AEB/Lectures/Neoplasia 2: Biology of neoplasia

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Key features of neoplasms

  • Clonality
  • Tumour heterogeneity

Consequences of these key features for

  • Cell growth
  • Cell differentiation
  • Relationship to surrounding cells
  • There is a spectrum over time where neoplasms slowly become more neoplastic and more dangerous

Benign and malignant neoplasms - malignant neoplasms can disrupt surrounding cells and spread elsewhere in the body: poor prognostic indicator (note that sometimes there are cells that appear microscopically as though they will become malignant, but haven't done so yet).

Characteristics of benign and malignant neoplasms

  • Cellular differentiation - malignant is less than benign
  • Relationship to surrounding tissues - tissue invasion
  • Benign
    • Noninvasive
    • Nonmetastatic
    • Well differentiated; look very much like the cells of origin
    • Small
    • Well demarcated
    • Slow growing; few mitotic figures
  • Malignant
    • Large
    • Poorly demarcated
    • Rapidly growing with hemorrhage and necrosis (+ mitotic figures; tissue pressure due to rapid growth prevents blood reaching the centre of the tumour)
    • Locally invasive
    • Metastatic
    • Poorly differentiated
  • Leio = smooth; myoma = muscle benign
  • Leiomyoma in uterus= fibroid, very common

Image of leiomyoma

Image of lipoma

  • Have no malignant potential
  • Removed for cosmetic reasons

Malignant tumour in peritoneal cavity

  • Compressing bowel loops
  • Large and dark - avascular
  • Liposarcoma

Breast neoplasm - benign

  • Round, regular edge
  • Benign tumour
  • Covered in dense, fibrous pseudocapsule
  • Fleshy tumour in the middle
  • Fibroadenoma

Breast neoplasm - malignant

  • Blue area = proliferation of cells
  • Invasion into surrounding tissue
  • Malignant tumour of secretory origin = adenocarcinoma

Thyroid - benign

  • Round thyroid adenoma
  • Demarcated fibrous tissue surrounding it (desmoplasia)

Thyroid - malignant

  • Large and invasive
  • Thyroid carcinoma (can't tell how differentiated it is; need histological examination; if it was differentiated at all, it would be adenocarcinoma)

Kidney - malignant

  • Large, well-circumscribed, contained within the capsule of the kidney, due to the strong capsule over the kidney
  • Malignant because of destroying a lot of the upper pole of the kidney and because of haemorrhage and necrosis

Kidney - malignant, sneaky

  • Used to be called renal cortical adenoma
  • Even small tumours in the kidney will metastasise
  • In the kidney: if it's >10mm then it's a carcinoma
  • This is >10mm, so it's a renal cell carcinoma

Effects of cancer

  • Effects of the tumour mass
  • Effects of direct spread
  • Effects of metastatic spread
  • Paraneoplastic effects

Effects of the tumour mass

  • In sella turcica, we see benign tumour of pituitary gland
  • Frontal sinus bigger than normal - person has a big head. Due to excess growth hormone as a result of pituitary gland tumour and its hormones: acromegaly
  • Pituitary adenoma
  • Can cause a particular type of blindness that is very distinctive, due to the compression of the optic nerves

Effects of direct spread

  • Continuous invasion of the tissue into the neighbouring structures
  • Poorly defined opacity filling the apex of the Lt lung
  • In this case, it's a cancer
  • Symptoms alone: cough
  • Direct spread can produce pleurisy, pleural effusion, and brachial plexus or cervicothoracic ganglion invasion (Horner's syndrome) because it's position at the top of the lung
  • Hilar lung cancers: obstructs airways, atelectasis, pneumonia, mediastinal involvement. The further the spread, the harder to treat

Effects of metastatic spread

Modes of metastatic spread

  • Lymphatic
  • Haematogenous
  • Other:
    • Transcavitatory
    • Implantation
  • Lymph nodes are a very important source of spread of carcinomas (epithelial cells have a lot of lymph drainage)
  • Image: white mass = tumour that has come from bowel cancer nearby; it enlarges and destroys the node

Sites of haematogenous spread

  • Depend on type of tumour and nature of vascular supply
  • Common sites of clinical importance include lung, liver, bone and brain
  • Very common for tumour cells to get into bloodstream, but it's much harder for them to lodge in distant tissues and grow
  • Depends on a) vascular support of organ and b) the ability of the tumour to grow in that environment

Lung metastases

  • Produce rapidly growing mets that are small and round and many
  • Can spread to pleural surface drectly
  • Pulmonary metastases are different from lung cancer (mets are from another source)
  • Cough, pleural effusion, shortness of breath

Hepatic metastases

  • Not liver cancer; instead hepatic metastases
  • Liver is a strong site for metastases
  • Mets gradually replace the parenchyma of the liver, which becomes very large. Palpable below costal margin

Cerebral mets

  • Lung and breast cancers like to go to the brain
  • Most commonly in cerebrum
  • Well circumscribed
  • At the junction of the grey/white matter
  • Can increase intracranial pressure, damage underlying tissue, produce seizures/epilepsy
  • 20% of people who die of malignancy have cerebral mets

Bone metastases

  • Breast and prostate cancer love going to bone
  • Dark area = radiolucency; loss of Ca due to lytic lesion; one possible effect of bone mets
  • In vertebrae, can get osteosclerosis rather than osteolysis, producing more bone in the vertebra and making it weaker (paradoxically). Classically occurs in prostate cancer

Bone scan

  • Inject person with radioactive isotope that is taken up by osteoblasts, to see where bone turnover is highest
  • Lytic and sclerotic lesions show up
  • Bony mets tend to involve axial skeleton (pelvis, vertebrae); if they involve the appendicular skeleton, it's usually the proximal ends of these bones
  • Can get fractures
  • Involvement of the vertebral column can affect the spinal cord, causing paralysis

Transcavitatory spread

  • Tumour cells get out, go to other organs

Paraneoplastic effects

  • Constitutional (lose weight, feel unwell, wasting (cachexia))
  • Endocrine
  • Vascular
  • Neurological
  • Musculoskeletal

Diagnosis of neoplasia

  • Note critical role of pathological diagnosis (done by pathologists)
  • Histopathological examination of biopsy
    • Incision, excision, endoscopic, core needle biopsies
  • Cytology
    • Examination of individual cells

Predicting outcomes with cancer

  • Pathological assessment
    • Histopathological classification (typing)
    • Histopathological grading
  • Clinicopathological staging (TNM)
    • T=Tumour size or extent of spread
    • N=Presence of nodes
    • M= Presence of metastases
  • Stage is typically reported as I-IV
  • Staging systems vary with different malignancies, but use the TNM model
  • Staging using the TNM system is very important in predicting prognosis, and sorting out a treatment