Editing Cancer (section)

== '''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)