Exam V: Neoplasia Flashcards
Neoplasia
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)
Two Components of Neoplasms
Two basic components:
- Neoplastic cells- constitute the tumor parenchyma
- 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
Desmoplasia
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
Benign Tumors
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
Papillomas vs. Polyps
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
Cystadenomas and Papillary Cystadenomas
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
Malignant Tumors: Leukemia vs. Lymphoma
Leukemias(WBC): malignant tumors arising from blood-forming cells
Lymphoma: malignant tumors of lymphocytes or their precursors
Malignant Tumors: Carcinoma
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
Malignant Tumors
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
Sarcoma
Sarcomas (sar = fleshy): malignant tumors arising in solid mesenchymal tissues
Examples:
Fibrosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma
Mixed Tumors
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
Teratoma
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
Dermoid Cyst
Ovarian cystic teratoma
Differentiates principally along ectodermal lines
Cystic tumor lined by skin replete with hair, sebaceous glands, and tooth structures
Harmartoma
Hamartoma: disorganized benign masses composed of cells indigenous to the involved site
Choristoma
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
Differentiation vs. Anaplasia
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
Pleomorphism
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
Abnormal Nuclear Morphology
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
Mitoses
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
Metaplasia
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
Dysplasia
“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
Carcinoma In Situ
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
Local Invasion: Benign Tumors
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
Local Invasion: Malignant Tumors
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
Metastasis
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
Metastasis Likelihood
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
Pathways of Metastasis
Three pathways:
- Direct seeding of body cavities or surfaces
- Lymphatic spread
- Hematogenous spread
Iatrogenic spread of tumor cells on surgical instruments may occur
Biopsies of testicular masses are never done
Seeding of Body Cavities
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
Lymphatic Spread
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
Lymphatic Spread of Breast Cancer
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)
Hematogenous Spread
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
Teratoma: Benign vs. Malignant
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
Cancer Incidence: Men vs. Women
Most common tumors in men
Prostate, lung, and colon/rectum
Most common tumors in women
Breast, lung, and colon/rectum
Environmental Cancer Risk Factors: Infection, Smoking, and Alcohol
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
Environmental Cancer Risk Factors: Diet, Obesity, and Reproduction
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
Age and Cancer Risks
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
Acquired Conditions and Cancer
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
Cancer Precursor Lesions
Examples:
1. Barrett esophagus
2. Squamous metaplasiaof the bronchial mucosa and bladder mucosa
3. Colonic metaplasiaof 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: colonicvillous adenoma–progresses to cancer in about 50% of cases
Immunodeficiency States and Cancer
Deficits in T-cell immunity: increased risk for cancers
Oncogenic viruses can become lymphomas, carcinomas sarcomas, and sarcoma-like proliferations
Environmental Carcinogens
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)
Angiogenesis
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
Cancer Cachexia
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
Paraneoplastic Syndromes
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
Grading of Tumors
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
Staging of Tumors
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 Tfor primary tumor Nfor regional lymph node involvement Mfor metastases
Histologic and Cytologic Methods
Adequate, representative, and properly preserved specimen
Excision or biopsy- H & E stains of tissue
Needle aspiration
Cytologic smears
Frozen section
Fine Needle Aspirations
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
Cytologic Smears
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
UV vs. Ionizing Radiation
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.
Human T-cell Leukemia Virus Type 1 (oncogenic RNA virus)
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
Human Papilloma Virus (oncogenic DNA virus)
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
Epstein-Barr Virus (oncogenic DNA virus)
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
Hepatitis B and C Virus (oncogenic DNA virus)
Hep B and C: cause of 70-85% of hepatocellular carcinomas worldwide
Multifactorial: chronic inflammation, hepatocellular injury or proliferation
Helicobacter pylori
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
Immunohistochemistry
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
Flow Cytometry
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
