Table 2.

Distinct modalities of cell death

Cell death mode	Morphological features	Notes
Apoptosis	Rounding-up of the cell Retraction of pseudopodes Reduction of cellular and nuclear volume (pyknosis) Nuclear fragmentation (karyorrhexis) Minor modification of cytoplasmic organelles Plasma membrane blebbing Engulfment by resident phagocytes, in vivo	‘Apoptosis’ is the original term introduced by Kerr et al.14 to define a type of cell death with specific morphological features. Apoptosis is NOT a synonym of programmed cell death or caspase activation.
Autophagy	Lack of chromatin condensation Massive vacuolization of the cytoplasm Accumulation of (double-membraned) autophagic vacuoles Little or no uptake by phagocytic cells, in vivo	‘Autophagic cell death’ defines cell death occurring with autophagy, though it may misleadingly suggest a form of death occurring by autophagy as this process often promotes cell survival.15,16
Cornification	Elimination of cytosolic organelles Modifications of plasma membrane Accumulation of lipids in F and L granules Extrusion of lipids in the extracellular space Desquamation (loss of corneocytes) by protease activation	‘Cornified envelope’ formation or ‘keratinization’ is specific of the skin to create a barrier function. Although apoptosis can be induced by injury in the basal epidermal layer (e.g., UV irradiation), cornification is exclusive of the upper layers (granular layer and stratum corneum).17,18
Necrosis	Cytoplasmic swelling (oncosis) Rupture of plasma membrane Swelling of cytoplasmic organelles Moderate chromatin condensation	‘Necrosis’ identifies, in a negative fashion, cell death lacking the features of apoptosis or autophagy.4 Note that necrosis can occur in a regulated fashion, involving a precise sequence of signals.