Neoplasia I: Definition and Classification

• What is neoplasia?


  Abnormal mass of tissue, the growth of which is uncoordinated with that of normal tissues and persists after the stimulus is removed
• What is a tumour?


  Swelling, generally without inflammation, caused by an abnormal growth of tissue whether benign or malignant
• What are the major categories for cell types of origin for tumours?

  Epithelium

  Connective tissue

  Lymphoid/haematopoietic tissue

  Germ cells
• What is tumour differentiation?

  Tumour differentiation refers to how well the tumour resembles its normal counterpart, both morphologically & functionally
• Are well differentiated lesions more or less proliferative than the poorly differentiated ones?

  Generally, they are less proliferative & less aggressive, with less potential for metastatic spread than their poorly differentiated counterparts

  There are exceptions
• What are the different grades of tumours?

  Grade 1/well differentiated

  Grade 2/moderately differentiated

  Grade 3/poorly differentiated
• What are some important definitions regarding abnormalities of growth & can you give examples of each one?

  Hyperplasia: Bone marrow cells in people living at high altitudes

  Hypertrophy: Bodybuilders/athletes

  Atrophy: Muscle atrophy in a dis-used limb

  Involution: Breast tissue on cessation of breastfeeding

  Metaplasia: Barrett’s oesophagus

  Dysplasia: Cervical screening

  
• How do you differentiate benign neoplasia from malignant neoplasia?

  Benign:Well differentiated, likely to resemble tissue of originSlow growthMitotic figures rare and normalWell demarcatedExpansible growthDo not metastasise

  Malignant:Spectrum of differentiation from well to poorly differentiatedGrowth rate variable and less predicableMitotic figures may be numerous and atypicalPoorly demarcatedLocally invasiveRegional and distant metastasis

  Metastasise = Spread to other parts of the body

  
• Which tumours are more common?

  Epithelial2 multiple choice options
• What are the general rules for tumour nomenclature?

  Generally speaking forepithelial tumours, if the suffix is carcinoma it's malignant and if it's papilloma or adenoma, it's benign

  Formesenchymal tumours, if the suffix is sarcoma, it's malignant and if it's just -oma, then it's benign

  The prefix of the tumour will always refer to the type of tissue of origin e.g. osteoma (osteo meaning bone)

  
• What are some individual tumour names we should be familiar with?

  Lymphoma- malignant tumours of the lymphoid system

  Melanoma- malignant tumour of melanocytes

  Leukaemia- malignant tumour of bone marrow cells

  Teratoma- a tumour which includes elements of all 3 embryonic germ layers

  Hamartoma- a developmental anomaly (not actually a tumour)
• What can cause tumours?

  Genetic predisposition, surrounding tissues e.g. inflammation, environmental/social/infectious factors

  
  

  Some cancers can also be caused by viruses and infection

  
• What are the different ways that malignant tumours spread?

  Direct- local infiltration

  Lymphatic- to regional lymph nodes

  Haematogenous- lungs, liver, bone

  Peri-neural-salivary tumours

  Trans-coelomic- pleura, pericardium, peritoneal

  
• What forms the lining of the oral mucosa?

  Squamous epithelium

  
• How do squamous cells infiltrate & become malignant cells?

  They undergo genetic changes & lose those tight attachments to each other

  
  

  They disrupt/dissolve the basement membrane & then they gain the ability to enter connective tissues and acquire mobility

  
• What are the sequence of events that makes it go from a primary to a metastatic tumour?

  Tumour cells secrete vascular growth factors- encouragesangiogenesis (formation of new blood vessels)

  Well vascularised tumour has good supply of nutrients & oxygen so can keep growing at an abnormal rate

  Large sheets of tumour cellsdetachby downregulating proteins that normally mediate their connections

  Then,invasion of connective tissuestowards blood vessels & lymphatic channels happens and this involves acquiring mobility

  Evasion of host defencesfollows

  Then,migration through vessel wall& aformation of a tumour embolushappens as well asfurther evasion of host defences

  Next we haveadhesion to vessel wall, and they can utilise processes very similar to inflammatory cellextravasationto gain access to the tissues

  Finally, there isinvasion of new host tissue&angiogenesisagain

  
• What are some non-malignant effects of tumours?

  Increased tendency to thrombosis

  Cellular overactivity

  Paraneoplastic phenomenon -set signs and symptoms that are a consequence of the presence of the tumour but not directly attributable to it.
• What are some factors that affect prognosis of tumours?

  Tumour type

  Site and size; resectability

  Differentiation

  Degree of cellular atypia (cellular state of not being typical)

  Depth and extent of invasion

  Mitotic index and degree of mitotic atypia

  Regional lymph node involvement

  Distant metastasis
• What prognostic index is used for melanoma?

  Clark Levels (level 1 being the least invasive and level 5 being the most)

  
• What prognostic index is used for colorectal cancer?

  Dukes staging:

  
  

  Dukes A being confined to the bowel wall whereas Dukes D is distant metastases

  
• What prognostic index can we use for histological images?

  Mitotic count,
• How do you diagnose a tumour?

  You need a tissue sample for diagnosis of presence of a tumour and also to sub-type it

  
  

  Radiology can help to define size, extent and structures involved and might give some clues as to the tumour type Tissue:

  
  

  -Fine needle aspirate (FNA)

  -Histology (biopsy)
• What is screening?


  The systematic search for cancer in people who have no signs or symptoms of cancer
• What are a couple of issues with screening?

  False positives

  Over diagnosis e.g some people with papillary thyroid cancer are not affected at all during their lifetime
• Why is screening common for cervical, breast, & colorectal cancer but not for lung, thyroid, & prostate cancer?

  Lung:CT screening 70-90% patients had 1 false positive result–remember radiological examination does not diagnose cancer and consider the radiation dose for a CT chest

  Prostate: PSA screening 25-30% of patients had 1 false positive result–equally a simple blood test cannot differentiate a hyperplastic prostate from a malignant one
• What is the difference between staging and grading?

  Gradingis tumour differentiation (well, moderate, poor)

  Staginguses aT N Mclassification (T-tumour;N-lymph nodes;M-metastasis) and it's all about prognosis
• Questions to answer: