Editing Cancer


A group of disease involving abnormal cell growth with the potential to invade or spread to other parts of the body.

== Definitions: ==

* Neoplasia - 'new growth'. The collection of cells and stroma composing new growths are referred to as neoplasms.
* Tumour - now equated with neoplasm, although originally described swelling caused by inflammation.
* Oncology - the study of tumours or neoplasms.
* Benign tumours remain localised at their site of origin
* Malignancy/cancer: a tumour that can invade and destroy adjacent structures and spread to distant sites.
** Sarcoma - malignancy arising in solid mesenchymal tissues
** Carcinoma - malignancy arising from epithelial cells
** Lymphoma - malignancy originating from lymphocytes
** Leukaemia - malignancy arising from blood-forming cells
* Carcinoma in situ: severe dysplasia involving the full thickness of the epithelium, but without penetrating the basement membrane
* Dysplasia - disordered growth. May be a precursor to malignant transformation, but does not always progress to cancer.
* Metaplasia - the replacement of one type of cell with another type, usually in response to tissue damage, repair and regeneration
* Metastasis - the spread of a tumour to sites are physically discontinuous with the primary tumour, an event that unequivocally marks a tumour as malignant
* Differentiation - the extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells, both morphologically and functionally
* Anaplasia - lack of differentiation
* Sentinel lymph node - the first node in a regional lymph node basin that receives lymph flow from the primary tumour

== '''Characteristics of malignant neoplasms''' ==

* '''Differentiation and anaplasia'''
** Benign tumours are generally well-differentiated
** Malignant neoplasms usually have characteristic morphological changes
*** Pleomorphism - variation in cell size and shape
*** Abnormal nuclear morphology
*** Proportion of cells in mitosis, reflecting rate of proliferation
*** Loss of polarity - orientation of cells with respect to each other or to other external supporting structures
*** Presence of ischaemic necrosis due to outgrowing their blood supply
* '''Local invasion'''
** Progressive invasion and destruction of surrounding tissue - poorly-demarcated, without well-defined cleavage planes.
** Benign tumours usually grow and expand slowly, and hence usually develop a rim of compressed fibrous tissue called a capsule. The capsule consists of ECM deposited by fibroblasts in response to hypoxic damage. This makes the benign tumour discrete, non-fixed, and easily enucleated.
* '''Metastasis'''
** Unequivocally marks a tumour as malignant
** Invasiveness permits malignant tumours to penetrate blood vessels, lymphatics and body cavities, providing the opportunity for spread
** All malignant tumours ''can'' metastasise
** 'Liquid' tumours (leukaemias and lymphomas) are metastatic at diagnosis
** '''The metastatic cellular cascade'''
*** Invasion of the extracellular matrix
**** ''Must breach the basement membrane, traverse the interstitial connective tissue, and penetrate the vascular BM''
**** Dissociation of cancer cells from one another (E-cadherin function lost)
**** Degradation of BM/connective tissue - secretion of proteolytic enzymes - matrix metalloproteinases (MMP), cathepsin D, and urokinase plasminogen activator
**** Tumour cells change the way they attach to ECM proteins, making them less 'fixed' in place
**** Locomotion through degraded basement membranes and zones of matrix proteolysis
*** Vascular dissemination, tissue homing, and colonisation
**** Could relate to anatomical vascular drainage, tropism of particular types of tumour cells (?complementary homes to originating tissue), and escape from tumour dormancy in target tissue
**** Extravasation required at target tissue - little is known
** '''Pathways of spread'''
*** Direct seeding
**** When a cancer penetrates into an open field lacking physical barriers (peritoneal, pleural, pericardial, subarachnoid, joints)
*** Lymphatic
**** Most common pathway for carcinomas
*** Haematogenous 
**** Typical of sarcomas, but also sometimes carcinomas
**** LVI is a concerning feature in the primary tumour
**** Metastatic cells often come to rest in the first capillary bed they encounter (liver, lungs)


== Staging: ==

* Local
* Locally advanced: Cancer that has spread from where it started, to nearby tissues or nodes.
* Metastatic

[[Category:Oncology]]