Neoplasia: General Approach Flashcards
What makes neoplasia benign or malignant?
benign tumors are localized; malignant tumors invade and metastasize
What does a circumscribed tumor mean?
benign; smooth and encapsulated edge
Why can you not discriminate between benign and cancerous tumors based on their ability to cause harm?
even benign tumors can cause harm- spinal cord compression, airway compression, hemorrhage, and hormone secretion
All tumors are composed of two components. What are these?
neoplastic cells that constitute the tumor parenchyma and reactive stroma made up of connective tissue, blood vessels, and cells of the adaptive and innate immune system
the classification of tumors and their biologic behavior are based primarily on?
the parenchymal component
what is the growth and spread of tumors critically dependent on?
their stroma
Why is induction of scar-like tissue around a tumor helpful for us?
it gives us a hard detectable lump (scirrhous)
what is an invasive cervical carcinoma surrounded by?
dense lymphatic infiltrate
What are malignant tumors arising in solid mesenchymal tissues called?
sarcomas
what are some mesenchymal tissues that come off the mesoderm?
supportive tissues: fibrous tissue, fat, bone, cartilage, muscle (smooth muscle)
Where does our epithelium come from?
endoderm or ectoderm
What might be considered epithelium?
lining of all of our visceral organs or lining of our glands, or skin surface
What are malignant tumors arising from blood-forming cells?
leukemias or lymphomas
what are malignant neoplasms of epithelial cell origin called?
carcinomas
What is a teratoma from? and how is it defined?
totipotent stem cells; defined on the basis of more than one germ cell layer
What are hamartomas?
overgrowth of mature tissue that normally occur in that area, but they are disorganized
what are choristomas?
mass of tissue histologically normal, but in the wrong location (heterotopic or ectopic)
What is the effect of metaplasia?
the new cell type is prone to acquisition of genetic damage
what does metaplasia that acquires additional genetic damage become?
dysplasia
how can dysplasia be defined?
dysplasia is the first step on the route to cancer; it is disorder growth
what is carcinoma in situ?
severe dysplasia; something is malignant but incapable of spreading (because it has to go through that basement membrane in order to invade and metastasize)
how would you define a neoplasm that resembles the cells of origin a lot?
well-differentiated
how would you define a neoplasm that does not resemble the cells of origin at all?
poorly differentiated: anaplasia
What is one of the most common areas where metaplasia occurs and one of the most common places that gives us disease?
Respiratory epithelium (columnar–> squamous)
What do you call a malignant tumor of the gastric epithelium?
gastric adenocarcinoma
What morphologic feature (microscopically viewable) can reflect that tumor’s rate of growth?
mitotic figures
What are 5 telltale morphology features of malignancy?
anaplasia, pleomorphism, abnormal nuclear morphology, increased or abnormal mitosis, loss of polarity
what is pleomorphism?
variability of cell size/shape
How can we use techniques of staining/immunostaining to diagnose tumors?
the way a tumor stains for something will help you identify differentiation; you can use what a tumor produces (eg. mucin or keratin) to identify what kind of differentiation it has
what if you find mucin in a tumor?
it means that it is a glandular epithelial neoplasm
How might you prove that a tumor was of thyroid origin?
we could do a special immunostain for thyroglobulin
What are endocrine tumors often associated with?
they are usually well-differentiated and are often associated with hormone secretion (they can produce excess amounts of different hormones)
What are the tumor markers for the breast in females?
CA 15-3
what are the tumor markers for the Liver/bile duct in females and males?
CEA, AFP, CA19-9
what are the tumor markers for the ovaries?
CA-125
what are the tumor markers for the stomach/pancreas in females/males?
CEA, CA19-9
what is the tumor markers for the colorectal in males and females?
CEA, CA19-9
what is the tumor marker for the prostate?
PSA
what is the tumor marker for the testicle?
AFP and BHCG
What are the different types of leukemia differentiation?
acute vs chronic
in acute leukemias, where have the cancerous cells halted maturation?
at the blast stage
in chronic leukemias, what do the cancer cells look like?
more mature cells (chronic leukemias show full maturation)
What separates the two different types of leukemias from a biological standpoint?
where the arrest occurs
What is one of the most common benign breast tumors?
fibroadenoma
What are the three different types of metastasis?
lymphatic spread, hematogenous spread, trans-coelomic spread (direct seeding of body cavities)
what occurs during trans-coelomic spread (direct seeding)?
gain of entry into a free compartment (like the peritoneal space)
What organ uses all three modes of metastasis?
the bowel
What is the most common route of spread for carcinomas?
lymphatic spread (however they are not restricted to just lymph spread)
what is lymphatic spread dependent on?
regional drainage
What is a sentinel lymph node biopsy?
at the time of surgery, a tracer dye is injected into the tumor; the first node to take up the dye are the “sentinel nodes” and these nodes are removed
what does a sentinel lymph node biopsy prevent?
more extensive lymphadenectomy
Where is virchow’s node located?
supraclavicular area (usually left)
what is typically associated with supraclavicular lymphadenopathy (virchow node)?
any thoracic or abdominal carcinoma
How do cancers way below the clavicle get all the way up to virchow node?
the thoracic duct is responsible for the end lymphatic drainage for everything below the diaphragm, the entire left hemithorax, and the entire left head, neck, and arm
Where does the thoracic duct eventually drain into?
the left subclavian vein (in that site is virchow’s node)
What is the classic mechanism for metastasis for sarcomas?
hematogenous route
what organs are the primary targets for hematogenous mets coming from the original site?
lung, liver, and bone
How do you stage tumors?
TNM staging
what does the T indicate in TNM staging?
tumor size, and the extent of invasion (primary tumor)
what does the N stand for in TNM staging?
Degree of lymph node involvement
what does the M stand for in TNM staging?
presence/absence of distant mets
What is the leading site of new cancer in males in the US?
prostate
what is the leading site of new cancer in females in the US?
breast
What is the leading cause of death from cancer in males in the US?
lung and bronchus
what is the leading cause of death from cancer in females in the US?
lung and bronchus
Why is liver cancer high in some countries?
viral hepatitis
why is non-hodkin’s lymphoma high in some countries?
Epstein-barre virus
What causes Kaposi sarcoma?
HIV
What does exposure to asbestos lead to?
mesothelioma
what does exposure of benzene lead to?
acute myeloid leukemia
what is the typical use or occurrence of benzene?
dry cleaning; adhesives, coatings, and detergents
what does exposure to radon and its decay products lead to?
lung carcinoma
what is the typical use or occurrence of radon?
from decay of materials containing uranium; underground mines
what does exposure to vinyl chloride lead to?
hepatic angiosarcoma
what is the typical use or occurrence of vinyl chloride?
it is a refrigerant
What sets many childhood cancers apart from adult cancers?
germline mutations
What are some acquired predisposing conditions for cancer?
chronic inflammation; precursor lesions; immunodeficiency
Why does screening work?
it identifies cancer early; it identifies cancers before they are cancers
What is an example of something used to identify cancer before its cancer?
colon polyps–> they are the adenoma to carcinoma sequence
benign neoplasms are not typically the precursor to their malignant counterparts; what is the exception to this?
the colon adenoma–> carcinoma sequence
What may offer protection to certain individuals to lung cancer (even though they have an extensive history of smoking)?
P450 halotypes may offer protection
What else may play a role in a BRCA1 mutated patients getting breast cancer?
diet and reproductive history
What is a paraneoplastic syndrome?
when the tumor secretes substances such as PTH-rP and ACTH; and the tumor also evokes the elaboration of other factors such as autoantibodies and cytokines
What are two lung cancers with typical paraneoplastic syndromes?
squamous carcinoma and small cell neuroendocrine carcinoma
what paraneoplastic syndrome does squamous carcinoma cause?
humoral hypercalcemia of malignancy
what occurs during humoral hypercalcemia of malignancy?
there is elaboration of PTHrP secretion; this works on PTH receptors to give patients hypercalcemia
what paraneoplastic syndrome is associated with small cell neuroendocrine carcinoma?
cushing syndrome
what occurs during the paraneoplastic syndrome of cushing syndrome?
Hypercortisolism due to excessive ACTH secretion by tumor cells
What is Trousseau syndrome?
a paraneoplastic thrombophilia classically associated with pancreatic carcinoma
When might you suspect Trousseau syndrome?
if someone comes in with a thrombosis and you can’t explain it, you may want to start looking for cancer
What is another example of a vascular and hematologic manifestation that could occur in some cancers besides Trousseau syndrome?
Disseminated intravascular coagulation
what cancer might cause DIC?
acute promyelocytic leukemia
what occurs in acute promyelocytic leukemia to cause DIC?
the leukemic cells express tissue factor which activates factor X, high levels of Annexin II receptors on plasma cells convert plasminogen into plasmin; both TF and Annexin II are highly expressed by APL cells
What is the philadelphia chromosome?
When you combine the ABL from chromosome 9 and the BCR from chromosome 22, to give you a changed chromosome 22: BCR-ABL
what is the protein that results from the philadelphia chromosome?
a constitutively active tyrosine kinase; creates a perpetually diving cell clone
When you see a BCR-ABL chromosome, what can you do?
diagnose the patient with CML, treat, and monitor
how do you treat a patient with a philadelphia chromosome?
give them Imatinib (a tyrosine kinase inhibitor); this is extremely effective at controlling this cancer clone
how can you test for the philadelphia chromosome?
we can use a BCR-ABL PCR test to look for even tiny amounts of this transcript–> so you can tell if your therapy is working or not
What defines a successful treatment of CML with a tyrosine kinase inhibitor?
molecular response (a negative BCR-ABL PCR)
What are the two different categories of carcinogens and what is the difference between them?
direct vs indirect; direct carcinogens are carcinogenic right away (there is no need for conversion); indirect carcinogens require a metabolic process to take place for the substance to become an active (ultimate) carcinogen
what is responsible for converting most indirect carcinogens to their active forms?
cytochrome p450
What effect does an increased amount of thymine dimers have?
these dimers distort the DNA, which blocks the progress of DNA and RNA polymerase
Removal of thymine dimers is primarily accomplished utilizing what?
nucleotide excision repair
what happens if you don’t have nucleotide excision repair?
it is a hereditary disorder: Xeroderma pigmentosum
what happens if you overwhelm your nucleotide excision repair (especially by excess exposure to UV light)?
sporadic melanomas and other skin cancers
what cancers resulted after the atomic bombs were dropped in Hiroshima and Nagasaki?
there was an increase in leukemias within 5-7 years; solid tumors increased such as colon carcinoma, breast carcinoma, and lung carcinoma
What was the Chernobyl accident in 1986?
exposure to radioactive iodine, which caused a sharp increase in thyroid carcinoma
What is Human T cell Leukemia Virus (HTLV-1) associated with?
endemic T cell leukemias/lymphomas
What is hepatitis B and C viruses associated with?
hepatocellular carcinomas
what is helicobacter pylori bacterium associated with?
B cell lymphomas of the stomach
what is Human papillomavirus associated with?
squamous carcinoma of the cervix, anogenital region, and pharynx/larynx
What are the viral proteins of human papillomavirus associated with oncogenesis?
E6 and E7
What occurs as progressive integration of E6/E7 proteins occurs?
there is inactivation of tumor suppressor genes and upregulation of oncogenic pathways
What is epstein Barr virus implicated in oncogenesis of?
in B-cell lymphomas as well as certain carcinomas
What was the first virus associated with cancer and what was this cancer?
Epstein Barr Virus; associated with endemic Burkitt lymphoma
what does EBV result in?
immortalization and increased replication of B lymphocytes
What is the role of EBNA 2?
it upregulates oncogenes
what is the role of LMP?
it induces cell proliferation
What causes Burkitt Lymphoma?
the IgH/MYC translocation
What benign sounding designations are always always always malignant?
lymphoma, melanoma, mesothelioma, and seminoma
What are some epithelial tissues?
surface epithelium (skin, mucosa), glandular epithelium, “specialized” epithelium
What is a benign uterine smooth muscle tumor called?
leiomyomata
what is a malignant uterine smooth muscle tumor called?
leiomyosarcoma
