Skin biopsies
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Skin biopsies
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Up to 10% of general practice consultations are for skin disease. While in many cases the diagnosis is clear, often it is not. In some circumstances a skin biopsy may help establish the diagnosis and then enable specific treatment.
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Locating the pathology
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Skin rashes may be classified into epidermal and dermal conditions. Epidermal conditions are characterised by scale, vesicles, erosions, or colour change. Dermal rashes usually have swelling or redness with intact skin markings and no distortion of the epidermis.
The conditions that cause epidermal (ie red scaly) rashes are includedTable 1.
The diagnosis of epidermal rashes can usually be established by examining the rash and taking skin scrapings for fungal microscopy and culture where appropriate. A biopsy may sometimes be required for these disorders; however, the biopsy will shed limited light on the diagnosis unless it is taken from carefully selected sites and accompanied by detailed clinical information.
Pityriasis lichenoides, pityriasis rubra pilaris, mycosis fungoides, lichen planus, chronic cutaneous (discoid) lupus erythematosus and Darier’s disease have reasonably specific histology and if these disorders are suspected, a biopsy to confirm the diagnosis is recommended. In addition, the management of some of these disorders is complex, and a pretreatment biopsy to document the diagnosis histologically, before the morphology of the rash is altered by treatment, is helpful.
However, if the differential diagnosis of the red scaly rash in question is confusing, consultation with a dermatologist may be more appropriate than proceeding to biopsy.
Dermal rashes have a variety of causes (see Table 2 ).
Many dermal rashes will require biopsy for confirmation of the diagnosis and it is reasonable to proceed immediately to biopsy in these circumstances. Consultation with a dermatologist may still be required for management in many of these cases.
Occasionally, rashes will be polymorphous with some sites showing epidermal change and others dermal change. This is common in epidermal rashes, particularly when they are partly treated. By definition, dermal rashes show no epidermal change whatsoever and if only 5% of the rash shows epidermal involvement it is still considered an epidermal rash.
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infections |
tinea, candidiasis, pityriasis versicolor, impetigo, scabies, warts |
dermatitis |
atopic, discoid, hand and foot (pompholyx), asteatotic (dry), gravitational, contact, erythrodermic |
psoriasis and pityriasiform[Note1] |
psoriasis (plaque, guttate, flexural, palmo-plantar, pustular and erythrodermic variants), pityriasis rosea, pityriasis versicolor, seborrhoeic dermatitis, mycosis fungoides |
lichen planus |
|
chronic cutaneous (discoid) lupus erythematosus |
|
drug eruptions |
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[Note 1] pityriasiform refers to red scaly rashes that have a well-defined border and fine powdery scale |
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Granulomas |
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infectious |
tuberculosis, syphilis, deep fungal infection, bacterial botryomycosis |
noninfectious |
sarcoid, granuloma annulare, necrobiosis lipoidica, rosacea |
Infiltrates |
 |
noncellular |
solar elastosis, porphyria, colloid milium, amyloid, mucin, xanthoma |
cellular |
polymorphs – Sweet’s syndrome mast cells – mastocytosis plasma cells – plasmacytoma eosinophils – insect bites, Well’s syndrome lymphocytes – T-cell and B-cell lymphomas, leukaemia, lymphocytoma cutis, Jessner’s infiltration, lupus erythematosus histiocytes – histiocytosis Langerhans cell and nonLangerhans cell |
Vascular |
vasculitis, panniculitis, Kaposi’s sarcoma |
Erythema |
annular erythema, toxic erythema, urticaria, livedo reticularis, erythema nodosum, cellulitis |
Neoplasia |
primary, secondary |
Skin biopsies: information, techniques, investigations and procedure
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The minimum clinical information required for a histopathologist to accurately report a skin biopsy is the site of the rash, its duration, appearance (eg macular, papular, vasculitic, vesicular), whether it is itchy, and what topical treatment has been used. As the histological appearances mirror the clinical evolution of the eruption, information on whether the biopsy has been taken from a recent, established or resolving area of the rash is also useful.
Include a drug history. If possible, provide a provisional diagnosis and one or two differential diagnoses.
Often multiple biopsies from different sites are helpful. These should be taken from lesions in different stages of development.
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Excisional biopsy is one of the most commonly used techniques and is the best for pigmented lesions and skin tumours. It is usually elliptical. Orientation of the specimen may be achieved by placing a suture at one edge and designating that margin, if appropriate. When possible, the long axis of the wound should parallel the natural cutaneous creases.
Incisional biopsy is a narrow ellipse of skin, approximately 5 mm long and 2 mm wide, deep enough to include fat and taken at right angles to the edge of a rash or tumour (if inappropriate for primary excisional biopsy). With rashes, it should include perilesional skin (at least 1 mm). It is especially useful in the diagnosis of panniculitis and annular, maculopapular and vesiculobullous rashes. This technique provides more tissue for histological assessment than does punch biopsy.
Punch biopsy is quick and convenient to perform. The instrument is a variable diameter cylinder with a sharp cutting edge, attached to a plastic handle (disposable type). The range of diameters generally available is 2 to 8 mm. A 3 mm punch is usually sufficient for diagnostic specimens. Tumours should be biopsied centrally, and typical areas of a rash should be sampled (eg an entire single papule or vesicle, or the central portion of a macule). Excoriated areas should be avoided as the secondary changes can confuse the histology. It is preferable not to punch biopsy pigmented lesions unless the lesion is small enough to be completely removed by the biopsy itself.
Shave biopsy is performed by shaving off the lesion flush with the surrounding skin. It is particularly useful in the removal of superficial, raised, plaque-like lesions such as seborrhoeic keratoses. It can also be used to remove benign melanocytic naevi, particularly protuberant types of intradermal naevi. It should be used with some caution in this setting, however, as the lesion is not usually completely removed and the deep aspect of the naevus may not be included (maturation of naevus cells and lack of deep mitotic activity are important factors in assessment of naevus versus melanoma). Melanocytic naevi may recur following incomplete removal and may demonstrate atypical histological appearances simulating melanoma. Hence when such areas of recurrent pigmentation are biopsied, it is important to indicate the previous surgery on the request form.
Curettage may be performed with a disposable or nondisposable curette and is commonly followed by cautery. It is useful to treat seborrhoeic keratoses, viral warts and solar keratoses. It is also commonly used to remove basal cell carcinomas (particularly the superficial multifocal type). As the specimen is frequently fragmented, it is not possible to comment on completeness of removal. Pigmented melanocytic lesions should not be removed by this method.
Snip biopsy is performed on pedunculated lesions (eg skin tags) by grasping the lesion with forceps and snipping the base with scissors.
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excisional |
·           single lesion removal, usually elliptical ·           diagnostic and margin assessment |
incisional |
·           include fat in suspected panniculitis and perilesional skin for comparison |
punch |
·           minimum 3 to 4 mm ·           requires accurate sampling ·           diagnostic and margin assessment (larger excisional punches) |
shave |
·           protuberant intradermal melanocytic naevi and seborrhoeic keratoses ·           diagnostic +/- margin assessment |
curettage |
·           seborrhoeic keratoses, solar keratoses, viral warts, basal cell carcinomas ·           followed by cautery ·           diagnostic (margins usually not assessable) |
snip |
·           skin tags |
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1. Prepare the skin surface: clean the skin gently without disrupting keratotic scale or blisters. 2. Mark the lesion. 3. Local anaesthesia: approximately 1 mL of an appropriate local anaesthetic is sufficient to provide anaesthesia for most lesions and will not distort the histology. 4. Depth of biopsy: the depth required will reflect where the pathology is anticipated. In general, it is best to include subcutis to ensure the entire thickness of skin is present. Subcutis must be included when panniculitis is suspected. 5. Care of tissue: handle the biopsy carefully with skin hooks, fine forceps or needle tips, to avoid crush artefact. 6. Fixative: place in specimen container with 10% neutral buffered formalin, except if immunofluorescent or microbiological studies are required. 7. Labelling: ensure all containers are labelled with patient details and that they match those on the request slip. |
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The major applications of immunofluorescence are in the diagnosis of cutaneous lupus erythematosus (preferably biopsy the centre of the lesion) and vesiculobullous disorders (preferably perilesional skin for suspected bullous pemphigoid or nonlesional skin for pemphigus or dermatitis herpetiformis). It is best to provide the specimen as a separate biopsy (rather than dividing one specimen) to prevent crush artefact in the component to be examined histologically. The specimen must be received fresh (not in formalin), either in saline-soaked gauze or in a special transport medium (Michel’s medium). Ideally, the laboratory should receive the specimen within 4 hours of removal and freeze it on arrival. It will remain preserved on saline-soaked gauze for up to 24 hours; however, the risk of a false negative result is greater.
Cutaneous disorders may be infective in nature. If infection is suspected, a separate biopsy from the lesion should be submitted fresh in a sterile container. Ideally, it should be placed on sterile saline-soaked gauze and received by the laboratory within 4 hours.
 Parasitic skin and soft tissue infections
Cutaneous larva migrans
Animal hookworms usually cause this condition. Although self-limiting, treatment alleviates symptoms.
1 |
ivermectin (child >5 years) 200 micrograms/kg orally, as 1 dose |
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OR |
2 |
albendazole (child <=10 kg: 200 mg) 400 mg orally, daily for 3 days. |
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