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Neoplasia Block > MOD 2 lectures (infectious agents & soft tissue tumors) > Flashcards

MOD 2 lectures (infectious agents & soft tissue tumors) Flashcards

1
Q

What occurs during viral oncogenesis

A

virus inserts genome into host genome, virus enters latent state, early genes essential for transformation, then those cells replicate w virus
-virus can also insert next to proto-onco turning it into onco (insertional mutagenesis)

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2
Q

HPV

A

most common STI in world

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3
Q

which hpv cause benign squamous papillomas (warts)?

A

types 1,2,4,7

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4
Q

which hpv types cuase low risk geneital warts (condyloma accuminatum)

A

types 6 and 11

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5
Q

which hpv types can cause squamous cell carcionma of vervix, angogenital, and upper resp tract

A

16, 18, 31, 33, 35, 51

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6
Q

Why are some types of HPV benign?

A

benign hpv stays extrachromosal, doesnt integrate into host genome (but for cancer it does)

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7
Q

integration of HPV 16 and 18

A

HPV dna interrupted at e1/e2 rdg frame of viral genome, e2 suppr transcr of early viral genes E6/7, so now theyre over expressed

  • E6 binds p53 and interferes with cell cycle reg, and E8 binds Rb and p21 and does same
  • so HPV 16/18 cause overexpr of E6/7, which bind and degrade TSGs
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8
Q

Retinoblastoma (Rb)

A

-recap: Rb hypo-phos and bound to E2F, then prolif signal upregulates cyclin D1 which bind to CDK, and this coplex phosphorylates Rb, which now frees E2F to go to nucl and transcribe cell cycle progression genes

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9
Q

High-risk HPV

A

Rb and p21 degradation causes incr rel of E2F, so uncontrolled cell cycle
-p53 activated in resp to DNA dmg, so now DNA cant be repaired/no apop etc

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10
Q

HHV-4 aka EBV aka Epstein-Barr virus– what can it cause?

A
  • causes infectious mononucl
  • in africa causes BURKITT LYMPHOMA
  • B-cell lymphoma in immunosuppressed
  • also hodgkin lymphoma, nasopharyngeal carcinoma, NK/T-cell lympoma
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11
Q

MOA of EBV

A

targets orophar epith cells and B cells via CD21, EBV genome remains episomal in B cell, no rep, becomes immortalized
-LMP-1 (late membrane protien 1) viral gene can mimic activated CD40 and trick B cells into prolif as if stimulated by T cells (normal activation paths), stim of JAK/STAT etc, B cell prolif

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12
Q

Other cells involved in B cell immortalization in EBV

A

EBV nuclear antigen 2 (EBNA-2) activates cyclin D1 to promote cells to go from G0 to G, and incr transcr of LMP1

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13
Q

What does LMP-1 in EBV do overall

A

LMP-1 mimics helper T cell signal that stimualtes CD40, causing B-cell prolif

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14
Q

Burkitt lymphoma chromosomal translocation

A

8 and 14 (pathognomonic)

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15
Q

What causes burkitt lymphoma

A

EBV esp in african version (for most ppl EBV doesnt cause burkitt lymphoma if healthy immune sys)

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16
Q

what gene amplification causes all cases of burkitt lympohma

A

c-myc oncogene amplification
(on 8, translocated to IgH gene on chrom 14)
-polyclonal b cell mitogen, cell cycle checkpoints overwhelmed so translocations and mutations more frequent (worse for AIDS and immunosuppr/def)

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17
Q

burkitt sx

A

disfiguring jaw mass

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18
Q

what happens to EBV infected cells in transplant

A

undergo polyclonal b cell prolif, but immune sys eventually regresses them, if not they become monoclonal neoplasms (LMP-1 overexpr at first)

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19
Q

Nasopharyngeal carcinoma cause

A

100% contain EBV (incidence high in China, Africa, and Arctic)

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20
Q

HBV`(hepatitis B virus) assoc cancer

A

associated with HCC (hepatocell carcinoma) esp asia/africa (most HCC caused by HBV)

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21
Q

How does HBV cause cancer

A

insertional mutagenesis, (near protoonco), but more likely is chronic hepatocell inflammation and injury (bc more regeneration/cell div so more chance of mutation)
-or HBx prot (encoded by HBV DNA)

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22
Q

What does HBx protein do in HBV cancer

A

disrupt normal growth of infected liver cells, activates growht pormoting genes like IGF and binds p53 decr effectiveness and suppressing growth

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23
Q

What is an example of an oncogenic RNA virus

A

Human T-cell leukemia VIrus (HTLV)-1

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24
Q

What cancer is HTLV-1 assoc with/ sx?

Other assoc/location?

A

adult t-cell leukemia/lymphoma (ATLL), neoplasm made of flower-like lympocytes (look like purple flowers on slides)
-endemic in japan, carrib, and assoc with tropical spastic paraparesis (paralysis or weakness of lower extremities)

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25
Q

Which virus is assoc with weakness of lower extremities, and what is this sx called?

A

HTLV-1

tropical spastic paraparesis

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26
Q

How is HTLV 1 similar to HIV

A

infects CD4+ T cells, transmitted thru STI, v long latency period, only smol % get leukemia

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27
Q

What gene in HTLV-1 is essential for leukemic transformation

A 
Tax gene (doesnt involve insertional oncogenes)
Tax gene dysregulates cell cycle, inactivates cell cycle inhibs and enhances cyclin D, stops DNA repair and inhibits checkpoints!
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28
Q

H pylori bacteria and cancer assoc

A

curved gram neg bacillus assoc with development of gastric carcinoma and lymphoma
-dev of small B-cell lympohma of MALT (mucus assoc lymph tissue), 100% assoc

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29
Q

Pathologic features of H pylori

Tx

A

Tx with antibiotics

  • lymph infiltration and lots of germinal ctrs, lesion on stomach, made of monocytoid B cells which look like fried egg and are CD20 positive
  • lympoepithelial lesions are monocytoid B cells that invade and destroy gastric glands
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30
Q

H pylori MOA

A

irritates gastric mucosa, inflamm response, causing extra lympoid tissue to dev and B cell prolif, causing accum of mutations, dev of B cell lympohma
(metaplasia–>dysplasia–>invasive carcinoma)

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31
Q

What are tumors usually combatted by

A

recognized as non self by CD8+ cells, macros, and NK

  • CD8 fight tumor ag expressed on MHC 1 and protecc against viral tumors
  • NK cells destroy those that downreg MHC1
  • macros work with both cells via IFN-gamma (prod by both cells)
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32
Q

Tumor immunology: immune surveillance and immunoediting

A
  • immune surveillance: normal immune sys can destroy cancer

- cancer immunoediting: immune sys elim tumor variants that are unrecogniziable

33
Q

What are the 7 categories of tumor antigens

A

1) Mutated oncogenes
2) Mutated self-proteins
3) Over-expression/aberrantly expressed proteins
4) Oncogenic viruses and associated tumor antigens
5) Oncofetal proteins
6) Abnormal cell surface glycoproteins/glycolipids
7) Differentiation agents

34
Q

1 mutated oncogenes

A

processed by MHC I/II and destroyed by CD4/8 cells

35
Q

2 mutated self proteins

A

radiation or chemical induced etc, same response as prev

36
Q

3 over/aberrently expressed self prots

A

normal prots overexpressed, or embryo genes expressed during non embryo (if in tumor, immune sys will rec as aberrant)

37
Q

4 oncogenic viruses and associated tumor antigens

A

viral tumros produced prots, recognized as foreign (latent DNA viruses like EBV and HPV are most potent) (eg vaccine allows immuen sys to make abs to HPV)

38
Q

5 oncofetal ag’s

common tumor markers?

A

prots expr in embryonic tissue but shouldnt be in adult, some tumors make these so immune sys can recognize (but can also occur in inflamm)
-CEA and AFP commonly used as tumor markers

39
Q

6 abnormal cell surface glycoprots/lipids

A

includes gangliosides, blood group antigens, and mucins CA125,CA19-9,MUC-1

  • dont only mean tumors, but higher in cancer cells
  • tumors may have weird carb side chains or weird peptide cores (targt of mabs and vaccines)
40
Q

7 differentiation antigens

A

lineage specific antigens, can give mabs against these for immunotherapy (eg rituximab as antiCD20 for b cell lymphoma)

41
Q

Why do ppl still get cancer?

A

tumors fail to produce ag’s rec by immune cells, hide surface antigens in glycocalyx molecs, reduced MHC expression or costim by tumor, tumor produces immunosuppressive prots, Fas ligand expression by tumor cells can cause T cell apoptosis

42
Q

INfectious viruses (4) and bacteria assoc with cancer?

A 
HPV
EBV
HBV
HTLV-1
H pylori
43
Q

What are the 3 categories of soft tissue tumors (from soft tissues neoplasia handout)

A

Benign
intermediate (locally aggressive and recurring but dont metastisize)
Malignant (sarcoma)

44
Q

What is a soft tissue tumor called

A

sarcoma

45
Q

Sarcoma features

A

oft in extremeities, below fascia, large, high mortality, ~10% metastasis

46
Q

WHAT 2 FEATURES IS SARCOMA GRADING BASED ON

A

MITOTIC RATE

DEGREE OF NECROSIS

47
Q

What env factor and what 3 syndromes are sarcomas assoc with?

A
  • irradiation (10 yr)
  • gardners syndrome (mesenteric fibromatosis)
  • NF1 (schwannomas, malig nerve sheath tumors)
  • Li-Fraumeni syndrome (p53, soft tissue/bone sarcoma)
48
Q

Types of cells in soft tissue tumors

A 
spindle cell (rod shaped, fibroblast/SM cell)
round cell (small, lympho sized, little cytoplasm (ewings, rhabodmyosarcoma)
epithelioid: round, larger w lots of cytoplasm (epith like)
49
Q

Benign fibroblastic tumors

A

nodular fasciitis

fibromatosis

50
Q

nodula fasciitis

A

benign fibroblastic tumor of soft tissue: subcutaneous (superficial) fast growing spindle cell lesion of extremities/trunk
-can be excised, recurrence rare

51
Q

fibromatosis

A

benign fibroblast tumor (soft tissue)

locally aggressive lesion of fibroblasts, benign spindle cells set in collagenous background

52
Q

fibromatosis IHC

A

BETA-CATENIN POSITIVE

53
Q

fribromatosis types

A

superificial: plantar fascia, palmar fibrromatosis
deep: mesenteric (gardners), extra-abdominal desmoid type

54
Q

Benign vascular tumors

A 
capillary hemangioma (incl pyogenic granuloma)
cavernous hemangioma
55
Q

capillary hemangioma

A

incl pyogneic granulama

-hyper prolif of small vascular spaces, esp in kids, regress w age

56
Q

cavernous hemangioma

Endoth markers?

A

large vascular spaces, doesnt regress, may be assoc with Maffucci’s
-Vascular tumors (+) for endothelia markers CD31 and CD34

57
Q

Benign peripheral nerve tumors

A

Granular cell tumor

Schwannoma

58
Q

Granular cell tumor

and IHC profile

A

benign neural tumor, round cells w pink cyto granules, positive for S-100 portein (schwann cell origin)

59
Q

Schwannoma and IHC

A

benign PNS tumor with pallisading spindle cells, risk of malig transformation in NF1, acoustic neruomas in NF2, S100 positive by IHC

60
Q

Benign adipocytic tumors

A

lipoma-most common soft tissue tumor, subcutaneous

intramuscular lipoma- benign but locally inflitrates SKM, rare recurrence

61
Q

Malignant soft tissue tumors (sarcomas) list

A 
DFSP (dermatofibrosarcoma)
Fibrosarcoma
Malign fibrous histiocytoma (undiff pleomorphic sarcoma)
Liposarcoma (well diff)
Synovial sarcoma 
Leiomyosarcoma
Angiosarcoma
Rhabdomyosarcoma
62
Q 
Dermatofibrosarcoma protuberans (DFSP)
IHC and cells
A

int, rarely metas, nodular lesion superficial, prominent spindle cell storiform patterns
-CD 34+ spindle cells! (also expr by endoth cells)

63
Q

Fibrosarcoma

A

middle aged adults, deep soft tissue exp extremities and trunk, fish-flesh appearance in high grade, hypercell spindle cell with herringbone pattern, no consistent IHC

64
Q

malignant fibrous histiocytoma

A

undifferentiated pleomorphic sarcoma
-late adult life, deep soft tissue extrem and trunk, fibro/myofibro/blastic and plemoprhic histyocyte like cells, no consistent IHC

65
Q

Liposarcoma (well-differentiated)
Which gene is amplified?
Myxoid variant translocation?

A

most common in middle age, deep tumor esp in retroperitoneum, lipocytes with enlarged nuclei (lipoblasts), supernummerary ring chromosomes

  • MDM2 gene amplification (conventional)
  • Myxoid variant has t(12;16) translocation
66
Q

synovial sarcoma
IHC
translocation

A

young adults, knee/thigh/foot, biphasic epith/spindle pattern, rearr of SYT gene

  • IHC epith markers CYTOKERATIN and EPITHELIAL MEMBRANE ANTIGEN (EMA)
  • translocation x;18
  • always grade 3
67
Q

Leiomyosarcoma

IHC

A

malig SM tumor, spindle cells in fascicles and eosinophilic cytoplasm
IHC: smooth muscle ACTIN and DESMIN

68
Q

Angiosarcoma

IHC

A

malig sarcoma of blood vessels, can be post radiation

IHC CD31 and CD34

69
Q

Rhabdomyosarcoma
IHC
Types

A

Malig sarcoma of SKM, kids, can be spindle or round cell
IHC: DESMIN and MYOGENIN
-Types: embryonal (incl botryoides variant (grape like mass in GU of kids), alveolar (1 and 2;13 translocation)

70
Q

+/- profile of sarcomas in general?

A

VIMENTIN POSITIVE

CYTOKERATIN NEGATIVE

71
Q

where else does leiomyosarcoma occur?

A

Gi tract
deep soft tissue of extremities
retroperitoneum

72
Q

Gardner’s syndrome Sx, and what is it a part of?

Gene involved?

A

Part of FAP (familial adenomatous polyposis)
Sx: colon polyps, abd desmoid fibromatosis tumors, skin fibromas, jaw pain/lesions, bone tumors (osteosarcomas)
-Gene: adenomatous polyposis coli (APC)

73
Q

What gene is usually mutated in fibromatoses/desmoid tumors

A

BETA-CATENIN

74
Q

Diffs between benign and malig soft tissue tumors

A

malig: doesnt resemble normal tissue, irreg nuclei (grainy), large, deep to fascia, necrosis, high grade

75
Q

Fibromatosis can be assoc with

A

peyronies disease (penis plaque) and dupuytren’s contracture (trigger finger, invol)

  • deep called desmoid
  • mesenteric type can inv gardners (in mesentary or retroperit), abd etc
76
Q

Other tumors

A

SKM: myositis ossificans
Glomus: modified SM cells, a-v anastamoses, females, triggered by cold temp or touch, thermal reg (benign)
-pyogenic granuloma (type of hemangioma), ulceration/inva, skin/gums/lips/tongue
Lipoma found in neck and back
Giant cell tumor of tendon sheath: fingers, yellow, histiocytes, lobulated mononucl appearance
-MFH: malig fibrous histiosarcoma: (undiff pleomorphic sarcoma) in extrem/trunk, radiation, fibro/histio cells, inflam
-angiosarcoma v aggressive

77
Q

Which sarcoma is the only one that stains with epithelial markers>

A

synovial sarcoma

EMA and cytokeratin

78
Q

What is an SKM marker

A

mygenin (eg rabdomyosarc)

Neoplasia Block (16 decks)

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