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316 Cards in this Set
- Front
- Back
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What does it mean for a neoplasm to be clonal?
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All the cells are descended from a single progenitor cell
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What does "neoplasm" mean?
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new growth
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What is another word for = swelling
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Tumor
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The term that refers to the growth of fibrous or connective tissue
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desmoplasia
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What cells/tissues are endodermal in origin?
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Epitheilial cells of liver, lungs and the GI tract
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What cells are mesenchymal (progenitors) in origin?
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Mycoytes
osteoblasts chondrocytes adiopcytes endothelal cells |
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What origin is bone marrow cells and RBCs embryologically?
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Hematopoetic from mesoderm
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What cells are derived from ectoderm?
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Keratinocytes, neurons, ologodendrocytes, ependymal cells
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What suffix implies that a tumor is benign and slow growing (with a few exceptions)?
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"-oma"
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Benign epithelial neoplasms Derived from or forming glands, also kidney, or liver
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Adenoma:
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benign epithelial cyctic mass that arise from product of neoplastic glandular cells
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cystadenoma
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Means to form finer like projections...
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Papiloma
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What is a polyp and what are they types
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Growth projections above the skin or mucoasl surface
Sessile: Flat Pedunculated: mushroom Papillary: fingerlike |
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Benign neoplasm of the thyrod gland called?
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Adenoma
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benign cystic mass lained by glands of an ovary?
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cystadenoma
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Smooth muscle benign tumor?
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leiomoma
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Skeletal muscle benign turmoe?
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Rhabdomyoma
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Benign fat tumor?
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Lipoma
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Benin tumors derived of blood vessles?
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Hemeangioma or angioma
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Lymph vessel benign tumor
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lymphangioma
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What two word parts indicate that a tumor is malignant?
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-Carcinoma
-Sarcoma |
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Malignant epithelial tumors
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‐carcinoma
(Skin, hari, sweat, glands, ducts, etc) |
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Malignant mesynchimal derived tumors
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-sarcoma
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What does and adenocarcinoma refer to?
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a malignant epithelial (gland, duct or cpllumnar cell origin) tissue
-Adeno means gland |
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Name the two neoplasms of neuroectodermal cells / melanocytes.
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Nevus ‐ benign, synonym mole
Malignant melanoma (melanoma) Remember melanocytes are found in the eye and skin so you can see these in the eye as well! |
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What two tumors are derived from the placenta?
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‐ Hydatidiform mole: benign
Choriocarcinoma malignant ‐ t |
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What is a seminoma?
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• Germ cell epithelium that is malignant, seen in TESTES
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the most common neoplasms of the salivary and lacrimal gland? What are the characterisitcs?
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mixed tumor or pleomorphic adenoma
(behavior is usually benign) Neoplasms of mroe than one cell type, but derived from 1 germ layer |
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What is the most common benign tumor of breast?
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Fibroadenoma
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What is the most common kidney tumor of children?
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Nephroblastoma, Wilm’s tumor (malignant)
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Wht is a neoplasm that:
‐ Tumor with origin from totipotential cells Solid/cystic, expresses any/all germ layers |
Teratoma
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What as a mature teratoma?
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usually cystic variety that is benign
(ex dermoid cyst, harir ovary with teeth) |
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Waht is an immature teratoma?
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a malignant teratoma that often turns into a teratocarcinoma
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What prefix means mucous in appearance/mucoid?
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Myxo-
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What is the name for a benign tumor of mesenchyme (stroma; matrix) with a mucoid appearance?
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Myxoma
Most common tumor of heart in adults may kill by virtue of location impingements |
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What is a hepatoma
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a MALIGNANT hepatocellullar carcinoma
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Are melanomas cancerous?
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Yes, they should be named malignant melanomas
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What is a multiple myeloma?
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A plasma cell malignancy
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What brain tumor doesn't soud malignant by its name, but actuall is?
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Gliomas
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What are the two types of hematopoetic neoplasms?
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Lymphoma & Lukemia
Both always malignant even if name doesn't sound like it |
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Malignant neoplasm that is formed of
masses of lymphocytes in lymph nodes or extranodal tissues |
Lymphoma
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What malignancy has blood forming cells that
involves bone marrow diffusely (no mass) and neoplastic cells may circulate in peripheral blood? |
Leukemia:
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What are the Three Neoplasms of the nervous system?
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Meningioma - Benign (unless bad location)
Neuroma- Benign Glioma- always malignant neoplasm of brain :( |
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Define heterotopia. Give an example
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-topia = place
Normal tissue present at an abnormal site: tissue is from one organ ex: lingual thyroid pancreatic or gastric tissue in meckels diverticulum endometriosis |
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Define choristoma. Give example
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-Related to heterotopia.
one or more mature tissues aggregate to form a tumor mass at inappropriate site ex: Complex choristoma of the conjunctiva tumor‐like mass of mature adipose tissue tumor‐like mass of mature adipose tissue,cartilage, smooth muscle and lacrimalgland |
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A benign tumorlike malformation resulting from faulty development in an organ and composed of an abnormal mixture of tissue elements that develop and grow at the same rate as normal elements but are not likely to compress adjacent tissue.
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Hamartoma
-Photos in lecture of LUNG |
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What is a malignant change in a target cell referred to as?
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Transformation
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What is differentiation?
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The extent to which neoplastic
cells resemble comparable normal cells Highly differentiated means it still looks normalish. |
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What is Anaplasia?
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lack of differentiation
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What are the charateristics of malignant anaplastic tumors?
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Pleomorphic (vary in size/shape)
Hyperchromatic nuclei Increase nuclear/cytoplamic ration Increased mitotic activity loss of polarity other tumor giant cells or necrosis |
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What is tumor grading and how are malignant tumors graded?
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Tumor grade: degree of differentiatioMalignant tumors are graded‐ 1 through 3 or 4
Grade 1: well differentiated; low gradGrade 2: moderately differentiated Grade 3: poorly differentiated; high grade |
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What is dysplasia? How does it look?
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Disordered growth; precancer
-BM intact -Loss of cellular polarity -Dysplasia mild, moderate, severe according to thickness of epitheloum involved |
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What does it mean for a lesion to be called "carcinoma in situ"?
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It is a continuation of the dysplastic process, and still considered precancer. Differs in that it involves the FULL thickness of epithelium however the BM is still intact
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What is a growth fraction? How is it measured?
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It is the number of cells that are actively proliferating and what cancer treatments activly targer. They are masured vy S-Phase or proliferative markers.
High GF means it is growing fast. |
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What is the origin of cancer?
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Monocolonal arises from mutations in progenitors or stem cells
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What is tumor progression?
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acquisition of more aggressive behavior and greater malignant potential
• Incrementally acquired multiple mutations in different tumor cells, include: ‐‐ Accelerated growth ‐‐ Invasiveness Ability to form distant metastases |
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What is Tumor Heterogeneity?
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populations of cells that differ with
respect to phenotype |
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Invasion producing a desmoplastic stroma is called?
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Infiltration. It is the cancers invading and destroying surrounding tissue
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What is Local extension of a neoplasm?
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direct tumor invasion of
adjacent tissue or organ |
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Waht percentage of cancers are metastatic at diagnosis?
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30%
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What 2 malignancies are the exception in that they don't metastisize?
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Gliomas & basal cell carcinomas
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List the three pathways of metastisis.
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• Seeding
• Lymphatic metastases • Blood borne metastases |
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What is the most important determinant of
prognosis for most cancers? |
Staging!
it is based on how far cancer has spread by extension and above routes |
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Describe seeding. What caners spread this way?
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Cancer breaks through to an “open field” and spreads onto surfaces of space
• Peritoneal seeding ‐ ovarian cancer gastric carcinoma; pancreatic carcinoma ‐ some intestinal malignancies • Pleural cavity, pericardium: ‐ seeded by lung cancer Other: CNS ; urinary tract seeding |
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What cancers spread va the lyphatics?
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Carcinomas- they invade lymphatic channels at the periphery of a tumor.
ex: • Oral cancers: cervical (neck) lymph nodes • Breast cancer to axillary and other nodes • Lung cancer to perihilar lymph nodes • Colon cancer to paracolic lymph nodes |
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What cancers spread via the hematogenous route?
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-Initially sarcomas, but can also be carcinmas later.
Vessle invation allows tumor emboli to spread. Usually venous, however areterial spread from/via lungs |
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What is staging based on?
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Statistical studies from tumor outcomes, thus it will vary from organ to organ
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What is TNM staging?
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T=Primary tumor size/depth of invasion
N=Nodal involvement, N0= No nodes, N1= regional nodes M-Blood borne metastasis M0= None, M1= Metast present (always stage IV) Unknown, use "X" |
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What does the staging "Tis" indicate?
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in situ
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What is a T1 stage mean?
(Favorite Question) |
always invasive; relatively small and
confined to the organ in which the tumor arises (primary site) |
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Describe a stage I cancer?
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Stage I = small invasive primary tumor, no nodes,
no blood‐borne metastases |
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Describe a stage II & III cancer?
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Stages II and III: increasing tumor size,
d/ l extension, and/or LN involvement |
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If a tumor has blood born metastases then what stage must it be?
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Stage IV
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Most common causes of cancers in adult Males?
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Prostate
Lung Colon Urinary |
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Most common causes of cancer in adult females?
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Breast
Lung Coolon Uterine |
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Most common causes of cancer death in adult Males?
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Lung
Prostate Colon Pancreas |
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Most common causes of cancer death in adult females?
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Lung
Breast Colon Pancreas |
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What is the peak age for cancer in adults?
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50-85 years
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What cancers are associated with EtOH abuse?
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Head and Upper neck
‐ Oropharynx ‐ Larynx ‐ Esophagus Hepatocellular carcinoma secondary to cirrhosis of the liver |
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What cancers are associated with tocacco smoke?
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Head/neck
Pancreas Urinary Tract Cervical |
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What cancers are associated with UV radiation?
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Skin Cancers
(squamous, basal and malignant) |
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What cancer is an increased risk for forming with exposure to arsenic
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Lung, skin, angioscarcoma
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What cancer is an increased risk for forming with exposure to asbestos
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lung, mesothelioma
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What cancer is an increased risk for forming with exposure to benzene
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leukemia and lymphoma
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What cancer is an increased risk for forming with exposure to beryllium
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lung
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What cancer is an increased risk for forming with exposure to ethylene oxide
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lukemia
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What cancer is an increased risk for forming with exposure to napthylamines?
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bladder cancer
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What cancer is an increased risk for forming with exposure to Radon?
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Lung
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What cancer is an increased risk for forming with exposure to vinyl chloride?
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Angioscaroma of the Liver
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What is the association of chronic inflammation with predisposition for cancer?
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-Cytokines stimulate growth and increase stem cell pool
-Inflamation generates ROS |
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What are some other acquired predispositions for cancer?
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‐Endometrial hyperplasia due to estrogen
‐ Repair from injury (burns) ‐ Chronic inflammation/infection |
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What percent of cancers are related to a familial cancer gene?
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less than 1%
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What are the characteristics of familial cancer syndromes?
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+2 or more relatives
+tend to be younger but most peat at over 50 +multiple or bilateral cancers +AD or multifactorial penetrance +genes tend to be tumor suppressors |
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What are the common familial cancers?
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breast
colon ovary brain malignat melanoma endocrine (More) |
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What is the percentage of breast cancer that is due to an inherited cancer gene
(familial cancer)? |
10% is familial
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What genes are mutated in Breast Ovarian Cancer Syndrome?
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BRCA1 and BRCA2
Patients are born with one mutated copy and only one good copy which is highly vulnerable |
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What is significant about the failure in the BRCA‐1 and BRCA‐2 mutations?
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They are mutations in tumor supressor genes.
BRCA1- assocaiated with breast and ovarian BRCA2- just breast; is also implicated in male breast cancer |
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Describe autosomal dominant inherited syndeomes
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Only one mutated copy of the gene will be necessary for a person to be affected by an autosomal dominant disorder. There is a GERM LINE MUTATION which increases the risk of developing cancer if the second good gene is damaged
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What is the inheritance and gene in retinoblastoma?
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Autosomal Dominant
Rb (this disorder can also be sporadic) |
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What does it mean to have an Inherited cancer syndromes with marker phenotype?
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It means that there are physical changes that you can see they have a mutatuion:
Familial adenoamatous polyps of colon Multiple endocrine neoplasia Neurofibromatosis types 1 and 2 |
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What are the characteristics and gene responsible for neurofibromatosis type 1?
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Defect in Tumor suppressor gene
-Neurofibromas -Cafe au Lait spots Lisch nodules NF-1 gene |
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What are the 4 Autosomal resessive cancer syndromes with defective DNA repair?
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• Xeroderma pigmentosum
• Ataxia telangiectasia • Bloom syndrome • Fanconi’s anemia |
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What are the characteristics and gene associated with xeroderma pigmentosa
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NER - nucleotide excision repair gene
UV-b light forms pyrimidine dimers that can become carcinogenic if not repaired |
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What are the characteristics and gene associated with Ataxia telangiectasia?
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As name implies + IgA deficience
ATM is mutated gene ATM binds to damaged DNA and posporilates TP53 Risk for lukemia and lymphoma. Sensitive to radiation |
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What are the characteristics and gene associated with Bloom syndrome?
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• Cutaneous manifestations
• Immunodeficiency • Sensitivity to UV radiation • Risk for leukemia/lymphoma BLM mutations |
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What are the characteristics of Fanconis anemia?
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• Physical abnormalities
• Pancytopenia (blood cell types: RBCs, Pancytopenia (blood cell types: RBCs, platelets and neutrophils all reduced) • Chromosome fragility • Risk for leukemia, squamous cell carcinoma and hepatoma |
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What is initiation?
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Rapid, irriversable DNA damage
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What is promtion/promotors?
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Reversible effects that allow induce INITIATED cells to proliferate
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What DNA mutation occurs with benzopyrene? Tobacco smoke?
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p53 is mutated
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What is the downside of cyclophosphamide for chemo?
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It is a direct acting carcinogen in and of itself
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Where dies aflatoxin B1 come from aand what does it do?
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Potent indirect acting product of aspergillis that is associated with hepatocellular carcinoma and a p53 mutation
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Is cigarette smoking an initiator or promoter? What about alcohol?
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Smoking is both
Alcohol is a promoter |
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What type of virus is HTLV‐1 and what disease
is it associated with? |
RNA, retrovirus
• Causes T‐cell leukemia/lymphoma |
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What neoplasms are related to HPV infection?
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Verruca vulgaris (warts)
Condyloma accuminatum Dysplasia Carcinoma in situ Squamous papilomas |
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What is the pathophys of high risk HPV?
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Viral genome integrated into nuclear DNA
E2 viral repressor is lost Repressor loss promotes overexpression of E6 & E7 |
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What does E6 do?
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inactivates p53 product,
degrades BAX; activates telomerase g ; |
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What does E7 do?
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• E7 protein binds to RB (cell cycle inhibitor)
promoting progression of cell cycle |
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Epstein‐Barr virus‐associated cancers (4 Main)
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• Burkitt’s lymphoma (African)
• B‐cell lymphoma ‐ immunosuppressed • Hodgkin disease / Hodgkin lymphoma • Nasopharyngeal carcinoma |
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What does LMP‐1 (latent membrane protein) do?
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It activates and immortalizes BCL2 resulting in immortalization!!!
(component of EBV/B-lymphoma story) |
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Describe burkett lymphoma
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its a 8:14 chromosomall translocation of the MYC gene where b cells proliferate
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What is the role of vIL 10 in EBV?
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It is the major transforming factor that allows for the activation of cytotoxic t-cells
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What EBV sub cancer occurs more frequently in southern china, eskimos and parts of Africa? The viral genome is present in erology even before the person shows sx of disease
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Nasopharyngeal carcinoma
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What internal signalings promote exucution capases?
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The BAX family
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What internal cell regulators inhibit execution caspases?
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BCL-2
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What type of genome is viral hep c caused by?
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RNA
can lead to hepatocellular ca |
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What type of genome is viral hep b caused by? Where is it endemic?
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DNA virus
Hepatitis B is endemic in Asia and Africa with high rate of hepatocellular carcinoma |
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Why can hep c and b lead to cancer?
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Chronivv viral hepititis and viral replication leads tohepatocyte death which calls in cytokines which are damaging. It also presents more opportuinity for genome damage when cells are regenerating
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What two viruses work together to cause kaposi scaroma? How?
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HIV and human herpes virus 8 (HIV not required thought)
KS is a proliferation f blood vessles or vessel forming mesenchyme Cytokines and tat gene product from HIV infected CD4 T lymphs induce KS –infected infected cell proliferation |
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What malignancy/malignancies are associated
with Helicobactor pylori infection? What other py disease(s) does this infection cause? |
-adenocarcinoma of the stomach
-gastric lymphoma of mucosa-associated lymphoid tissue Also see peptic ulcer disease |
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what cytotoxin is associated with H.Pilori adenocarcinoma?
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CagA (cytotoxin‐associated A) gene that mimics growth factor initiating signaling
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What are some of the general effects of tumors on hosts?
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Cachexia
Local impingment/dysfunctionts Metastases Hormone synthesis Paraneoplastic syndromes |
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What factors are associated with cachexia
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TNF-a, IL1 and IFN-gamma (generral pro inflammatory) PLUS
‐ PIF (proteolysis inducing factor) LMF (lipid mobilizing factor): increasesfatty acid oxidation and pro‐inflammatory cytokines |
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What doe cytokines and PIF activation do
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Activate ubuiquitin‐proteosome pathway ‐‐ myosin degraded
causes loss of skeletal muscle membrane and dystrophing loss |
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What is superior vena cava syndrome?
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When there is a growth or carcinoma around and into the vena cava blocking blood return. Often caused by an uncurable cancer
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What is paraneoplastic?
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It is hormones being produced by non-endocrine tumors
Occurs in 10% of patients with malignancy |
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What are the two paraneoplastic syndromes
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‐ Endocrinopathies‐ elaboration of hormone‐like substances like hypercalcemia due to tumor production og PTH or Cushing syndrome due to ACTH from lung cancer
OR ‐Syndromes due to antibodies like myasthenia syndrome in lambert -Eaton |
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What skin changes might you see in a visceral malignancy, especially gastric carcinoma or also lung and breast cancer
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paraneoplastic acanthosis nigricans
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What are Serum Tumor Markers? What is the caution that must be taken in tehm?
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Blood tests for biochemical indicators of the presence of a tumor-
They do NOT MAKE THE DIAGNOSIS ex, PSA... You need a baseline |
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What is the tumor marker for colon cancer?
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CEA
Carcinoembryonic antigen |
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What is the tumor marker for liver and testicular cancers?
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Alpha-fetaoprotein
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What is the tumor marker for choriocarcinoma?
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Beta HCG
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What is the tumor marker for neuroblastoma
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VMA, HVA, NSE
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What is the tumor marker for breast cancer?
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CA-15-3
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What is the tumor marker for ovarian cancer?
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CA 125
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What are protooncogenes?
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Normal health cell proliferation and differentation regulators in the body. These are subject to conversion/mutation to Oncogenes which have mutations
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What is the mechanism for oncogene activation?
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It is a mutation that amplifies and overexpresses a gene product often activated by a translocation
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What causes Platelet derived growth factor - B to be over expressed?
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A problem with "sis" associated with glioblastoma
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What causes FGF (fibroblastic growth Factor) to be overecpressed
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The HST gene
seen in gastric and kaposi scarcoma |
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What signaling does growth factors liek PDGF and FGF use?
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Transmembrane tyrosine kinase domain sugnaling
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What oncogenes are growth factor receptor problems and what disease are they associated with?
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ERB B1 = makes EGFR
ERB B2- Her-2 neu |
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What does a oncogenic ERB B1 causes?
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EGRM overxpression seen in some lung head and neck cancers
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What does a oncogenic ERB B2 causes?
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AKA her-2 neu
it is amplified in 25% of breast cancers and is associated with a poor prognosis. they respond well to Trastuzamab which is an anti her2 antibody |
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What are the general features of the RAS oncogene?
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Most common in 20% of tumors
it is a signal transdution protein highoccurance in adenocarcinomas Arises as POINT MUTATIONS |
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How does RAS noramlly work?
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Inactive RAS is bound to GDP
In response to growth signal, GDP-> GTP and results in transduction via RAS/RAF/MAP pathway It is inactivated by GAP making GTPase |
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What is mutated RAS doing?
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Evading GAP and staying bounda nd activated to GTP causing persistent signal transduction
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What is the function of the oncogene ABL?
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ABL is a non receptor tyrosine kinase that is normally turned way down. Mutation in 9;22 chromosome puts it near a promotor that causes it to be on and singaling too much
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How is ABL activated?
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A translocation of 9:22 that results in persistant tyrosine kinase signal transduction
BCR-ABL |
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Waht neoplasm is assocaited wtih activated ABL?
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Chronic myelogenous lukemia and some lymphoblastic lukemis
Treated with tyrosine kinase inhibitors |
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what is the role of transcriotpn factors and what are some examples?
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control entry and progression through the cell cycle
Ex: MYC, MY, JUN, and FOS |
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What is MYCs function?
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Activates transcription by binding to DNA
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when MYC is continuously or over expressed what cancers do you see?
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8:14 MYC - Burketts B Cell Lymphoma
N-MYC amplifies in neuroblastoma (pro prognosis) L-Myc in small cell cancer in ling |
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What are double minutes?
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are small fragments of extrachromosomal DNA, which have been observed in a large number of human tumors including breast, lung, ovary, colon, and most notably, neuroblastoma.
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Where do most comm cell cycle oncogenes act?
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G1/S
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What oncogene cell cycle regulators are commonly dysfunctional in cancers?
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Cyclin D and CDK4
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How many alleles are usually lost in tumor supressor malignancies?
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usually two
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What ar CpG islamdes
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cytosine-phosphodiester-guanine islands
they are common promoter regions of genes |
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What is the role of the CIP/WAF family?
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They are p21,p27 p57 and block several cyclin CDK complex actions
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What is the role of the INK4 Family?
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P15, p16, p18, p19
p16INK4 binds to cyclin D-CDK4 and inhibits RB! |
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What is the rle of RB in the cell cycle? How is it turned on and off?
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It si the break between G1/S checkpoint
When it is active it is HYPOphosphorilated and inhibits transcription factor E2F. When it is inactieve it is hyperhphos and allows E2F to transcribe S phase genes |
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What viruses act by neutralizing RB acitvites?
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HPV via the E7 protein
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What is the role of p53?
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IT is the "guardian of the genome"
When DNA is damaged p53 arrests teh cell cycle providing time for repair. if repair is made the cell reneters the cell cycle, if not it signals for apoptosis via BAX |
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What are the arbiters of senescence?
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p53 and RB
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What is the function of APC and where is it found?
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It regulates b catenin which binds to e-cadherin to maintain cell adhesiveness and it also is a vomponent of the WNT signaling pathway as a transcription activator
Chromosom 5q21 fo |
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What are dysfunctions with APC implicated in?
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Homozygous loss in precancerous colon polyps, cancers and hepatic cancers
It is what is mutated in familial adenomatous polyposis syndrome |
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What ist he gene product and neplasm associated with TBGF-B?
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Transforming Growth Facor Beta stimualtes CDKI p21 and p15 which inhibits CDKs, Cyclins and MYC
Seen in colon and gastric cancers |
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What is the gene product in NF-2?
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Merlin
seen in acousitc neuromas, schwannomas and meningiomas |
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What is the role of the VHL gene?
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It is a tumor suppressor that is involved with the ubiquitination and degradation of a hypoxia-inducible-factor (HIF). If HIF is not modulated VEGF and PDGF promote angiogenisis and growth.
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What diseases re caused by mutatiosn in the Von Hippel Lindau gene?
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hereditary renal cell carcinoma
Pheochromocytoma Hemangioblastomas |
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What are the functions related to PTEN?
|
PTEN is phospahte and tension homologue whichi is a pototn tumor supressor that shuts down the progrowth/prosurvival PI3K/AKT pathway (dephos)
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|
|
What cancers/syndromeas are assoctiated with PTEN mutations?
|
Cowden Syndrome whcih is a skin appendage that is at increase risk for cancers:
(hemartoma; cancer esp. breast) Sporadic monoallelic loss (breast, colon, prostate, lung, brain tumors) Homozygous mutation (endometrial) |
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|
Dysfunctional WT-1 tumor suppressor is implicated in what disorder (and chromosome)?
|
Chromosome 11
Wilms Tumor which is the most common renal neoplasm of children |
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|
Proapoptotic
|
Bax and BAK
Fas/FasL |
|
|
Antiapoptotic
|
BCLs
(akt and mTOR in autophagy) |
|
|
Autophagy facilitators
|
PTEN and Tuberous sclerosis proteisn
|
|
|
hereditary nonpolyposis clon cancer syndrome features
|
Problem with mismatch Repair MLH1 MSH2
If gene starts with M and is three letters it is a missmatch |
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|
Which disease is associated with nucleotide excision repair problems
|
Xeroderma Pigmentosa
|
|
|
What genes are assocaited with problems in DNA repaid by homologus recombination?
|
BRCAs 1 & 2
ATM |
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|
What factors are implicated in the degradation of the ECM that lets tumors spread
|
Tyoe IV Collagenase (MMP9) which is a matrix mealloproteinases
Cathepsin D Urokinase plaminogen activator |
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|
What factor lets cancer cells move?
|
Autocrine motility factor
|
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|
Where do prostate metastasis like to go?
|
lumbar vertebrae
|
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|
Where do bronchogenic metastasis like to go?
|
adrenals and brain
|
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|
Where do neuroblasomas metastasis like to go?
|
liver and bone
|
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|
Where do breast metastasis like to go?
|
bone, liver and lung
Attracted by chemokines |
|
|
Characterize interactions of malignant cells with their stromal environment (test Q)
|
Cross talk between ECM and tumor cells provides parcrine signaling
Inflammatory cells promote cancer survival and progression Fibroblasts in the stroma ma drive genetic changes in the tumor |
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|
What is the Warburg Effect
|
That metabolism of cancer shifts to aerobic glycolysis
Clinical Significance: The glucose-hunger of tumors is used to visualize them using PET scanning. |
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|
What is the multistep basis of cancer?
|
All cancers require the activation of at minimum 1 oncogenes and the loss of 2 or more tumor supressors
changes occur over time and are assocaiated with phenotypic changes |
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|
What are the immuniosuppressive cytokines? Immune cells?
|
Cytokines TGF-B and IL10 (IL4 & 6)
Cells: T Regs, macrophages and PMNs |
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|
What are the functions of TGF‐ß in cancer?
|
• Tumor suppressor gene
• Produced by regulatory T cells and fibroblasts in the stroma of invasive carcinoma • Effects related to invasion include: ‐ increased angiogenesis ‐ increased deposit of ECM ‐ immunosuppression |
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Qhat are the primary tumors of the heart?
|
Myxoma ‐ adults
Rhabdomyoma ‐ children Angiosarcoma‐ adults |
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|
Describe the clinical presentation and
behavior of cardiac myxoma. |
Clinical presentation
Ball valve obstruction‐heart failure Fragmentation with systemic embolization Systemic inflammatory reaction‐fever due to IL 6 from tumor |
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Where are myxomas most frequently seen?
|
Left more then right
Atria (90%) They are sessile and myxoid mesenchymal cells |
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|
What is the most common neoplasm of the heart of infants?
|
Rhabdomyoma
Rare, benign tumor or hamartoma |
|
|
What is a curies / becquerel?
|
the SI derived unit of radioactivity measured from a geiger counter
|
|
|
What is a rotogen?
|
unit of charge produced by x-rays:
|
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|
What is a rad?
|
dose of radiation expressed as gy/gram of tissue exposed gy g p
|
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|
What is a gray?
|
Dose of radiation given
(1 gray = 100 rads) |
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|
What is a sivert?
|
The doses of accumulated grays
Measured in a film badge in healthcare workers, ets as there is a max 50 exposure of mSV a year |
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|
What cells are most radiosensitive?
|
Those in G2/M that are rapidly dividing
Gem cells. epithelium, etc Bone and cartilage, muscles and nerves are pretty resistant in adults |
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What are the effect differences between low and high does radiation
|
Low dose causes radical damage and apoptosis. Low doeses with oxygen supplimentation is bad because it makes the problem even worse.
High doses cause tissue necrosis |
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|
What are the acute effects of radiation injury?
|
Cell death
Endothelium damage and "burns" Damage to crypt stemm cells causing GI syndrome of radiation sickenss |
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|
What are the Chronic/Delayed effects of radiation?
|
Vascular injury (fibrosis, thrombis or ectatic/dialated vessles)
Ischemia of organs Fibrosis |
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|
What is the time frame for cancer due to radiation?
|
For lukemia minumum 2 years, other cancers 10-20 years
|
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|
What cancers are associated with Hiroshim/Nagasaki survivors?
|
Adults: Lukemia
Children: thyroid breast GU amd GI |
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What are the effects of radiation exposure in preimplatiation?
|
Most lilkely lethal
|
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What are the effects of radiation exposure from weeks 1-9 in organocenis of fetus?
|
Malformations likely
|
|
|
What is the result of raditiaon exposure during the fetal perid?
|
CNS dysfunction, underdeveloped reproductive organs, increased rish for lukemia dn brain tumors
|
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|
What is the risk of radiation exposure in infants?
|
Bone growh retardation
CNS, teeth and eye development problems |
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|
What are the initial lung problems with radiation injury/
|
Pulmonary congestion / edema from
endothelial damage ‐ ARDS |
|
|
What are the later long problems with radiation injury
|
“Radiation pneumonitis”: interstitial fibrosis
decreased capacity, dyspnea, chronic cough ‐ Primary lung cancer |
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|
If a patient comes into your office thinkging they have been exposed to radiation, what can you do?
|
Check lympohcytes:
If they are low and pt has no other sxology then there was subclinical exposure If there is a decrease it will show immidately and neutrophils wil frop in the next day to one week from exposure This is non lethal syndrome at this phase, but there could be DNA damage |
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|
Your patient with acute radiation syndrome didn't see yoou for 2-6 weeks and now will require a bone marrow transplant. What labs and clinical presentation do you expect to see?
|
Lymphocytopenia (immidate)
Leukopenia, thrombocytomenia with hemmorrhage vomiting epilatiion lethal in 80% of persons If the GI sx came on before this time it is most likely lethal |
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|
A person comes into the ER after radiation exposure with burnig skin, vomitine, coma convulsions and immidiate onset of sx (1-4 hours) and has hardly any lymphocytes. What is the prognosis
|
Death within hours
|
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|
Describe strawberry hemangiomas
|
Present at birth
increase and size and regress by school age often serious only if it impinges on eye or obstructs airway |
|
|
What are the features of "Port wine stain"?
|
Present at birth
Never regresses usually unilateral variations include Sturge-Weber |
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|
What is special about sturge weber port wine stains?
|
they have an intertrigeminal distribution and vascular anomilies that can extend into the eye and run risk for glaucoma
|
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|
What are as Lymphangiomas? Where are they located?
|
• Tumor of lymph vessels
Characterized by cystic or cavernous spaces • May be neoplasm or hamartoma • Locations - Skin - Cystic hygroma: deep neck, axilla, mediastinum, retroperitoneum |
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|
Where are teratomas usually located in young children? What is the usual behavior?
|
Peak up to age 2 and 2nd peak in adolescence. Mostly saocroccygeal but can also be midline and at gonads
most are mature/benign |
|
|
How do malignant tumors in kiddos vary from adults?
|
*kids have higher incidence of sequelae and second malignancies
Morphologically anaplasia is less common and "-blastomas" or primitive ebyronic appearence of tumors is more common |
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|
Lsit some common malignant tumors seen in Kiddos under 4
|
• Acute leukemia-most common TABLE 10-8
• Posterior fossa CNS tumors, medulloblastoma , • Neuroblastoma - most common solid nonCNS • Retinoblastoma • Retinoblastoma • Wilm’s tumor • Hepatoblastoma • Rhadomyosarcoma, other soft tissue tumors y , • Teratoma |
|
|
What is the Characteristic histology of the most primitive
tumors of childhood |
Small round blue cell tumors (SRBCT)
|
|
|
What is the most common primary site of neroblastoma?
|
adrenal medulla
|
|
|
What morphology gives neuroblastoma away?
|
They are small round blue cell tumors with pseudoreosettes
|
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|
What is the difference between neuroblastoma, ganlioma dn ganglioneuroblastoma
|
How differentiated they are
Neuroblastoma is Malignnt Ganlioneuroblasoma is intermediate adn ganglioma is benign |
|
|
What is the staging for neuroblasoma?
|
• Staging: Stage I-IV
• Stage I: tumor localized; completely excised ipsilateral disease without nodal metastases • Stage III: tumor extends across the midline; Stage III: tumor extends across the midline; unresectable • Stage IV: distant metastases- bone, liver • Stage IVs (special): localized primary tumor with extensive metastatic disease to liver, skin, bone marrow (limited to infant <1year old) bone marrow |
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|
Where can you see bluberry muffin syndrome?
|
Neuroblastoma
|
|
|
What are the serum tumor markers for
Neuroblastoma? |
- elevated blood levels of catecholamines
- elevated urine levels of metabolites- VMA: vanyllymandelic acid and HVA: homovanillic vanyllymandelic acid |
|
|
What are the prognostic factors foe neruoblastoma?
|
• Age and stage are most important
• Stage I, II excellent ~75% of children present stage 3 or 4 tumors • < 18 mon excellent prognosis regardless • < 18 mon., excellent prognosis regardless of stage • Age 18 mon -5yrs survival intermediate • Age > 5 : extremely poor outcomes |
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|
How does ploidy relate to neuroblastoma prognostis?
|
Hyper-diploid to triploid is good!
Diploid or near diploid is bad Amplification of the N-myc oncogene is bad. You will see double minutes |
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|
Which is goood prognositc for neuroblastoma? Trk-A or Trk-B?
|
A is good nerve growth factor receptor
B is bad and targetd by tyrosine kinase inhibitors |
|
|
What is the synonym for Wilms tumor?
|
Nephroblastoma
Malignt associated with WT1 or WT2 inactivation or deletion |
|
|
The mutation in WAGR that corrosponds to a mutation in the WT-1 gene causes what problem?
|
No irises!
Possible genital malformation Mental retardation Risk of wilms tumor |
|
|
What is Beckwith-Wiedeman syndrome?
|
Issue wtih WT-2 gene on chromosome 11:
Enlargemetn of organs and macroglossia present Infancy can be a critical period because of low blood sugar (hypoglycemia), omphalocele (when present), and an increased rate of tumor development. Wilm's tumor and adrenal carcinoma are the most common tumor's in patients with this syndrome. |
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|
What is the microscopic morphology of Wilm’s tumor?
|
Gross of Wilms tumor
- Large, solitary circumscribed mass; tan to gray • Triphasic microscopic orphology - Recapitulation of stages of nephrogenesis - blastema; stroma and epithelial cell types Unfavorable histology: diffuse anaplasia |
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|
aA 1 year old presents to your office with "cats eye refle" What is this called? What is the potential disease? Treatment? Prognosis
|
Leukocoria
Most likely retinoblasoma tx: enucleation and radiation/chemo Kid will die eventually without tx, but has good prognosis if gets treatment. If from familial rentioblasoma kid is at rish for 2nd cancer of other organs |
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|
Name four things a frozen section may be used for?
|
Presence or absence of malignancy
Presence or absence of inflammation/organisms Whether surgical margins are free of neoplasm Whether diagnostic tissue is present |
|
|
What are the five intermediate filaments?
|
keratins
Desmin Vimentin Glial Neurofilaments |
|
|
Keratins found in tumor cells suggest what cancer types?
|
Carcinomas
mesothelioma |
|
|
Desmin found in tumor cells suggest what cancer types?
|
Muscle tumors: smooth or striated
|
|
|
Vimentin found in tumor cells suggest what cancer types?
|
mesenchymal tumors
some carcinomas |
|
|
Glial filaments found in tumor cells suggest what cancer types?
|
Gliomatous tumors
|
|
|
Neurofilaments found in tumor cells suggest what cancer types?
|
Neuronal tumors
|
|
|
Estrogen and progesterone positive Receptors are better prognostically than what detectable molecule?
|
HER-2/NEU it is an unfavorable marker
|
|
|
What two things can flow cytometry
measure? |
cell characteristics such as membraneantigens and DNA content of tumor cells
|
|
|
DNA content or ploidy can be divided into what two subsets?
|
Diploid-Good
Anuploidy-bad (high S phase even worse) |
|
|
What are the cluster designations for t-cells
|
CD 1,3,4,5,8
|
|
|
What are the cluster designations for b-cells
|
10,19,20,21,23
|
|
|
What are the cluster designations for Monocytes and Macrophages?
|
11,13,14,15
|
|
|
What are the cluster designations for Natural Killer cells
|
16,56
|
|
|
What are the cluster designations for stem cells
|
34
|
|
|
What are the cluster designations for Activation markers>
|
30
|
|
|
What CD marker is present on all leukocytes?
|
45
|
|
|
What does a DNA microarray analysis
measure? |
Expression levels of thousands of genes
Gives molecular profile for each tissue analyzed |
|
|
What are the main uses for FISH? what advantage does itprovide
|
Detection of specific DNA or RNA sequences or Viral infections
Advantage over immunohistocyto because it can detect subgroups and types... It is more specific It can also be preformed on cells in both resting and dividing stages |
|
|
What six areas are genomic approaches having an impact on?
|
Tumor classification
Prognostic markers Predictive indicators of drug response The development of new drug therapies Strategies for monitoring disease Management of susceptibility to cancer |
|
|
What two features are helpful to divide blood vessels into benign and malignant categories?
|
Degree of well formed vascular channels present
Extent and regularity of the endothelial cell proliferation |
|
|
How does endothelial cell proliferation look in benign blood vessel tumors?
|
Benign have vascular channels filled with blood Benign have vascular channels filled with blood (lymphatics have lymph), lining is usually
monolayer of normal endothelial cells, no atypia |
|
|
How does endothelial cell proliferation look in malignant blood vessel tumors?
|
malignant more solidly cellular with anaplasia, mitosis, usually no well‐organized vessels
|
|
|
What are the three categories of
hemangiomas? |
Capillary
Cavernoys Pyogenic Granuloma aka lobar capillary hemangioma |
|
|
Capillary hemangiomas are found
predominantly in what locations? |
Usually in skin, subcutaneous tissue and mucous membranes
|
|
|
What is the natural course of the strawberry or juvenile type of capillary hemangioma?
|
Found in newborn, grows rapidly for few months then fades at one to three years, 80% gone by age 7
|
|
|
Describe cavernous hemeangioma
|
Formation of large, cavernous vascular channels
– Occur within cerebellum, brain stem in von Hippel‐Lindau |
|
|
What are the gross and microscopic
characteristics of a pyogenic granulomas? 1/3 develop after what? |
Peduncular red nodules on skin oral mucosa
1/3 develop after trauma Seeb often in pregnancy espically on the gums |
|
|
• Where do glomus tumors occur?
• What are they composed of? what distinctive clinical symptom do they have? |
Fingernails
Composed of Glomus bodies (smooth muscle cells) Very painful and temperature sensitive |
|
|
What is the common name for nevus
flammeus? |
Birthmark (stork bite)
it is a dilation of vessels in the dermis |
|
|
What causes bacillary angiomatosis? Who gets it?
|
Infectious disease, non‐neoplastic proliferation of vessels in skin, lymph nodes and visceral organs of HIV patients or immunocompromised pts.
• Gram‐negative bacilli of Bartonella genus |
|
|
What is the treatmetn for bacillar angiomatosis?
|
Treat with macrolide antibiotics
(erythromycin) |
|
|
What are the two intermediate grade blood vessel tumors?
|
Hemangioendothelioma
Epitheliod Hemangioendothelioma |
|
|
What are the four types of Kaposi sarcoma?
|
– Chronic ‐ classic, European form
– Lymphadenopathic African Kaposi’s – Transplant‐associated – AIDS associated |
|
|
What is considered the underlying infectious cause of Kaposi Scarcoma??
|
human herpesvirus 8
|
|
|
What are the three phases of Kaposi Sarcoma?
|
Patch
Plaques Nodules |
|
|
What are the microscopic hallmarks of Kaposi Scarcoma?
|
Spectrum of lesions, red‐purple coalescent patch, plaques and nodules
– Early ‐ jagged, thin walled, dilated vascular spaces in epidermis with interstitial inflammatory cells and extravasated red cells – Later ‐ plump, spindle shaped stromal cells with irregular, angulated, slit‐like spaces filled with red cells |
|
|
What are the two malignant blood vessel
tumors? |
Angiosarcoma (Hemangiosarcoma)
Hemangiopericytoma |
|
|
• What three carcinogens are hepatic
angiosarcomas associated with? |
• Arsenic
• Thorotrast • Polyvinyl chloride (PVC) |
|
|
What are the two types of lymphangiomas?
|
Simple - small masses in lymph channels in sub q head and neck
Cavernous- Cavernous spaces in necks of children |
|
|
Where are hemangiopericytomas derived from
|
Pericyted in capillaries and venules
|
|
|
What is the other term for cavernous
lymphangioma? |
Cystoc hygroma
|
|
|
What syndrome is asspciated with lymphangioma particularly cavernous lymphagnioma?
|
Turners Syndrome
|
|
|
What is lymphangioscaroma
|
Rare, develops after prolonged lymphatic obstruction with lymphedema
– Most cases seen after radical mastectomy |
|
|
What is lymphangioscaroma
|
Rare, develops after prolonged lymphatic obstruction with lymphedema
– Most cases seen after radical mastectomy |
|
|
v-sis
|
the growth factor that signals the gene to make b-derived growth factor
|
|
|
v-erb
|
the growth factor that signals the gene to make epidermal derived growth factor receptor
|
|
|
Over expression of PDGF and v-sis is associated with what cancer?
|
glioblastoma
|
|
|
FGF (fibroblastic GF) signals what and is associated with which cancers?
|
HST gene; gastric and kaposi scarcoma
|
|
|
Most common benign tumors in women? men?
|
Leyomyoma in Uterus
Men=lipomas |
|
|
Familial cancers tend to be due to what gene problems?
|
Tumor Supressor gene issues
|
|
|
BRCA‐1 and BRCA‐2 mutations are what type of genes?
|
Tumor supressor
|
|
|
What is the inheritance of familial cancer ?
|
Somatic not x linked
Single mutant gene in 1 of 2 alleles is inherited – germ line mutation – greatly increasing the risk of developing cancer increasing the risk of developing cancer |
|
|
AD Inherited Cancer Syndromes (3)
|
familial adenomatous polyposis;
neurofibromatosis, MEN 2B |
|
|
What gene and phenoype is assocaited with Multiple endocrine neoplasia (MEN) 2B?
|
‐ Marfanoid habitus / ganglioneuromas
of tongue, RET gene |
|
|
What are ‐ Lisch nodules?
|
– hamartomas of melanocytes in the irises seen in nerurofibromatosis
|
|
|
What does ATM mean? What is its job?
|
ataxia telectanasia mutated
ATM gene binds to damaged DNA; phosphorylates P53 |
|
|
For the following oncogene, what is the associated tumor?
abl |
CML
|
|
|
For the following oncogene, what is the associated tumor?
c-myc |
burkitts lymphoma
|
|
|
For the following oncogene, what is the associated tumor?
bcl-2 |
follicular and undifferentiated lymphomas
|
|
|
For the following oncogene, what is the associated tumor?
erb-B2 |
breast, ovarian and gastric
|
|
|
For the following oncogene, what is the associated tumor?
ras |
colon carcinoma
|
|
|
For the following oncogene, what is the associated tumor?
L-myc |
Lung tumor
|
|
|
For the following oncogene, what is the associated tumor?
N-Myc |
Neuroblastoma
|
|
|
For the following oncogene, what is the associated tumor?
ret |
Multiple endocine neoplasia types I and II
(MEN I and II) |
|
|
For the following tumor suppressor gene, what is the associated tumor?
Rb |
Retinoblastoma & Osteoscaroma
|
|
|
For the following tumor suppressor gene, what is the associated tumor? BRCA 1 amd 2
|
Breast and ovarian
|
|
|
For the following tumor suppressor gene, what is the associated tumor?
p53 |
Li-Fraumeni and most himan cancers
|
|
|
For the following tumor suppressor gene, what is the associated tumor?
p16 |
Melanoma
|
|
|
For the following tumor suppressor gene, what is the associated tumor?
APC |
colorectal
|
|
|
For the following tumor suppressor gene, what is the associated tumor?
WT1 |
Wilms Tumor
|
|
|
For the following tumor suppressor gene, what is the associated tumor?
NF1 or NF2 |
Nerufibromatosis type 1 or 2
|
