Neoplasia 1 Flashcards

1
Q

tumour

A
  • neoplastic lesions which are benign or malignant
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2
Q

neoplasia

A
  • 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)
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3
Q

oncology

A
  • study of neoplastic lesions and cancer
  • surgical or medical specialty relates to management of patients with cancers and malignancies
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4
Q

benign

A
  • proliferate slowly
  • generally do not cause major disease
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5
Q

dysplasia

A
  • abnormality of development
  • alteration in size, shape, and organization of cells
    • congenital dysplasias are not premalignant
    • epithelial dysplasias are premalignant
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6
Q

premalignant

A
  • 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
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7
Q

intraepithelial neoplasia

A
  • 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
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8
Q

carcinoma in situ

A
  • 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
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9
Q

malignant

A
  • rapidly, aggressively, and uncontrolalby proliferating cells
  • can invade and destroy other tissue
  • can metastasize
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10
Q

cancer

A
  • common term for malignant leisions:
    • can invade and metastasize
    • malignant generally the type which causes death
      • benign is far less common
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11
Q

uncertain malignant potential

A
  • 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
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12
Q

anaplasia

A
  • extreme of poorly differentiated cells
  • difficult to tell which cell lineage they are from
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13
Q

metastasis

A
  • spread of cancer cells throughout the body
  • occurs via:
    • lymphatic route
    • haematogenous route (blood)
    • transcoelemic route (peritoneal, pericardial, pleural cavities)
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14
Q

What are the differences between benign and malignant neoplastic lesions?

A

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
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15
Q

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

A

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
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16
Q

What are the common routes of metastases?

A

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
17
Q

What are the common sites of metastases?

A
  • liver
  • brain [melanoma]
  • lungs
  • bone [prostate]
  • within organ
18
Q

What is glandular differentiation?

A
  • differentiation from glandular cells of the epithelial cell line
  • prefix is adeno-
  • tumour cells that form glands or lumina, contain or secrete mucin
19
Q

What is squamous differentiation?

A
  • 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
20
Q

What is smooth muscle cell differentiation?

A
  • 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
21
Q

How are cancers named?

A
  • 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
22
Q

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

A
  • 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
23
Q

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

A
  • 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
24
Q

What are the most common cancers of men? Women?

A

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

25
Q

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

A

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
26
Q

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

A
  • enlarged pleoimorphic nuclei
  • disorganised cells
  • increased proliferation
  • incomplete cellular maturation
27
Q

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

A

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

28
Q

What are the original hallmarks of cancer?

A
  • sustaining proliferative signalling
  • evading growth suppressors
  • activating invasion and metastasis
  • enabling replicative immortality
  • inducing angiogenesis
  • resisiting ceal death
29
Q

What are the histopathological features of neoplastic cells?

A
  • 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
30
Q

neoplastic cells

A

enlarged nuclei, prominent nucleoli, nuclear pleomorphism

31
Q

What do the arrows indicate?

A

mitotic figures; these cells are neoplastic and hyperchromatic

32
Q

What is desmoplasmic stroma?

A
  • 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
33
Q

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

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