stimulating cell replication. This may enhance clonal selection, resulting in cells with increasingly deleterious DNA changes.
How does exposure to UV radiation contribute to carcinogenesis?
1) In the form of sunlight is clearly related to the frequency of skin cancers such as squamous cell and basal cell carcinomas and melanomas.
2) Thought to act by inducing dimer formation between neighboring thymine pairs in DNA. In most cases, such dimers are successfully repaired by enzymatically mediated mechanisms. That skin cancer may be induced by such dimer formation is suggested by the greatly increased incidence of skin tumors seen in Xeroderma pigmentosum, an autosomal recessive disorder characterized by failure of DNA excision repair mechanisms.
What is ionizing radiation and how is it carcinogenic?
1) Classic cause of cancer, exemplified by the increased incidence of cancers in those exposed to radiation.
2) skin cancer and myeloid leukemias in radiologists.
3) Lung cancer in uranium miners
4) Thyroid cancer in patients who have received head and neck radiation therapy
5) Acute and chronic myeloid (but not lymphoid) leukemias in survivors of atomic blasts.
6) Osteosarcoma in radium watch-dial workers.
How do DNA viruses contribute to carcinogenesis?
1) Integrate viral DNA into host genomes, perhaps resultig in host cell expression of viral mRNA coding for specific proteins
2) Include haman papillomavirus, EVB, hepatitis B virus as prominent suspects that play a role in human carcinogenesis.
How do retroviruses contribute to carcinogenesis?
1) Marked by transcription of viral genomic RNA sequences into DNA by action of viral reverse transcriptase.
2) In the case of retroviruses that are tumorigenic in experimental animals, are frequently characterized by substitutions of genomic sequences known as viral oncogenes.
What are viral oncogenes?
1) named with a three-seter abreviation preceded by v for viral
2) exhibit homology for DNA sequences of man and other eukaryotic species; these eukaryotic DNA sequences are called proto-oncogenes, or cellular oncogenes, and are identified with the same three-letter abbreviations preceded by c for cellular.
What are the characteristics of Ras and G proteins?
1) Located at the plasma membrane and have GTP binding and GTPase activities. GTPase hydrolytically converts active ras-GTP to ras-GDP.
2) Inactivated by ras-GTPase mediated by GTPase-activating protein (GAP)
3) GTP activation of ras can stimulate or depress adenylate cyclase activity, altering intracellular cAMP levels, thus affecting cellular behavior.
Describe the mutation of the ras gene.
1) Usually occurs at codon 12
2) Results in an aberrant p21 protein product with intact GTP binding but with a loss of GTPase activity. Mutant ras proteins can be activated by GTP binding but cannot be inactivated by GTPase activity.
3) ras is mutated in 25%-30% of malignancies.
What is growth factor or GF receptor activity in regard to oncogenesis?
alterations in expression or structural changes in oncogene products may result in inappropriate activvation of receptor proteins or their oncogenic analogs, thus mimicking the actions of growth factors.
2) On stimulation with the appropriate growth factor, receptor proteins often demonstrate tyrosine kinase activity of their cytoplasmic domains.
3) Significant homologies occur between several oncogenes and the genes for cellular growth factors and their receptors:
a) v-sis and the gene for beta chain of PDGF
b) v-erb and the gene for EGF receptor
c) v-fms and the gene for CSF-1 receptor
d) c-neu and the gene for EGF receptor
What are nuclear proteins in regard to oncogenesis?
Some oncogene products, including the protein products of myc, fos, and myb, are confined to the cell nucleus.
What is promoter insertion in regard to oncogenes?
1) Insertion of retroviral promoter or enhancer sequences into the host genome can lead to increased expression of a nearby oncogene.
2) This mechanism is similar to the promoter-induced hyperexpression associated with translocations characteristic of several human leukemias and lymphomas.
What are point mutations in regard to oncogenes?
Exemplified by a single nucleotide changes in codon 12 of the ras family of genes associated with a number of human tumors.
What are chromosomal translocations in regard to oncogenes?
Frequent association with malignancy seen in these genetic rearrangements has been clarified by demonstrating that important genes are situated at the sites of chromosomal breaks
What is 8;14 translocation?
Burkitt lymphoma
c-myc proto-oncogene on chromosome 8 is translocated to a site adjacent to the imunoglobulin heavy chain locus on chromosome 14. Major regulatory sequences within the immunoglobulin gene are thought to increase the expression of c-myc
What is 14;18 translocation?
Follicular lymphoma
Immunoglobulin heavy chain locus on chromosome 14 si transposed to a site adjacent to bcl-2, an oncogene on chromosome 18. This results in enhanced expression of bcl-2, thus inhibiting apoptosis.
What is 9;22 translocation?
Chronic myeloid leukemia (CML)
1) c-abl proto-oncogene on chromosome 9 is transposed to a site adjacent to bcr, an oncogene on chromosome 22.
2) The union of bcr adn abl results in a hybrid, or chimeric, bcr-abl fusion gene that codes for a protein with increased tyrosine kinase activity.
3) Altered chromosome carrying this hybrid gene, the Philadelphia chromosome, can be demonstrated by cytogenetic techniques in hematopoietic cells of patients with CML.
What is 15;17 translocation?
Acute proyelocytic leukemia (FAB M3 AML)
1) The translocation involves the PML gene on chromosome 15 and the retinoic acid receptor (RAR) alpha gene on chromosome 17.
2) Therapy wiht the retinoic acid analogue all-trans retinoic acid can result in maturation of these leukemic cells and clinical remission.
Describe gene amplification.
1) Reduplication of the gene, with multiple resultant genomic DNA copies, and can sometimes result in a thousand or more copies of the amplified gene.
2) Extensive amplification can result in small free chromosome-like bodies called double minute chromosomes or in band-like structures within chromosomes called homogeneously staining regions (HSRs), which are both demonstrable cytogenetically
Name two neoplasms associated with gene amplification.
Neuroblastoma and some Breast Cancers.
What is amplified in neuroblastoma?
N-myc; correlates inversely with the degree of differentiation of the neuroblastoma cells.
What is amplified in some breast cancers?
HER-2/neu oncogene; such amplification is associated with poor prognosis.
What are cancer suppressor genes (anti-oncogenes)?
In contrast to oncogene mechanisms, cancer suppressor genes promote cellular proliferation when the gene is inactivated (most often by deletion). A single residual copy of the anti-oncogene suppresses tuor formation, but homozygous inactivation promotes the expressoin of the neoplastic phenotype.
Describe the anti-oncogene process using retinoblastoma.
1) An intraocular childhood tumor caused by inactivation of the Rb gene. The two hit hypothesis of Knudson holds that two mutagenic events are requird to induce alterations on both chromosomes.
2) In the familial forms of retinoblastoma, the gene on one chromosome in teh germline is inactivated or deleted, and the gene on the other chromosome is affected by a somatic mutation.
3) In sporadic nonfamilial cases of retinoblastoma, both deletions occur as somatic mutations.
What is the p53 tumor suppressor gene?
1) Mutated in over 50% of all malignant tumors.
2) Has been called teh "guardian of the genome"
3) In the seting of DNA damage, causes cell cycle arrest in G1, providing time for DNA repair.
4) If repair is successful, cells re-enter the cell cycle.
5) If not successful, p53 product causes cell death by apoptosis.
6) Familial loss causes the Li-Fraumeni syndrome, which is characterized by a wide variety of tumors: breast, soft tissue sarcomas, brain tumors, and leukemias.
What are WT-1 and WT-2 tumor suppressor genes?
1) Are located on chromosome 11
2) Inactivation or deletion of either is associated with Wilms timor, the most common renal neoplasm of children.
What is the APC tumor suppressor gene?
Inactivation is common in familial polyposis coli and adenocarcinoma of the coon as well as a few other tumors; gastric and esophageal.
What is the BRCA-1 tumor suppressor gene?
Inactivation is associated with familial propensity to breast and ovarian carcinomas.
What is the BRCA-2 tumor suppressor gene?
Inactivation is associated with breast cancer.
What is von Recklinghausen neurofibromatosis type 1 and NF-1?
1) Characterized by multiple benign neurofibromas, cafe au lait spots, iris hamrtomas, and an increased risk of developing fibrosarcomas.
2) Caused by mutations in the NF-1 tumor suppressor gene (which functions as a GAP protein that inactivates ras)
What is multiple endocrine neoplasia type II?
1) Familial occurence of the combination of medullary thyroid carcinoma, bilateral pheochromocytomas, and hyperparathyroidism due to hyperplasia or tumor.
2) Caused by mutations of teh ret proto-oncogene that are transmitted i the germline. Thus, demonstration of a ret mutation in a patient with medullary thyroid carcinoma would indicate the need for surveillance for the development of pheochromocytoma or hyperparathyroidism.
What is hereditary nonpolyposis colon cancer (HNPCC, or Lynch syndrome)?
1) Caused by an inherited mutation in certain DNA repair genes, resulting in genomic instability.
2) Predisposes to mutations in other genes more diretly related to transformation.
What is Xeroderma pigmentosum?
1) An autosomal recessive disorder
2) Manifest by an increased incidence of skin cancers (basal cell carcinoma, squamous cell carcinoma, malignant melanoma) caused by hypersensitivity to ultraviolet light.
3) Involves defects in genes that function in nucleotide excision repair, which is required for repair of ultraviolet-induced pyrimidine (often thymine) dimers (cross-linked pyrimidine residues).
Describe the grading of cancer.
Histopathologic evaluation of the lesion based on teh degree of cellular differentiation.
Describe the staging of cancer.
1) Clinical assessment of the degree of localization or spread of the tumor.
2) Generally correlates better with prognosis than does histopathologic grading. However, both approaches are useful.
3) Exemplified by teh generalized TNM system, which evaluates the size and the extent of the tumor (T), lymph node involvement (N), and metastasis (M).
4) Sometimes oriented toward specific tumors, as exemplified by teh Dukes system for colorectal carcinoma and teh Ann Arbor system for Hodgkin disease adn non-Hodgkin lymphomas.