Neoplasia 1

Question 1

tumour

Answer 1

• neoplastic lesions which are benign or malignant

Question 2

neoplasia

Answer 2

• new growth where growth/proliferation of cells is uncontrolled
  
  • includes both cancerous (malignant) and benign lesions
• begins in a single cell
  
  • adult stem cells, progenitor cells, or transit amplifying cells
• generally involves mutations affecting the cell cycle, cell proliferation, characteristics, and behaviour
  
  • eg protoncogenes, TSGs
• can be mutations to apoptotic and DNA repair pathways
• involves acqusition of other features that enable progression:
  
  • ability to dissociate, allowing for metastasis
  • motility to move through tissues (metastasis)
  • release of factors such as VGEF (angiogenesis)

Question 3

oncology

Answer 3

• study of neoplastic lesions and cancer
• surgical or medical specialty relates to management of patients with cancers and malignancies

Question 4

benign

Answer 4

• proliferate slowly
• generally do not cause major disease

Question 5

dysplasia

Answer 5

• abnormality of development
• alteration in size, shape, and organization of cells
  
  • congenital dysplasias are not premalignant
  • epithelial dysplasias are premalignant

Question 6

premalignant

Answer 6

• cells that are not yet malignant but have a reasonable chance of becoming malignant
• they are non-invasive precursors of malignancy
• if dx and tx they can prevent malignancy from developing
• this is largely relevant to carcinomas (cancers arising in the epithelium), the most common type of cancer

Question 7

intraepithelial neoplasia

Answer 7

• eptihelial dysplasia
  
  • many invasive carcinomas thought to arise as a result of progression and invasion of these premalignant epithelial lesions
• can be graded:
  
  • mild/mod/severe, or grades 1-3:
    
    • grade 1 - less likely to progress to invasive malignancy
    • grade 3 - severe, more likely
  • implications for tx

Question 8

carcinoma in situ

Answer 8

• severe or Grade 3 dysplasia
• cells show significant cytological atypia and appear malignant
• cells are still in-situ and have not invaded through the BM into the underlying stroma
• more likely to progress

Question 9

malignant

Answer 9

• rapidly, aggressively, and uncontrolalby proliferating cells
• can invade and destroy other tissue
• can metastasize

Question 10

cancer

Answer 10

• common term for malignant leisions:
  
  • can invade and metastasize
  • malignant generally the type which causes death
    
    • benign is far less common

Question 11

uncertain malignant potential

Answer 11

• only seen in certain organs eg ovary
• difficult to determine histologically whether they are malignant or benign
  
  • particular features that overlap
  • some may be low-grade maligancies, others benign
  • difficult to predict behavour
  • few metastasize

Question 12

anaplasia

Answer 12

• extreme of poorly differentiated cells
• difficult to tell which cell lineage they are from

Question 13

metastasis

Answer 13

• spread of cancer cells throughout the body
• occurs via:
  
  • lymphatic route
  • haematogenous route (blood)
  • transcoelemic route (peritoneal, pericardial, pleural cavities)

Question 14

What are the differences between benign and malignant neoplastic lesions?

Answer 14

natural history, potential complications, morphology

• benign lesions proliferate slowly and generally do not cause major disease
• malignant lesions proliferate rapidly, aggresively, and uncontrollably
  
  • they can invade and destroy tissue, and metastasize to other tissues
• there are some highly aggressive and less aggressive malignancies
• there are lesions in the middle of this continuum that are not defined as either benign or malignant = borderline

Question 15

What macroscopic and microscopic features distinguish beningn and malignant lesions? What are the exceptions?

Answer 15

Benign

• locally expansile, slow growth, often well cicumscribed (+/- encapsulated)
• well differentiated cells
  
  • appear similar to mature, fully-differentiated cells
• unable to metastasize
• rarely life-threatening (depending on site)

Malignant

• locally invasive, rapid destructive growth, often poorly circumscribed
• induce desmoplasia in stroma as they invade
  
  • release of cytokines and growth factors (TGFb) from malignant cells induce surrounding fibroblasts to proliferate, ++ECM within and around the tumour cells
• sometimes necrosis if outgrows glood supply, some apoptosis
• variable differentiation: well, moderate, poor, anaplastic
• potential to metastize
  
  • lymphatic, haematogenous, transcoelomic (pleural, peritoneal, pericardial cavities)

Exceptions:

uncertain malignant potential/borderline

• only certain organs eg ovary
• features overlap between benign and malignant
• few metastasize

Question 16

What are the common routes of metastases?

Answer 16

lymphatic spread

• spread to local lymph nodes via lymphatic vessels
• travel to other lymphatics
• can enter venous system via thoracic duct (haematogenous spread)

haematogenous (blood-borne) spread

• access blood via capillaries, into the venous system
• can spread to lungs, brain, bones

transcoelomic spread

• spread along body cavities (pleural, peritoneal, pericardial)
• commonly associated with excess fluid production from serousal capillaries
  
  • ascities, pleural effusion

Question 17

What are the common sites of metastases?

Answer 17

• liver
• brain [melanoma]
• lungs
• bone [prostate]
• within organ

Question 18

What is glandular differentiation?

Answer 18

• differentiation from glandular cells of the epithelial cell line
• prefix is adeno-
• tumour cells that form glands or lumina, contain or secrete mucin

Question 19

What is squamous differentiation?

Answer 19

• refers to stratified squamous differentiation, not simple
• intracellular bridges form spikes of tissue between cells
• keratinization can be internal swirls rather than just on the surface

Question 20

What is smooth muscle cell differentiation?

Answer 20

• tumour cells that differentiate from a smooth muscle (mesenchymal) cell line
• they appear like smooth muscle cells
  
  • elongated nuclei with rounded ends
  • cells are elongated
• prefix is leiomyo

Question 21

How are cancers named?

Answer 21

• Prefix refers to line of differentiation or cell linage:
  
  • Adeno = glandular
  • squamous cell
  • leiomyo = smooth muscle
  • osteo = osteoid forming
• Suffix refers to:
  
  • benign -oma
  • malginant:
    
    • -carcinoma if epithelial
    • -sarcoma if mesenchymal
• there are many exceptions
  
  • eg seminoma - malignant testicular tumour from germ cells; lymphoma - malignant lymphatic neoplasias
• examples:
  
  • adenoma = benign glandular lesion
  • adenocarcinoma = malignant glandular epithelial lesion
  • leoimyoma = benign smooth muscle lesion
  • leiomyosarcoma = malignant smooth muscle mesenchymal lesion

Question 22

What is the degree of differentiation, and how is this determined?

Answer 22

• determined histologically
• neoplastic lesions are generally classified as well, moderate or poorly differentiated, or anaplastic
  
  • ​well:
    
    • ​closelet resemble mature cells (less cytologic atypia, less mitotic activity)
    • less architectural disorganization
  • poorly:
    
    • ​poorly resemble mature cells (more cytologic atypia, more mitotic activity +/- atypical mitoses)
    • more architectural disorganization
  • anaplastic:
    
    • ​extremely poorly differentiated cells
    • cannot tell lineage of origin
• differentitiation in malignant tumours is referred to as its grade
• benign are typically well differentiatied
• malignant can be any

Question 23

What are the components of a malignant tumour microenvironment? What role does the tumour microenvironment play in its progression?

Answer 23

• tumour stroma
  
  • fibroblasts, ECM, endothelial cells, immune cells, cytokines
• tissue where the tumour is located
  
  • important for tumour growth
    
    • important target of treatment research
• may vary within the tumour
• remodeling occurs via cellular communication btw cell, stroma, and matrix, or cytokine and growth factor secretion
• important in establishment and growth of metastases
  
  • eg environment promotes metastasis, like in the liver or lung

Question 24

What are the most common cancers of men? Women?

Answer 24

Men:

• prostate
• bowel
• lung

Women:

• breast
• bowel
• melanoma

squamous cell and basal cell carcinoma of the skin are the most common, but have good prognoses and are not included in epidemiological figures

Question 25

What is the role of dysplasia/intraepithelial neoplasia in carcinogenesis?

Answer 25

eg in gut * normal layer of simple columnar epithelial cells with small uniform nuclei * 1 stem cell or progenerate cell starts to mutate and proliferate out of control * see more mitotic figutes * nuclei become larger and more pleiomorphic * nuclear changes progess and become more severe * architectural disorganization occurs and eventually the lesion invades the BM * apical cells now seen in the adjacent stroma * cells must release enzymes such as matrix metalloproteinases to break down the BM collagen

Question 26

What are the morphological features of dysplasia/intraepithelial neoplasia in carcinogenesis?

Answer 26

* enlarged pleoimorphic nuclei * disorganised cells * increased proliferation * incomplete cellular maturation

Question 27

How can dysplasia/intraepithelial neoplasia be used in the prevention of malginancy?

Answer 27

dx and tx of dysplasia/intraepithelial neoplasia can prevent development to malignancy and metastasis

Question 28

What are the original hallmarks of cancer?

Answer 28

* sustaining proliferative signalling * evading growth suppressors * activating invasion and metastasis * enabling replicative immortality * inducing angiogenesis * resisiting ceal death

Question 29

What are the histopathological features of neoplastic cells?

Answer 29

* cytological atypia: * larger, pleomorphic nuclei * coarser nuclear chromatin (clumping rather than fine distribution) * hyperchromatic nuclei (stain darker with H due to additional DNA, chromosomes) * larger, more prominent nucleoli (more active) * more mitotic activity, abnormal mitotic features * architectural disorganization

Question 30

neoplastic cells

Answer 30

enlarged nuclei, prominent nucleoli, nuclear pleomorphism

Question 31

What do the arrows indicate?

Answer 31

mitotic figures; these cells are neoplastic and hyperchromatic

Question 32

What is desmoplasmic stroma?

Answer 32

* only seen in invasive malignant tumours * stroma is abnormal * between tumour cells, not just around them * highly cellular (lymphocytes, macrophages, fibroblasts) * induced by desmoplasia, the release of cytokines and growth factors from cancer cells that promote fibroblast activity

Question 33

What type of necrosis is associated with cancerous cells (if present)?

Answer 33

* typically **not** coagulative * see pynknotic (condensed) or karreorhectic (fragmented) nuclei