Intro to Neoplasia

Question 1

How do tumours develop?

Answer 1

• Tumours are clonal – from one parent
  o BUT as they grow, they acquire mutations
  o Different shape, size, and molecular biology
  o Each mutation adds a new characteristic
  o Autonomous or normal growth signals

Question 2

What are the stages of tumorigenesis?

Answer 2

Hyperplasia: proliferation of cells within an organ or tissue, may result in the formation of a benign tumour.

Dysplasia: abnormality in growth and maturation of cells within a tissue, often indicative of an early neoplastic process (pre-cancerous)

Carcinoma in situ: cells beome primitive in capability, invasive potential, may result in the formation of a malignant tumour.

Invasive cancer: cells have ability to invade and/or metastasise

Question 3

What is hyperplasia?

Answer 3

• Between the normal and highly malignant tissue the cytoarchitecture varies widely
• Hyperplastic cells
  o Excessive number of cells, can assemble into tissue appears reasonably normal
• Examples:
  o Benign prostatic hyperplasia (BPH)
  o Atypical lobular hyperplasia (breast)
  o Atypical ductal hyperplasia (breast)

Question 4

What is metaplasia?

Answer 4

• A normal cell layer is replaced by a cell type not normally found in that location
  o Invading cells are microscopically normal
  o Often occurs in epithelial transition zones (e.g. junction of cervix and uterus and oesophagus and stomach)
• Example: Barrett’s oesophagus (30x increased risk of developing oesophageal adenocarcinomas)
• Squamous epithelia which is damaged by gastroesophageal reflux disease (GERD) is replaced by metaplastic columnar epithelium which have migrated from stomach – secreting mucus

Question 5

What is dysplasia?

Answer 5

• Abnormal growth
• Some but not all features of malignancy are present
• Transitional state between benign and pre-malignant
• Dysplasia MAY develop into malignancy
• Example:
  o Colonic polyps
  o Uterine cervix
• Grading the dysplastic changes usually depends on the thickness of the involved epithelium

Question 6

What are examples of abnormal cytology?

Answer 6

-	Abnormal cytology
o	Variable nuclear size and shape
o	> nuclear : cytoplasmic ratio
o	Increased mitotic activity
o	Change in the relative numbers of specific cell types
o	-> Major changes In cytoarchitecture

Question 7

What are anaplastic tumours (‘to form backwards’)?

Answer 7

• A progression in abnormality occurs so no longer possible to morphologically determine tissue of origin
• Malignant neoplasms which are poorly differentiated or dedifferentiated – anaplastic – hallmark of malignancy
• These malignant cells have the potential to be life threatening – cancer of unknown primary (CUP)
• Nuclear and cytoplasmic hyperchromatism (darker staining in cytoplasm and nucleus)
• Enlarged nuclei and multiple nucleoli

Question 8

What are the features of anaplasia?

Answer 8

• The following changes are seen in anaplastic cells:
  o Pleomorphism
  o Abnormal nuclear morphology
  o Mitoses (abnormal)
  o Loss of polarity
   Normal cells are anchored and oriented to the basement membrane
   Anaplastic cells lose this orientation and grow in a disorganised way
  o Other things
   Tumour giant cells
   Ischemic necrosis (as tumour outgrows its blood supply)

Question 9

What is pleomorphism?

Answer 9

-	Variation in cell shape and size often larger than normal
o	Cellular pleomorphism
o	Nuclear pleomorphism
o	Hyperchromatic nuclei
o	Tumour giant cells

Question 10

What is abnormal nuclear morphology?

Answer 10

• Hyperchromasia
• Chromatin clumping
• Prominent nucleoli
• Little cytoplasm
• Increased nuclear : cytoplasmic ratio (>1:5 to 1:1)
• Frequent mitosis (yellow arrows)

Question 11

What is abnormal mitosis?

Answer 11

• Proliferative activity is very high (mitotic rate is high)
• Increased number mitotic figures
• Spindles
  o Tripolar (yellow arrow)
  o Quadripolar (red arrow)
  o Multipolar spindles
• NB also:
  o Prominent nucleoli
  o Pleomorphism

Question 12

What are features of normal prostate glands and of malignant glands in prostate adenocarcinoma?

Answer 12

Normal glands

• Columnar and some cuboidal luminal cells (red arrow)
• Pale cytoplasm
• Inconspicuous nucleoli
• Basal cells (yellow arrow)
• Flattened/cuboidal

Malignant glands

• Note size of nucleus: cytoplasm and prominent nucleoli (green arrows)
• Absence of basal cell layer
• Hyperchromasia

Question 13

What are sarcomas, where are they derived from, and what are the main types?

Answer 13

-	Two main types: (rare ~1000/year)
o	Bone
o	Soft tissue
	Muscle (skeletal and smooth)
	Cartilage
	Fat
	Nerves
	Fibrous tissue, such as ligaments and connective tissue
	Blood vessels
	Lymph vessels

Question 14

What are the two types of blood cancer and where do they come from?

Answer 14

• Leukaemia – malignancies of the bone marrow (abnormal white blood cells)
  o Lymphoid
  o Myeloid
  o Acute
  o Chronic
• Lymphoma – malignancies of the lymphoproliferative system
  o Hodgkins – lymph nodes, spleen and liver
  o Non-Hodgkins – lymph nodes and extra-nodal including gastrointestinal tract, skin and bone
• Multiple Myeloma – neoplastic proliferation of B cells in bone marrow -> plasma cells producing a characteristic paraprotein (abnormal antibody)

Question 15

Summarise neoplasia.

Answer 15

• Tumorigenesis is a multistage process in which normal cells undergo a series of dysplastic changes
• The major cancers are carcinomas which are derived from epithelia and often display characteristic abnormal cellular and nuclear morphology