onco-intro-neoplasia Flashcards
Is neoplasm monoclonal in origin?
Yes, it arises from a single progeny tumor cell
Abnormal mass of tissues, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change
Neoplasm
Neoplasm are heritable (genetic) changes that allow excessive and unregulated proliferation that is independent of…
Independent of physiologic growth-regulatory stimuli
A characteristic of neoplastic cells which said to be transformed because they continue to replicate, apparently oblivious to the regulatory influences that control normal cell growth.
Cellular autonomy
T/F: some neoplasms require endocrine support, and such dependencies sometimes can be exploited to the disadvantage of the neoplasm
True
Types of neoplasm are based on…
Neoplasm’s potential clinical behaviour
T/F: benign tumors are sometimes responsible for serious disease.
True
T/F: benign tumors can not produce more than one localized lumps
False. It can produce more than one localized lump
Malignant tumors are collectively known as
Cancers
T/F: all cancers pursue to deadly course
False. Not all cancers are deadly, some are less aggressive and are treated successfully, but the designation MALIGNANT constitutes a RED FLAG.
Basic components of tumor
Parenchyma and stroma
Component of tumor that is made up of transformed or neoplastic cells
Parenchyma
Component of tumor that largely determines its biologic behaviour
Parenchyma
Component of tumor from which derives its name
Parenchyma
T/F: parenchymal cells in a neoplasm, whether benign or malignant, are different from each other.
False, they resembles each other, as though all had been derived from a single progenitor.
Component of tumor that is supporting, host-derived, non neoplastic.
Stroma
Component of tumor that is made up of connective tissue, blood vessels, and host-derived inflammatory cells.
Stroma
Component of tumor that Determines its growth and evolution.
Stroma
Benign epithelial neoplasm producing gland patterns. Or neoplasms derived from glands but not necessarily produce gland patterns
Adenoma
Benign epithelial neoplasms, growing on any surface, that produce microscopic finger like fronds
Papilloma
Malignant neoplasm arising in mesenchymal tissue or its derivatives.
Sarcoma
Malignant neoplasm of epithelial cell origin
Carcinoma
Malignant neoplasm of epithelial cell origin that grow in a glandular pattern
Adenocarcinoma
Malignant neoplasm that produces squamous cells.
Squamous cell carcinoma
Tumors that are characterized by divergent differentiation
Mixed tumor
Preferred designation of mixed tumors
Pleomorphic adenoma
Mixed tumor with obvious epithelial components dispersed throughout a fibromyxoidstroma, sometimes harboring islands of glands, cartilage or bone.
Pleomorphic adenoma - mixed tumor of salivary gland
Mixed tumor which is benign and contains mixture of proliferated Ductal elements(adenoma) embedded in a loose fibrous tissue
Fibroadenoma of female breast
Tumor that contain recognizable mature or immature cells or tissues representative of more than one germ cell layer and sometimes all three.
Teratoma
Teratoma originates from what kind of stem cells
Totipotential stem cells (that normally presented in the ovary and testis and abnormally present in sequestered midline embryonic rests
Tumor that has the capacity to differentiate into any of the cell types found in the adult body
Teratoma
Tumor that may give rise to neoplasms that mimic, in a helter-skelter fashion, bits of bone, epithelium, muscle, fat, nerve and other tissue
Teratoma
Malformation that presents as a mass of disorganized tissue indigenous to the particular site
Hamartoma
Heterotopic rest of cells
Choristoma
Choristoma may be replete or filled with..
Islets of langerhans and endocrine glands
Benign tumor of fibrous tissue
Fibroma
Malignant tumor of fibrous tissue
Fibrosarcoma
Benign tumor of fat cells
Lipoma
Malignant tumor of fat cells
Liposarcoma
Benign tumor of cartilage
Chondroma
Malignant tumor of cartilage
Chondrosarcoma
Benign tumor of bone
OSTEOMA
Malignant tumor of bone
Osteogenic sarcoma
Benign tumor of blood vessels
Hemangioma
Malignant tumor of blood vessels
Angiosarcoma
Benign tumor of lymph vessels
Lymphangioma
Malignant tumor of lymph vessels
Lymphangiosarcoma
Benign tumor of synovium
None
Malignant tumor of synovium
Synovial sarcoma
Benign tumor of mesothelium
None
Malignant tumor of mesothelium
Mesothelioma
Benign tumor of Brain coverings
Meningioma
Malignant tumor of Brain coverings
Invasive meningioma
Benign tumor of hematopoietic cells
None
Malignant tumor of hematopoietic cells
Leukemia
Benign tumor of lymphoid tissue
None
Malignant tumor of lymphoid tissue
Lymphoma
Benign tumor of smooth muscles
Leiomyoma
Malignant tumor of smooth muscle
Leiomyosarcoma
Benign tumor of striated muscle
Rhabdomyoma
Malignant tumor of striated muscle
Rhabdomyosarcoma
Benign tumor of stratified squamous
Squamous cell papilloma
Malignant tumor of stratified squamous
Squamous cell / epidermoid carcinoma
Benign tumor of basal cells of skin or adnexa
None
Malignant tumor of basal cells of skin or adnexa
Basal cell carcinoma
Malignant counterpart of adenoma
Adenocarcinoma
Malignant counterpart of papilloma
Papillary carcinoma
Malignant counterpart of cystadenoma
Cystadenocarcinoma
Benign tumor of respiratory passage
Bronchial adenoma
Malignant tumor of respiratory passage
Bronchogenic carcinoma
Benign tumor of renal epithelium
Renal tubular adenoma
Malignant tumor of renal epithelium
Renal cell carcinoma
Benign tumor of liver cells
Liver cell adenoma
Malignant tumor of liver cells
Hepatocellular carcinoma
Benign tumor of urinary tract epithelium
Transitional cell / urothelial papilloma
Malignant tumor of urinary tract epithelium
Transitional cell / urothelial carcinoma
Benign tumor of placental epithelium
Hydatidiform mole
Malignant tumor of placental epithelium
Choriocarcinoma
Benign tumor of testicular epithelium (germ cells)
None
Malignant tumor of testicular epithelium (germ cells)
Seminoma
Embryonal carcinoma
Benign tumor of melanocytes
NEVUS
Malignant tumors of melanocytes
Malignant melanoma
More than one neoplastic cell type: Mixed tumors, usually derived from one germ layer
Benign tumor of salivary gland
Pleomorphic adenoma
More than one neoplastic cell type: Mixed tumors, usually derived from one germ layer
Malignant tumor of salivary gland
Malignant mixed tumor of SG origin
More than one neoplastic cell type: Mixed tumors, usually derived from one germ layer
Benign tumor of renal anlage
None
More than one neoplastic cell type: Mixed tumors, usually derived from one germ layer
Malignant tumor of renal anlage
Wilms tumor
More than one neoplastic cell type: Teratogenous-derived from more than one germ layer
Benign tumor of totipotential cells in gonads/ embryonic rests
Mature teratoma, dermoid cyst
More than one neoplastic cell type: Teratogenous-derived from more than one germ layer
Malignant tumor of totipotential cells in gonads/ embryonic rests
Immature teratoma, teratocarcinoma
Four fundamental features of benign and malignant tumors
- Differentiation and anaplasia
- Rate of growth
- Local invasion
- Metastasis
Which component of tumor is referred in differentiation and anaplasia?
Parenchymal cells (which constitutes the transformed elements of neoplasm)
It refers to the extent to which cells resemble their normal forebears morphologic ally and functionally.
Differentiation
T/F: stroma does not aid in the separation of benign from malignant ones
True
It determines the consistency of a neoplasm
Stroma
Cancers which induce a dense, abundant fibrous stroma (desmoplasia), making them hard
Scirrhous tumor
T/f: in well diff benign tumors, mitosis are extremely scant in number and are of normal configuratio
True
Benign/malignant tumors are composed of well-diff cells that closely resembles their normal counterparts.
Benign
Benign/malignant tumors are characterized by a wide range of cell differentiation, form well-diff to completely undiff.
Malignant
The better the differentiation of the cell, the more completely it retains the ____ found in its normal counterparts.
Functional capabilities
Exception to the the principle of retaining functional capabilities as having better differentiation.
Certain lung carcinomas
T/f: the more rapidly growing and the more anaplastic tumor, the less likely to have specialized functional activity
True
“To form backward”
Anaplasia
It impose de differentiation, or loss of structural and functional differentiation of normal cells
Anaplasia
It is the most extreme disturbance in cell growth encountered in the spectrum of cellular proliferations
Anaplasia
Hallmark of malignancy
Anaplasia
Anaplastic cells displays marked…
Pleomorphism (variation in size and shape)
Marked pleomorphism do anaplasia is characterized by:
- Nuclei are variable and bizarre in size and shape
- Hyperchromatic and large nuclei
- 1:1 nuclear-to-cytoplasmic ratio (normal 1:4 / 1:6)
- Coarse and clumped chromatin and large nucleoli
- Atypical and numerous mitosis
- Presence of Tripolar or quadripolar forms of anarchic multiple spindles
- Fails to develop recognizable patterns of orientation to one another (lose normal polarity)
Describes disorderly but non neoplastic proliferation
Dysplasia
DYSPLASIA is encountered principally in..
Epithelia
It is loss of uniformity of individual cells and in their architectural orientation.
DYSPLASIA
Characteristics do dysplastic cells
- Pleomorphic
- Hyperchromatic and large nuclei
- Mitotic figures are abundant than usual
- Mitosis appear in abnormal locations within the epithelium
- Considerable architectural anarchy
Refers to marked dysplastic changes involving the ENTIRE thickness of the epithelium
Carcinoma-in-situ
Pre-invasive stage of cancer
Carcinoma-in-situ
T/F: dysplasia without qualifications does not indicate cancer
True
T/F: dysplasia do not necessarily progress to cancer
True
T/F: Mild to moderate changes that do not involve entire thickness of epithelium may be reversible, but even with the removal of the putative inciting causes, the epithelium can’t revert to normal.
It is TRUE that it is reversible however, with the removal of the inciting cause, it CAN REVERT to NORMAL.
Factors affecting the rate of growth of neoplasms
- Hormones
- Blood supply
- Location
T/F: rate of growth of malignant tumors correlates in general with their level of differentiation.
True. Rapidly growing tumors tend to be poorly diff.
T/F: most, if not all, cancers take years and sometimes decades to evolve into clinically overt lesions
True
Why is that growing malignant tumor often contain a central ischemic necrosis?
Because the blood supply of tumor, which is derived form the host, fails to keep pace with the oxygen needs of the expanding mass of cells.
T/F: not all benign tumors are encapsulated
True. As leiomyoma of uterus
T/F: lack of capsule implies that the tumor is malignant.
False. Some benign tumors neither encapsulated nor demarcated, such as benign tumor of dermis.
Cancers grow by progressive…
Infiltration, invasion, destruction and penetration of the surrounding tissues.
Ned to the development of metastasis, what is the most reliable feature that distinguishes malignant from benign?
Local invasiveness
what is the most reliable feature that distinguishes malignant from benign?
Metastasis
It connotes the development of secondary implants discontinuous with the primary tumor in remote tissues.
Metastasis
Not all of the cancer have equivalent ability to metastasize. What are the examples?
Basal cell carcinoma of skin - highly invasive in primary site but rarely metastasize;
Osteogenic sarcoma - usually metastasize to lungs at the time of initial discovery
In general, the more anaplastic and large the primary neoplasm, the more likely is metastatic spread
However some small cancers have been known to metastasize and conversely, some large and ominous-looking lesions may not spread.
Malignant neoplasms disseminate by..
- Spread by seeding
- Hematogenous spread
- Lymphatic spread
Metastasis that occurs when neoplasm invades a natural body cavity.
Spread by seeding
Sample of cancers that spread by seeding
Cancers of ovary
Medulloblastoma or ependymoma (cerebral ventricles, may be carried by CSF to re implant on meningeal surface)
Metastatic spread by carcinoma
Lymphatic spread
Metastatic spread by sarcoma
Hematogenous spread
The pattern of lymph node involvement depends principally on…
On the site of primary neoplasm and natural pathways of lymphatic drainage of the site
Lymphatic spread of lung carcinoma
Arising form respiratory passages metastasize first to regional bronchial lymph nodes, then tracheobronchial and hilar nodes
Lymphatic spread of breast carcinoma
Arising in the upper outer quadrant and first spreads to axillary nodes. Median breast lesion may spread through chest wall to the nodes along the internal mammary artery. Thereafter, in both instances, supraclavicular and infraclavicular node may be seeded.
First lymph node in a regional lymphatic basin that receives lymph flow from a primary tumor.
Sentinel lymph node
Sentinel lymph nodes can be delineated by injection of..
Blue dyes or radiolabelled tracers
T/F: sentinel lymph nodes allow determination of the extent of spread of tumor, and can be used to plan treatment
True
T/F: enlargement of nodes near a primary tumor should arouse strong suspicion of metastatic spread and will always imply cancerous involvement.
False. Does not always imply cancerous involvement
The necrotic changes in the neoplasm and tumor antigens often evoke reactive changes in the nodes.. Such as
Lymphadenitis (enlargement and hyperplasia of follicles) and Sinus histiocytosis (proliferation of macrophages in the sub capsular sinuses)
Most feared consequence of cancer
Hematogenous spread
In hematogenous spread, which is less readily penetrated? Arteries or veins?
Arteries
With venous invasion, the blood-borne cells follow the venous flow draining the site of neoplasm, with the tumor cells often stopping in …
The first capillary bed they encounter
Most frequently involved secondary sites in hematogenous dissemination.
Liver and lungs
Why is that the liver and lungs are the most frequently involved secondary sites in hematogenous spread?
Because all portal area drainage flows to the liver and all caval blood flows to the lungs
Cancers arising near the vertebral column often embolize through the …
Paravertebral plexus
Cancers arising near the vertebral column often embolize thru paravertebral plexus; this pathway is involved in the frequent vertebral metastasis of carcinoma of..
Thyroid and prostate
Hematogenous spread of renal cell carcinoma
Invades the Rena veins to grow to snake like fashion up to IVC, reaching the right side of heart
Prostatic carcinoma preferentially spreads to
Bone
Bronchogenic carcinoma tend to involve
Adrenals and brain
Neuroblastoma spread to
Liver and bones
T/F: skeletal muscles are rich in capillaries therefore it is commonly the site if secondary deposits.
False.
Benign tumor with hollow spaces inside
Cystadenoma
Carcinoma/sarcoma: they are fleshy because it has little connective tissue
Sarcoma
Benign tumors that projects upward forming a lump. It is macroscopically visible projection.
Polyp
Next step after Carcinoma in situ
Invasive carcinoma
Differentiation: any cell type/only epithelial cells
Dysplasia: only neoplastic/non neoplastic cells
Differentiation: only neoplastic cells of any cell type
Dysplasia: only epithelial cells of non neoplastic cells
Lymph node that is first to be affected
Sentinel lymph node
T/F: the entire population of cells within a tumor arises from a single cell that has incurred genetic changes
True
Well diff/ undiff cancers:
Cells evolve from maturation / specialization as they proliferate.
Well diff
Well diff/ undiff cancers:
Cells are derived from proliferation without complete maturation of transformed cell.
Undiff
Cancer stem cell characteristics
Self renewing capacity
Malignant tumor that do not or rarely metastasize
Glioma
Basal cell carcinoma
T/f: fast growing tumor have high cell turnover (cell prolif=apoptosis)
True
Fraction of cells that are Actively proliferating
Growth fraction
Clinically detectable tumor contains ____ cells
10 billion cells
Cancer occurs mostly at age >55 because of accumulation of somatic mutation and decline of Immune surveillance. It is the main cause of death in women in ages… And in men in ages…
Women: 40-79
Men: 60-79
RB gene
Retinoblastoma
p53
Li-fraumeni syndrome
P16/INK4A
Melanoma
APC
Familial adenomatous polyposis colon Ca
NF1, NF 2
Neurofibromatosis
BRCA1 and BRCA2
Breast, and ovarian Ca
MEN1 and RET
Multiple endocrine neoplasia 1&2
MSH2&6, MLH1
Hereditary non polyposis colon Ca
PTCH
Nevoid BCC syndrome
PTEN
Cowden syndrome
LKB1
Peutz-Jegher syndrome
VHL
RCC
WT1
Wilms tumor
Chronic inflammation of Ca
- Increases the pool of stem cells that can be subject to the effects of mutagens
- Produces cytokines and GF to drive cell survival and proliferation
- Promotes genome instability by producing ROS
Nomenclature of specific malignant tumors is based in their appearance and presumed cell of origin
Precancerous condition is a misnomer. There is no malignant transformation that occurs, most malignant tumors arise de novo.
Fundamental principles in molecular basis of Ca
- Non-lethal genetic damage underlies carcinogenesis
- tumor develops as a clonal progeny of a single genetically damaged progenitor cell
- 4’classes of normal regulatory genes are targeted by genetic damage
4’classes of normal regulatory genes are targeted by genetic damage
- Growth promoting proto oncogenes
- Growth inhibiting tumor suppressor genes
- Genes for apoptosis
- Gens for DNA repair
Essential alteration for malignant transformation
- Self sufficiency in growth signals
- Insensitivity to growth inhibitory signals
- Evasion of apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Ability to invade and metastasize
- Ability to escape immune recognition and regulation
Cancer is characterized by proliferation in the absence of…
Growth promoting signals
Oncogenes promotes..
Autonomous cell growth
DNA repair genes are not directly carcinogenic. Defects can occur in 3 types of DNA repair system:
- Mismatch repair (eg. Hnccs)
- Nucleotide excision repair (xeroderma pigmentosa)
- Recombination repair (p53, brca1&2)
Cancer cells preferentially utilize glycolysis rather than oxidative phosphorylation. It is to shun important precursor molecule into new lipid and nucleotide synthesis
Metabolic alteration - Warburg effect
Hypercalcemia
SCC
Breast Ca
RCC
Cushing’s syndrome
SCLC
Pancreatic Ca
SIADH
SCLC
Hypoglycemia
Ovarian Ca
Fibrosarcoma
Carcinoid syndrome
HCC
Bronchial adenoma
Pancreatic Ca
Polycythemia
Gastric Ca
RCC
HCC
Myasthenia
Bronchogenic Ca
Disorder of cns and pns
Breast Ca
Acanthosis nigricans
Gastric Ca
Bronchogenic Ca
Uterine Ca
Dermatomyositis
Bronchogenic Ca
Breast Ca
Osteoarthropathy
Bronchogenic Ca
Vascular and hematologic
Pancreatic Ca
Bronchogenic Ca
Grading is based on
The degree of differentiation and architectural features and no of mitosis.
Used as parameters of clinical gravity of the disease.
Staging is based on…
Tumor size, lymph node involvement and extent of spread.
It aids in treatment choice and prognostication
Most important method of diagnosis
Histologic examination
T/F. False negative result is more common in histo.exam.
True
Lab diagnosis which involves monoclonal ab to identify cell products or surface markers
Immunohistochemistry
Use of immunohistochemistry
- Categorize undiff tumors
- Determine site of origin of metastatic tumors
- Detect prognostic and therapeutic markers
Serum tumor markers
Carcinoembryonic ag (Ca of colon, pancreas, stomach, breast)
Alpha-fetoprotein (yolk sac and liver)
Prostate-specific ag
In inherited Ca syndrome, a single mutant gene increases cancer risk by..
- Pt mutation of 1 allele (RB, APC)
2. Silencing of 2nd allele somatically (C deletion or recombination)
Prototypic anti apoptotic protein which limits the exit of cytochrome c from mitochondria
BCL2
Doubling time of normal cell
60-70 doublings
Sustained angiogenesis is achieved thru:
Neurovascularization, ILGF, PDGF
Tumors can’t grow___ cm without new blood vessels
> 1-2cm
Angiogenesis factors
Thrombospondin-1
Angiostatin
Endostatin
Carcinogenic agents
- Chemical carcinogens
- Radiant energy
- Oncogenic viruses and other microbes
Cause of ionizing radiation
Chromosome breakage, translocation
Cause of UV light
Causes formation of pyrimidine dimers
Most common Ca that is caused by ionizing radiation
Myeloid leukemia>thyroid Ca
Least common Ca caused by ionizing radiation
Skin, bone, gut