Path - Neoplasia 1, 2, 3
What are the number 1 and number 2 leading causes of death in the US?
1 = Heart disease 2 = Cancer
What tumor weight/size is the minimum to be clinically detectable?
1 g (30 doublings)
What tumor weight/size is the maximum compatible with life?
1 kg (40 doublings)
Identify the four steps and mechanisms of invasion
1. Detachment of tumor cells from each other 2. Attachment to matrix component 3. Degradation of ECM 4. Migration of tumor cells
**Carcinomas typically spread through the lymphatic system. Identify the four carinomas that spread hematogenously:
1. Follicular CA of thyroid 2. Choriocarcinoma 3. Renal cell CA 4. Hepatocellular CA Four Carcinomas Route Hematogenously
Identify the four steps in metastatic cascade - the ability to invade and metastasize
1. Invasion of basement membrane 2. movement through ECM 3. vascular dissemination 4. homing
Identify the top three incidence of cancer and cancer related deaths in children age 0-14
1. Leukemia 2. Brain and CNS 3. Neuroblastoma (same order for incidence and mortality)
Identify the various routes of metastasis
1. Seeding of body cavities 2. lymphatic spread 3. hematogenous spread
Identify two way to identify the origin of poorly differentiated and anaplastic carcinoma
1. identify the expression of cell markers unique to certain tissues 2. cytogenetics or molecular diagnosis
What two features can be seen in anaplasia, dysplasia and well-differentiated tumors?
1. loss of cellular polarity 2. Cellular atypia
Identify the two characteristics of metastatic tumors in the liver
1. multiple lesions 2. areas of central umbilication due to ischemia
Compare adenoma, carcinoma and papilloma
Adenoma = benign, epithelial neoplasm of glandular tissue Papilloma = benign, epithelial neoplasm of non-glandular tissue Carinoma = malignant, epithelial neoplasm
Lung cancer most commonly metastasizes to which site?
Adrenal and liver (brain)
Chromosomes breaks at centromeres and sister chromatids move to opposite ends of the cell during which phase of mitosis?
Anaphase
Define: Complete lack of differentiation of cells in a malignant neoplasm.
Anaplasia
The pathology report comes back from your sample of a tumor. It states that the tumor is anaplastic. What does this mean for your patient?
Anaplasia means means that the tumor is poorly differentiated. Anaplasitic tumors are more aggressive and come with a poorer prognosis.
What is the indicator of apoptosis?
Apoptotic body (fragmentation and condensation of nuclear chromatin)
Define: ↓ in tissue mass due to ↓ in size and/or number of cells. Causes include disuse, denervation, loss of blood supply, loss of hormonal stimulation, poor nutrition.
Atrophy
Define: a pathologic term for a structural abnormality in a cell. It is used to describe atypical cells. Seen in only pre-malignant (dysplasia) and malignant tumors (neoplasia)
Atypia
Why does the degree of differentiation depend on the percentage of cells within the cell cycle?
Because cells within the cell cycle cannot differentiate. Therefore the larger proportion of cells in the cell cycle, the lower the percentage of cells will be differentiated and the more likely the tumor is to be poorly-differentiated.
How does differentiation vary in benign vs malignant tumors?
Benign tumors = well differentiated because typically only 1-10% of cells are in the cell cycle. Thus cells/tissues typically resemble normal cells/tissues Malignant tumors = poorly differentiated because 20-80% of cells are in the cell cycle, thus cells and tissues typically do not resemble mature cells/tissues
Patients working in industries involving the manufacture/use of aniline dyes have an increased incidence of which cancer?
Bladder
Prostate cancer most commonly metastasizes to which site?
Bone
Are most of the bone tumors metastatic or primary?
Bone metastasis >> primary bone tumor
Compare carcinomas and sarcomas
Both malignant, but: carcinoma = epithelial cells sarcoma = mesenchymal tissue
A 68-y-o Japanese immigrant presents with fatigue, dyspepsia, and loss of weight. He has a 30 year history of chronic gastritis. Biopsy of stomach mucosa indicates adenocarcinoma. The metastatic potential of cancer cells would be enhanced by upregulation of the following proteins? CD2, CD4, CD8, CD22, CD44
CD44
Which cancers are more susceptible to chemo and radiotherapy? Cancers with rapid growth or cancers with slow growth?
Cancers with rapid growth
What term refers to the spatial difference in shape, structure and function of cells, exhibited by almost all cells, which allows them to carry out specialized functions.
Cell polarity
Ki-67 and PCNA are indicators of what?
Cell proliferation
What is the clinical significance of difference in growth rate of tumors?
Cells within the cell cycle are susceptible to chemo and radiotherapy
Define: normal tissue found in a foreign location
Choristoma
Pancreatic tissue in mucosa of the stomach or intestines is an example of what?
Choristoma
What population has an increased incidence of carcinoma of oropharynx, esophagus, pancreas, bladder and lung?
Cigarette smokers
**Identify the most common primary tumors that metastasize to the liver
Colon >> stomach > pancreas
What is the most important challenge you will face as a pathologist?
Decide whether the tumor is benign vs malignant
Hyperplasia of activated fibroblasts and production of abundant collagen in the stroma leads to what neoplastic process?
Desmoplasia
Linitis plastica in diffuse stomach cancer, breast cancer (invasive ductal carcinoma), prostate cancer and Cholangiocarcinoma are all examples of what neoplastic process?
Desmoplasia (blue = collagen; pink = muscle)
Define: Fibrous tissue formation in response to neoplasm (e.g., linitis plastica in diffuse stomach cancer)
Desmoplasia (often a stoney hard tumor due to the collagen secreted by active fibroblasts)
Define: The degree/extent to which neoplastic parenchymal cells resemble the corresponding normal mature parenchymal cells (tissue of origin), both morphologically and functionally
Differentiation
What factor determines the growth rate of tissues?
Doubling time The shorter, the quicker growth rate
Define: Disordered, non-neoplastic cell growth. Term used only with epithelial cells. Reversible when mild; severe usually progresses to carcinoma in situ
Dysplasia
Benign tumor cells remain attached to each other by adhesion molecules such as...? (In malignant tumors, invasive subclone occurs due to mutation and this molecule is not produced, causing the cohesiveness of tumor cells to be reduced)
E-cadherin
Why do malignant tumors show central necrosis?
Eventually, the tumor outgrows the blood supply, and areas of ischemic necrosis appear the diffusion of nutrients is limited to a diameter of 1-2mm
Which of the following tumors is a benign tumor? melanoma, hepatoma, seminoma, astrocytoma, fibroma
Fibroma
In general, carcinomas spread early to the lymphatics in order to metastasize. What are the exceptions?
Four Carcinomas Route Hematogenously F = Follicular CA of thyroid C = Choriocarcinoma R = Renal cell CA H = Hepatocellular CA
A patient presents with an autosomal dominant genetic disease characterized by the development of benign polyps in the GI tract + hyperpigmented macules. You diagnose this as Peutz-Jeghers syndrome. This is an example of type of tumor/lesion?
Hamartoma
Define: Non-neoplastic tumor-like lesions with disorganized and haphazard growth of tissues normally found at a given site
Hamartoma
Compare the consistency of a mass: Hard. Soft. Rubbery.
Hard = abundant of collagenous stroma: stony hard (desmoplasia or cirrhosis) Soft = stroma scant. Tumor is soft and fleshy Rubbery = between soft status and hard status.
Which route of metastasis is the most common for sarcoma? Seeding of body cavities, lymphatic spread, hematogenous spread
Hematogenous spread
Define: abudant DNA, extremely dark staining
Hyperchromasia
Define: an increase in cell numbers. May be a risk for future malignancy but not considered premalignant
Hyperplasia
Define: increase in size of cells
Hypertrophy
What does a higher percentage of abnormal mitoses tell you about a neoplasm?
It is more likely to be malignant
Which cancer rate is highest in Japan? New Zealand?
Japan = gastric cancer New Zealand = skin
What pair of molecules is important for malignant tumors tight attachment to matrix components?
Laminin receptor/laminin
Colorectal cancer most commonly metastasizes to which site?
Liver
What is the most important criteria to differentiate an EARLY benign vs malignant neoplasm? rate of growth, differentiation, local invasion, metastasis.
Local invasion (metastasis is #2, but may not be present in an early neoplasm)
Which route of metastasis is the most common for carcinoma? Seeding of body cavities, lymphatic spread, hematogenous spread
Lymphatic spread (will eventually spread hematogenous)
Which of lymphoma or leukemia originates from the bone marrow? Which from the lymphoid tissue?
Lymphoma originates in lymphoid tissue Leukemia originates in bone marrow stem cells
What are the top three causes of cancer related death in males and females
Males: 1 = lung, 2 = prostate, 3 = colorectal Females: 1= lung, 2 = breast, 3 = colorectal
What are the top three cancer incidence in males and females
Males: 1 = prostate, 2 = lung, 3 = colorectal Females: 1= breast, 2 = lung, 3 = colorectal (but... skin cancer has highest incidence for both male and female, but we dont count it in epidemiology)
Compare a mature teratoma vs immature teratoma
Mature teratome = benign Immature teratoma aka teratocarcinoma = malignant
Patients exposed to asbestos have an increased incidence of which cancer?
Mesothelioma
Chromosomes line up at the equatorial plane of the cell in which phase of mitosis?
Metaphase
Barrett esophagus is an example of what type of cellular change?
Metaplasia
Define: Replacement of one cell type by another. Usually due to exposure to an irritant, such as gastric acid or cigarette smoke. Reversible if the irritant is removed but may undergo malignant transformation with persistent insult
Metaplasia
Define: Spread of a tumor to sites that are physically discontinous with the primary tumor?
Metastasis
Which cell changes are irreversible? Hyperplasia, hypertrophy, atrophy, neoplasia, dysplasia, metaplasia
Neoplasia (Dysplasia and metaplasia can become irreversible if chronic irritant persists)
Match neoplasia, hyperplasia, and tumors with monoclonal or polyclonal
Neoplasia/tumors are monoclonal Hyperplasia is polyclonal
Define: a monoclonal proliferation of cells that is uncontrolled and excessive. Can be benign or malignant
Neoplasm
Is hyperplasia premalignant?
No
Compare the two types of bone metastasis: osteoblastic vs osteolytic
Osteoblastic: reactive bone formation, increase serum alk phosphatase, dense bone on Xray, prostate cancer is most common Osteolytic: tumor produce PGE2 and osteoclast activating factor (IL-1) activate osteoclasts, hypercalcemia, lucencies on Xray, breast cancer is an example
What effect does decreased P53 have on angiogenesis?
P53 inhibits VEGF and promotes thrombospondin-1 production. Decreased P53 will lead to an increase in VEGF and a decrease in thrombospondin-1, both contributing to an increase in angiogenesis
*A tumor derives its name based on?
Parenchyma
*Which of stroma or parenchyma is composed of monoclonal neoplastic cells?
Parenchyma
Define: variation in size and shape of cells and nuclei
Pleomorphism
Define: club-shaped growth projecting from mucosal surface into lumen of a hollow viscus?
Polyp (Can be benign epithelial tumor = papilloma, or hyperplasia)
Which of the following bone metastasis can cause osteoblastic metastasis? lung, kidney, prostate, thyroid, breast
Prostate (always causes osteoblastic) Breast (can cause both osteoblastic and osteo lytic) all other bone metastases are lytic
Presence of a small (less than 2cm) firm, discreet, non-neoplasic calcification inside the lung is an example of what process?
Pulmonary hamartoma
What is the most common site of metastasis?
Regional lymph node (followed by liver and lung)
Most sarcomas spread hematogenously. Which sarcoma is the exception and invades locally instead of spreading through the blood
Rhabdomyosarcoma
Primary pulmonary cancer, sub-arachnoid cancer, GI cancers and ovarian cancer, all share which route of metastasis? Seeding of body cavities, lymphatic spread, hematogenous spread
Seeding of body cavities
Define: the 1st node in a regional lymphatic system that receives lymph flow from primary tumor
Sentinel lymph node
What type of vessels are susceptible to invasion?
Small venules or capillaries (smooth muscle of arteries prevents penetration)
Which is more important for describing a tumor? Grade or stage
Stage (both have some effect on predicting outcome but staging is more important)
Differentiate the 4 grades of cancer
Stage 1 = well differentiated Stage 2 = moderately differentiated Stage 3 = poorly differentiated Stage 4 = nearly anaplastic
*The growth and spread of a tumor are critically dependent on its?
Stroma
*Which of stroma or parenchyma is composed of connective tissue, blood vessels and immune cells
Stroma
Which of stroma or parenchyma determines the consistency of a mass?
Stroma
As a tumor progress from early (submicroscopic phase) to later stages, how does the percentage of cells in the proliferative pool change?
Submicroscopic phase has a higher percentage of cells in the proliferative phase as tumors progress to later stages, a lower percentage of cells are in the proliferative pool
Differentiate the 3 stages of cancer: T, N and M
T = size of primary tumor N = Nodal involvement M = Distant metastases
A tumor secreting what factors allows it to grow larger than 1-2 mm
TAF (tumor angiogenic factors = HIF, VEGF, bFGF, Ras, myc and decreased P53) which all stimulate proliferation and in-growth of blood vessels, enabling tumor growth to be supported by perfusion
What type of tumor is composed of more than one parenchymal cell type and can be derived from more than one germ layer; but all cells arise from a single clone capable of producing all of these cell types
Teratoma
A 58-y-o woman presents with a lump in her left breast. A 3 cm hard mass is found by physical exam and excisional biopsy indicates breast cancer. The growth of cancer cells would be enhanced by down regulation of the gene for which of the following? VEGF, bFGF, Thrombospondin-1, Ki-67, PCNA
Thrombospondin-1
*Which of the following are anti-angiogenic factors? VEGF, angiostatin, Thrombospondin-1, bFGF, tumstatin, HIF, endostatin
Thrombospondin-1 and all the -statins, angiostatin, tumstatin, endostatin
What is the key difference between sarcomas and carcinomas?
Tissue of origin Sarcoma = mesenchymal cell origin (both have s's) carcinoma = epithelial cell origin
Which type of cancer is most closely associated with tracheal lymph nodes? Axillary lymph nodes?
Tracheal lymph nodes = lung cancer axillary lymph nodes = breast cancer
True or false: Metastasis unequivocally marks a tumor as malignant
True
What is the most important factor determining the rate of growth for tumors?
Tumor angiogenesis
Which cell type is the main secreter of motility factor? Stromal cells or tumor cells?
Tumor cells
Presence of a cell with a single huge polymorphic nucleus or 2 or more nuclei that are hyperchromatic and large are indicative of what?
Tumor giant cells that represent anaplasia
What quality of tumor vessels enhances the ability of tumor metastasis?
Tumor vessels are more leaky and dilated compared to normal vessels. This makes it easier for tumor cells to enter the vessels and spread to other areas of the body.
*Which of the following are pro-angiogenic factors? VEGF, angiostatin, Thrombospondin-1, bFGF, Tumstatin, HIF, endostatin
VEGF, bFGF, HIF
Identify the most common site for bony metastasis?
Vertebral column
Stomach adenocarcinoma most commonly metastasizes to which site?
Virchow's LEFT supraclavicular node
In terms of differentiation. Which tumors that closely resemble their tissue of origin. And which tumors look almost nothing like their tissue of origin.
Well-differentiated closely resemble tissue of origin (less aggressive) Poorly-differentiated look nothing like their tissue of origin (more aggressive)
Tissue demonstrating a nuclei/cytoplasm ratio of 1:1, cellular pleomorphism and nuclear changes can be described as?
cellular atypia
An increased stroma/parenchyma ratio is a sign of what?
desmoplasia
What receptor is expressed on tumor cells binds with fibronectin in the plasma or the tissues and helps the tumor invade (migrate)?
fibronectin receptor
Which of the following are not tumors? hamartoma, hepatoma, fibroma, melanoma, seminoma, chondroma, hematoma, osteoma, lymphoma, astroycytoma, granuloma, choristoma.
hamartoma, hematoma, granuloma and choristoma
*Which of the following tumors are malignant? hamartoma, hepatoma, fibroma, melanoma, seminoma, chondroma, hematoma, osteoma, lymphoma, astroycytoma, granuloma, choristoma.
hepatoma, melanoma, lymphoma, seminoma and astrocytoma
What is the key difference between benign vs malignant neoplasms?
invasion of metastisis Benign tumors = non-invasive, non-metastatic (capsule) Malignant tumors = invasive with metastatic potential. (No capsule)
Melanoma most commonly metastasizes to which site?
liver and lung
Testicular tumors most commonly metastasizes to which site?
local lymph nodes (para-aortic nodes)
Loss of the ability to differentiate epithelial cells by shape and size leading to an inability to tell the top from the bottom of skin describes what process?
loss of cellular polarization seen in dysplasia
**Identify the most common primary tumors that metastasize to the brain
lung > breast > melanoma, colon, kidney (lubmeck)
Breast cancer most commonly metastasizes to which site?
lung and bone
What two organs are most commonly involved in sarcomas spreading through the blood?
lungs and liver (brain also possible)
What is secreted by tumor cells and plays a critical role in migration?
motility factor
How do newly formed endothelial cells stimulate the growth of adjacent tumor cells?
newly formed endothelial cells secrete growth factors such as IGF and PDGF, which stimulate the adjacent tumor cells
Compare the percentage of cells that are able to proliferate (enter cell cycle) in normal tissue vs benign tumor vs malignant tumor
normal tissue = 1% benign tumor = 1-10% malignant tumor = 20-80%
Identify the most common symptom of bone metastasis?
pain
*The biological behavior of a tumor is based primarily on its?
parenchyma
What molecule is produced by tumor cells and leads to the degradation of the ECM?
type IV collagenase (MMP)