Glossary of dermatopathological terms
Acantholysis is the separation of keratinocytes within the epidermis due to the loss of adhesion between keratinocytes. Acantholysis occurs due to failure of the integrity of the intercellular/intraepidermal cell junctions. This leads to separation of the epithelial cells with swelling of the epithelial cells (‘ballooning degeneration’). In pemphigus foliaceus, there is acantholysis of keratinocytes just below the granular layer of the epidermis. In comparison, in pemphigus vulgaris there is separation in the basal layer leading to a ‘tombstone pattern’ of keratinocytes where there is retention of some but not all keratinocytes on the basement membrane.
Acantholytic dyskeratos is the reaction pattern characterised by suprabasilar clefting and acantholysis and dyskeratotic keratinocytes. Acatholytic dykeratosis may be seen in various conditions but classically Darier disease, Hailey-Hailey disease, and Grover disease. Characteristic dyskeratotic cells of acantholytic dyskeratosis are corps rounds and corps grains. Corps ronds are round dyskeratotic cells with dense basophilic (blue) cytoplasm (normally acidophilic, pink) with a light area around the nucleus (or peri-nuclear halo), usually found near the basal layer. Corps grains are small cells, with elongated nuclei and found in the upper layers of the epidermis.
Acanthosis is thickening of the epidermis and elongation of the rete ridges due to thickening of the spinous layer +/- enlargement of rete pegs. Typical examples include chronic eczematous reactions.
Anagen is the growth phase of the hair follicle.
Apoptosis is the regulated, normal physiological process by which a cell undergoes a process of dying/self destruction in the presence of a suitable signal(s) from the cell's command centre, the nucleus. In the epidermis, apoptotic keratinocytes are usually solitary, sparse and located in the basal layer. They typically have a dark, condensed nucleic chromatin (pyknosis), margination of chromatin under the nuclear membrane, followed by fragmentation of the nucleus (karyorrhexis). Apoptotic cells are smaller than healthy keratinocytes, usually single cells in the basal cells in the epidermal layer, sometimes a few scattered in the higher layers of the epidermis.
- Apoptosis of basal layer keratinocytes are called ‘Civatte bodies’ (in lichen planus and other lichenoid type reactions) or ‘sunburn cells’ (in acute sunburn).
- Civatte body is synonymous with ‘cytoid body’, ‘colloid body’ or ‘keratin bodies’ and refers to a eosinophilic remnant of a keratinocyte within the basal layer or upper papillary dermis. ‘Hyaline bodies’ are equivalent but occur in connective tissue.
- In some drug reactions, apoptotic keratinocytes may be seen in the basal layer or scattered in the lower layers of the epidermis.
- In graft versus host disease, the apoptotic keratinocytes are seen in association with one or two adjacent lymphocytes in the basal layer and is called ‘satellite cell necrosis’.
Atrophy refers to reduction in the size of an organ or part of an organ. In the skin, it may be reduction in the thickness of the various layers of the skin, eg epidermal atrophy, dermal atrophy, atrophy of panniculus.
- Epidermal atrophy is characterised by the reduction in the number of epidermal cells leading to leading to reduced thickness of the epidermis. Epidermal atrophy can occur after inflammation of the dermal skin (eg lichen sclerosus) or can occur following some treatments to the skin (eg after prolonged use of topical corticosteroids).
- Dermal atrophy is due to thinning of the dermal layer due to loss of collagen and/or elastin. It may occur in aplasia cutis, atophroderma, or following severe inflammatory reactions in the skin affecting the superficial dermis.
- Atrophy of the panniculus is called lipoatrophy. Lipoatrophy may be congenital, or acquired — following inflammation to the skin (e.g. morphoea profundus, lupus profundus), drug treatments (eg some anti-HIV drugs), or trauma.
The basement membrane is a thin, non-cellular layer between the epidermis and dermis and is composed of various protein structures linking the basal layer of keratinocytes to the basement membrane (hemidesmosomes), and the basement membrane to the underlying dermis (anchoring fibrils). The basement membrane has an important role in making sure the epidermis adheres to the underlying dermis. On electrom microscopy, the basement membrane consists of 3 layers:
- lamina lucida
- lamina densa
- lamina reticularis.
Birefringence is the physical property of substances to refract light differently depending on the direction of the light and the state of polarisation of the light. Amyloid deposits show ‘apple green’ birefringence with polarised light.
Bulla(e) large fluid-filled blister(s) arising from separation within the epidermis (intraepidermal blister) or below the basement membrane (subepidermal blister). Small blisters are called vesicles.
Calcinosis cutis refers to deposition of calcium in the skin.
Catagen is the involutional phase of the hair cycle. There is apoptosis of the cells of the lower part of the hair follicle.
Cornoid lamella is a tall intraepidermal layer of parakeratotic skin scale overlying a focal area of hypogranulosis and dyskeratotic keratinocytes. Cornoid lamellae are the characteristic feature of porokeratosis and some rare forms of epidermal naevi.
Crust is the dry concretion of parakeratotic keratinocytes, serum and inflammatory cells within the stratum corneum.
A cyst is a thin walled closed capsule or sac like structure, filled with fluid, solid or semisolid material. Cysts have an epithelial lining. A pseudocyst is a similar lesion but lacks a epithelial lining.
Dermal oedema is the process by which fluid leaks out from blood and lymphatic channels into the surrounding dermis leading to separation of the collagen bundles.
The dermis is the fibrous layer of the skin immediately below the epidermis. This layer contains predominantly collagen but also elastin fibres which contribute to the pliability of the skin . Also contains blood vessels, nerves, adnexal structures like hair follicles, eccrine (sweat) glands, sebaceous glands and other structures. The dermis has 2 distinct regions:
- the uppermost papillary dermis containing fine collagen fibrils
- the thicker, deeper layer which as coarse collagen bundles.
Dyskeratosis is the presence of premature or altered/ abnormal keratinocyte differentiation. Histologically the abnormal keratinocytes have increase/accumulation of keratin filaments leading to a hypereosinophilic cytoplasm (pinker on H&E) and shrunken hyperchromatic nuclei (ie, they are small and dark-staining).
Elastosis is a histological process of increasing the amount of elastic fibres in the skin. Elastic fibres are responsible for the pliability of the skin, contributing to dexterity of the fingers.
Flame figures are pink (eosinophilic) degenerate collagen bundles and eosinophil granules. Flames figures may be seen in Wells syndrome (eosinophilic cellulitis).
Foam cells are lipid (or fat)-laden histiocytes/ macrophages.
The epidermis is the top most layer of the skin. It consists of 4 layers, from deepest to most superficial:
- Stratum basale (basal layer)
- Stratum spinosum (spiny layer)
- Stratum granulosum (granular layer)
- Stratum corneum (horny layer)
The stratum basale contains the regenerative cells of the epidermis and is sometimes called the ‘Malphigian layer’.
Epidermolytic dyskeratosis is abnormal epidermal maturation characterised by vacuolar degeneration of the stratum granulosum and stratum spinulosum with compact hyperkeratosis of the stratum corneum. Epidermolytic dyskeratosis may be seen in some forms of palmoplantar keratoderma, bullous ichthyosis, in association with linear or systematised epidermal naevi, epidermolytic acanthomas, or focally in some epidermal lesions.
Epidermotropism is the abnormal migration of atypical lymphocytes into the epidermis of the skin. It is the hall mark of early stage cutaneous T-cell lymphoma (mycosis fungoides). The term is sometimes used to refer to invasion of malignant cells into the epidermis.
Exocytosis is the random migration of inflammatory cells, such as lymphocytes, neutrophils, basophils, into the epidermis. It is induced by cytokine release in inflammatory processes of the epidermis.
Fibrinoid necrosis refers to extravasation of fibrin into vessel walls and surrounding dermal interstitium in association with leucocytoclastic vasculitis.
Fibrosis is the process by which the body lays down collagen as part of the healing process. Fibrosis may be a consequence of the normal healing response leading to a scar, or it may be produced in abnormal amounts (eg scar formation) and/or in abnormal patterns (eg keloid scar formation). Mild increase in papillary dermal collagen deposition vertical/parallel to the rete ridges (“streaking”) can be seen in chronic inflammatory conditions (eg lichen simplex chronicus, chronic eczematous reactions).
Follicular plugging is an abnormal accumulation of keratin at the shoulder region of the hair follicle in response to an inflammatory reaction. It may be seen in the lichenoid reaction pattern, especially lichen planopilaris, pityriasis rubra pilaris and cutaneous lupus erythematosus.
A granuloma is a chronic inflammatory pattern characterised by the localised aggregation of histiocytes with or without other inflammatory cells (eg plasma cells, eosinophils, neutrophils), with or without necrosis, with or without vasculitis, with or without calcification, with or without foreign bodies. May be due to infection or chronic inflammatory disease or reactions to foreign material.
Grenz zone is an apparent area of uninvolved zone of papillary dermis which separates the epidermis from an inflammatory or tumour cell infiltrate of the dermis.
Haemophagocytosis is the presence of histiocytes/ macrophages phagocytosing red cells, leucocytes, red cells or platelets in bone marrow or other tissues. The phagocytosing cells are called “bean bag cells”. Haemophagocytosis can occur in haemophagocytic lymphohistiocytosis in various infections (EBV), malignancy, genetic and autoimmune syndromes.
Haemosiderin deposition is the process by which iron released from degraded extravasated red blood cells are deposited in the dermis on the skin leaving dark brown or rusty-orange marks. Commonly seen on lower legs following any inflammatory process eg capillaritis, venous stasis eczema.
Horn cyst is a keratin-filled space within a island of epithelium. Seen commonly in seborrhoeic keratoses and some melanocytic naevi.
Hypergranulosis is an increase in the intracellular granules of keratinocytes within the of granular layer. Commonly seen in viral warts.
Hyperkeratosis is thickening of the epidermis due to thickening of the stratum corneum with normal epidermal differentiation. In normal skin, there is a loose ‘basket weave’ appearance. In hyperkeratosis there is usually thickening and lamination or compaction of the stratum corneum.
Hyalinisation of collagen
Hyalinisation (or homogenisation) of collagen refers to degeneration of the collagen of the superficial dermis giving a smooth, granular layer. Commonly seen in lichen sclerosus.
Inflammation is the complex coordinated multi-step process by which the body attempts to remove or contain foreign material/organisms from the body and/or repair any injury sustained by tissues. The inflammatory process may be acute or chronic in nature, reflecting the time frame over which this takes place.
Interface dermatitis generally refers to a mild lichenoid-like reaction in the interface between epidermis and dermis. There is sparse scattered lymphocytic infiltration centred around the basal layer +/- vacuolar degeneration of the basal layer. Unlike a classical lichenoid reaction, the inflammatory infiltrate does not obscure the basement membrane.
Keratinisation is the process by which epidermal cells (keratinocytes) undergo maturation and differentiation, as the cell migrates from the basal layer to the stratum corneum. There is gradual loss of nuclear function (with eventual loss of nuclei in the stratum corneum), loss of cytolasmic structures and progressive formation of keratin filaments to form the cornified envelope.
Koilocytes are epidermal cells infected by wart virus. The cells appear pale with vacuolated cytoplasm and have small dark and condensed (pyknotic) nucleus. The cells have prominent keratohyaline granules in the cytoplasm (hypergranulosis).
Leucocytoclasia is the disintegration of neutrophil nuclei into fragments or nuclear dust. Often seen in inflammatory disorders with intense neutrophil rich inflammatory infiltrate eg vasculitis, Sweet syndrome.
Lichenoid reaction is a dense lymphocytic inflammatory infiltrate centred on the basal layer of the epidermis and upper dermis. The basement membrane is obscured and there is often vaculolar degeneration or Civatte bodies in the basal layer of the epidermis. The lichenoid pattern of inflammation is seen in lichen planus, drug reactions, cutaneous lupus erythematosus, lichen nitidus, erythema multiforme.
Mucinosis, or myxomatous change, is the deposition of fine, granular and stringy basophilic material into structures or layers within the skin, within the dermis (eg dermal mucinosis), epidermis (eg small foci seen associated with squamous cell carcinomas, basal cell carcinomas) or within skin structures such as hair follicles (eg follicular mucinosis). Mucinosis may occur in association with inflammatory disorders of the skin, eg lupus erythematosus, reticular erythematous mucinosis. Dermal deposition of mucin in the dermis is usually acid mucopolysaccharide (glycosaminoglycan), eg pretibial myxoedema, papular mucinosis, scleromyxoedema.
Necrobiosis is an accumulation of acid mucopolysaccharides around collagen bundles giving a bluish (basophilic), indistinct or blurry appearance of collagen bundles. Necrobiosis may be seen in granuloma annulare and necrobiosis lipoidica.
Necrosis is death of a cell or tissue induced by toxins, trauma, infection or factors external to the cell or tissue. Types of necrosis include:
- coagulative necrosis (normal tissue becomes gel like but retaining tissue structure, usually due to ischaemia)
- liquefactive necrosis (tissue becomes liquid due to digestion of tissue with loss of structure, usually seen with purulent infections)
- gangrenous necrosis (a type of coagulative necrosis leading to mummification of tissue, may be complicated by liquefactive necrosis)
- caseous necrosis (a mix of coagulative and liquefactive necrosis leading to which friable cheese like, for example mycobacterial infection)
- fat necrosis (a specific type of necrosis induced by lipase, eg pancreatitis)
- fibrinoid necrosis (necrosis induced by vascular damage from the formation of immune complexes, eg vasculitis).
Neoplasm is a proliferation and accumulation of an abnormal cell(s) due to mutation(s) or factors which promote cellular growth and/or loss of inhibition of cell death and/or loss of ability of immune function — which allow identification and destruction of abnormal cells. The cells of a neoplasm are usually derived from the same cell line (a clonal proliferation) but may come from unaffected normal skin. Neoplasms may be benign (ie, they have no potential to spread to distant sites via the blood or lymphatic system) or malignant (ie, they have the potential to spread to distant sites on the body, also called a metastasis. Neoplasms may grow locally with no propensity to spread into the blood or lymphatic systems.
Nodular infiltrate is a nonspecific term that describes inflammation within the skin in a discrete (“nodular”) area in the skin.
Oedema is an accumulation of plasma into the tissues leading to sweeping of the layer affected. Oedema may occur in the dermal interstitium (dermal oedema), due to reduced hydrostatic pressure in blood vessels, reduced albumin or secondary to inflammation or within the epidermal layer (spongiosis).
Osteoma cutis is ectopic development of bone in the skin, most commonly following acne.
Orthokeratosis is the normal ‘basket weave’ appearance of the stratum corneum seen in normal skin. In acral skin (palms or soles), the stratum corneum exhibits thickening and compaction (“compact orthokeratosis”).
Pagetoid spread refers to the proliferation of cells within the epidermis in a random pattern of distribution giving a ‘buckshot’ scattered appearance. This appearance can be seen in malignant melanoma, extramammary Paget disease and occasionally in squamous cell carcinoma in situ.
The panniculus is the deepest layer of the skin and is predominantly composed of fat cells.
Panniculitis is an inflammatory process centred around the fat. Panniculitis may be due to trauma, vasculitis or primary inflammatory infiltrates centred around the structures of the panniculus (subcutaneous fat).
- Inflammation centred around the collections (or lobules) of fat cells is called lobular panniculitis.
- Inflammation centred around the fibrous septa of the panniculus (the areas of coursing through the fat cells which contain the arterioles, venules, nerves, lymphatics, fibrohistiocytic cells), is called septal panniculitis.
- Panniculitis often exhibits a mixed pattern with lobular and septal components. Panniculitis may be seen in association with vasculitis and/or granulomata.
Papillary mesenchymal bodies
Papillary mesenchymal bodies are the characteristic feature of trichoepithelioma, where there is attempted but aborted focal aggregation of fibroblasts below epithelium in attempt to form hair follicles.
Papillomatosis is the hyperkeratotic and undulating appearance of the epidermis above the surrounding normal skin. Papillomatosis is associated with hyperproliferation of keratinocytes. Papillomatosis may be seen in viral warts, seborrhoeic keratoses, confluent and reticulate papillomatosis.
Parakeratosis is the abnormal retention of keratinocyte nuclei within the stratum corneum. The presence of parakeratosis indicates that the epidermis has been inflamed or injured.
Pautrier microabscess is an intraepidermal collection of lymphocytes within the stratum basal and stratum spinosum in cutaneous T-cell lymphoma (mycosis fungoides).
Peri-adnexal inflammation is the presence of lymphohistiocytic inflammation around pilosebaceous and adnexal structures, eg hair follicles, sebaceous glands, eccrine glands.
Perivascular lymphocytic infiltrate
Perivascular lymphocytic infiltrate refers to inflammation centred around the small vessels in the skin. It is usually a lymphocytic or lymphohistiocytic inflammatory infiltrate, without evidence of vascular damage/ death (vasculitis).
Pigment incontinence is the deposition of melanin in upper dermis due to inflammation affecting the melanocytes within the basal layer. Pigment incontinence is most commonly seen following, or in association with, established lichenoid reactions.
Pseudoepitheliomatous hyperplasia is pronounced thickening due to proliferation of all layers of the epidermis with irregular elongation of the rete pegs. Pseudoepitheliomatous hyperplasia may be seen in chronic inflamed lesions. It can mimic a well-differentiated squamous cell carcinoma.
Psoriasiform hyperplasia is epidermal hyperplasia with elongation of the ret pegs in a regular, uniform pattern. The appearances are classically seen in psoriasis and other psoriasifom inflammatory conditions.
A pustule is a collection of neutrophils in the epidermis or within a hair follicle.
- Microabscesses are small pustules.
- Intraepidermal microabscesses are seen in various inflammatory dermatoses.
- Munro micro-abscess is a collection of neutrophils, fibrin and cellular debris in the parakeratotic stratum corneum in acute or subacute psoriasis.
- The spongiotic pustules of Kogoj are small collections of neutrophils with surrounding spongiosis in the the spinous layer in acute or subacute psoriasis.
- Papillary microabscesses are collection of neutrophils, with or without eosinophils in the tips of papillary dermis, in conditions such as dermatitis herpetiformis, cicatricial pemphigoid.
- Subcorneal pustules are collections of neutrophils below the stratum corneum, eg, subcorneal pustular dermatosis, impetigo, acute generalised exanthematous pustulosis.
Pyknosis is the histological appearance of the changes of the nuclear chromosomal material (chromatin) of the nucleus, as it undergoes apoptosis. It is characterised by compaction and darkening of the chromatin (pyknosis) followed by fragmentation of the nucleus (karyorrhexis) and then disappearance of the nucleus (karyolysis).
Scale crust is localised areas of stratum corneum, where there are parakeratosis, inflammatory cells and serum that arise from inflammatory skin disease, eg infected eczematous skin conditions.
Solar elastosis is degenerative basophilic change of elastin and collagen fibres of the dermis in chronically sun damaged skin.
Spongiosis is the widening of the intercellular spaces between keratinocytes due to intercellular oedema that occurs when the epidermis is inflamed. Spongiosis is classically seen in association with eosinophilic infiltrates in the skin (eosinophilic spongiosis) but can also be seen in association with neutrophils (neutrophilic spongiosis).
- Eosinophilic spongiosis is the inflammatory pattern seen in atopic eczema, bullous pemphigoid, acute phase of incontinentia pigmenti.
- Neutrophilic spongiosis may be seen in fungal infections, psoriasis (spongiotic pustules of Kogoj), acute generalised exanthematous pustulosis.
- Follicular spongiosis may be seen in the epidermis of the infundibulum of hair follicles in atopic dermatitis, miliaria, eosinophilic folliculitis
Squamous eddy is the arrangement of concentric keratinocytes surrounding a central area of keratinisation and arises in squamous cell carcinomas.
Telogen is the resting phase of the hair follicle and lasts months. Telogen occurs after catagen and precedes anagen.
Transepidermal (or transepithelial) elimination is the histological reaction pattern where collagen or elastin (and rarely other substances) is extruded from the dermis through the epidermis. Examples include acquired perforating collagenosis, elastosis performs serpiginosa.
Tumour is an abnormal proliferation of cells and normally implies the presence of a benign or malignant neoplasm. This term is also used by clinicians to describe a macroscopic swelling or a lump on the skin.
Vacuolar degeneration (also called liquefaction degeneration) is the intracellular vacuole formation in injured basal keratinocytes and separation of the plasma cell membrane from the underlying basement membrane. Vacuolar degeneration is seen in lichenoid reactions like cutaneous lupus erythematosus, dermatomyositis, drug reaction. If the injury is severe, the cell undergoes apoptosis and becomes a Civatte body (colloid body).
Vasculitis is an inflammatory process characterised by damage (endothelial swelling) and/or death of endothelial lining cells of blood vessels due to infiltration by inflammatory cells (usually neutrophils). Leucocytoclastic vasculitis refers to endothelial damage by neutrophils, with disintegration of neutrophil nuclei (leucocytoclasia) into fragments or nuclear dust. If the cells are lymphocytes, it is referred to a ‘lymphocytic vasculitis’, however, there is usually no leucocytoclasia present. Some forms of vasculitis are associated with granulomatous inflammation (‘granulomatous vasculitis’).
A vesicle is a small fluid-filled blister within or below the epidermis.
Viral inclusion bodies
Viral inclusion bodies are small abnormal structures within the nucleus or cytoplasm or both, and is due to viral infection of a cell. Viral inclusions in epidermal skin cells have different morphologies depending on the virus and can be seen in human papilloma virus (verruca), herpes virus, molluscum contagiosum infections.