Histopathology of dermatitis can be performed in uncertain cases of inflammatory skin condition that remain uncertain after history and physical examination.
Sampling Generally a skin biopsy: For punch biopsies, a size of 4 mm is preferred for most inflammatory dermatoses. Panniculitis or cutaneous lymphoproliferative disorders: 6 mm punch biopsy or skin excision. A superficial or shave biopsy is regarded as insufficient.
Fixation Generally: Buffered 4% formaldehyde. In suspected immunologic disease:Page 678 in: Fixation for immunofluorescence, with for example Michel's solution. For details, see immunofluorescense of skin tissues
Staining Generally 3 sections for H&E staining and one section with periodic acid Schiff (PAS)PAS is for evaluation of the epidermal basement membrane, blood vessels, and the presence of fungal organisms If suspected bacterial and fungal microorganisms, consider Gram stain and Gomori methenamine silver stain.
Microscopic evaluation One approach is to classify into mainly either of the following, primarily based on depth of involvement: Epidermis, papillary dermis, and superficial vascular plexus: Vesiculobullous lesions Pustular dermatosis Non vesicullobullous, non-pustular With epidermal changes Without epidermal changes. These characteristically have a superficial perivascular inflammatory infiltrate, and can be classified by type of cell infiltrate: Lymphocytic (most common) Lymphoeosinophilic Lymphoplasmacytic Mast cell Lymphohistiocytic Neutrophilic Continue in corresponding section:
Non vesicullobullous, non-pustular lesions with epidermal changes Spongiotic dermatitis It is characterized by epithelial intercellular edema. Characteristics Micrograph Photograph Acute Subacute Chronic Generally/Not otherwise specified Typical findings: Variable degree of epidermal spongiosis and vesicle formation, filled with proteinaceous fluid containing lymphocytes and histiocytes. Usually superficial dermal edema with perivascular lymphocytic infiltrate, with exocytosis. No acanthosis or parakeratosis. Typical findings: Mild to moderate spongiosis and exocytosis of inflammatory cells Irregular acanthosis and parakeratosis. Superficial dermal perivascular lymphohistiocytic infiltrate Swelling of endothelial cells Papillary dermal edema are present Typical findings: The spongiosis is mild to absent Pronounced irregular acanthosis, hyperkeratosis, and parakeratosis Minimal dermal inflammation and exocytosis of inflammatory cells are present. Possibly fibrosis of papillary dermis PAS stain is essential to exclude fungal infection. Subacute Allergic/contact dermatitis or atopic dermatitis As above. Eosinophils may be present in the dermis and epidermis (eosinophilic spongiosis). Allergic dermatitis Atopic dermatitis Seborrheic dermatitis Typical findings: Topic Completed: 1 August 2011. Revised: 26 March 2019 Focal, usually mild, spongiosis with overlying scale crust, with a few neutrophils The crust is often centered on a follicle The papillary dermis is generally mildly edematous Dilated blood vessels in the superficial vascular plexus Mild superficial perivascular infiltrate of lymphocytes, histiocytes and occasional neutrophils. There is some exocytosis of inflammatory cells but not as prominent as in nummular dermatitis Typical findings: Psoriasiform hyperplasia, initially slight, with mild spongiosis Usually numerous yeast-like organisms in the surface keratin Same changes as seen in acute stage. Typical findings: More pronounced psoriasiform hyperplasia Only minimal spongiosis Presence of scaling crusts in a folliculocentric distribution, distinguishes from psoriasis.
In addition to above, an unspecific spongiotic dermatitis can be consistent with nummular dermatitis, dyshidrotic dermatitis, Id reaction, dermatophytosis, miliaria, Gianotti-Crosti syndrome and pityriasis rosea.
Interface dermatitis These are sorted into either: Interface dermatitis with vacuolar change Interface dermatitis with lichenoid inflammation
Interface dermatitis with vacuolar change
An interface dermatitis with vacuolar alteration, not otherwise specified, may be caused by viral exanthems, phototoxic dermatitis, acute radiation dermatitis, erythema dyschromicum perstans, lupus erythematosus and dermatomyositis.
Interface dermatitis with lichenoid inflammation Main conditions Characteristics Micrograph Photograph Generally/Not otherwise specified Typical findings: In the papillary dermis: a confluent, band-like, dense inflammation of mainly small lymphocytes and a few histiocytes, along or hugging the dermoepidermal junction. Often vacuolar degeneration of basal keratinocytes and apoptotic bodies (colloid or Civatte bodies). Lichen planus Irregular epidermal hyperplasia with a jagged "sawtooth" appearance, compact hyperkeratosis or orthokeratosis, foci of wedge-shaped hypergranulosis, basilar vacuolar degeneration, slight spongiosis in the spinous layer, and squamatization. The dermal papillae between the elongated rete ridges are frequently dome shaped. Necrotic keratinocytes can be observed in the basal layer of the epidermis and at the dermal-epidermal junction. Eosinophilic remnants of anucleate apoptotic basal cells may also be found in the dermis and are referred to as "colloid or civatte bodies". Whickham striae are usually seen in the areas of hypergranulosis. Vacuolar degeneration at the basal layer may be noted leading to focal subepidermal clefts (Max Joseph spaces). Squamatization occurs as a result of maturation and flattening of cells in the basal layer. It happens in areas of marked hypergranulosis with prominence of the sawtooth pattern of rete ridges. Wedge-shaped hypergranulosis can occur in the eccrine ducts (acrosyringia) or hair follicles (acrotrichia). In the hypertrophic subtype, the associated hyperkeratosis, parakeratosis, hypergranulosis, papillomatosis, acanthosis, and hyperplasia markedly increased with thicker collagen bundles forming in the dermis. Moreover, the rete ridges are more elongated and rounded as opposed to the typical sawtooth pattern. In atrophic LP, loss of the rete ridges and dermal fibrosis is prominent. In vesiculobullous LP, the disease progression is quicker. Hence, some of the distinctive features such as hyperkeratosis, hypergranulosis, or dense lymphocytic dermal-epidermal infiltrate may not be present. LP lesion may resolve with residual hyperpigmentation caused by a persistent increase in the number of melanophages in the papillary dermis.- Attribution 3.0 Unported (CC BY 3.0) Lichenoid drug reaction Can virtually be indistinguishable from cutaneous LP both clinically and histopathologically. Typically, lesions have a photodistribution in the absence of oral mucosal involvement. Characteristically parakeratosis, a dermal eosinophilic infiltrate, and a perivascular lymphocytic infiltrate affecting the reticular dermis. Epidermal changes are less common in lichenoid drug eruptions when compared to classic lichen planus. However, a higher concentration of necrotic keratinocyte and eosinophils in the infiltrate can be helpful in distinguishing lichenoid drug reaction from cutaneous lichen planus. A lengthy interval between the commencement of drug therapy and the onset of lesions does not exclude a diagnosis of lichenoid drug reaction. Resolution of the lesions often occurs within weeks to months after discontinuation of the offending drug. Lichen nitidus Localized granulomatous lymphohistiocytic infiltrate in an expanded dermal papilla Thinning of overlying epidermis and downward extension of the rete ridges at the lateral margin of the infiltrate, resulting in a typical "claw clutching a ball" appearance. Lichen amyloidosis Presence of amyloid, possibly with direct immunofluorescence and Congo red staining. Interface dermatitis with lichenoid inflammation, not otherwise specified, can be caused by lichen planus-like keratosis, lichenoid actinic keratosis, lichenoid lupus erythematosus, lichenoid GVHD (chronic GVHD), pigmented purpuric dermatosis, pityriasis rosea, and pityriasis lichenoides chronica. Unusual conditions that can be associated with a lichenoid inflammatory cell infiltrate are HIV dermatitis, syphilis, mycosis fungoides, urticaria pigmentosa, and post-inflammatory hyperpigmentation. In cases of post-inflammatory hyperpigmentation, it is important to exclude potentially harmful mimics such as a regressed melanocytic lesion or lichenoid pigmented actinic keratosis.
Psoriaform dermatitis Examining multiple deeper levels is recommended if initial cuts do not correlate well with the clinical history.
Psoriaform dermatitis typically displays: Regular epidermal hyperplasia, elongation of the rete ridges, hyperkeratosis, and parakeratosis. Usually:A superficial perivascular inflammatory infiltrate Often: Thinning of epidermal cells overlying the tips of dermal papillae (suprapapillary plates), and dilated, tortuous blood vessels within these papillae
Further histopathologic diagnosis is performed by the following parameters: +Psoriasiform dermatitis Condition Hyperkeratosis Parakeratosis Acanthosis Suprapapillary plate Granular cell layer changes Spinous cell layer changes Basal cell layer changes Other distinctive feature Micrograph Photograph Psoriasis Present Diffuse Regular Thin Decreased or absent Increased mitoses; minimal spongiosisClubbed rete pegs Absent Microabscesses Psoriasiform drug reaction Present Focal Regular and irregular Normal or thick Normal Spongiosis; eosinophilic infiltrate Inflammatory cells; Civatte bodies Chronic allergic/contact and atopic dermatitis Present Focal; crust may be present Irregular Normal or thick Normal Spongiosis; eosinophilic infiltrate Absent Fungal infection Compact Focal; crust may be present Irregular Normal or thick Normal Occasional neutrophiles; Absent Lichen simplex chronicus Present Focal; thick crust Regular or irregular Thin or thick Thickened; hypergranulosis ±minimal inflammatory infiltrate Absent Scabies Present Focal or diffuse Irregular Normal or thick Normal Inflammatory infiltrate; eosinophilic spongiosis Absent Seborrheic dermatitis and HIV dermatitis Present Focal Irregular Normal or thick Normal Spongiosis; lymphocytic and neutrophilic infiltrate Absent Pityriasis rubra pilaris Compact Shoulder parakeratosis;Parakeratotic mounds at the edge of follicular ostia. alternating orthokeratosis and parakeratosis Regular or irregular Normal or thick Normal Spongiosis; lymphocytic infiltrate; rare acantholysis Occasional vacuolar change Pityriasis rosea Present Focal Irregular Normal or thick Normal Small foci of spongiosis; lymphocytic infiltrate Occasional necrotic keratinocytes Syphilis Present Focal Regular or irregular Normal or thick Normal Lymphocytes and neutrophils Interface change Pityriasis lichenoides chronica Present Caps of parakeratosis Irregular Normal Normal Mild spongiosis, lymphocytic infiltrate; necrotic keratinocytes Necrotic keratinocytes Mycosis fungoides Present Focal Regular or irregular Normal Normal Minimal or no spongiosis; ±Pautrier microabscess Atypical lymphoid cells lining the dermo–epidermal junction
Non vesicullobullous, non-pustular lesions without epidermal changes Lymphocytic infiltrate Main conditions Characteristics Micrograph Photograph Urticaria, lymphocyte predominant Perivascular location. Mast cells are relatively sparse, potentially demonstrated with special stains, preferably tryptase stain. Extravasated erythrocytes are present in about 50% of the cases. No vasculitis. Dermal edema [solid arrows in (A,B)] and a sparse superficial predominantly perivascular and interstitial infiltrate of lymphocytes and eosinophils without signs of vasculitis (dashed arrow). Fungal skin infection Often visible fungus. Other signs depend on fungus species. Pigmented purpuric dermatosis Perivascular infiltrate, but may involve the dermis, further away from blood vessels.