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HemOnc Week 2 > ICL 7.1: Neoplasia > Flashcards

ICL 7.1: Neoplasia Flashcards

1
Q

what is neoplasia?

A

the formation or presence of a new, abnormal growth of tissue

it’s a disorder of cell birth that’s triggered by a series of mutations effecting a single cell and its progeny

so tumors are derived from a single cell!

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2
Q

how do you name benign and malignant tumors?

A

benign: tissue of origin + “oma”

malignant:
epithelial origin = carcinoma
mesenchymal origin = sarcoma

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3
Q

what are the characteristics of a benign tumor?

A
  • well differentiated (closely resemble original tissue they can from)
  • structure is usually typical of tissue of origin
  • usually slow rate of growth, may come to a standstill or regress - normal mitosis
  • usually cohesive, expansile, well demarcates masses that don’t invade or infiltrate surrounding tissues
  • no metastasis
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4
Q

what are the characteristics of malignant tumors?

A
  • some lack differentiation = anaplasia
  • structure is often atypical/different than tissue or origin
  • erratic rate of growth, may be slow to rapid - abnormal mitosis
  • locally invasive, infiltrate surrounding tissue
  • frequent metastasis
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5
Q

what are the two phases of the metastatic cascade?

A
  1. invasion of extracellular matrix (ECM)

2. vascular dissemination, homing of tumor cells and colonization

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6
Q

what are the steps to a tumor becoming invasive?

A
  1. loosening of intercellular junctions = cells need to separate
  2. degradation = cells need to breakdown the components of the basement membrane with enzymes like collagenase
  3. attachment = cell needs to be able to attach to certain receptors on the ECM
  4. migration = cell secretes motility factors so it can move around
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7
Q

what happens after a tumor cell has become mobile during the metastasis process?

A
  1. intravasation = cell penetrates a blood vessel

tumor cells encounter has defense cells and some tumor cells are destroyed but survival in the circulation is enhanced by platelet-tumor aggregates that protect tumor cells

  1. extravasation from blood vessel - the cell leaves the blood and establishes a new site

establishment of metastatic tumor relates to anatomic location of primary tumor, natural pathways of lymphatic drainage, and microenvironment of target tissue

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8
Q

what are the steps of tissue invasion?

A
  1. loosening of cell-cell contacts
  2. degradation of ECM
  3. attachment to novel ECM components
  4. migration of tumor cells
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9
Q

how are cell-cell contacts lost?

A

by the inactivation of E-cadherin through a variety of pathways

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10
Q

when a tumor cell is becoming invasive, what is happening during the degradation step?

A

so first the cell-cell contacts are lost due to e-cadherin enzyme

then proteolytic enzymes secreted by tumor cells and stroll cells degrade the basement membranes and interstitial matrix!

proteolytic enzymes also release growth factors sequestered in the ECM and generate chemotactic and angiogenic fragments from cleavage of ECM glycoproteins

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11
Q

how can you predict the metastatic site of tumors?

A

they’re easily predicted by the location of the primary tumor and the normal pattern of lymphatic drainage

lots of tumors stop in the first capillary bed they encounter (usually the lung and liver**)

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12
Q

what are the most common locations of metastasis?

A

lung and liver

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13
Q

what is organ tropism?

A

it’s when there’s preferential metastasis sites

like for example, lung and prostate cancer cells tend to like to metastasize to bone

probably due to the expression of adhesion or chemokine receptors whose ligands are expressed by endothelial cells of the metastatic site

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14
Q

what are the local effects of tumors on the body?

A
  1. impingement on vital tissues impairing their function or causing death of tissues and providing a nidus for infection
  2. obstruction (like in the GI tract or biliary tract)
  3. bleeding and secondary infections when tumors ulcerates through natural surfaces

both benign and malignant tumors have these local effects!

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15
Q

how can a tumor cause bleeding?

A

when the tumor ulcerates through natural surfaces

the bleeding can be from erosive destructive growth or expansile pressure of the tumor

ex. melena (bloody stool) or hematuria (bloody urine)

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16
Q

what are the hormonal effects of tumors?

A

neoplasms in an endocrine gland can cause clinical problems by producing hormones

non-endocrine tumors may produce hormones or hormone-like products that give rise to paraneoplastic syndromes

both malignant and benign tumors can have hormonal effects!

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17
Q

what types of tumors are more likely to have hormonal effects?

A

more typical of well-differentiated benign tumors

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18
Q

what is cancer cachexia?

A

progressive loss of body fat and lean body mass accompanies by profound weakness, anorexia and anemia

we have no idea how this happens but it’s probably due to the interplay between cancer and the immune system - TNFα major suspect

only happens with malignant tumors!!**

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19
Q

what are the characteristics of cancer cachexia?

A
  • equal loss of both fat and lean muscle
  • elevated basal metabolic rate
  • systemic inflammation = increase in acute phase reactions
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20
Q

what’s the most likely enzyme involved in cancer cachexia?

A

TNFα

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21
Q

what’s the difference between cancer cachexia and starvation?

A

in starvation you preferentially have loss of body fat before you lose muscle but with cachexia you lose muscle and fat at the same time

with starvation you have a decrease of BMR while in cancer cachexia you have increase of BMR

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22
Q

what are paraneoplastic syndromes?

A

symptom complexes in cancer patients that cannot be readily explained by either the local or distant spread of the tumor OR by elaboration of hormones indigenous to the tissue in which the tumor arose

it’s a series of symptoms!

ex. a malignant neoplasm in the pancrease, if it’s producing insulin that’s NOT considered a paraneoplastic syndrome

10% of people with cancer have paraneoplastic syndromes

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23
Q

why are paraneoplastic syndromes important?

A
  • they may be the earliest warning of a neoplasm!!
  • they may cause significant clinical problems, even death
  • they may mimic metastatic disease and confound treatment
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24
Q

what are the types of paraneoplastic syndromes?

A
  1. endocrinopathies (most common)
  2. neuromyopathic
  3. dermatologic
  4. osseus
  5. vascular & hematologic
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25
Q

what are some types of dermatologic paraneoplastic syndromes?

A
  • acanthuses nigricans: dark, velvety skin that if present is more than 50% indicative of a neoplasm (almost looks like diabetes but bigger)
  • dermatomyositis
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26
Q

what’s a type of osseus paraneoplastic syndromes?

A

hypertrophic osteoarthopathy

proliferation of bone at the ends of long bones commonly seen with lung cancer = clubbing of digits

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27
Q

what are some types of vascular & hematologic paraneoplastic syndromes?

A
  • disseminated intravascular coagulation (DIC)
  • migratory thrombophlebitis
  • non-bacterial thrombotic endocarditis
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28
Q

what are the types of endocrine paraneoplastic syndromes?

A
  1. Cushing Syndrome
  2. syndrome of inappropriate ADH secretion
  3. hypercalcemia
  4. hypoglycemia
  5. polycythemia
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29
Q

what is the mechanism and underlying cancer of Cushing syndrome?

A

Cushing syndrome is an endocrine paraneoplastic syndrome

cancer: small cell carcinoma of lung, pancreatic carcinoma or neural tumors
mechanism: tumor produced ACTH or ACTH-like substance that causes production of cortisol

30
Q

what is the mechanism and underlying cancer of syndrome of inappropriate ADH secretion?

A

syndrome of inappropriate ADH secretion is an endocrine paraneoplastic syndrome

cancer: small cell carcinoma of lung or intracranial neoplasms
mechanism: tumor secretes antidiuretic hormone or atrial natriuretic hormones that cause fluid retention

31
Q

what is the mechanism and underlying cancer of hypercalcemia?

A

hypercalcemia is an endocrine paraneoplastic syndrome

cancer: squamous cell carcinoma of lung, breast carcinoma, renal carcinoma, adult T-cell leukemia/lymphoma
mechanism: tumor secretes parathyroid hormone-related protein TGF, TNF, IL-1

32
Q

what is the mechanism and underlying cancer of hypoglycemia?

A

hypoglycemia is an endocrine paraneoplastic syndrome

cancer: ovarian carcinoma or fibrosarcoma & other sarcomas
mechanism: tumor secretes insulin or insulin-like substance

33
Q

what is the mechanism and underlying cancer of polycythemia?

A

polycythemia is an endocrine paraneoplastic syndrome

cancer: renal carcinoma, cerebellar hemangioma, or hepatocellular carcinoma
mechanism: tumor secretes erythropoietin

34
Q

what is acanthosis nigricans?

A

black looking skin spots like in diabetes

associated cancer: gastric carcinoma, lung carcinoma, uterine carcinoma

mechanism: tumor secretes grey-black verrucous hyperkeratosis of skin, immunologic, secretion of EGF

35
Q

what is dermatomyositis?

A

cancer: bronchogenic carcinoma, breast carcinoma
mechanism: immunologic

36
Q

what is hypertrophic osteoarthropathy?

A

clubbing of digits

cancer: bronchogenic carcinoma, thymic neoplasms
mechanism: periosteal new bone formation tat ends of long bones, mechanism unknown

37
Q

what is neuromyopathic syndrome?

A

cancer: small cell carcinoma of lung, thymic neoplasms
mechanism: immunologic; antibodies induced against tumor cells that cross-react with neurons

38
Q

what is non-bacterial thrombotic endocarditis?

A

cancer: mutinous colorectal and pancreatic cancers
mechanism: sterile vegetations on mitral valve related to hypercoagulability

39
Q

what is migratory thrombophlebitis?

A

aka Trousseau phenomenon

cancer: pancreatic carcinoma
mechanism: tumor products (muffins) activate clotting

40
Q

what is DIC?

A

cancer: acute promyelocytic leukemia and prostate carcinome
mechanism: tumor products activate clotting

41
Q

what is red cell aplasia?

A

cancer: thymic neoplasms
mechanism: unknown

42
Q

what is seborrheic keratosis?

A

cancer: gastric carcinoma
mechanism: sudden appearance of skin lesions

43
Q

what is nephrotic syndrome?

A

various cancers

mechanism: membranous glomerulopathy, tumor antigens

44
Q

what is tumor grading?

A

the degree of differentiation = the degree to which tumor cells recapitulate normal structures and the number of mitoses with the tumor

45
Q

how is tumor grading broken down?

A

I = well differentiated (low grade, not as aggressive)

II = moderately differentiated

III = poorly differentiated (high grade)

IV = undifferentiated (aplastic)

correlates with tumor aggressiveness!!

46
Q

what is tumor staging?

A

staging = severity of disease

based on tumor size, extent of invasion, presence or absence of metastasis in nearby lymphocytes nodes and distant organs

super important for deciding the course of treatment, more important than tumor grading

47
Q

what is the TNM system?

A

used by pathologists to classify tumors

T = tumor
N = regional lymph nodes
M = distant metastasis
48
Q

what is the T part of the TNM system?

A

T0 = no evidence of primary tumor

Tis = carcinoma in situ

T1,T2,T3,T4 = increasing size and/or local extension of the primary tumor (T4 means invading nearby organs, T1-T3 is within the primary organ)

TX = primary tumor cannot be assessed

T score only applies to primary organ, not metastases

49
Q

what is the N part of the TNM system?

A

N0 = no regional lymph node metastases

N1,N2,N3 = increasing number or extent of regional lymph node involvement

NX = regional lymph nodes cannot be assessed

50
Q

what is the M part of the TNM system?

A

M0 = no distant metastases

M1 = distant metastases present

51
Q

what lab tests can you used to diagnose cancer?

A
  1. histologic and cytologic methods
  2. flow cytometry
  3. serum tumor markers (not as specific)
  4. molecular diagnosis
52
Q

what are some types of histologic and cytologic methods to diagnose cancer?

A
  • paraffin embedded, H&E stain sections (most common)
  • frozen section
  • cytology: exfoliative or fine needle aspiration
  • immunohistochemistry
  • electron microscopy

samples must be adequate (big enough), representative and well preserved**

53
Q

what is routine histology?

A

take a sample from a specific tissue

process the tissue overnight (24 hours)

dehydrate the tissue then embed the tissue in a hot paraffin wax

then you can cut sections from the tissue and stain it

the final product is the pink histology slides that you see all the time!

54
Q

what is a frozen section?

A

you get a section in 15 minutes!

the surgeon finds something weird, he can stop and ask for a frozen section since it’s a quick process

also used to evaluate the adequacy of recession of a tumor to make sure the tissue around the tumor is negative - it directs the direction of surgery!

55
Q

what is electron microscopy?

A

not as common

useful for classification of soft tissue tumors and renal tumors

helpful because there’s a structure that’s very specific to a certain tumor

ex. a mesothelioma has microvilli that are easily visible on EM

56
Q

what is fine needle aspiration?

A

minimal risk to patient

great for superficial things like lymphnodes or subcutaneous legions

you place a needle and suck up cells and then spread them on a glass and stain them

you can’t tell if there’s invasion though with a fine needle aspiration

blue slide with red stained cells

57
Q

what is a pap smear?

A

you’re looking at cells that would normally be shed or obtained by scraping

ex. fluid accumulations, urine samples, pap smears

58
Q

what are the uses of immunohistochemistry?

A
  • categorization of undifferentiated or poorly differentiated tumors
  • categorization of leukemias and lymphomas
  • determination of site or origin of metastatic tumors
  • detection of molecules that have prognostic or therapeutic significance
59
Q

what are cytokeratins?

A

epithelial markers that indicate a carcinoma

can help you tell what something that is really undifferentiated is

60
Q

what is vimentin?

A

very ubiquitous marker but usually it stains mesenchymal cells and points you towards a sarcoma

61
Q

what are the breast cancer prognostic markers?

A

ER

Her2/neu

62
Q

what is flow cytometry?

A

requires fresh live cells! and it’s now the standard of care

it identifies cell-surface antigens which are used to classify leukemias and lymphomas

it also detects ploidy (DNA content) –> the relationship between the amount of abnormal DNA content and prognosis is pretty common for a lot of malignancies

63
Q

what are serum tumor markers?

A

they’re biochemical indicators of the presence of a tumor

they can be hormones, enzymes, oncofetal antigens, immunoglobulins and glycoproteins

not used to diagnose but they’re helpful in supporting diagnosis, determining response to therapy and detecting relapse

64
Q

what cancer is the AFP tumor marker associated with?

A

AFP = α- fetoprotein

hepatocellular carcinoma

yolk sac tumor or ovary or testes

65
Q

what cancer is the hCG tumor marker associated with?

A

hCG = human chorionic gonadotropin

trophoblastic tumors

non-seminomatous testicular tumors

66
Q

what cancer is the CEA tumor marker associated with?

A

CEA = carcinoembryonic antigen

carcinomas of the colon

pancreas

lung

stomach

heart

67
Q

what cancer is the Bence Jones protein tumor marker associated with?

A

multiple myeloma

Waldenstrom macroglobulinemia

68
Q

what cancer is the CA19.9 tumor marker associated with?

A

pancreatic

colorectal carcinomas

69
Q

what cancer is the CA-125 tumor marker associated with?

A

ovarian cancer

70
Q

what cancer is the LDH tumor marker associated with?

A

LDH = lactate dehydrogenase

malignant lymphoma

71
Q

what cancer is the NSEtumor marker associated with?

A

NSE = neuron specific enolase

small cell carcinoma of lung

neuroblastoma

72
Q

what cancer is the PSA tumor marker associated with?

A

PSA = prostate specific antigen

prostate carcinoma

HemOnc Week 2 (14 decks)

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