Neoplasia Flashcards

1
Q

Neoplasia

A

‘Any new autonomous growth (independent of growth)

New growth’

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2
Q

Classification of neoplasms

A
A. Benign (oma):
 1. Epithelial
  Papilloma, adenoma 
 2. Mesenchymal
B. Malignant:
 1. Epithelial
  Carcinoma
 2. Mesenchymal
  Sarcoma
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3
Q

Papilloma

A
  1. Finger like projections with fibrovascular core

2. Adenoma : tumour of a gland

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4
Q

Exceptions of nomenclature of neoplasms

A

Malignancies like:

Seminoma, lymphoma, chordoma, chloroma, melanoma

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5
Q

Mixed tumours

A
1. Single germ layer
 Pleomorphic adenoma
2. More than one germ layer
 Teratoma:
   A. Cystic/ dermoid cyst
   B. Mature teratoma: benign
   C. Immature teratoma: malignant
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6
Q

Choriostoma

A

Normal tissue in abnormal location (Ectopic crest of normal tissue)
Not a neoplasm or cancer

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7
Q

Hamartoma

A

Abnormal tissue in normal location
The abnormal tissue is disorganised/ haphazard
Eg., pulmonary hamartoma

Recently, it is discovered that they show clonal chromosomal rearrangements and therefore can be considered as tumours

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8
Q

Anaplasia

Hallmark of malignancy

A
Lack of differentiation
1. Pleomorphism is seen (variation in shape and size of cells)
2. High N/C ratio of 1:1 (instead of (1:4-1:6)
3. Hyperchromatic nuclei
4. Prominent nucleoli 
5. Loss of polarity
6. Abnormal mitosis
Seen in malignant tumour, not in benign
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9
Q

Molecular basis of cancer, or Hallmarks of cancer

A
  1. Self sufficiency in growth signals (oncogenes)
  2. Insensitivity to growth inhibitory signals (tumour suppressor genes)
  3. Evasion of apoptosis
  4. Limitless replicative potential
  5. Sustained angiogenesis
  6. Invasion and metastasis
  7. Altered cellular metabolism
  8. Escape of immune recognition
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10
Q

Protooncogenes

A
  1. Growth factors
  2. Growth factor receptor
  3. Signal transduction proteins
  4. Nuclear transcription factors
  5. Cyclins and CDKs
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11
Q

Examples of growth factors leading to cancers

A
  1. sis (PDGF-β) ➡️ astrocytoma
  2. Hepatocyte GF ➡️ Hepatocellular carcinoma HCC
  3. HST-1 ➡️ osteosarcoma

Their overexpression leads to these cancers

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12
Q

Examples of growth factor receptor that leads to cancer

A
  1. C-kit (CD-117) ➡️ GIST via point mutation
    Via overexpression of EGFR:
  2. EGFR-1 (ERB-1) ➡️ adenocarcinoma
  3. EGFR-2 (ERB-2) ➡️ breast and ovarian cancer
  4. RET ➡️ Medullary carcinoma of thyroid and MEN-2 syndrome via point mutation
  5. ALK➡️ various cancers
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13
Q

Loss of function mutation in RET leads to

A

Hirshsprung’s disease

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14
Q

ALK gene and cancer

A
Anaplastic lymphoma kinase gene of chromosome 2
Gene for a growth factor receptor
Mutation leads to:
1. ALCL (anaplastic large cell lymphoma)
2. Inflammatory myofibroblastic tumours
3. Adenocarcinoma of lung
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15
Q

Signal transduction proteins leading to cancer

A
  1. ABL ➡️ CML, ALL
  2. RAS (most common oncogene mutated in human malignancy)
  3. BRAF V600
  4. NOTCH ➡️ ALL
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16
Q

ABL as protooncogene

A

ABL (9th chromosome) undergoes translocation with BCR t(9:22) ➡️ bcr:abl fusion transcript ➡️constitutive activation of tyrosine kinase ➡️ leukaemia :

  1. P210 kDa➡️ CML or
  2. P190 kDa ➡️ ALL (poor prognosis)
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17
Q

RSA as protooncogenes

A

Point mutation of RSA➡️
GAPs (GTPase activation proteins become ineffective ➡️
GTP RAS not inactivated to GDP RAS ➡️
cancer

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18
Q

Cancers caused by RAS gene mutation

A

Most common oncogene mutated in human malignancy
K. K-RAS ➡️ colon, pancreas, lung cancer
H. H-RAS ➡️ bladder/ kidney tumours
N. N-RAS ➡️ melanoma

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19
Q

Cancers caused by BRAF V600 mutation

A
P. Papillary carcinoma of thyroid
L. Langhan’s cell histiocytosis
A. Astrocytoma
C. Colon cancer
H. Hairy cell leukaemia
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20
Q

Nuclear transcriptions factors leading to cancers

A

myc oncogene
3 types:
L. L-myc➡️ small cell carcinoma of lung (via amplification)
N. N-myc ➡️ neuroblastoma (via amplification)
C. C-myc ➡️ Burkit’s lymphoma (via t(8:14)

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21
Q

Cyclins and CDKs leading to cancers

A

Mantle cell lymphoma
t(11:14) ➡️ leads to overexpression of cyclin D ➡️ cell proliferation continues

11 chromosome ➡️ cyclin D
14 chromosome ➡️ IgH

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22
Q

Rb gene

A
Gene on chromosome 13q14
Governor of cell cycle
Regulated G1-S transition
Rb two forms:
1. hypophosphorylated ➡️ active
2. hyperphosphorylated ➡️ inactive
Mutation of Rb leads to:
1. Retinoblastoma
2. Osteosarcoma
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23
Q

Knudson’s two hit hypothesis

Loss of heterozygosity

A

Both alleles of Rb must be mutated for retinoblastoma Rb to develop
In familial Rb, 1 copy of mutated allele by birth, 2nd by mutation after birth
Thus ‘Loss of heterozygosity’ occurs

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24
Q

p53

Properties

A

Gene in chromosome 17p
Mutation of p53 ➡️ Difraumeni syndrome (autosomal dominant)
Guardian of genome/ molecular policeman of cell
Mutation in >50% of malignancy

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25
Q

Functions of p53

A
  1. Induces p21 ➡️ CDK inhibitor ➡️ cell cycle arrest
  2. GAF 45 ➡️ repair cells ➡️ re enter cell cycle, if this fails ➡️
  3. Activates pro apoptotic factor BAX, BAK ➡️ apoptosis
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26
Q

Examples of chemical carcinogens

A
Polycyclic aromatic hydrocarbons (PAH)
Aflatoxin 
Arsenic
Asbestos
PVC
Diethyl stilbestrol
Benzene
β-Naphthylamine/azo dyes
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27
Q

Polycyclic hydrocarbons cause

Aflatoxin causes

A

Bronchogenic cancers

Hepato Cellular Carcinoma

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28
Q

Arsenic causes

Asbestos causes

A

Skin cancer, lung cancer

Lung cancer (adenocarcinoma), malignant mesothelioma

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29
Q

Polyvinyl chloride PVC causes

Diethyl stilbesterol causes

Cadmium causes

A

Hepatic angiosarcoma

Vaginal cancer

Prostate cancer

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30
Q

Benzene causes

β-Naphthylamines/azo dyes of dry cleaning causes

A

Leukaemia

Bladder cancer

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31
Q

Ionising radiation causes cancers like

A
  1. All leukaemias except CLL
  2. Papillary carcinoma, thyroid,
    breast cancer, lung cancer,
    saliva gland cancer (mucoepidermoid cancer)
32
Q

Microbial carcinogens

A
  1. H pylori: gastric adenocarcinoma, maltoma
  2. HPV
  3. HBV, HCV
  4. HTLV-1
  5. HHV-8
  6. EBV
33
Q

Diseases caused by HPV

A
1. Low risk:
HPV-6,11
Condyloma acuminatum
2. High risk:
HPV-16,18
Cervical, Anogenital and Laryngeal cancer
3. Intermediate risk:
HPV-31,33
34
Q

Pathogenesis of human papilloma virus

Microscopy

A

E6+p53 ➡️ inactivated
E7+Rb ➡️ inactivated

Microscopy:
Koilocytic changes:
 Cell with thick membrane
 Resin like nucleus
 Perinuclear halo/hoff
35
Q

Cancers caused by

HBV, HCV and HTLV-1

A

HBV and HCV ➡️ Hepatocellular carcinoma

HTLV-1 (Human T cell Leukaemia Virus) ➡️ T cell leukaemia

36
Q

Diseases caused by HHV-8

A

Human Herpes Virus-8 causes:

  1. Kaposi’s sarcoma
  2. 1° effusion lymphoma
  3. Multicentric Castleman disease
37
Q

Ebstein Barr virus (EBV) causes:

A
  1. Hodgkin’s lymphoma and non Hodgkin’s lymphoma like
  2. Extra nodal T cell lymphoma
  3. Nasopharyngeal carcinoma
  4. Burkitt’s lymphoma
  5. Post transplant lymphoproliferative disorders (PTLD)
    Non neoplastic lesion: infectious mononucleosis
38
Q

EBV properties

A

Affects B-lymphocytes
Binds to CD-21
Pathogenesis:
1. LMP-1 (Latent membrane protein) ➡️ activates NF-kβ (growth signaling pathway) ➡️ cell proliferation
2. EBNA-2 ➡️ activates cyclin D ➡️ cell proliferation

39
Q

Two malignancies which do not metastasise

A

Glioma

Basal cell carcinoma (rodent ulcer)

40
Q

Desmoplasia

A

Abundant collagenous tissue producing tumour is called desmoplasia

41
Q

Dysplasia

A

Disordered proliferation
Contains features of anaplasia
Limited by a basal membrane so also called ‘carcinoma in situ’
Reversible in early stages, whereas metaplasia is reversible

42
Q

Routes of metastasis

A
1. Lymphatics: 
 most carcinomas
2. Hematogenous: 
 most sarcomas
 to lung, liver,...
 venous > arteriolar
3. Direct seeding of body cavities:
 Pseudomyxoma peritonii
4. Trans-coelomic spread:
 Krukenberg’s tumour
43
Q

Carcinomas which do not metastasise via lymphatic route

A
  1. Choriocarcinoma
  2. Hepatocellular carcinoma
  3. Renal cell carcinoma
    These metastasise via hematogenous route
44
Q

Sarcoma which do not metastasise via hematogenous route

A
  1. Alveolar Rhabdomyo sarcoma
  2. Synovial sarcoma
    Metastasise via lymphatic route
45
Q

Tumours that spread via CSF

A
  1. Medulloblastoma:
    Drop metastasis to cauda equina
  2. Ependymoma
46
Q

Tumours that undergo spontaneous regression

A
  1. Retinoblastoma, Neuroblastoma
  2. Renal cell carcinoma
  3. Malignant melanoma
  4. Chriocarcinoma
47
Q

Small round blue cell tumours of childhood

A
  1. Retinoblastoma: Flexner Wintersteiner rosette
  2. Neuroblastoma: Holmer Wright rosette
  3. Nephroblastoma (Wilm’s tumour)
  4. Hepatoblastoma and Medulloblastoma
  5. Ewing’s sarcoma
  6. PNET
  7. Rhabdomyosarcoma
  8. Few lymphoma
    Rossetes are seen
48
Q

Most radiosensitive phase of cell cycle

Most radioresistant phase

A

G2M (M)

S phase

49
Q

Longest phase of cell cycle

A

Interphase

50
Q

Cyclin-CDK pairs

A

D4,6
E2
A2
B1

Eg., cyclin D ➡️ CDK 4 and CDK 6

51
Q

Earliest cyclin to increase in cell cycle is

A

Cyclin D
Which combines with CDK-4,6 during G2➡️S

Last is cyclin B + CDK1

52
Q

Cyclins involved during G1S transition

A

Cyclin D + CDK4 (more important)

Cyclin E + CDK2

53
Q

Cyclins involved in G2M transition

A

Cyclin A + CDK2

Cyclin B+ CDK1 (more important)

54
Q

CDK inhibitors

A
1. Cip/Kip family
 P21- induced by p53
 P27- induced by TGF β
 P57
2. INK 4A/ARF
 P14,15,16,18
 P16 is most important among these
55
Q

Role of Rb in cell cycle

A
2 forms:
 Hypophosphorylated-active
 Hyperphosphorylated-inactive
E2F transcription factor in its pocket in active state
When Cyclin D + CDK4 increases ➡️ 
Rb is inactivated ➡️ 
release of E2F, which is required for S phase
G1-S transition regulation
56
Q

Important tumour suppressor genes and the chromosomes they are located in

A
  1. p53: 17p
  2. Rb: 13q14
  3. NF-1: 17
  4. NF-2: 22
  5. BRCA-1: 17
  6. BRCA-2: 13
  7. WT-1: 11
  8. WT-2: 11
  9. PTEN: 10
  10. VHL: 3
  11. APC: 5
57
Q

Tumour suppressor genes and the cancers related to them

A
  1. p53
  2. Rb
  3. NF-1: Neurofibromas, meningeomas
  4. NF-2: Schwannoma
  5. BRCA-1: breast, ovarian cancer
  6. BRCA-2: male breast cancer, prostate cancer
  7. WT-1 and WT-2: Wilm’s tumour
  8. PTEN: Endometrial cancer, prostate cancer
  9. VHL: clear cell renal carcinoma, cerebellar hemangioblastoma
  10. APC: FAP, adenocarcinoma colon
58
Q

Example of evasion of cell death causing cancer

A

Follicular lymphoma

t(14:18) i.e, IgH+BCL2 ➡️ increased expression of BCL-2 (anti-apoptotic)➡️ evasion of cell death

59
Q

Examples of pro angiogenic factors

A
  1. VEGF-vascular endothelium
  2. PDGF-platelet derived
  3. FGF-fibroblast derived
60
Q

Examples of anti angiogenic factors

A
  1. Vasculostatin
  2. Endostatin
  3. Angiostatin
  4. Thrombospondin-1
61
Q

Warburg effect

A

Cancer cell in presence of normal O2 concentration produces ATP via glycolysis only
This is utilised in PET scan

62
Q

Steps in invasion and metastasis by tumour cells

A
  1. Detach from each other by decreased expression of E-cadherin
  2. Attach to ECM by integrins which combines with laminin,fibronectin
  3. ECM degradation and breakdown of basement membrane by MMPs and type 4 collagenase
  4. Cells enter blood vessels
  5. Cells +platelets➡️ tumour emboli to organs and ,via venules, the lymph nodes
63
Q

MMPs

A

Matrix metalloproteinases for ECM degradation and breakdown of basement membrane along with toe 4 collagenase
Two types are used: 2 and 9
9 is more important

64
Q

Repair pathway defects

A
  1. Nucleotide exclusion repair:
    xeroderma pigmentosa
  2. DNA repair: …
  3. Mismatch repair: HNPCC/ MSI
65
Q

Defect in DNA repair causes

A

Bloom’s syndrome
Fanconi anaemia
Ataxia telangiectasia

66
Q

Mismatch repair defect causes

A

HNPCC (hereditary non polyposis colorectal carcinoma)

Also called MSI (microsatellite instability defect)

67
Q

Paraneoplastic syndrome

A

Symptom complexes in cancer patients which cannot be explained by the local or indigenous spread of the tumour
Most common: hypercalcemia
Small cell carcinoma produces the most paraneoplastic syndrome

68
Q

List of paraneoplastic syndromes

Part 1

A
  1. SIADH: small cell carcinoma of lung (ADH)
  2. Cushing’s syndrome: “” (ACTH)
  3. Hypertrophic pulmonary osteoarthropathy: “”
  4. Hypercalcemia: squamous cell carcinoma of lung, carcinoma breast (PTHrp)
  5. Polycythemia: renal cell carcinoma (erythropoietin)
69
Q

List of paraneoplastic syndrome

Part 2

A
  1. Hypoglycaemia: ovarian carcinoma, fibrosarcoma (insulin, IGFs)
  2. Migratory thrombophlebitis: carcinoma pancreas, colon
  3. Myasthenia gravis: thymoma, carcinoma lung
  4. Acanthosis nigricans: carcinoma stomach, colon (EGF)
70
Q

List of tumour markers, part 1

A
  1. PSA and PAP (prostate acid phosphatase): prostate cancer
  2. AFP: HCC hepatocellular carcinoma, NSGCT- yolk sac tumour
  3. β-HCG: choriocarcinoma, gestational trophoblastic disease
  4. CA-125: Ovarian cancer
71
Q

List of tumour markers, part 2

A
  1. CA 19-9: cancer colon, pancreas
  2. Carcino embryonic antigen: “”
  3. CA-15-3: breast cancer
  4. Catecholamines: pheochromocytoma
  5. Immunoglobulins: multiple myeloma
  6. Calcitonin: medullary carcinoma thyroid
72
Q

Immunohistochemical markers of tumour part 1

A
  1. Carcinomas: cytokeratin
  2. Sarcomas: vimentin
  3. Glial: Glial Fibrillary Acidic Protein GFAP
  4. Smooth muscle: Smooth Muscle Actin (SMA)
  5. Skeletal muscle: Desmin, myogenin, Myo D-1
73
Q

Immunohistochemical markers of tumour part 2

A
  1. Vascular: vWF, CD-31, VEGF
  2. Neuroendocrine: synaptophysin, chromogranin, neuron specific enolase
  3. GIST: CD-117 (c-KIT), DOG-1, CD-34
  4. Malignant melanoma: HMB-45, S-100
  5. Malignant mesothelioma: Calretinin, CK-5/6
74
Q

Immunohistochemical markers part 3

A
  1. Ewing’s sarcoma: CD-99 (MIC-2)
  2. Hepatocellular carcinoma: Hep par-1, arginase-3
  3. Osteosarcoma: osteopontin, osteonectin, osteocalcin
  4. Chrondrosarcoma: S-100
  5. Liposarcoma: “”
75
Q

Micro RNAs involved in cancer

A
1. Oncogenic role:
 Micro RNAs 155,200 ➡️ B-cell lymphoma
2. Tumour suppressor role:
 Micro RNA 15,16 
 Affected in CLL
76
Q

Chromothripsis

A
Chromosomes are shattered, then they join rapidly ➡️:
1. Oncogenic role increases
2. Tumour suppressor role decreases 
Produces cancers like:
1. Osteosarcoma
2. Glioma