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Introduction

  • Neoplasia
    • A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues, and persists in the same excessive manner after cessation of the stimulus which evoked the change
    • Autonomous, abnormal
    • All neoplasms are monoclonal, thought to be derived from a single neoplastic cell
      • Unlike hyperplasia which is polyclonal
    • 1/4 deaths are due to malignant neoplasms. 1/3.5 people get a cancer.
    • Prostate cancer is the top in males, breast cancer is the top in females. Then bowel for both, then melanoma for both, then lung for both.
    • Top killer in both is lung (poorest prognosis), while most people don't die of prostate or breast cancer. Only 1/3 of those with bowel cancer dies
    • Pancreatic cancer has a very poor prognosis
    • Cancers start as a single neoplastic cell
  • It takes 30 doublings (assume: all in cell cycle, no apoptosis or necrosis) for a single cell to form 10^9 cells, which is 1cm^3, or 1g (smallest we can detect)
  • Then 3 more doublings will form 10^12 cells, to form a 1kg lump, which is the largest you can live with
    • Hence a tumour lives 3/4 of its life before it is clinically detectable. Hence there is so much mutation potential before we detected it, hence it is likely that before it's clinically detectable, it has developed the ability to invade and metastasise
      • Hence we want to detect them before they're lumps

Benign vs malignant

  • Malignant
    • Invade surrounding tissues (crab-like feet to latch onto surrounding tissues)
    • May be less differentiated (not always). Anaplasia = complete lack of differentiation (they occur, but they're not common).
    • Rapid growth. Heterogenous due to necrosis and haemorrhage and cystic degeneration (due to rapid growth blocking blood supply)
    • Metastatic potential
  • Benign
    • Usually encapsulated (pseudocapsule) and don't invade (grow slowly by expansion)
    • More differentiated, resemble tissue of origin very closely
    • Slow growth. Homogeneous
    • No metastatic potential
  • Primary malignancies: large and single
  • Secondary malignancies (metastases): small and multiple

Leiomyoma

  • Tissue resembles myometrium
  • Spherical lesions in subserosal area
  • Benign neoplasm of smooth muscle origin = leiomyoma
    • Laypeople = fibroid
  • Hormonal dependent benign tumour, undergoes atrophy after menopause. All good if it's not causing symptoms (e.g. pain, infertility)
  • If malignant, you call it leiomyosarcoma
  • Sarcoma = mesothelial differentiation. Carcinoma = epithelial differentiation. Carcinoma more common than sarcoma (wide distribution, exposed to environmental problems and lots of stem cells(greater proliferative capacity))

Breast cancer

  • Common: chance of woman getting BC is 1/9
  • Risk factors:
    • Family history (first degree relative: father/mother/sis/bro/son/daughter)
    • Genetic (BRCA1, BRCA2: autosomal dominant; account for 5-10% of BC, but if you have it, then your chance of BC is very high)
    • Female gender (99% of BCs are female)
    • Estrogen exposure (early menarchy, late menopause, obese post-menopausal women (estrone produced in adipose tissue from adrenal androgens, HRT (>1 year), COCP unknown/small risk (but protects from endometrial and ovarian cancer))
    • Alcohol
    • Radiation exposure
    • Viruses (mouse mammary tumour virus)

History of a breast lump

  • How long it's been there
  • If it's changing
  • If it changes with the menstrual cycle (fibrocystic change alters with the menstrual cycle; 50-60% of women have fibrocystic change, causes lumpy breasts)
    • Fibroadenoma also varies with the menstrual cycle, typically in younger women
    • Both of these get larger, tender in the luteal phase, reduce in size after menstruation. Because progesterone causes potential fluid swelling of breast tissue
  • Pain is an uncommon presentation (only 5% are painful). Having pain doesn't exclude cancer
  • Nipple discharge - most breast cancers don't cause nipple discharge (some do)
  • Nipple changes: unilateral recent inverted nipple (cancer pulling the suspensory ligament)
    • Paget's disease of the breast - cancer cells infiltrating the skin causing redness
  • Examination
    • Check for mobility
    • Axillary lymph nodes
    • Other breast and axilla, look for other lumps
    • Look for distant metastases
  • Imaging
    • Mammogram or ultrasound (use mammogram in older people, ultrasound in young people (more glandular and fibrous tissue in a younger woman, making the breast more radiodense, making it hard to distinguish the opacity from a cancer))
    • Looking for:
      • Screening - catch neoplasm before it's become invasive. We want to find DCIS. It forms proliferation within the breast ducts of neoplastically transformed cells. In the centre of the ducts there is necrosis of these cells and this may produce microcalcifications, that may be linear with branching.
        • LCIS is not so easily detected by screening mammography. It is thought all breast cancers go through CIS stage first
      • Known lump - look for stellate density that may or may not be associated with calcifications
  • Biopsy
    • Fine needle aspiration - individual cells from the lump, which are put on a slide for examination of cytological features of malignancy. No anaesthetic required. No tissue architecture is seen. May be a sampling error (no diagnostic tissue). Equivocal - either need repeat or core biopsy is needed.
    • Core biopsy - can do a histopathological assessment.
    • Excision
  • Triple assessment
    • Clinical history and examination
    • Imaging
    • Biopsy
  • Mastectomy for the lesion; tissue is removed surgically
  • Most common type of DCIS is that of no special type: scirrhous (scar-like). Feels very hard due to induction of CT stroma (desmoplasia) that makes the breast solid.
    • The pathologist then look at the grade (degree of differentiation) and the stage (based on TNM)
      • Low grade tumour (well differentiated) has much better long-term survival than high grade tumour
      • Most important prognostic gadget is staging
        • Pathologist can say how big the tumour is (T), lymph node involvement (N; from sentinel node biopsy. If sentinel node biopsy is positive, we clear all the others; the number of nodes involved is an important indicator, which is why we clear all the lymph nodes).
          • Of course there is no point of doing sentinel node biopsy prior to surgery (LOL) - once core biopsy is confirmed
      • Aside from nodal spread, the tumour cells can spread haematogenously. Once entering the venous system, they can head to the lungs (most common site). After that, may head to bones (axial skeleton), brain and liver.
        • Liver function is only effected at very late stage
  • Causes of death in disseminated cancer (order of commonness)
    • Weight loss, weakness (cachexia), bed-ridden (due to TNF release; host inflammatory cells responding in the stroma. TNF = lose appetite and lean body mass), immobile, DVT and massive pulmonary embolism or pneumonia.
    • Expanding space occupying lesions in the CNS (herniation syndromes e.g. cerebellar tonsils down to medulla oblongata to compress respiratory centres -- coning)
    • Occasionally liver failure (>90% liver function lost)