Pathology chapter 5: Neoplasia

Carcinogenesis: what 4 classes of normal regulatory genes are the targets of these toxins?

1. Growth-promoting proto-oncogenes 2. Growth-inhibiting tumor suppressor genes 3. Apoptosis regulating genes 4. Genes for DNA repair

What fundamental changes are required for a malignant growth?

1. Self-sufficiency in growth signals 2. Be insensitive to growth- inhibitory signals 3. Evade apoptosis 4. Unlimited replicative potential 5. Sustained angiogenesis 6. Ability to invade and metastasize 7. Genomic instability resulting from defects in DNA repair

malignant tumors: what 3 variations can carcinomas be seen?

1. Squamous cell carcinoma 2. Transitional cell carcinoma 3. Adenocarcinoma

What four steps occur when invasion of the ECM (extracellular matrix) occurs?

1. loosening of tumor cells 2. degradation of the ecm (extracell matrix) by proteases 3. novel attachments to ecm components 4. migration of tumor cells

Cancer cell proliferation in cell cycle:

1. oncogenes express growth factor receptors that are sensitive even to minimal quantity of growth factors 2. they mutate genes that encode signaling pathways 3.these growth promoting stimuli promote entry of quiescent cells into the cell cycle

Final cancer cell proliferation step:

CDKIs that suppress the CDKs are silenced, CDKs go on forming uncontrolled cell cycle progression

what is the second leading cause of death in the US?

Cancer

Where are the preferential routes of metastasis?

Carcinomas (lymphatics), sarcomas (blood vessels), or RCC (veins)

examples of microbial agents as carcinogenic agents?

DNA viruses (HPV, EBV, HBV), RNA viruses (retroviruses like HIV), bacteria (H. pylori)

marked neoplastic proliferation of connective tissue surrounding a proliferating glandular epithelium

Fibroadenoma

this leads to point mutations of genes, translocations of genetic material between chromosomes, or gene reduplication with amplification- The proto-oncogenes may play a role in growth promotion and regulation in normal cells, perhaps in embryogenesis, but are typically "turned off" in adults. They are "turned on" by transformation.

Genetic damage with DNA alterations

Anaplasia

Hallmark of malignancy, in which tumor cells are undifferentiated (structurally and functionally)

When is the neoplasm termed poorly differentiated?

If little resemblance to tissue of origin is seen

malignant tumors: carcinoma?

Is a malignant tumor of epithelial origin (from ectoderm, endoderm, or mesoderm)

malignant tumors: sarcoma?

Is a malignant tumor of mesenchymal origin.

What are papillomas composed of?

Is composed of delicate finger-like epithelial processes overlying a core of connective tissue stroma that contains blood vessels.

what are sarcoma (malignant) tumors used with a prefix for?

Is often used with a prefix that denotes the tissue of origin of the tumors eg: osteosarcoma (bone), rhabdomyosarcoma (striated muscle), lieomyosarcoma (smooth muscle) liposarcoma (fatty tissue) fibrosarcoma (fibrous tissue) chondrosarcoma ( cartilage)

Dysplasia definition?

Loss in uniformity of individual cells in epithelia with total architectural variation/abnormality (non-neoplastic)

an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues, and persists in the same excessive manner after the cessation of the stimuli which evoked the change

Neoplasm

Definition of neoplasia?

New growth

Is the stroma neoplastic?

No; non-neoplastic

characterized by adenomatous papillary processes that extend into cystic spaces such as a cystadenoma of the ovary?

Papillary cystadenoma

what do alterations in DNA transform?

These alterations transform proto-oncogenes into oncogenes.

What are the growth patterns of benign tumors?

They do not metastasize, and they grow slowly

What grows at the expense of function and vitality of normal tissue without benefit to the host, and are largely independent of host control mechanisms?

Tumors

Examples of radiant energy as carcinogenic agents?

UV rays, x-rays, nuclear fission

Are benign tumors well or poorly differentiated and why?

Well- differentiated, because it closely resembles the tissue of origin

When is the neoplasm termed well-differentiated?

When the resemblance of parenchyma to tissue of origin is close

Are benign tumors typically encapsulated? When are they not?

Yes, except in the leiomyoma of the uterus

Types of anaplasia: mitosis normal or abnormal?

abnormal mitosis

Types of anaplasia: cellular dyspolarity

abnormal orientation

what Is a benign neoplasm arising from glandular epithelium or has a glandular pattern?

adenoma

Are anaplastic tumors aggressive or not?

aggressive

How are benign tumors classified?

based on their cells of origin Adenoma - from a gland or having a glandular pattern though not originating from a gland; Papilloma - having finger-like projections Polyp - a mass that projects above a mucosal surface Cystadenoma - hollow cystic masses

How are malignant tumors named?

based on tissue of origin, and cell pattern

why does hep C and B cause cancer?

because the chronic immune response from both of these, promotes tumorigenesis, not the actual virus

Does dysplasia occur before or after malignancy?

before

how do benign and malignant tumors grow/spread?

benign- generally remain localized to site of origin, do not infiltrate, invade, or metastasize. malignant: often invasive locally, metastasize to distant sites, spread different ways.

How is metastasis spread by sarcomas?

blood vessels- the liver and lung, which is drained by blood vessels is often involved

is teratoma malignant or benign?

both

How are benign tumors of mesenchymal origin named?

by the tissue of origin: leiomyoma, rhabdomyoma, lipoma, fibroma, and chondroma.

result of cancer cachexia?

calorie expenditure (use of calories) is high, despite low food intake- BMR is increased. breakdown of skeletal muscle protein also occurs

What are malignant tumors collectively referred to as?

cancer, meaning "crab" because they adhere to any part that they seize

what is the human papilloma virus?

causative virus for benign warts, squamous cell carcinoma of cervix, angiogenital, oropharyngeal regions and genital warts

The process of neoplasia begins with what?

cell transformation

What 3 classes of carcinogenic agents exist?

chemical agents, radiant energy, and microbial agents

staging

clinical assessment of the degree of localization or spread of the tumor

what is grading and staging?

clinical measures used for prognostic evaluation and planning of clinical treatment

What are stroma made of?

connective tissue, blood vessels, and inflammatory cells

What are parenchyma?

consisting of transformed or neoplastic cells, which determines the behavior of the tumor

Examples of endocrinopathies that are a type of paraneoplastic syndrome?

cushings syndrome, inappropriate secretion of ADH, hypercalcemia, hypoglycemia, polycythemia, hyperthyroidism

Types of anaplasia: hyperchromatism

darkly stained

examples of neurologic abnormalities that are a type of paraneoplastic syndrome?

dementia, cerebellar changes, peripheral neuropathies

examples of skin lesions that are a type of paraneoplastic syndrome?

dermatomyositis, acanthosis nigricans (dark velvety discoloration of skin)

benign tumors of mesenchymal origin: Hamartoma

disorganized, tumor-like overgrowth of cell types that are regularly found within the affected organ

Malignant tumor tissue of origin: what cells do carcinomas come from?

epithelial origin

do malignant tumors grow fast or slow?

faster

Malignant tumor cell pattern: what are adenocarcinomas?

glandular patterns

What do stroma provide support for?

growth of parenchymal cells

neoplastic definition

growth on tissue

what two types are benign tumors or mesenchymal origin?

hamartoma and choristoma

benign tumors of mesenchymal origin: choristoma

heterotopic rest of cells, when a small non-neoplastic area of normal tissue, which is misplaced within another organ

grading

histopathologic evaluation of a lesion based on the degree of cellular differentiation- establishes aggressiveness or level of malignancy

Metastasis

implantation into noncontiguous (non neighboring) sites

Acquired Preneoplastic Disorders: when does Hyperplastic and dysplastic proliferations occur?

in atypical endometrial hyperplasia, in dysplastic bronchial mucosa of smokers

Acquired Preneoplastic Disorders: where does Villous adenoma occur?

in colon

Acquired Preneoplastic Disorders: when does Persistent regenerative cell replication occur?

in margins of chronic fistula, long-unhealed skin wounds; cirrhosis of liver

Acquired Preneoplastic Disorders: when does Chronic atrophic gastritis occur?

in pernicious anemia, H. pylori infection

Types of anaplasia: nuclear cytoplasmic ration increased or decreased?

increased

What 3 characteristics do malignant tumors have?

invasion, metastasis, anaplasia

benign tumors of mesenchymal origin: example of hamartoma

irregular accumulation of blood vessels

why does HPV cause cancer?

it leads to loss of a tumor suppressor, activates cyclins, and inhibits apoptosis

how does dysplasia morphologically manifest?

manifests by disorderly maturation and cell spatial arrangement, marked variability in nuclear size/shape (pleomorphic), and increased/abnormal mitosis

Malignant tumor tissue of origin: what cells do sarcomas come from?

mesenchymal tissues

do malignant tumors resemble tissue of origin?

no

What is the direct acting of chemical carcinogenic agents?

no metabolic conversion is required here, weak carcinogens are involved. ex: alkylating agents

do malignant tumors retain functional capabilities of normal cells?

no- instead unexpected functions emerge

nonmelanoma versus menanoma cancers?

nonmelanoma-result of cumulative exposure to UV rays melanoma- occurs with intense intermittent exposures

Types of anaplasia: nuclei orientation?

nuclei bizzare in size, prominent nucleoli

Acquired Preneoplastic Disorders: where does Chronic ulcerative colitis Leukoplakia occur?

of buccal cavity, vulva, penis

These may play a role in growth promotion and regulation in normal cells, perhaps in embryogenesis, but are typically "turned off" in adults, once turned on in adults, they can begin to form fast growth of cells, even bad ones.

oncogenes

benign tumors of mesenchymal origin: example of choristoma?

pancreatic tissue within the stomach

what is a benign neoplasm most often arising from surface epithelium such as squamous epithelium of the skin, larynx, or tongue?

papilloma

What two basic components do all tumors have?

parenchyma and stroma

Malignant tumor cell pattern: scams cell carcinoma?

producing squamous cells

cancer cachexia

progressive loss of body fat and lean body mass with profound weakness, anorexia, and anemia

cause of cancer cachexia?

release of cytokines

What 3 pathways does metastasis occur?

seeding with body cavities, lymphatic spread, or hematogenous spread

How is metastasis spread by carcinomas?

sentinel lymph nodes, which is the first lymph node that receives lymph from a primary tumor

Malignant tumor cell pattern: what are mixed tumors?

showing divergent components- e.g. mixed tumor of salivary gland, fibroadenoma of breast has ductal elements and fibrous tissue

what type of cancer does untraviolet radiation cause?

skin cancers

what are paraneoplastic syndromes mediated by?

specific proteins synthesized by tumor cells

Invasion

spread into adjacent structures

does grading or staging correlate better with prognosis?

staging

How are benign tumors, and some malignant tumors named?

suffix of -oma, ex benign: lipoma, chondroma ex malignant: hepatoma, melanoma

what are paraneoplastic syndromes?

symptom complexes in cancer patients, that cannot be explained by local or distant spread of tumor , or by hormones

What do oncogenes synthesize, once they are turned on?

synthesize specific growth factors to which they are responsive

what is a neoplasm derived from all three germ layers, which may contain, mature or immature cells or tissues such as skin, bone, cartilage, teeth, and intestinal epithelium.

teratoma

What is the invasion of cells that turn them cancerous?

the aggressive infiltration of adjacent tissues by a malignant tumor

what is indirect acting of chemical carcinogenic agents?

these require metabolic conversion to carcinogens (ex: dyes, polycyclic hydrocarbons into fossil fuels, nitrates used as food preservatives)

why are paraneoplastic syndromes important for diagnosis and treatment of cancer?

they often can be present in earliest features of cancer which can cause significant clinical problems such as being confused with metastatic diseases, instead of cancer- wrong treatment may be used

how does the release of cytokines by the TNF cause cancer cachexia?

tnf suppressed appetite and inhibits release of free fatty acid from lipoproteins, by inhibiting the action of the lipoprotein lipase

what type of cells do teratomas come from, and where do they normally arise?

totipotential stem cells, ovaries or testes

Besides the skin/larynx/tongue, where else can papillomas develop?

transitional epithelium of the urinary bladder, urethra, or renal pelvis.

What type of HPV is cancerous?

type 16 and 18

Types of anaplasia: pleomorphism

variation in size and shape

How is metastasis spread by RCC?

veins, which spread to IVC(inferior vena cava) and right heart

What is the Epstein barr virus, and why does it give cause to cancer?

virus occurring only in immunocompromised people, high occurrence in Africa, virus leads to multiple types of cancers

Although benign tumors are relatively innocent, when can they be harmful?

when their growth compresses adjacent tissues

ionizing radiation?

x-rays, nuclear fission, radionuclides- this type causes chromosome breakage,translocations, and point mutation

Can carcinomas by the sentinel lymph node be used to plan treatment of this type of cancer?

yes

Do benign tumors resemble tissue of origin?

yes

Is dysplasia reversible?

yes

are coagulation abnormalities that are a type of paraneoplastic syndrome?

yes