Oncology

Question 1

Define cancer (2 points)

Answer 1

Cancer – abnormal cells divide in an uncontrolled way; some cancers may eventually spread into other tissues.

Question 2

List 7 risk factors for cancer

Answer 2

Risk factors for cancer:

1. Smoking
2. Excess alcohol intake
3. Carcinogenic diet
4. Excess sunlight
5. Physical inactivity
6. Chronic infection
7. Genetic predisposition

Question 3

Recall the cell cycle

Answer 3

The cell cycle:

• How a cell grows and divides – ‘life cycle’
• Interphase:
  
  • Growth of cell, no division (includes G₁, S, G₂)
  • Cells in this phase most of time
  • Except cancer cells (division)
• G₁: duplicate cell contents (e.g. organelles)
• S: duplicate chromosomes (23 to 46 pairs)
• G₂: prepare for mitosis
• G₀: no cell division (e.g. neurones)
• Mitosis: active cell division (cytokinesis)

Question 4

List the two classes of molecule which regulate the cell cycle

Answer 4

Two classes of molecule regulate the cell cycle through various checkpoints:

1. Cyclins (Cyc)
   
   • Specific Cyc are made at specific times.
2. Cyclin-dependent kinases (CDKs)
   
   • Inactive CDKs always present in cell, activated by Cyc

Question 5

List the 3 cell cycle checkpoints

Answer 5

Cell cycle checkpoints (3 points):

1. M checkpoint
2. G₁ checkpoint
3. G₂ checkpoint

Question 6

Describe positive cell cycle regulation

Answer 6

Positive regulation at internal checkpoints (allows for progression):

• The cell progresses through the cell cycle regulated through various checkpoints:
  
  • Cyclins (Cyc)
  • Cyclin-dependant kinases (CDKs)

Question 7

Describe negative regulation of the cell cycle at G₁ checkpoint

Answer 7

Negative regulation of the cell cycle (prevents progression from G₁ phase to S phase):

• At G₁ checkpoint:
  
  1. Tumour suppressor genes control the cell cycle
  2. Retinoblastoma protein (pRb) normally bound to E2F transcription factors
  3. When phosphorylated, pRb releases E2F transcription factors which bind to DNA and regulate expression of S phase proteins → progress to S phase
  4. When unphosphorylated, pRb remains bound to E2F transcription factors → halts progress to S phase
  5. Therefore, pRb is able to halt cell cycle if conditions are unfavourable (i.e. potential cancer).

Question 8

Describe the role of tumour suppressor genes (5 points)

Answer 8

Tumour suppressor genes control the cell cycle, p53 (“guardian of the genome”):

1. Activated p53 binds to DNA directly, leading to downstream activation of p21
2. p21 complexes to CDK2, inhibiting it
3. This prevents cell continuing onto cell division
4. Mutated p53 → means p21 not available to halt cell division → cancer
5. Mutated p53 is in > 50% human cancers.

Question 9

List 7 types of cancer cell

Answer 9

Types of cancer cells (7 points):

1. Carcinoma
2. Sarcoma
3. Leukaemia
4. Lymphoma and myeloma
5. Brain and spinal cord (CNS)
6. Mixed tumours
7. Teratoma

Question 10

Describe carcinoma and list 4 types

Answer 10

Carcinoma – originates in epithelial tissues (85% of UK cancers):

“Some Apples Taste Bad”

1. Squamous cell carcinoma
2. Adenocarcenoma
3. Transitional cell carcinoma
4. Basal cell carinoma

Question 11

Describe sarcoma and list 2 types

Answer 11

Sarcoma – originates in connective tissues e.g. bones, cartilage, tendons, and muscles (1% of UK cancers):

1. Bone sarcoma
2. Soft tissue sarcoma

Question 12

Describe leukaemia

Answer 12

Leukaemia – originates in blood-forming tissues, bone marrow (3% of UK cancers)

Question 13

Describe lymphoma and myeloma

Answer 13

Lymphoma and myeloma – cancers of the lymphatic system (5% lymphoma and 1% myeloma)

Question 14

Describe cancer of the central nervous system and name one type

Answer 14

Central nervous system cancers – originate in the cells of the brain or spinal cord (3% of UK cancers):

1. Glioma

Question 15

Describe mixed tumours and list 2 types

Answer 15

Mixed tumours – both epithelial and connective tissue components:

1. Carcinosarcoma
2. Pleomorphic adenoma

Question 16

Describe teratoma

Answer 16

Teratoma – originates in the germ cells:

Question 17

Recall the hallmarks of cancer (10 points)

Answer 17

Hallmarks of cancer are acquired functional capabilities that allow cancer cells to:

• Survive
• Proliferate
• Spread

These functions are acquired in different tumour types in the course of multistep tumourigenesis, via distinct mechanisms at different times (10 mechanisms; *considered in detail):

Question 18

List the two main types of cancer characteristics

Answer 18

Characteristics of cancer are grouped into two main types:

1. Emerging characteristics
2. Enabling characteristics

Question 19

List 2 emerging characteristics of cancer

Answer 19

Emerging characteristics of cancer:

1. Avoiding immune destruction
2. Deregulating cellular energetics

Question 20

List 2 enabling characteristics of cancer

Answer 20

Enabling characteristics of cancer:

1. Genome instability and mutation
2. Tumour-promoting inflammation

Question 21

Emerging characteristic of cancer

Describe how cancer cells avoid immune distruction

Answer 21

Avoiding immune destruction – active evasion by cancers cells from attack and elimination by immune cells (e.g. NK cells):

• Cancer immunoediting – tumour cells with downregulation or loss of MHC class I escape surveillance by cytotoxic T cells

Question 22

Emerging characteristic of cancer

Describe how cancer cells derugulate cellular energetics

Answer 22

Deregulation of cellular energetics

Cancer cells favour aerobic glycolysis pathway over normal respiration – inefficient but fast:

• Produces a lot less ATP per glucose but they make it much faster
• Increases glucose transporters to take in more glucose
• Produces intermediate precursors for building proteins and DNA needed by rapidly dividing cells

This phenomenom is referred to as the Warburg effect

Question 23

Describe the Warbug effect

Answer 23

The Warburg effect

Refers to the fact that cancer cells, somewhat counter intuitively, prefer fermentation as a source of energy rather than the more efficient mitochondrial pathway of oxidative phosphorylation.

Question 24

Enabling characteristic of cancer

Describe genetic instability and mutation for enabling cancer

Answer 24

Genetic instability and mutation:

• Certain genetic mutations confer selective advantage on a subset of cells, enabling outgrowth and dominance in local tissue environment.

Question 25

**Compare inherited vs acquired genetic mutations found in cancers**

Answer 25

The appearance of abnormal characteristics reflects altered patterns of gene expression in cancer cells, resulting from _inherited_ or _acquired_ mutations:

Question 26

**Enabling characteristic of cancer** ## Footnote **Describe how inflammation can enable tumour progression (4 key points)**

Answer 26

Tumour-promoting inflammation: * Historically thought that immune response was only to allow body to eradicate tumour (partly true) "**_I_**nflammation **_P_**romotes **_G_**rowth & **_S_**urvival" Inflammation _enables_ tumours by _supplying bioactive molecules_ to environment: 1. _Inductive signals_ activate epithelial mesenchymal transition 2. _Proangiogenic_ factors and ECM modifying enzymes facilitate angiogenesis, invasion and metastasis 3. _Growth factors_ sustain proliferative signalling 4. _Survival factors_ limit cell death

Question 27

**Recall the targeted therapies for the 10 different hallmarks of cancer**

Answer 27

Question 28

**Compare benign tumour (4 points) vs malignant tumour (4 points)**

Answer 28

Benign – non-cancerous tumour (4 points): 1. Enclosed in connective tissue 2. Confined to site of origin 3. May grow but does not spread to other parts of body (i.e. does not metastasize) 4. May turn malignant – best to resect when noticed Malignant – cancerous tumour (4 points): 1. Not enclosed in any tissue 2. Not confined to site of origin 3. Grows rapidly and spreads to other body parts via blood (metastases) 4. Earlier intervention tends to have better prognosis

Question 29

**Describe DNA point mutations and list 3 key types**

Answer 29

DNA point mutations: * Common types of mutations to DNA sequence include: 1. Substitution (a different nucleotide is substituted) 2. Insertion (the addition of a new nucleotide) 3. Deletion (the loss of a nucleotide) Point mutations because only one nucleotide is substituted, added, or deleted * _Insertions and deletions_ are usually _more harmful than a substitution_ * Results in a frame-shift that changes the reading of subsequent codons * Alters the entire amino acid sequence following the mutation, producing abnormal protein

Question 30

**List and describe 3 types of germline mutation**

Answer 30

Germline ⇒ germline is the population of a multicellular organism's cells that pass on their genetic material. Germline mutations can have large or small negative effects: 1. _Neutral_ mutations: * Non-coding sequence of DNA (intron) * Changes in DNA sequence but no noticeable effect on the phenotype of an organism 2. _Selected_ mutations: * Coding sequence of DNA (exon) * Defective gene, abnormal protein produced 3. _Mutations to control genes_: * Control genes regulate expression of other genes * Mutation causes big change occurs in phenotype * HOX genes germ line mutations: * Fly – legs instead of antennae – mutation in HOM-C * Human – microtia → mutation in HOXA2

Question 31

**List 7 chromosome mutations**

Answer 31

Chromosome mutations: 1. Chromosomal aneuploidy (abnormal number of chromosomes in a cell) 2. Point mutations 3. Deletions 4. Duplications 5. Amplifications 6. Translocations 7. Inversions

Question 32

**Describe epigenetics in cancer (4 points)**

Answer 32

Epigenetics – study of _heritable changes in gene expression_ that _do not involve changes in underlying DNA sequence_: * A _change in phenotype without a change in genotype_, which in turn affects how cells read the genes * _Inherited or environmental exposures_ during development and lifetime chemically modify DNA and the proteins bound to it

Question 33

**Describe chromosomes and the 4 primary functions of chromatin**

Answer 33

In a cell nucleus, _DNA is packaged into chromosomes_. Chromatin forms chromosomes: * _Complex of DNA and proteins_ * DNA tightly coiled around proteins called _histones_ – _support DNA structure_ _​_The primary functions of chromatin (4 points): 1. To _package_ DNA into a more compact, denser shape 2. To _reinforce_ the DNA macromolecule to allow mitosis 3. To _control_ gene expression and DNA replication 4. To _prevent_ DNA damage

Question 34

**Describe DNA methylation (4 points)**

Answer 34

DNA methylation: 1. Methylation of DNA and histones _causes nucleosomes to pack tightly together_ 2. _Transcription factors cannot bind the DNA_ → _genes are not expressed_ 3. DNA methylation is _almost exclusively found in CpG islands_ 4. In cancer typically, there is _hypermethylation of tumour suppressor genes_ and _hypomethylation_ _of oncogenes_

Question 35

**Describe histone acetylation and deacetylatoin (5 points)**

Answer 35

Histone acetylation: 1. Lysine residues of N-terminal tail protruding from the histone core of the nucleosome can be _acetylated_ and _deacetylate_ 2. _Histone acetylation_ results in _loose packing of nucleosomes_, _transcription factors can bind the DNA_ and _genes are expressed_ 3. _Histone acetylation_ induced by _histone acetyl transferases_ (HATs) and is associated with _gene transcription_ 4. _Histone hypoacetylation_ induced by _histone deacetylase_ (HDAC) activity is associated with _gene silencing_ 5. In cancer typically, _decrease in histone acetylation_ (hypoacetylation) is involved in _tumourigenesis_, _tumour invasion_ and _metastasis_

Question 36

**Outline the TNM classifcation system**

Answer 36

T – size or direct extent of the primary tumour: * Tx: tumour cannot be assessed * Tis: carcinoma in situ * T0: no evidence of tumour * T1, T2, T3, T4: size and/or extension of the primary tumour. N – degree of spread to regional lymph nodes: * Nx: lymph nodes cannot be assessed * N0: no regional lymph nodes metastasis * N1: regional lymph node metastasis present; at some sites, tumour spread to closest or small number of regional lymph nodes * N2: tumour spread to an extent between N1 and N3 (N2 is not used at all sites) * N3: tumour spread to more distant or numerous regional lymph nodes (N3 is not used at all sites). M – presence of distant metastasis: * M0: no distant metastasis * M1: metastasis to distant organs (beyond regional lymph nodes).

Question 37

**Define carcinogenesis (3 points)**

Answer 37

Carcinogenesis: the process by which _normal cells are transformed into cancer cells_ * A complex multistage process usually involving more than one genetic change * Mutations in _oncogenes_ and _tumour suppressor_ genes induce malignant change

Question 38

**Compare the function of oncogenes in health and in cancer**

Answer 38

Oncogenes: * Normal function: Proto-oncogenes normally control cell division, apoptosis and differentiation * In cancer: Activation of proto-oncogenes to oncogenes e.g. c-Myc gene * Mutant oncogene alleles are typically dominant

Question 39

**Compare the function of tumour supressor genes in health and in cancer**

Answer 39

Tumour suppressor genes in health and in cancer * Normal function: slow down cell division, repair DNA mistakes, initiate apoptosis * In cancer: inactivation of tumour suppressor genes e.g. TP53 gene (\> 50% human tumours) Mutant tumour suppressors alleles are usually recessive

Question 40

**Describe how tissues minimize progressive accumulation of mutations**

Answer 40

Mutations happen all the time, but cells have repair mechanisms: * Stem cell compartment – progenitor cells are _shielded from toxic agents_ * Transit-amplyifying cells – frequent mitosis increases risk of mutation * Post-mitotic, highly differentiated cells (e.g. hepatocytes) are exposed to toxic agents as part of their role * If irreparable damage, these terminal cells undergo _apoptosis_

Question 41

**Describe the two-hit hypothesis of cancer**

Answer 41

Knudson’s two hit-hypothesis – first proposed by A. G. Knudson (1971) for cases of retinoblastoma caused by _mutated tumour suppressor gene, Rb_: * Unlike oncogenes, _tumour suppressor genes generally follow the "two-hit hypothesis”_ * Implies that _both alleles_ that code for a particular protein (e.g. Rb) must be affected to promote malignancy (_hence "two-hit" ⇒ both alleles are mutated_) * If only one allele for the gene is damaged, the second can still produce the correct protein * _Mutant tumour suppressors alleles_ are _usually recessive_ whereas _mutant oncogene alleles are typically dominant_

Question 42

**Recall the difference betwen sporadic and hereditary retinoblastoma**

Answer 42

Sporadic retinoblastoma ⇒ (Rb+/Rb+) * Requires two mutations of (Rb+/Rb+) → (Rb/Rb) * Less likely to happen, and if it does, single tumour in one eye with late onset Hereditary retinoblastoma ⇒ (Rb/Rb+) * Only requires on mutation of (Rb/Rb+) → (Rb/Rb) * More likely to happen, and if it does, multiple tumours in both eyes with early onset

Question 43

**Describe the multistage model of carcinogenesis and list the 5 key stages**

Answer 43

Multistage model of carcinogenesis (Armitage-Doll model) Multistep process which involves a _series of cellular and molecular changes_, as a result of the _progressive accumulation of mutations_ and alterations in _proto-oncogenes and tumour suppressor genes_. 5 Key stages: 1. Normal 2. Dysplastic 3. Benign 4. Pre-malignant 5. Malignant Stages 1→3: proliferation and survival Stages 4→5: angiogenesis and invasiveness

Question 44

**Recall the multiage model of bowel cancer**

Answer 44

Question 45

**Describe HPV pathogenisis and carcinogenesis**

Answer 45

Pathogenesis of infection: 1. HPV _infects the epithelium._ The viral DNA either integrates into the DNA of the crypt-lining epithelial cells or remains in their cytoplasm. 2. Viral proteins _E6 and E7_ bind to and _inactivate the tumour suppressor proteins_ p53 and retinoblastoma protein respectively * Inhibiting apoptosis * Increasing cell proliferation * Generating genomic instability 3. After a prolonged _latent period of 20–30 years_, carcinoma may result. 4. Human papillomavirus–associated carcinomas almost always arise in the oropharynx, specifically in the tonsil and minor tonsils of _Waldeyer's ring_, around the _base of tongue_, _soft palate_ and _pharynx_. 5. Tonsil crypts are lined by non-keratinised and permeable epithelium designed to allow antigens to penetrate into the lymphoid tissue below (i.e. MALT). 6. The mechanisms are slightly different from the way HPV causes cancer of the uterine cervix, but the differences are not yet understood.

Question 46

**List the proteins involved in HPV-induced carcinogenesis (2 points)**

Answer 46

Oncogenic HPV E6 and E7 genes induce carcinogensis: 1. _E6_ binds to _p53_ and _induces its degradation_ 2. _E7_ binds the _pRb_ and _causes E2F transcription factor to become unbound and free_ 3. Results in _cell cycle activation_ and _unregulated proliferation of epithelial cells_

Question 47

**Recall the role of HPV strains in multistage cervical cancer**

Answer 47

HPV strains and multistage cervical cancer: * Low risk strains: * HPV6 * HPV10 * HPV11 * High risk strains: * HPV16 – also responsible for oral cancer (via loss of cell cycle control) * HPV18 * HPV31 * HPV33 * HPV45

Question 48

**Describe the multistage model of oral cancer (2 points)**

Answer 48

Multistage model of oral cancer: 1. Genetic alterations that are observed at the different stages of oral carcinogenesis 2. Mutations in p53 and pRb implicated in oral carcinogenesis

Question 49

**Describe the clonal expansion theory**

Answer 49

The theory of clonal expansion follows on from the multistage model: * Also _assumes that the accumulation of mutations causes cancer_ * But it _does not assume that all the mutations happen in the same cell_ * A _subset of mutations will confer a selective growth advantage/survival advantage_ and the _cells carrying those mutations will outgrow their neighbouring cells_.

Question 50

**Recall how a cross-section of a tumour would appear following clonal expansion**

Answer 50

Eventually if you take a cross section of a tumour following clonal expansion 1. Not all cells in the tumour will have the same mutations 2. Subset of tumour cells will have the ability to metastasise 3. Other subset of tumour cells will not

Question 51

**Define cancer stem cells**

Answer 51

Cancer stem cells (CSCs) – those cells within a tumour that can _self-renew_ and drive _tumourigenesis_

Question 52

**Describe the hallmark responsible for replicative immortality associated with oral cancer**

Answer 52

Hallmark for oral cancer – _immortalization_: * hTERT – human telomerase

Question 53

**Describe the role of telomeres in a healthy cell (5 points)**

Answer 53

Role of telomeres in health cells: * Telomeres are _located at the ends of chromosomes_ * _Protect genetic material_ and _allow cell division_ * _Get shorter as cell divides_ → _causing senescence_

Question 54

**Describe the role of human telomerase and hTERT (5 points)**

Answer 54

Hallmark for oral cancer – immortalization: * hTERT – human telomerase reverse transcriptase (catalytic subunit of the _enzyme telemorase_) Telomerase expression: * Human telomerase reverse transcriptase is _up-regulated in practically all human cancers_ * Telomerase enzyme _repairs telomeres_ – _increased expression_ in cancer cells and _prolongs survival (resisting cell death)_

Question 55

**Describe the role of epidermal growth factor in healthy cells (2 points) and cancer cells (3 points)**

Answer 55

Healthy cells require growth signals before they can progress through the cell cycle: 1. _Signalling transduction pathways initiated by growth factor_ acting at their receptors 2. Epidermal growth factor (EGF) _stimulates cell growth and differentiation_ by binding to its receptor, EGFR Cancer cells have: 1. _Increased production of EGF_ 2. Mutation in EGFR results in _constitutively active receptor_ 3. _Abnormal cell signalling and growth_

Question 56

**Describe the drugs (monoclonal antibodies) used to treat aberrant cell signalling associated with increased epidermal growth factors**

Answer 56

Monoclonal antibodies and protein kinase inhibitors: * Many tumours _overexpress growth factors_, stimulating cell proliferation and tumour growth: This can be inhibited by: 1. _Monoclonal antibodies_ → _bind to growth factor receptors_ (Trastuzumab, Cetuximab) or _neutralise growth factors_ (Bevacizumab) 2. _Protein kinase inhibitors_ → _prevent downstream signalling_ triggered by growth factors by _inhibiting specific oncogenic kinases_ (Imatinib).

Question 57

**Describe angiogenesis in cancer with reference to hypoxia and tumour vessel abnormalities (5 points)**

Answer 57

_Vascular endothelial growth factor (VEGF)_ – released to promote growth of new blood vessels. The transcription factor, _hypoxia-inducible factor 1 (HIF-1)_, is a major regulator of tumour cell adaptation to _hypoxic stress:_ * Hypoxia → _the angiogenic switch_ Tumour vessels are abnormal (3 × larger diameter): * _Leaky and vasculature architecture is haphazard_, but they do the job * Supply oxygen and nutrients to the tumour * Remove waste products from the tumour

Question 58

**Identify 2 key proteins which activate invasion of cancers into surrounding tissues**

Answer 58

PDPN – podoplanin: * Small membrane glycoprotein → _increased cancer cell invasion into lymphatic and blood vessels_ MMP1 – matrix metalloproteinase 1 * Enzyme which _breakdowns of extracellular matrix_

Question 59

**Describe how a cancer becomes metastatic with reference to epithelial-mesenchymal transition (8 points)**

Answer 59

In order to become metastatic cancers undergo _epithelial–mesenchymal transition (EMT)_: 1. Epithelial cells _lose their cell polarity and cell-cell adhesion_ 2. Gain _migratory and invasive properties_ to become _mesenchymal stem cells_ 3. _E-cadherin (epithelial)_ – cell adhesion molecule found in epithelial tissue 4. _ZO-1_ – tight junction protein binds actin cytoskeleton 5. _N-cadherin (neural)_ – cell adhesion molecule found in migrating neurons and mesenchymal cells during organogenesis 6. _Β-catenin_ – binding to N-cadherin and in turn interacts with the actin cytoskeleton

Question 60

**List the 5 sites by which head and neck cancers are classified**

Answer 60

Head and neck cancer refer to cancers of the UADT (upper aero digestive tract) This region is divided into _six_ sites by which cancers are classified (5 points): 1. Oral cavity 2. Pharynx 3. Larynx 4. Nasal cavity and the paranasal sinuses 5. Major and minor salivary glands 6. Skin

Question 61

**List the anatomical components of the oral cavity where cancers can develop (8 points)**

Answer 61

Oral cavity: 1. Lips 2. Buccal mucosa 3. Anterior tongue 4. Floor of the mouth 5. Hard palate 6. Upper gingiva 7. Lower gingiva 8. Retromolar trigone (anatomical triangle)

Question 62

**List and describe the 3 anatomical divisions of the pharynx where cancers can develop**

Answer 62

Pharynx – divided into the _nasopharynx_, the _oropharynx_, and the _hypopharynx_. 1. The nasopharynx – the narrow tubular passage behind the nasal cavity, is the upper part of the pharynx. 2. The oropharynx – the middle part of the pharynx, includes the tonsillar area, the tongue base, the soft palate, and the posterior pharyngeal wall. 3. The hypopharynx – which is the lower part of the pharynx, includes the pyriform sinuses, the posterior surface of the larynx (postcricoid area) and the inferoposterior, and inferolateral pharyngeal walls.

Question 63

**List and describe the 3 anatomic divisions of the larynx where cancers can develop**

Answer 63

Larynx is divided into three anatomic regions: 1. Supraglottic larynx, 2. Glottic larynx (true vocal cords and the anterior and posterior commissures) 3. Subglottic larynx.

Question 64

**List the nasal cavity and paranasal sinuses where cancers can develop (4 points)**

Answer 64

Nasal cavity Paranasal sinuses: 1. Maxillary sinus 2. Ethmoid sinus 3. Sphenoid sinus 4. Frontal sinus

Question 65

**List the major and minor salivary glands where cancers can develop (5 points)**

Answer 65

Major salivary glands: 1. parotid gland 2. submandibular gland 3. sublingual gland Minor salivary glands (multiple glands located throughout): 1. Submucosa of the mouth 2. Upper aerodigestive tract

Question 66

**List 5 key benign salivary neoplasms**

Answer 66

Key benign salivary neoplasms (5 points): "PWOHL" 1. **_P_**leomorphic adenoma\* 2. **_W_**arthin’s tumour\* 3. **_O_**ncocytoma\* 4. **_H_**aemangioma 5. **_L_**ymphangioma \*Considered in detail

Question 67

**Describe pleomorphic adenoma (4 points) and its signs (5 points)**

Answer 67

Pleomorphic adenoma – mixed tumour: 1. Mixed tumour: _contains both epithelial and mesenchymal elements_ 2. _Most common benign tumour of salivary glands_ 3. Can arise from _parotid, submandibular_ * Parotid – usually arises from its tail, deep lobe * Encapsulated 4. _Slow growing_ tumour Signs of pleomorphic adenoma: 1. Swelling in front, below and behind ear 2. Raises ear lobule 3. Retromandibular groove is obliterated 4. Any swelling which raises ear lobule is due to parotid gland neoplasm unless proved otherwise 5. It sends ‘pseudopods’ into surrounding gland → surgical excision of the tumour _should include normal tissue around it_: superficial parotidectomy

Question 68

**Describe Warthin's tumour (11 points)**

Answer 68

**_W_**arthin’s tumour (adenolymphoma) – rule of 7's: 1. Encapsulated 2. Exclusively in parotid gland 3. Parotid tail 4. Commonly seen between 5th – _7th_ decade 5. _Male_: female (_7_:1) 6. _~7%_ of salivary gland tumours 7. Usually fluctuant, slow growing 8. 10% of cases are bilateral 9. Histologically: epithelial and _lymphoid elements_ 10. _Never malignant_ 11. Treatment → **_w_**ide local excision (resection to remove) (**_W_**arthin's ⇒ **_W_**ide local excision)

Question 69

**Describe oncocytoma (6 points)**

Answer 69

Oncocytoma (oxyphil adenoma): 1. Rare – 2.3% of benign salivary tumours 2. Occurrence – 6th decade 3. Usually benign – malignant oncocytoma less common but can occur 4. Major salivary glands: parotid, submandibular gland 5. Minor salivary glands: palate, buccal mucosa, tongue 6. Treatment → superficial parotidectomy

Question 70

**List 6 key malignant salivary neoplasms**

Answer 70

Malignant salivary neoplasms (6 points): "_MACSAN_" 1. **_M_**ucoepidermoid carcinoma 2. **_A_**denoid cystic carcinoma 3. **_C_**arcinoma ex-pleomorphic adenoma 4. **_S_**quamous cell carcinoma 5. **_A_**denocarcinoma 6. **_N_**on-Hodgkin’s lymphoma

Question 71

**Describe mucoepidermal carcinoma (9 points)**

Answer 71

Mucoepidermoid carcinoma: 1. Most common salivary gland malignancy 2. Not encapsulated 3. Commonly found in parotid gland 4. Slow growing 5. May cause facial nerve palsy 6. Presentation: * _High-grade_: rapidly enlarging, +/- pain * _Low-grade_: slow growing, painless mass 7. Treatment → _total conservative parotidectomy_

Question 72

**Describe adenoid cystic carcinoma (9 points)**

Answer 72

Adenoid cystic carcinoma (cylindroma): 1. Second most common salivary gland malignancy 2. Slow growing 3. Infiltrates widely into the tissue planes and muscles 4. _Perineural spread_ 5. Commonly in submandibular gland, sublingual or minor salivary glands 6. Less commonly in parotid gland 7. Occasionally lymph node metastasis 8. Local recurrence after surgical excision (perineural and lymphatic spread) 9. Treatment: * Radical parotidectomy * Post-operative radiotherapy * Wide local excision of palate – for tumours of palate

Question 73

**Describe carcinoma ex-pleomorphic adenoma (2 points)**

Answer 73

Carcinoma ex-pleomorphic adenoma: 1. Usually from pre-existing pleomorphic adenoma (only 1% arise ab-initio) 2. Malignancy takes about 10 years to develop in an adenoma

Question 74

**Describe squamous cell carcinoma and adenocarcinoma**

Answer 74

Adenocarcinoma and squamous cell carcinoma: * Rare * Highly aggressive * Rapidly growing tumours * Local and distant metastases * Prognosis → very poor Squamous cell carcinoma (SCC) – rule out metastasis in the parotid gland from neighbouring skin cancer or other head and neck tumor. Pathology of SCC: * Squamous cell carcinomas account for 90 to 95 percent of the lesions in the head and neck * They can be categorized as _well differentiated_ (greater than 75 percent keratinization), _moderately differentiated_ (25 to 75 percent keratinization), and _poorly differentiated_ (less than 25 percent keratinization) tumours * Less common histologies include verrucous carcinoma (a variant of squamous cell carcinoma), adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinomas.

Question 75

**Recall the head and neck lymph nodes levels (7 points)**

Answer 75

Lymph node levels: * Level I: submental and submandibular * Level II: superior internal jugular (deep cervical) chain * Level III: middle internal jugular (deep cervical) chain * Level IV: inferior internal jugular (deep cervical) chain * Level V: posterior triangle * Level VI: central (anterior) compartment * Level VII: mediastinum and infraclavicular

Question 76

**Recall 4 common oral cancer presentations**

Answer 76

Question 77

**Describe oral cancer in white lesions (6 points)**

Answer 77

Oral cancer in white lesions (leukoplasia/leukoplakia): 1. Lesion which are white → keratinized 2. Incidence 0.2-4% 1. Wide variation in different populations 3. Malignant change 1. Most under 4% 2. Period prevalence * 2.5% in 10 years * 4% at 20 years 4. Most oral cancer originates in normal oral mucosa 5. Most cancers in high incidence areas (India) from potentially malignant lesions 6. Worldwide leukoplakia is 50–100 times more likely to become malignant than normal mucosa * Hence increased risk of cancer secondary to oral hairy leukoplakia

Question 78

**List 7 clinical features of oral hairy leukoplakia**

Answer 78

Question 79

**Describe oral cancer in red lesions**

Answer 79

Oral cancer in red lesions (erythroplasia/erythroplakia): * Erythroplakia is less frequent than leukoplakia * Higher risk of cancer * Greater dysplasia risk – ~50% are already malignant * Very few informative follow up studies

Question 80

**Recall the 4 diagnositic stages of cancers in reference to TNM staging**

Answer 80