Histopathology of the Skin: General Principles

Abstract

Dermatopathology deals with the microscopic study of skin, adjacent mucosa, and cutaneous adnexal structures. Dermatology and dermatopathology put much emphasis on clinical and pathological features and rely heavily upon the powers of observation and correct classification in order to obtain the correct diagnosis. Both specialties are in fact complementary and closely related to each other. A fundamental understanding of dermatopathological changes is necessary if one wishes to become an effective dermatologist. In this chapter, the histopathological basic principles of the skin are discussed.

Glossary/Diagnostic Terms in Dermatopathology

Abscess

Collection of neutrophils that can form in any part of the skin including epidermis, dermis, subcutaneous fat, hair follicle, eccrine glands.

Acanthosis

Refers to the increased thickness of the spinous layer of the epidermis. There is broad-based acanthosis – as seen in chronic dermatitis – and psoriasiform acanthosis with elongated rete-ridges – as seen in psoriasis.

Acantholysis

Loss of keratinocyte cohesion in the epidermis due to disruption of intercellular bridges (desmosomes) by immunoglobulins/complement or by external agents, for example, oil. This leads to intraepidermal blisters as can be seen in pemphigus vulgaris or HSV.

Ballooning degeneration

Destruction of cells secondary to increased intracellular fluid induced by cell injury (HSV infection).

Basement membrane

Thin amorphous zone between epidermis and dermis.

Civatte bodies

Are synonymous with colloid bodies and represent keratinocytes that have undergone cell death (apoptosis). They are nonnucleated eosinophilic structures in dermis and papillary dermis.

Cornoid lamella

Column of parakeratosis overlying defect in spinous and granular layer. Characteristic feature of porokeratosis and its variants but can be seen in a range of inflammatory and neoplastic conditions.

Corps ronds

Dyskeratotic epidermal cells with rounded nuclei and slightly basophilic cytoplasm on H&E stain (often seen in Darier disease).

Desmoplasia

Dense accumulation of fibrous tissue in response to benign or malignant tumor – activated by cytokines released from fibroblasts.

Dyskeratosis

Abnormal and premature keratinocyte cell death with condensation of cytoplasmic and nuclear proteins and leading to abnormal cornification (seen in Darier disease/sunburn).

Epidermotropism

Refers to migration of atypical cells into the epidermis (characteristically seen in cutaneous T-cell lymphoma in the lower half of epidermis). The migrated cells can have a surrounding halo.

Epidermal or epithelial giant cells

Multinucleated keratinocytes in blisters of HSV infection and identified with Tzanck smear.

Epithelioid cell

Cell rich in cytoplasm with vesicular nucleus – usually a macrophage – often seen in inflammatory infiltrates.

Exocytosis

Refers to migration of inflammatory cells into the epidermis – at any level. Often associated with spongiosis.

Erosion

Superficial epithelial/epidermal defect in which the basal cell layer remains intact.

Flame figure

Degenerated collagen fibers surrounded by major basic protein produced by eosinophils.

Fibrinoid necrosis

Extravasation of fibrin outside blood vessel secondary to vessel wall injury - seen in vasculitis.

Giant cells

Macrophages with multiple nuclei secondary to ingestion or fusion – seen in granulomatous conditions, for example, sarcoidosis, xanthogranuloma. There are three types depending on the arrangement of the nuclei in the giant cell: (a) foreign body type (nuclei are scattered), (b) Langerhans type (nuclei arranged in horseshoe pattern), (c) Touton type (nuclei are arranged as a wreath surrounding lipids).

Granuloma

Is a reaction pattern defined by collection of epithelioid histiocytes, lymphocytes, and multinucleated giant cells. There are different histological types of granulomas: tuberculoid, sarcoidal, foreign body, and suppurative.

Grenz zone

Literally means border zone. It is an area of normal dermis underneath the epidermis or adjacent to hair follicle that separates the rest of the involved dermis from the epidermis – can be seen in dermatofibroma.

Hemorrhage

Extravasation of erythrocytes within the epidermis or dermis – traumatic most commonly or due to vasculitis.

Hypergranulosis

Thickened granular layer of the epidermis – common in inflammatory disorders Lichen planus and HPV infections.

Hyperkeratosis

Thickened cornified layer either with retained nuclei (hyperparakeratosis) or with no nuclei (orthohyperkeratosis).

Inclusions

There are (a) cytoplasmic inclusions: collections of protein material in the cytoplasm – seen in molluscum bodies – and (b) nuclear inclusions: collections of cellular proteins within the nucleus

Interface dermatitis

Inflammation at the dermo-epidermal interface with vacuolar changes of cells in basal cell layer often with cell death and lymphocytic infiltrate (typical in lichen planus and lupus erythematosus).

Kamino bodies

Dull pink globules within the epidermis of a Spitz nevus. They are basement membrane substance and contain Collagen IV and VII.

Lentiginous melanocytes

Melanocytes are arranged in a picket fence line pattern at the dermo-epidermal junction. Seen in sun damaged skin – melanocytes are also atypical and often nested in lentigo maligna.

Leucytoclasia

Nuclear dust (karyorrhexis) and fragments of disintegrated neutrophils secondary to a hypersensitivity reaction, for example, leucocytoclastic vasculitis.

Lichenoid infiltrate

Band-like infiltrate at the dermo-epidermal junction and papillary dermis composed of lymphocytes and some histiocytes. Seen in lichen planus, lichenoid actinic keratosis, squamous cell carcinoma, melanoma.

Macrophages

Cell derived from bone marrow and active in phagocytosis. When present in tissue it is called histiocyte. Develops in epithelial or giant cell.

Metaplasia

Refers to the presence of a cell type in an area where it would not normally be expected to occur. Types of metaplasia include adipocytic (seen in naevus), cartilaginous and osseous metaplasia.

Munro microabscess

Collection of neutrophils within the cornified layer – a feature of Psoriasis.

Pagetoid spread

Upward migration of atypical melanocytes and nonmelanocytic cells in single or small groups into the epidermis (spinous and granular layer). Can be seen in melanoma, Paget’s and Bowen’s disease, intraepidermal sebaceous carcinoma and Merkel cell carcinoma, pagetoid reticulosis, and Langerhans cell histiocytosis.

Pautrier microabscess

Collection of atypical lymphocytes and Langerhans cells within the epidermis – a feature of cutaneous T-cell lymphoma.

Papillary microabscess

Collection of neutrophil in papillary dermis tip – commonly seen in dermatitis herpetiformis but also in linear IgA disease and cicatricial pemphigoid.

Papillomatosis

Finger-like upward projections of papillary dermis resulting into an uneven epidermis. Feature of squamous papilloma, viral wart, seborrheic keratosis, and verrucous carcinoma.

Parakeratosis

Retention of nuclei in the keratinocytes due rapid differentiation and elimination of keratinocytes. The nuclei appear flattened and are parallel to the underlying epidermis.

Perivascular inflammation

Collection of lymphocytes and macrophages around dermal blood vessels. Most common finding in many dermatoses with little diagnostic significance when present alone.

Pigment incontinence

Deposition of melanin in papillary dermis, dermo-epidermal junction and within macrophages – seen in inflammatory dermatoses and melanocytic abnormalities.

Pleomorphism

Variation in shape and size of nuclei and of the complete cell. Hallmark of malignancy.

Poikiloderma

Refers to the triad of epidermal atrophy, teleangiactasia, and mottled pigmentation – feature of many neoplastic and inflammatory conditions including lichen planus and cutaneous T-cell lymphoma.

Psoriasiform hypeplasia

Refers to acanthosis with regular elongation of rete ridges and occasional clubbing of the rete on H&E staining. Can be seen in many inflammatory conditions such as psoriasis, pityriasis rubra pilaris, lichen simplex chronicus.

Pustule

Collection of neutrophils or eosinophils within the epidermis.

Saw toothing

Epidermis projects into the dermis with thin pointed rete giving the appearance of the cutting edge of a saw – associated with lichenoid infiltrate in papillary dermis.

Solar elastosis

Refers to the pale blue structureless area in papillary dermis often associated with a varying degree of keratinocyte atypia and mild increase in melanocytes present in epidermis.

Spongiosis

Separation of keratinocytes in spinous layer secondary to intercellular edema produced by inflammation. Excessive spongiosis can lead to intraepidermal vesicle formation.

Spongiform pustule of Kogoj

Collection of neutrophils within the spinous layer – feature of psoriasis and its variants.

Storiform pattern

Refers to the arrangement of spindle and stellate cells around a central point and in a cartwheel formation. Commonly seen in dermatofibrosarcoma protuberans and other soft tissue tumors.

Subcorneal pustule

Collection of neutrophils beneath the cornified layer – seen in subcorneal pustular dermatoses, acute generalized exanthematous pustulosis, dermatophytosis, impetigo, and pemphigus variants.

Suprapapillary plate

Refers to the area in epidermis that is just above the dermal papilla. Thinning of suprapapillary plate is diagnostic for psoriasis.

Ulcer

Tissue defect involving full thickness skin.

Vacuolar degeneration

Formation of intracellular vacuoles (clear spaces) leading to cell damage and cell death of cells commonly in the basal cell layer and associated inflammation at dermo-epidermal junction.

Vasculitis

Endothelial cells swelling and damage to blood vessel wall by penetration of inflammatory cells (Edward and Yung 2012; Elston and Ferringer 2009; Kempf et al. 2008; Rapini 2005).