Exam V: Neoplasia

Question 1

Neoplasia

Answer 1

Defined as a disorder of cell growth
Triggered by a series of acquired mutations affecting a single cell and its clonal progeny
Causative mutations give the neoplastic cells a survival and growth advantage
Resulting in excessive proliferation that is independent of physiologic growth signals (autonomous)

Question 2

Two Components of Neoplasms

Answer 2

Two basic components:

1. Neoplastic cells- constitute the tumor parenchyma
2. Reactive stroma- CT, blood vessels, and cells of the immune system

Classification of tumors and their biologic behavior are primarily based on the parenchymal component (cell type present)

Growth and spread of tumors are critically dependent on their stroma because blood vessels and support are vital to growth

Question 3

Desmoplasia

Answer 3

Parenchymal cells stimulate the formation of abundant collagenous stroma

Have neoplastic cell nests and the body is trying to get rid of it
The parenchymal neoplastic cells will stimulate tissues around it
Abundant blue/gray surrounding tumor malignant islands = desmoplastic response; body’s way of reacting to the cells of the tumor

Question 4

Benign Tumors

Answer 4

Localized, innocent growth that will not spread to other sites
Amenable to local surgical removal
Designated by attaching the suffix-omato the name of the cell type of origin

Mesenchymal tumors:
Fibroma - benign tumor arising in fibrous tissue
Chondroma- benign cartilaginous tumor

Nomenclature of benign epithelial tumors—complex classification:
Some are classified based on their cells of origin, microscopic pattern, or macroscopic architecture

Adenoma- benign epithelial neoplasms derived from glands; may or may not form glandular structures

Question 5

Papillomas vs. Polyps

Answer 5

Papillomas: benign epithelial neoplasms; produce microscopically/macroscopically visible fingerlike or warty projections from epithelial surfaces

Polyp: can be benign or malignant
Macroscopically visible projection above a mucosal surface that projects into the lumen
If it has glandular tissue—-termed an adenomatous polyp
Mushroom like appearance

Question 6

Cystadenomas and Papillary Cystadenomas

Answer 6

Cystadenomas: large benign cystic masses, such as in the ovary; filled with serous fluid usually within the ovary or testicle

Papillary cystadenomas: benign papillary patterns that protrude into cystic spaces

Question 7

Malignant Tumors: Leukemia vs. Lymphoma

Answer 7

Leukemias(WBC): malignant tumors arising from blood-forming cells

Lymphoma: malignant tumors of lymphocytes or their precursors

Question 8

Malignant Tumors: Carcinoma

Answer 8

Carcinomas: malignant neoplasms of epithelial cell origin
Derived from any of the three germ layers (endo, meso, or ectoderm)

Squamous cell carcinoma: tumor cells resemble stratified squamous epithelium

Adenocarcinoma: lesion in which the neoplastic epithelial cells grow in a glandular pattern

Question 9

Malignant Tumors

Answer 9

Collectively referred to ascancers that adhere to any part that they seize on in an obstinate manner

Invade and destroy adjacent structures

Spread to distant sites (metastasize) to cause death

Question 10

Sarcoma

Answer 10

Sarcomas (sar = fleshy): malignant tumors arising in solid mesenchymal tissues

Examples:
Fibrosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma

Question 11

Mixed Tumors

Answer 11

Divergent differentiation of a single neoplastic clone

Example: mixed tumor of salivary gland
Epithelial components scattered within a myxoid stroma
May contain islands of cartilage or bone

All of these elements arise from a single clone capable of producing both epithelial and myoepithelial cells
Preferential term: pleomorphic adenoma

Can be benign or malignant

Question 12

Teratoma

Answer 12

Contains recognizable mature or immature cells/tissues
Tissues belong to more than one germ cell layer, sometimes all three

Originates from totipotential germ cells
Normally present in the ovary and testis
Differentiate into any of the cell types found in the adult body

May give rise to neoplasms: bone, epithelium, muscle, fat, nerve, and other tissues

Question 13

Dermoid Cyst

Answer 13

Ovarian cystic teratoma
Differentiates principally along ectodermal lines
Cystic tumor lined by skin replete with hair, sebaceous glands, and tooth structures

Question 14

Harmartoma

Answer 14

Hamartoma: disorganized benign masses composed of cells indigenous to the involved site

Question 15

Choristoma

Answer 15

Heterotopic rest of cells
Example: small nodule of well-developed and normally organized pancreatic tissue
Found in the submucosa of the stomach, duodenum, or small intestine
Caused by cells left behind during development that formed into the structure it was supposed to be

Question 16

Differentiation vs. Anaplasia

Answer 16

Differentiation
Extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells morphologically and functionally
Mitoses are usually rare and are of normal configuration

Anaplasia: lack of differentiation/ poorly differentiated
cells are regressing back to primitive appearance; must use stains to tell where cells came from
Lack of differ­entiation is considered a hallmark of malignancy

Question 17

Pleomorphism

Answer 17

Variation in size and shape
Cells within the same tumor are not uniform
Range: small cells with an undifferentiated appearance to tumor giant cells
Mostly associated with malignancy, but can be benign

Question 18

Abnormal Nuclear Morphology

Answer 18

Nuclei are disproportionately large for the cell
Nuclear-to-cytoplasm ratio may approach 1 : 1
Normal 1 : 4 or 1 : 6
Nuclear shape–variable and irregular

Chromatin: coarsely clumped when normally distributed along the nuclear membrane
Hyperchromatic
Abnormally large nucleoli

Question 19

Mitoses

Answer 19

Reflects the high proliferative activity of the parenchymal cells in a tumor
Presence does not necessarily indicate malignancy
Indicative of rapid cell growth

Seen in normal tissues exhibiting rapid turnover
Epithelial lining of the gut
Nonneoplastic proliferations—hyperplasia

Atypical, bizarre mitotic figures:
Tripolar, quadripolar, or multipolar spindles
Morphologic feature of malignancy

Question 20

Metaplasia

Answer 20

Replacement of one type of cell with another type
Found in association with tissue damage, repair, and regeneration
Replacing cell type is better suited to some alteration in the local environment

Example: Gastroesophageal reflux
Damages the squamous epithelium of the esoph­agus
Replacement by glandular (gastric or intestinal) epithelium

Question 21

Dysplasia

Answer 21

“Disordered growth”
Encountered principally in epithelia 
Loss in the uniformity of the individual cells
Loss in their architectural orientation
Considerable pleomorphism
Large hyperchromatic nuclei 
Increased nuclear-to-cytoplasmic ratio

Normally more immature cells at basement membrane, and are larger; by the time you get to the surface of the cells, they should be thinned out and smaller from maturation
If this does not occur = dysplasia

Question 22

Carcinoma In Situ

Answer 22

Dysplastic changes are marked and involve the full thickness of the epithelium
Lesion DOES NOT penetrate the basement membrane

Precursor to malignancy, HOWEVER, it does not always progress to cancer
Removal of inciting causes—may reverse
Mild to moderate dysplasia (not involving entire epithelium)
Dysplasia often occurs in metaplastic epithelium BUT…not all metaplastic epithelium is dysplastic

Question 23

Local Invasion: Benign Tumors

Answer 23

Progressive infiltration, invasion, and destruction of the surrounding tissue

Benign tumors:
Cohesive expansile masses that remain localized to their site of origin
Lack the capacity to infiltrate, invade, or metastasize to distant sites
Develop acapsule= rim of compressed fibrous tissue that separates them from the host tissue that consists of extracellular matrix deposited by stromal cells such as fibroblasts
Activated by actual hypoxic change- damage from expanding tumor and see infiltration with fibroblasts from body to wall it off
Creates a tissue plane that makes the tumor discrete, readily palpable, moveable (non-fixed), and easily excisable

Question 24

Local Invasion: Malignant Tumors

Answer 24

Malignant tumors:
Poorly demarcated from surrounding normal tissue
Well-defined cleavage plane is lacking
Do not recognize normal anatomic boundaries
Penetrate the wall of the colon or uterus
Fungate through the surface of the skin
Surgical resection–difficult or impossible
If epithelial in origin and penetrates the basement membrane = invasive carcinoma

Invasiveness: most reliable feature
Differentiates cancers from benign tumors

Question 25

Metastasis

Answer 25

Spread of a tumor to sites that are physically discontinuous with the primary tumor Unequivocally marks a tumor as malignant because benign neoplasms do not metastasize All malignant tumors can metastasize, some less frequently Malignant neoplasms of the glial cells (CNS)---gliomas Basal cell carcinomas of the skin

Question 26

Metastasis Likelihood

Answer 26

Likelihood of a primary tumor metastasizing correlates with: Lack of differentiation, aggressive local invasion, rapid growth, and large size Approximately 30% of newly diagnosed solid tumors present with metastases excluding skin cancers other than melanomas Metastatic spread strongly reduces the possibility of cure Blood cancers (leukemias and lymphomas): Disseminated at diagnosis Always malignant

Question 27

Pathways of Metastasis

Answer 27

Three pathways: 1. Direct seeding of body cavities or surfaces 2. Lymphatic spread 3. Hematogenous spread Iatrogenic spread of tumor cells on surgical instruments may occur Biopsies of testicular masses are never done

Question 28

Seeding of Body Cavities

Answer 28

Malignant neoplasm penetrates into a natural “open field”, and lacks physical barriers; Example: peritoneal cavity Characteristic of carcinomas arising in the ovaries Mucus-secreting appendiceal carcinomas or ovarian carcinomas Fill peritoneal cavity with a gelatinous neoplastic mass= Pseudomyxoma peritonei

Question 29

Lymphatic Spread

Answer 29

Most common pathway for the initial dissemination of carcinomas Sarcomas may also use this route Pattern of lymph node involvement Follows the natural routes of lymphatic drainage Local lymph nodes, however, may be bypassed= skip metastasis Venous-lymphatic anastomoses Inflammation or radiation has obliterated lymphatic channels

Question 30

Lymphatic Spread of Breast Cancer

Answer 30

Breast cancer: axillary lymph node involvement is important for assessing disease and therapeutic strategies Biopsy of sentinel nodes: assesses the presence or absence of metastatic lesions in the lymph nodes Sentinel lymph node: defined as “the first node in a regional lymphatic basin that receives lymph flow from the primary tumor” Sentinel node mapping: injection of radiolabeled tracers or colored dyes Examination of frozen sections of the sentinel lymph node (during surgery)

Question 31

Hematogenous Spread

Answer 31

Typical of sarcomas, but also seen with carcinomas Arteries--thicker walls: less readily penetrated than veins Liver and the lungs--most frequently involved in spread Cancers in close proximity to the vertebral column embolize through the paravertebral plexus Frequent vertebral metastases of carcinomas of the thyroid and prostate Invasion of veins: Renal cell carcinoma: invades the branches of the renal vein and then the renal vein itself Hepatocellular carcinomas: portal and hepatic radicles to grow within them into the main venous channels

Question 32

Teratoma: Benign vs. Malignant

Answer 32

In the ovary, if composed of immature/primitive cells then it is malignant, but if more uniform than it is benign In the testicles, if pre-puberty it is benign, but is post-puberty than it is malignant. It does not depend on the cell type, just the age of the patient

Question 33

Cancer Incidence: Men vs. Women

Answer 33

Most common tumors in men Prostate, lung, and colon/rectum Most common tumors in women Breast, lung, and colon/rectum

Question 34

Environmental Cancer Risk Factors: Infection, Smoking, and Alcohol

Answer 34

Infectious agents: 15% of all cancers worldwide Human papilloma virus (HPV)--cervical carcinoma and increasing head and neck cancers Smoking: implicated in cancer of the mouth, pharynx, larynx, esophagus, pancreas, bladder; about 90% of lung cancer deaths Alcohol abuse: increases the risk of carcinomas of the oropharynx (excluding lip), larynx, and esophagus and, by the development of alcoholic cirrhosis, hepatocellular carcinoma Alcohol and tobacco together: synergistically increase the risk of cancers in the upper airways and digestive tract

Question 35

Environmental Cancer Risk Factors: Diet, Obesity, and Reproduction

Answer 35

Diet: incidences of colorectal carcinoma, prostate carcinoma, and breast carcinoma has been ascribed to differences in diet Obesity: most overweight individuals in the U.S. population have 52% (men) to 62% (women) higher death rates from cancer Approximately 14% of cancer deaths in men and 20% in women can be attributed to obesity Reproductive history: strong evidence of lifelong cumulative exposure to unopposed estrogen stimulation Increased risk of cancers of the breast and endometrium aka no children = higher risk

Question 36

Age and Cancer Risks

Answer 36

Most carcinomas occur in the later years of life (>55 years) Cancer is the main cause of death Women aged 40 to 79 Men aged 60 to 79 Accumulation of somatic mutations associated with the emergence of malignant neoplasms Decline in immune competence that accompanies aging Cancer accounts for slightly more than 10% of all deaths in children younger than age 15 in the US Second only to accidents

Question 37

Acquired Conditions and Cancer

Answer 37

Chronic inflammations Tumors arising in this context: Mainly carcinomas, mesotheliomas, lymphomas Example: H. pylori infection = gastric cancer Precursor Lesions: localized morphologic change associated with a high risk of cancer, especially in epithelial surfaces Immunodeficiency states: viral induced cancers

Question 38

Cancer Precursor Lesions

Answer 38

Examples: 1. Barrett esophagus 2. Squamous metaplasia of the bronchial mucosa and bladder mucosa 3. Colonic metaplasia of the stomach (pernicious anemia and chronic atrophic gastritis) 4. Noninflammatory hyperplasias: endometrial hyperplasia 5. Leukoplakia: thickening of squamous epithelium can give rise to squamous carcinoma Oral cavity, penis, or vulva 6. Benign neoplasms: colonic villous adenoma--progresses to cancer in about 50% of cases

Question 39

Immunodeficiency States and Cancer

Answer 39

Deficits in T-cell immunity: increased risk for cancers | Oncogenic viruses can become lymphomas, carcinomas sarcomas, and sarcoma-like proliferations

Question 40

Environmental Carcinogens

Answer 40

Well-characterized environmental carcinogens: Ambient environment, workplace, food, and in personal practices can lead to exposure to carcinogenic factors Ultraviolet [UV] rays, smog Drink well water (arsenic, particularly in Bangladesh) Medications (methotrexate) Work (asbestos) Lounging at home (grilled meat, high-fat diet, alcohol)

Question 41

Angiogenesis

Answer 41

A tumor cannot enlarge beyond 1 to 2 mm in diameter unless it has the capacity to induce angiogenesis 1- to 2-mm zone represents the maximal distance across which oxy­gen, nutrients, and waste can diffuse from blood vessels Growing cancers stimulate neoangiogenesis Vessels sprout from previously existing capillaries Dual effect on tumor growth: Perfusion supplies needed nutrients and oxygen Newly formed endothelial cells stimulate the growth of adjacent tumor cells Secrete growth factors

Question 42

Cancer Cachexia

Answer 42

Progressive loss of body fat and lean body mass Profound weakness, anorexia, and anemia Associated with: Equal loss of both fat and lean muscle Elevated basal metabolic rate Evidence of systemic inflammation

Question 43

Paraneoplastic Syndromes

Answer 43

Someone has a specific tumor, but they have symptoms that don’t correlate with the type of tumor they have Elaboration of signs and symptoms: Not explained by the anatomic distribution of the tumor Not explained by the elaboration of hormones indigenous to the tissue from which the tumor arose Clinical importance: May be the earliest manifestation of an occult neoplasm Cause significant clinical problems and may even be lethal May mimic metastatic disease and therefore confound treatment

Question 44

Grading of Tumors

Answer 44

Based on the degree of differentiation of the tumor cells Number of mitoses Architectural features Grading schemes Evolved for each type of malignancy Range from two categories (low grade and high grade) to four categories Histologic grading is useful…however… Correlation between histologic appearance and biologic behavior/clinical use is less than perfect AKA may look histologically aggressive, but clinically isn’t doing much

Question 45

Staging of Tumors

Answer 45

Based on: Size of the primary lesion Extent of spread to regional lymph nodes Presence or absence of blood-borne metastases ``` American Joint Committee on Cancer Staging (AJCC) TNM system T for primary tumor N for regional lymph node involvement M for metastases ```

Question 46

Histologic and Cytologic Methods

Answer 46

Adequate, representative, and properly preserved specimen Excision or biopsy- H & E stains of tissue Needle aspiration Cytologic smears Frozen section

Question 47

Fine Needle Aspirations

Answer 47

Aspirating cells and attendant fluid with a small-bore needle followed by cytologic examination of the stained smear Most commonly used in assessment of palpable lesions: Breast, thyroid, and lymph nodes Less invasive More rapidly performed than needle biopsies

Question 48

Cytologic Smears 

Answer 48

``` Screen for carcinoma of the cervix Endometrial carcinoma Lung carcinoma Bladder and prostatic tumors Gastric carcinomas Identification of tumor cells in abdominal, pleural, joint, and cerebrospinal fluids ```

Question 49

UV vs. Ionizing Radiation

Answer 49

UV: particularly in fair skinned individuals, exposure to UV increases the risk of squamous cell carcinoma, basal cell carcinoma, and melanoma of the skin. The risk depends on intensity of UV rays, type of UV rays, and amount of protective melanin. Formation of pyrimidine dimers in the DNA, distorting the helix. Ionizing Radiation: electromagnetic (gamma and x-rays) and particulate (alpha, beta, protons, and neutrons) are all carcinogenic by causing chromosome breakage, translocations, and point mutations.

Question 50

Human T-cell Leukemia Virus Type 1 (oncogenic RNA virus)

Answer 50

HTLV-1: retrovirus endemic in Japan, Caribbean, South America, and Africa that causes adult T cell leukemia/lymphoma Polyclonal expansion of T cells, and after latent period, the cancer is developed from acquisition of additional mutations

Question 51

Human Papilloma Virus (oncogenic DNA virus)

Answer 51

HPV: cause of benign warts, cervical cancer, and oropharyngeal cancer Integration of the HPV into the host genome along with additional mutations Vaccinations are available to prevent these cancers

Question 52

Epstein-Barr Virus (oncogenic DNA virus)

Answer 52

EBV: herpes virus causing Burkitt lymphomas, B cell lymphomas in T cell suppressed patients, among other cancers Stimulation of B cell pathways causes B cell growth and transformation, and without T cells, this process can become aggressive whereas normal T cell levels have a lower risk of this occurring

Question 53

Hepatitis B and C Virus (oncogenic DNA virus)

Answer 53

Hep B and C: cause of 70-85% of hepatocellular carcinomas worldwide Multifactorial: chronic inflammation, hepatocellular injury or proliferation

Question 54

Helicobacter pylori

Answer 54

H. pylori: in gastric adenocarcinoma and MALT lymphoma Multifactorial: chronic inflammation and gastric cell proliferation H. pylori infections can lead to polyclonal B cell proliferations that give rise to monoclonal B cell tumor (MALT) of the stomach as a result of accumulation of mutations

Question 55

Immunohistochemistry

Answer 55

The availability of specific Ab that identify specific cell products or surface markers Categorization of undifferentiated malignant tumors Determination of site of origin of metastatic tumors Detection of molecules that have prognostic or therapeutic significance

Question 56

Flow Cytometry

Answer 56

Can rapidly and quantitatively measure several individual cell characteristics, but mainly used to identify cellular antigens expressed by "liquid" tumors, those that arise from blood-forming tissues B and T cell lymphomas and leukemias, as well as myeloid neoplasms Advantage: multiple antigens can be assessed simultaneously on individual cells using combinations of specific Ab linked to different fluorescent dyes