Basic Concepts in Skin Biopsy. Part I | Actas Dermo-Sifiliográficas

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Parte I" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1332 "Ancho" => 751 "Tamanyo" => 204423 ] ] "descripcion" => array:1 [ "en" => "Exposed internal jugular vein during surgery to remove a cervical sentinel lymph node." ] ] ] "textoCompleto" => "IntroductionThe skin is easy to examine clinically and it is also easily accessible for carrying out small surgical procedures, which must nonetheless be done thoughtfully, not mechanically.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Biopsy procedures are a key step in medical diagnosis, particularly in dermatology because valuable histopathologic information derives from samples that are very readily obtained.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> In the hands of a trained dermatopathologist skin biopsy becomes a valuable tool, and often a simple one, that can facilitate the accurate diagnosis and treatment of diverse dermatoses, particularly tumors. Although most skin biopsies are of good quality, diagnostic challenges arise when an inadequate sample is taken. Therefore, obtaining an adequate biopsy specimen is a complex process involving steps that must be followed carefully, starting with selecting the most appropriate biopsy technique, followed by proper preparation and handling of instruments; the process culminates with a competent dermatopathologist's examination of the tissue under a microscope.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>The clinical dermatologist must have clearly established indications for the procedure, fully explain the intervention to the patient, obtain informed consent, and finally take a tissue specimen that is representative. Clinicians often submit specimens that are too small,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> however, or that have superficial defects due to electrocoagulation or inappropriate use of forceps, or that show signs of drying before they were placed in a fixing solution.The clinical dermatologist also often chooses an inappropriate site or technique, or may fail to provide the pathologist with even minimal clinical information, making diagnosis difficult.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a>Another important problem that is often underestimated is the clinician's lack of experience in interpreting histopathologic findings, particularly in inflammatory skin diseases.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> The nature of dermatopathologic nomenclature, and the fact that dermatoses can have multiple names, can also lead to misunderstandings between the clinician and the dermatopathologist. A solid understanding of dermatopathology is therefore necessary if clinicians are to fully take advantage of the possibilities that skin biopsy offers. One study of biopsies of inflammatory lesions taken by dermatologists and other specialists found that the dermatologists’ specimens more often yielded information that led to a specific diagnosis (77% of cases vs 41% for nondermatologists) and that the sites the dermatologists sampled were more appropriate.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Some US dermatologists have used extenders—other physicians or nurses—to perform biopsies; these dermatologists report that such assistants have a certain tendency to submit ever smaller specimens of inadequate depth for the suspected diagnosis.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Dermatologists themselves, therefore, should do these procedures in the interest of avoiding diagnostic and therapeutic delays.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Bearing these problems in mind, and in spite of the lack of consensus-based practice guidelines to help with deciding what size of specimen to take or skin biopsy technique to choose,<a class="elsevierStyleCrossRef" href="#bib0035">7</a> we will summarize the principles and concepts which are important from the perspective of the dermatopathologist and which we believe should be taken into consideration when a skin biopsy is performed. In this first paper we will cover the following points:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Functions of skin biopsy: the role of clinical information and technical aspects of the procedure</li><li class="elsevierStyleListItem" id="lsti0010">2.The biopsy: processing the specimen</li><li class="elsevierStyleListItem" id="lsti0015">3.Complications of dermatologic surgery</li><li class="elsevierStyleListItem" id="lsti0020">4.Selecting the biopsy site</li></ul>Functions of Skin BiopsySkin biopsy is performed mainly to assist in the accurate diagnosis of a skin disease. For the diagnosis of skin tumors, biopsy provides the best information; biopsy can also help with prognosis if the tumor proves malignant (by showing Breslow depth in melanoma) and can orient treatment, for example in relation to whether or not tumor-free margins are observed on inspection of the specimen (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Biopsy information is also useful in inflammatory dermatoses, allowing several clinical diagnoses to be weighed and finally confirmed or ruled out.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The specimen may be studied by means of conventional staining techniques, direct immunofluorescence, electron microscopy, immunohistochemical staining, tissue culture, polymerase chain reaction techniques, or fluorescence in situ hybridization.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>Skin biopsies are also taken for legal reasons, such as when a dermatopathologic diagnosis is needed to support clinical suspicion,<a class="elsevierStyleCrossRef" href="#bib0045">9</a> and the procedure may also strengthen good physician–patient relations by re-establishing confidence that a correct diagnosis has been made.Finally, skin biopsies are sometimes required for monitoring purposes, to obtain objective evidence of clinical course, response to treatment, and possible side effects.Clinical InformationProviding the dermatopathologist with sufficient clinical information to work with might seem obvious, but unfortunately the necessary details are not always communicated. Given that time pressures rule in most clinical settings, too little information is often sent to the laboratory with the specimen.Lack of detail may be of little importance if the patient has seborrheic keratosis or if an intradermal nevus has been removed for cosmetic reasons. However, the situation is quite different when inflammatory dermatoses or rare neoplastic lesions are involved.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> In such cases differential diagnosis demands the careful consideration of correlations between clinical and histopathologic data; hence the dermatopathologist will need to know the patient's age and sex, the biopsy site, the clinical presentation and time course, the signs and symptoms, and the various local or systemic treatments the patient was using or had used in the past.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>In certain situations, knowledge of earlier biopsy findings might also be useful: this is particularly true in cases of recurrent or persisting melanocytic nevi or other skin tumors that have not been fully excised. Previous biopsy findings can also reveal histologic changes (eg, psoriasis vulgaris, pityriasis rubra pilaris, seborrheic dermatitis, atopic dermatitis, or mycosis fungoides) that prove indispensable for orienting a treatment approach for generalized exanthems (erythroderma).Some events in the patient's medical history, such as having received a transplant, must be reported, however irrelevant they might seem, because they are associated with certain dermatoses.Photographs of the lesions may also prove useful, particularly when the tissue specimen is sent for analysis to an external laboratory.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>Technical Aspects of Biopsy ProceduresKnowledge of certain basic principles of dermatopathology are essential for selecting the best biopsy site and technique.The level of the lesion in the skin must be known (involvement of the epidermis, dermis or subcutaneous tissue) and the specific characteristics of skin at the biopsy site must be understood (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). These considerations are not trivial. For example, dermatopathologists often receive superficial biopsy specimens that contain only the stratum corneum, taken from the palms or soles, where that layer is of greater thickness. Likewise, scalp biopsies often fail to include subcutaneous tissue (making assessment of the hair bulb impossible), and sometimes only the dermis of the lower limbs might have been biopsied in patients with clinical suspicion of panniculitis (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<a class="elsevierStyleCrossRef" href="#bib0015">3</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Various skin biopsy techniques are available, as follows:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025">1.Tangential cut, with scissors.</li><li class="elsevierStyleListItem" id="lsti0030">2.Curettage, with a spoon-shaped curette.</li><li class="elsevierStyleListItem" id="lsti0035">3.Shave biopsy.</li><li class="elsevierStyleListItem" id="lsti0040">4.Punch biopsy, with a circular blade.</li><li class="elsevierStyleListItem" id="lsti0045">5.Elliptical biopsy, which may be either incisional or excisional, according to whether the lesion is partially or completely removed.</li></ul>Tangential Cut, With ScissorsThis procedure is optimal for removing superficial lesions, especially pedunculated ones such as pendulous fibromas (polyps, acrochordons, or fibroepithelial papillomas) or seborrheic keratoses (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). A local anesthetic is rarely necessary and the wound is usually confined to the papillary dermis.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>CurettageCurettage can be useful in dermatology for removing superficial lesions confined to the epidermis. Examples are seborrheic dermatoses, epidermal nevi, common warts, molluscum contagiosum, actinic keratoses, and superficial basal cell epitheliomas. When many small lesions are present, curettage may provide an adequate sample for dermatopathologic diagnosis, although the fragmentation of the specimen or incomplete excision of a tumor may open up questions of malpractice later on.This technique can be used after application of a cryoanesthetic spray (such as ethyl chloride or liquid nitrogen) or a local anesthetic. The lesion should be grasped firmly between the thumb and index finger with enough pressure to allow a level cut to be made. If the operator cuts too deeply, below the papillary dermis, the incision may leave a scar.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> Essential for executing the technique properly is to hold the lesion firmly enough with one hand to immobilize it and to work deftly with the operating hand. The curette should preferably be held like a pen and rotated with the fingers (the “fountain-pen” technique) or can be grasped with the fingers against the palm of the hand so that the metacarpophalangeal joints can move the blade (the “potato-peeler” technique—in fact, practicing with a potato can help in adjusting the depth of the slice).<a class="elsevierStyleCrossRef" href="#bib0060">12</a>Curettage is contraindicated when a melanocytic lesion is suspected or in any neoplastic lesion of uncertain diagnosis.Shave BiopsyA fine shaving-like motion is made tangential to the surface of the lesion,<a class="elsevierStyleCrossRef" href="#bib0065">13</a> using either a blade (mounted or not on a scalpel handle) or a disposable curette.To avoid tissue shrinkage on submerging the specimen in a formol solution, which can make interpretation difficult, place it on a piece of filter paper before fixing.A shave biopsy is indicated for superficial lesions that are usually exophytic, and excellent cosmetic results can be obtained<a class="elsevierStyleCrossRef" href="#bib0070">14</a> with no need for sutures.This technique should not be used in inflammatory dermatoses and it is formally contraindicated when melanoma is suspected.Punch BiopsyCircular blades for punch biopsies are available in diameters from 2 to 8mm. Small diameters (eg, 2mm), which are used only exceptionally, are reserved for cosmetically sensitive sites such as the face. A punch of 4mm is usually large enough.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Smaller sizes are challenging to the diagnosing dermatopathologist, leading some authors to suggest punches of 6mm, particularly if complementary microbiologic procedures and/or direct immunofluorescence are foreseen, as these will require division of the material.<a class="elsevierStyleCrossRefs" href="#bib0040">8,11</a>Punch biopsy is typically performed under local anesthetic; the skin to be biopsied is pinched between two fingers, parallel to the skin tension lines, and the punch is applied perpendicularly. When the punch is rotated, the blade cuts a cylindrical specimen, which can then be pulled up out of the skin, though scissors may be required to separate it from the base. The resulting wound can be sutured if necessary, although the wound may sometimes be left to heal by secondary intention, especially when a small diameter punch has been used.Elliptical BiopsyThe main reason for choosing to perform an elliptical biopsy is to fully excise a tumor, whether benign or malignant. This procedure is also highly useful in non-neoplastic dermatoses such as panniculitis, scarring alopecia, and vasculitis (especially in conditions affecting larger vessels, such as polyarteritis nodosa or thrombophlebitis, in which an excessively superficial biopsy could lead to diagnostic error)<a class="elsevierStyleCrossRef" href="#bib0080">16</a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). An elliptical biopsy is also called for when ulceration is present and it will be useful to compare healthy and diseased skin.<elsevierMultimedia ident="fig0020"></elsevierMultimedia>The endpoints of the incision should be noted on the skin with a sterile marker. After injection of local anesthetic into the area, an incision is made perpendicular to the surface and deep enough to reach subcutaneous tissue.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> The angle between the first and second incision should not exceed 30° and the width between the 2 cuts should be no more than a third the length in the interest of preventing excessive tension once the wound is closed. The incisions should follow the skin tension lines and aesthetic units should be respected.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Other than taking care to follow these basic principles, the operator should consult more specialized literature for information on such surgical techniques as flap and graft repairs of biopsy sites.The Biopsy: Processing the SpecimenThe tissue sample should be removed carefully with forceps or a hypodermic needle to avoid damage. Tissue that is to be stained with hematoxylin–eosin should be fixed in a 10% formol solution (4% formaldehyde in water) for about 24hours, though the time required can vary according to the thickness of the specimen.If possible, use transparent containers for transport so that the contents can be seen easily.Ideally the formol-to-volume ratio should be 20:1, or at least 5:1<a class="elsevierStyleCrossRef" href="#bib0005">1</a>; therefore, a variety of collection containers must be on hand in the clinic. To avoid confusion, each biopsy should be placed in a separate, properly labeled receptacle.Tumor excision biopsies must be inspected to ensure they are complete and that the borders of the lesion are included. One side of the prepared specimen should be marked, usually by placing a suture to designate the cephalad border, trying to leave the strand loose enough so that the specimen remains undamaged when the suture is removed; otherwise evaluation may be difficult. Once the suture is removed in the laboratory, the specimen is marked again and cut into cross-sections. If there is residual lesion, it will be possible to verify its exact location.When material is to be used for immunofluorescence, the specimen must be divided into 2 parts. One will be processed as already described, by fixing it in formol. The other portion will be wrapped in gauze moistened with normal saline solution and placed in an appropriate receptacle, which does not need to be filled with saline since it is only necessary to keep the tissue moist. If transporting the specimen to an external laboratory will take more than 24hours, it should be placed inside a larger, isothermal carrier packed with dry ice. The specimen might also be placed in Michel's transport medium (an ammonium sulfide, N-ethylmaleimide, and magnesium sulfate solution), which will preserve the specimen well for as long as 10 days.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>For diagnosis on the basis of frozen specimen sections, as in Mohs micrographic surgery, the tissue is preserved in a special medium, usually an optimum cutting temperature (OCT) medium composed of water-soluble glycols and resins; the specimen is embedded and then frozen for cryostat sectioning.A specimen to be studied by electron microscopy must be placed for 2hours in a 0.5% Karnovsky solution (0.5% glutaraldehyde, 2% paraformaldehyde in a 0.2M cacodylate buffer at a pH of 7.3) and later fixed in osmium tetroxide in the same buffer solution.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> In this technique, the specimen must be dried before cutting into thin sections for staining (eg, with uranyl acetate); this treatment is useful, for example, for immune phenotyping of amyloidosis in abdominal fat biopsies.<a class="elsevierStyleCrossRef" href="#bib0100">20</a>When obtaining specimens for microbiology, a sterile receptacle should be used and the tissue wrapped in gauze soaked in normal saline (ie, a nonbacteriostatic solution). Samples for viral culture can be transported in a liquid medium. Contact the microbiology laboratory for specific instructions if in doubt.Patient Considerations and Complications of Dermatopathologic SurgeryAs a well informed patient is more cooperative, the dermatologist should explain the reasons for the biopsy, the surgical technique that will be used, and the possible side effects.Dermatologic surgery does not usually lead to life-threatening complications, although anaphylactic reactions or arrhythmias may occur; therefore, it is important to be ready to perform basic resuscitation maneuvers if need be.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>Most complications involve bleeding, infection and unsightly scars or changes in pigmentation. In taking the medical history, therefore, it is important to note predisposing factors such as malnutrition, advanced age, metabolic disease or genodermatoses, medication, smoking or alcohol intake, or previous therapeutic procedures.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>The possibility of doing a shave biopsy should be discussed, particularly if a melanocytic tumor is suspected, considering the cosmetic advantages of this technique but also the medical disadvantages.The possibility of injuring delicate anatomical structures, such as large vessels, nerves or articular capsules might constitute a relative contraindication.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Particular care must be taken when working near large pulsatile vessels in the trunk or head and neck (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). The presence of structures deep to the biopsy site (such as neurovascular bundles and even spinal fluid) must also be taken into consideration (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). Thorough knowledge of the anatomy of the biopsy site is therefore essential.<a class="elsevierStyleCrossRef" href="#bib0105">21</a><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia>Disinfection of the SiteAlcohol reduces skin flora by 75% within a minute of application and is usually adequate for disinfection, but it is mainly effective against gram-positive microorganisms. A povidone–iodine solution's effect is slower than that of alcohol,<a class="elsevierStyleCrossRef" href="#bib0005">1</a> but its antibacterial spectrum is broader, as it acts against some gram-negative microorganisms as well as gram-positive ones. Chlorhexidine, which is also effective against both types, has a rapid onset of effect that lasts for several hours. This disinfectant should not be used near the eye to avoid irritation, but it is the most effective antiseptic agent both for prevention and for application on the surgical field.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Several antiseptics can be used in combination.AnesthesiaThe biopsy site can be adequately anesthetized with an infiltration anesthetic such as lidocaine, to which epinephrine (1:100000) can be added to prolong the effect and curb bleeding; mepivacaine and bupivacaine are possible alternatives. The local anesthetic can also be combined with the use of a cryogen or topical anesthetic, for example, EMLA cream (an eutectic mixture of prilocaine and lidocaine) or 4% lidocaine cream.No product is risk-free and there have been reports of erythema, contact urticaria, irritative dermatitis, and more rarely, methemoglobinemia and purpura in association with EMLA cream.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>Prophylactic Antibiotic TherapyWound infection is one of the factors that can delay healing. Presurgical antibiotic therapy to prevent endocarditis is not recommended in patients undergoing surgery on clean, noninflamed skin under any circumstances.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> However, prophylaxis is recommended for high-risk patients (those with prosthetic valves or a history of endocarditis or complex cyanotic congenital heart disease) when surgery will affect mucosas, central areas of the face, or genitalia; prophylaxis is also recommended before Mohs micrographic surgery involving evaluation of fresh tissue.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Prophylaxis should cover the usual skin flora, mainly gram-positive microorganisms (staphylococci and streptococci). Oral cephalexin (2g before surgery and 500mg 6hours later if indicated) is the treatment of choice, although it is also possible to use amoxicillin (2g orally) or cloxacillin (2g orally). In allergic patients, use erythromycin (1g orally before surgery and 500mg afterwards), azithromycin (500mg orally), clarithromycin (500mg orally), or clindamycin (600mg orally).<a class="elsevierStyleCrossRef" href="#bib0110">22</a> The presurgical dose should be given 30–60minutes beforehand.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> The decision to prescribe prophylaxis for patients who have recently (within the past 2 years) been implanted with a prosthesis should be made on a case-by-case basis after discussion between the dermatologist and surgeon.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Similar infection rates have been reported in patients using bacitracin or mupirocin cream on the biopsy site and those using petroleum jelly.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>If oral antibiotics are prescribed, they should be reserved for cases in which there will be flap or graft repair in the area around the nose, the wound closure will be subject to tension, or the surgeon will be acting on infected lesions<a class="elsevierStyleCrossRef" href="#bib0105">21</a> or on sites at higher risk of infection or where functional consequences could be significant (eg, the hand).<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Anticoagulant and Antiplatelet TherapyImportant factors to take into account are whether the patient is taking oral anticoagulants or has a systemic disease that increases the risk of coagulation disorders, thrombocytopenia, or immune system compromise. The presence of diabetic angiopathy, lower limb edema or chronic venous insufficiency should also be taken into account, particularly when the biopsy site is on the lower extremities.In a recent review, Bassas et al.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> concluded that warfarin therapy should not be suspended before dermatologic surgery, although the surgical technique should be planned carefully, with strict hemostatic measures, and there should be adequate postoperative follow-up. An international normalized ratio between 2.5 and 3 would be acceptable in patients treated with warfarin who are candidates for dermatologic surgery.<a class="elsevierStyleCrossRefs" href="#bib0125">25,26</a>Less is known about the use of antiplatelet therapy (with acetylsalicylic acid or other cyclooxygenase inhibitors). Although it seems that combined use of clopidogrel and acetylsalicylic acid increases the risk of complications in Mohs surgery,<a class="elsevierStyleCrossRef" href="#bib0135">27</a> suspending therapy does not seem to be necessary.<a class="elsevierStyleCrossRefs" href="#bib0125">25,28</a>Selecting the Biopsy SiteInflammatory skin diseases have successive phases. For that reason it is not always possible to perform biopsies during an acute episode, when the most information will be obtained because the later changes present in advanced lesions are often nonspecific and do not contribute to the diagnosis (and may even make it more difficult). The patient does not always seek care as soon as lesions appear, however, and biopsy is sometimes delayed.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Certain biopsies can be avoided, such when cutaneous mastocytosis is suspected after Darier's sign is elicited; in this disease, degranulating mast cells are barely discernible even with immunohistochemistry.Bullous dermatoses (bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, etc) often begin with an urticarial rash that has a histologic pattern of eosinophilic spongiosis affecting the epidermis and papillary dermis. This pattern can also be seen in other conditions: allergic contact eczema, nummular eczema, dermatitis medicamentosa, bites from insects and other arthropods, scabies, urticaria, incontinentia pigmenti, and Leiner disease (toxic erythema).<a class="elsevierStyleCrossRefs" href="#bib0145">29,30</a> Bear in mind that after the site has been treated with corticosteroid creams the eosinophil count will decrease and diagnosis may become more difficult. When diagnosing blistering diseases, examination of the site of cleavage can be useful. If biopsy has been delayed, the only observations may be erosion and ulceration, or repair processes or signs of bacterial colonization. Histologic findings vary according to the phase when the biopsy is performed in certain diseases (leukocytoclastic vasculitis, juvenile xanthogranuloma [<a class="elsevierStyleCrossRef" href="#fig0035">Fig. 7</a>] or pityriasis lichenoides et varioliformis acuta) and may initially be nonspecific (<a class="elsevierStyleCrossRef" href="#fig0040">Fig. 8</a>). Several biopsies may therefore be required before a precise diagnosis can be made. For annular lesions (eg, granuloma annulare, dermatomycosis, erythema chronicum migrans, erythema annulare centrifugum, cutaneous lupus erythematosus, porokeratosis and others), tissue must be sampled from the active border (<a class="elsevierStyleCrossRef" href="#fig0045">Fig. 9</a>).<elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="fig0040"></elsevierMultimedia><elsevierMultimedia ident="fig0045"></elsevierMultimedia>From either a clinical or histologic perspective, an etiologic diagnosis is hard to achieve in erythroderma, also known as exfoliative dermatitis. When taking the medical history, questions about medication and substance use must be included as well as investigation of previous skin diseases. A thorough physical examination should include palpation to detect masses, organomegaly, and lymphadenopathy. Even so, several biopsy procedures are necessary for diagnosis in over half the cases, and the diagnosis usually rests on a combination of histopathologic and clinical factors.<a class="elsevierStyleCrossRef" href="#bib0155">31</a>Whenever possible, the operator should take samples from several representative sites on the trunk or proximal extremities, given that skin on the distal lower extremities nearly always shows a degree of inflammatory infiltrate and changes related to superimposed stasis dermatitis; moreover, surgical wounds in distal areas will heal more slowly.<a class="elsevierStyleCrossRef" href="#bib0160">32</a>For the accurate diagnosis of panniculitis lesions, biopsy plays a crucial role. Deep incisional biopsies are required to ensure taking an adequate sample of adipose tissue. If the operator chooses to do a punch biopsy, the blade should be at least 6mm in diameter. To interpret the findings, it will be important to know the location or distribution of the infiltrate (predominantly lobular or septal), the predominating cell populations, and the presence or absence of vasculitis.<a class="elsevierStyleCrossRefs" href="#bib0165">33,34</a>To study pigmentation changes, particularly postinflammatory hypopigmentation or vitiligo, the operator should take a sample that contains both lesional and healthy skin (for comparison within the same specimen). Specific stains, such as Masson–Fontana stain, and immunohistochemical analysis (eg, with S-100, Melan-A) can help pinpoint the diagnosis. Periodic acid–Schiff (PAS) staining should also be performed to rule out or identify fungal infections (mainly pityriasis versicolor) (<a class="elsevierStyleCrossRef" href="#fig0050">Fig. 10</a>). PAS staining can also help identify hyphae and spores when pigmentation changes are present in patients who have been treated with antifungal agents.<elsevierMultimedia ident="fig0050"></elsevierMultimedia>Conflicts of InterestsThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres95625" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec82783" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres95624" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec82784" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Functions of Skin Biopsy" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Clinical Information" ] 1 => array:3 [ "identificador" => "sec0020" "titulo" => "Technical Aspects of Biopsy Procedures" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Tangential Cut, With Scissors" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Curettage" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Shave Biopsy" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Punch Biopsy" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Elliptical Biopsy" ] ] ] ] ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "The Biopsy: Processing the Specimen" ] 7 => array:3 [ "identificador" => "sec0055" "titulo" => "Patient Considerations and Complications of Dermatopathologic Surgery" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Disinfection of the Site" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Anesthesia" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Prophylactic Antibiotic Therapy" ] 3 => array:2 [ "identificador" => "sec0075" "titulo" => "Anticoagulant and Antiplatelet Therapy" ] ] ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Selecting the Biopsy Site" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflicts of Interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-02-13" "fechaAceptado" => "2011-05-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec82783" "palabras" => array:6 [ 0 => "Skin biopsy" 1 => "Pathology" 2 => "Dermatopathology" 3 => "Histological preparation" 4 => "Technique" 5 => "Surgical complication" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec82784" "palabras" => array:6 [ 0 => "Biopsia cutánea" 1 => "Anatomía patológica" 2 => "Dermatopatología" 3 => "Preparación histocitológica" 4 => "Técnica" 5 => "Complicación quirúrgica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The aim of these reviews is to describe the reasons for performing skin biopsy, to provide indications for the choice of area to be biopsied and the preparation of the sample, and to summarize the various complications of dermatologic surgery. In addition, we present a guide for selecting the biopsy technique based on the suspected diagnosis and on the area to be biopsied. Finally, the various artifacts that can complicate interpretation of results are described, together with the methods used to prevent their appearance insofar as is possible. The aim of this guide is to improve the diagnostic yield of biopsies and to highlight the importance of a correct clinical–histological correlation." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "En estas revisiones se pretende abarcar las diversas funciones de la biopsia cutánea, ciertas nociones básicas acerca de la elección del área a biopsiar y de la forma de procesar la muestra, así como las diversas complicaciones de la cirugía dermatológica de una manera breve. Además, se ofrece una guía del método a elegir para la realización de la biopsia en función tanto del diagnóstico de sospecha, como de algunas localizaciones que ofrecen mayores dificultades. Por último se analizan diversos artefactos que pueden dificultar la interpretación de las lesiones ofreciendo pautas para evitarlos en lo posible. Con esta guía básica pretendemos mejorar la rentabilidad de la biopsia y resaltar la importancia de realizar una correcta correlación clínico-histológica." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as. Llamas-Velasco M. Paredes BE. La biopsia cutánea: bases fundamentales. Parte I. Actas Dermosifiliogr. 2012;103:12-20." ] ] "multimedia" => array:11 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 780 "Ancho" => 975 "Tamanyo" => 244905 ] ] "descripcion" => array:1 [ "en" => "Hematoxylin–eosin, original magnification ×20. Dermatofibrosarcoma protuberans extending to the deep margin of the excisional biopsy." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 900 "Ancho" => 1402 "Tamanyo" => 352604 ] ] "descripcion" => array:1 [ "en" => "A, Hematoxylin–eosin, original magnification ×20. Suspected diagnosis, erythema nodosum. Slight perivascular lymphocytic infiltrate. Adipose tissue is scarce and a specific diagnosis cannot be made. B, Hematoxylin–eosin, original magnification ×40. Advanced erythema nodosum with septal panniculitis, granulomatous inflammation, and fibroplasia." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 732 "Ancho" => 976 "Tamanyo" => 106867 ] ] "descripcion" => array:1 [ "en" => "Scissors are used to make a tangential cut biopsy of a fibroma." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 661 "Ancho" => 976 "Tamanyo" => 224593 ] ] "descripcion" => array:1 [ "en" => "Hematoxylin–eosin, original magnification ×20. Epidermal and dermal necrosis with thrombi and parietal hyalinosis, findings compatible with a diagnosis of livedoid vasculopathy. Vessels at the dermal–hypodermal junction show foci of segmental fibrinoid necrosis indicating a diagnosis of polyarteritis nodosa." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1332 "Ancho" => 751 "Tamanyo" => 204423 ] ] "descripcion" => array:1 [ "en" => "Exposed internal jugular vein during surgery to remove a cervical sentinel lymph node." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 699 "Ancho" => 973 "Tamanyo" => 142172 ] ] "descripcion" => array:1 [ "en" => "Exposure of the fascia covering the flexor tendons of the hand during excision of a melanoma." ] ] 6 => array:7 [ "identificador" => "fig0035" "etiqueta" => "Figure 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 780 "Ancho" => 976 "Tamanyo" => 335644 ] ] "descripcion" => array:1 [ "en" => "Hematoxylin–eosin, original magnification ×40. Incipient juvenile xanthogranuloma." ] ] 7 => array:7 [ "identificador" => "fig0040" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 776 "Ancho" => 976 "Tamanyo" => 248712 ] ] "descripcion" => array:1 [ "en" => "Hematoxylin–eosin, original magnification ×100. Perivascular lymphocytic infiltrate with leukocytoclasia. Leukocytoclastic vasculitis was suspected and later confirmed after additional biopsies." ] ] 8 => array:7 [ "identificador" => "fig0045" "etiqueta" => "Figure 9" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr9.jpeg" "Alto" => 1049 "Ancho" => 976 "Tamanyo" => 337097 ] ] "descripcion" => array:1 [ "en" => "A, Hematoxylin–eosin, original magnification ×100. A, Actinic porokeratosis. B, Periodic acid–Schiff stain, original magnification ×100." ] ] 9 => array:7 [ "identificador" => "fig0050" "etiqueta" => "Figure 10" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr10.jpeg" "Alto" => 1159 "Ancho" => 976 "Tamanyo" => 333257 ] ] "descripcion" => array:1 [ "en" => "A, Hematoxylin–eosin, original magnification ×400. Long and oval-shaped structures, bluish in color, corresponding to Malassezia species, can be seen in the stratum corneum. B, Periodic acid–Schiff stain, original magnification ×40. Hyphae can be observed in the stratum corneum: diagnosis, tinea infection." ] ] 10 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Epidermis and papillary dermis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Melanocytic nevus, age spots, seborrheic keratosis, fibroepithelial polyps, common wartSuperficial basal cell carcinoma, melanoma in situ, mycosis fungoides, actinic keratosis, Paget disease (mammary and extramammary)Contact dermatitis (allergic and irritant), atopic dermatitis, seborrheic dermatitis, plaque psoriasis, scabies, lichen ruber planus, Gibert pityriasis rosacea, vesiculobullous dermatoses \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Papillary and reticular dermis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Melanocytic nevus, neurofibroma, hemangioma, glomangioma/glomus tumor, sebaceous nevi (hamartomas of the sebaceous follicle), follicular cystsBasal cell carcinoma (solid, sclerodermiform), melanoma, squamous cell carcinomaPhotoallergic dermatitis, phototoxic dermatitis: polymorphic light eruption, scleroderma, morphea, scabietic nodules, leukocytoclastic vasculitis, cutaneous lupus erythematosus, urticaria, granuloma annulare \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reticular dermis and subcutaneous tissue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blue nevus, lipoma, dermatofibroma, epidermoid or trichilemmal cystsMelanoma, cutaneous lymphoma, dermatofibrosarcoma protuberans, metastasis (melanoma, breast cancer, etc.)Panniculitis, sarcoidosis, rheumatoid nodules, nodular vasculitis, polyarteritis nodosa, thrombophlebitis, granuloma annulare \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab181987.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Sites of Common Skin Diseases." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Die Hautbiopsie und die Dermatopathologie für den Kliniker" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B. 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Practical Dermatology

Basic Concepts in Skin Biopsy. Part I

La biopsia cutánea: bases fundamentales. Parte I

M. Llamas-Velascoa,

Corresponding author

mar.llamasvelasco@gmail.com

Corresponding author.

, B.E. Paredesb

a Departamento de Dermatología, Hospital Universitario de La Princesa, Madrid, Spain

b Dermatopathologie Friedrichshafen, Friedrichshafen, Germany

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        "titulo" => "La biopsia cut&#225;nea&#58; bases fundamentales&#46; Parte I"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The skin is easy to examine clinically and it is also easily accessible for carrying out small surgical procedures&#44; which must nonetheless be done thoughtfully&#44; not mechanically&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Biopsy procedures are a key step in medical diagnosis&#44; particularly in dermatology because valuable histopathologic information derives from samples that are very readily obtained&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In the hands of a trained dermatopathologist skin biopsy becomes a valuable tool&#44; and often a simple one&#44; that can facilitate the accurate diagnosis and treatment of diverse dermatoses&#44; particularly tumors&#46; Although most skin biopsies are of good quality&#44; diagnostic challenges arise when an inadequate sample is taken&#46; Therefore&#44; obtaining an adequate biopsy specimen is a complex process involving steps that must be followed carefully&#44; starting with selecting the most appropriate biopsy technique&#44; followed by proper preparation and handling of instruments&#59; the process culminates with a competent dermatopathologist&#39;s examination of the tissue under a microscope&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The clinical dermatologist must have clearly established indications for the procedure&#44; fully explain the intervention to the patient&#44; obtain informed consent&#44; and finally take a tissue specimen that is representative&#46; Clinicians often submit specimens that are too small&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> however&#44; or that have superficial defects due to electrocoagulation or inappropriate use of forceps&#44; or that show signs of drying before they were placed in a fixing solution&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The clinical dermatologist also often chooses an inappropriate site or technique&#44; or may fail to provide the pathologist with even minimal clinical information&#44; making diagnosis difficult&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Another important problem that is often underestimated is the clinician&#39;s lack of experience in interpreting histopathologic findings&#44; particularly in inflammatory skin diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The nature of dermatopathologic nomenclature&#44; and the fact that dermatoses can have multiple names&#44; can also lead to misunderstandings between the clinician and the dermatopathologist&#46; A solid understanding of dermatopathology is therefore necessary if clinicians are to fully take advantage of the possibilities that skin biopsy offers&#46; One study of biopsies of inflammatory lesions taken by dermatologists and other specialists found that the dermatologists&#8217; specimens more often yielded information that led to a specific diagnosis &#40;77&#37; of cases vs 41&#37; for nondermatologists&#41; and that the sites the dermatologists sampled were more appropriate&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Some US dermatologists have used extenders&#8212;other physicians or nurses&#8212;to perform biopsies&#59; these dermatologists report that such assistants have a certain tendency to submit ever smaller specimens of inadequate depth for the suspected diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Dermatologists themselves&#44; therefore&#44; should do these procedures in the interest of avoiding diagnostic and therapeutic delays&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Bearing these problems in mind&#44; and in spite of the lack of consensus-based practice guidelines to help with deciding what size of specimen to take or skin biopsy technique to choose&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> we will summarize the principles and concepts which are important from the perspective of the dermatopathologist and which we believe should be taken into consideration when a skin biopsy is performed&#46; In this first paper we will cover the following points&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Functions of skin biopsy&#58; the role of clinical information and technical aspects of the procedure</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0040" class="elsevierStylePara elsevierViewall">The biopsy&#58; processing the specimen</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Complications of dermatologic surgery</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Selecting the biopsy site</p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Functions of Skin Biopsy</span><p id="par0055" class="elsevierStylePara elsevierViewall">Skin biopsy is performed mainly to assist in the accurate diagnosis of a skin disease&#46; For the diagnosis of skin tumors&#44; biopsy provides the best information&#59; biopsy can also help with prognosis if the tumor proves malignant &#40;by showing Breslow depth in melanoma&#41; and can orient treatment&#44; for example in relation to whether or not tumor-free margins are observed on inspection of the specimen &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Biopsy information is also useful in inflammatory dermatoses&#44; allowing several clinical diagnoses to be weighed and finally confirmed or ruled out&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The specimen may be studied by means of conventional staining techniques&#44; direct immunofluorescence&#44; electron microscopy&#44; immunohistochemical staining&#44; tissue culture&#44; polymerase chain reaction techniques&#44; or fluorescence in situ hybridization&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Skin biopsies are also taken for legal reasons&#44; such as when a dermatopathologic diagnosis is needed to support clinical suspicion&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and the procedure may also strengthen good physician&#8211;patient relations by re-establishing confidence that a correct diagnosis has been made&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Finally&#44; skin biopsies are sometimes required for monitoring purposes&#44; to obtain objective evidence of clinical course&#44; response to treatment&#44; and possible side effects&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Clinical Information</span><p id="par0075" class="elsevierStylePara elsevierViewall">Providing the dermatopathologist with sufficient clinical information to work with might seem obvious&#44; but unfortunately the necessary details are not always communicated&#46; Given that time pressures rule in most clinical settings&#44; too little information is often sent to the laboratory with the specimen&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Lack of detail may be of little importance if the patient has seborrheic keratosis or if an intradermal nevus has been removed for cosmetic reasons&#46; However&#44; the situation is quite different when inflammatory dermatoses or rare neoplastic lesions are involved&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In such cases differential diagnosis demands the careful consideration of correlations between clinical and histopathologic data&#59; hence the dermatopathologist will need to know the patient&#39;s age and sex&#44; the biopsy site&#44; the clinical presentation and time course&#44; the signs and symptoms&#44; and the various local or systemic treatments the patient was using or had used in the past&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In certain situations&#44; knowledge of earlier biopsy findings might also be useful&#58; this is particularly true in cases of recurrent or persisting melanocytic nevi or other skin tumors that have not been fully excised&#46; Previous biopsy findings can also reveal histologic changes &#40;eg&#44; psoriasis vulgaris&#44; pityriasis rubra pilaris&#44; seborrheic dermatitis&#44; atopic dermatitis&#44; or mycosis fungoides&#41; that prove indispensable for orienting a treatment approach for generalized exanthems &#40;erythroderma&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Some events in the patient&#39;s medical history&#44; such as having received a transplant&#44; must be reported&#44; however irrelevant they might seem&#44; because they are associated with certain dermatoses&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Photographs of the lesions may also prove useful&#44; particularly when the tissue specimen is sent for analysis to an external laboratory&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Technical Aspects of Biopsy Procedures</span><p id="par0100" class="elsevierStylePara elsevierViewall">Knowledge of certain basic principles of dermatopathology are essential for selecting the best biopsy site and technique&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The level of the lesion in the skin must be known &#40;involvement of the epidermis&#44; dermis or subcutaneous tissue&#41; and the specific characteristics of skin at the biopsy site must be understood &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; These considerations are not trivial&#46; For example&#44; dermatopathologists often receive superficial biopsy specimens that contain only the stratum corneum&#44; taken from the palms or soles&#44; where that layer is of greater thickness&#46; Likewise&#44; scalp biopsies often fail to include subcutaneous tissue &#40;making assessment of the hair bulb impossible&#41;&#44; and sometimes only the dermis of the lower limbs might have been biopsied in patients with clinical suspicion of panniculitis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Various skin biopsy techniques are available&#44; as follows&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1&#46;</span><p id="par0115" class="elsevierStylePara elsevierViewall">Tangential cut&#44; with scissors&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2&#46;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Curettage&#44; with a spoon-shaped curette&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3&#46;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Shave biopsy&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">4&#46;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Punch biopsy&#44; with a circular blade&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">5&#46;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Elliptical biopsy&#44; which may be either incisional or excisional&#44; according to whether the lesion is partially or completely removed&#46;</p></li></ul></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Tangential Cut&#44; With Scissors</span><p id="par0140" class="elsevierStylePara elsevierViewall">This procedure is optimal for removing superficial lesions&#44; especially pedunculated ones such as pendulous fibromas &#40;polyps&#44; acrochordons&#44; or fibroepithelial papillomas&#41; or seborrheic keratoses &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; A local anesthetic is rarely necessary and the wound is usually confined to the papillary dermis&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Curettage</span><p id="par0145" class="elsevierStylePara elsevierViewall">Curettage can be useful in dermatology for removing superficial lesions confined to the epidermis&#46; Examples are seborrheic dermatoses&#44; epidermal nevi&#44; common warts&#44; molluscum contagiosum&#44; actinic keratoses&#44; and superficial basal cell epitheliomas&#46; When many small lesions are present&#44; curettage may provide an adequate sample for dermatopathologic diagnosis&#44; although the fragmentation of the specimen or incomplete excision of a tumor may open up questions of malpractice later on&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">This technique can be used after application of a cryoanesthetic spray &#40;such as ethyl chloride or liquid nitrogen&#41; or a local anesthetic&#46; The lesion should be grasped firmly between the thumb and index finger with enough pressure to allow a level cut to be made&#46; If the operator cuts too deeply&#44; below the papillary dermis&#44; the incision may leave a scar&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Essential for executing the technique properly is to hold the lesion firmly enough with one hand to immobilize it and to work deftly with the operating hand&#46; The curette should preferably be held like a pen and rotated with the fingers &#40;the &#8220;fountain-pen&#8221; technique&#41; or can be grasped with the fingers against the palm of the hand so that the metacarpophalangeal joints can move the blade &#40;the &#8220;potato-peeler&#8221; technique&#8212;in fact&#44; practicing with a potato can help in adjusting the depth of the slice&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Curettage is contraindicated when a melanocytic lesion is suspected or in any neoplastic lesion of uncertain diagnosis&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Shave Biopsy</span><p id="par0160" class="elsevierStylePara elsevierViewall">A fine shaving-like motion is made tangential to the surface of the lesion&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> using either a blade &#40;mounted or not on a scalpel handle&#41; or a disposable curette&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">To avoid tissue shrinkage on submerging the specimen in a formol solution&#44; which can make interpretation difficult&#44; place it on a piece of filter paper before fixing&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">A shave biopsy is indicated for superficial lesions that are usually exophytic&#44; and excellent cosmetic results can be obtained<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> with no need for sutures&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">This technique should not be used in inflammatory dermatoses and it is formally contraindicated when melanoma is suspected&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Punch Biopsy</span><p id="par0180" class="elsevierStylePara elsevierViewall">Circular blades for punch biopsies are available in diameters from 2 to 8<span class="elsevierStyleHsp" style=""></span>mm&#46; Small diameters &#40;eg&#44; 2<span class="elsevierStyleHsp" style=""></span>mm&#41;&#44; which are used only exceptionally&#44; are reserved for cosmetically sensitive sites such as the face&#46; A punch of 4<span class="elsevierStyleHsp" style=""></span>mm is usually large enough&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Smaller sizes are challenging to the diagnosing dermatopathologist&#44; leading some authors to suggest punches of 6<span class="elsevierStyleHsp" style=""></span>mm&#44; particularly if complementary microbiologic procedures and&#47;or direct immunofluorescence are foreseen&#44; as these will require division of the material&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;11</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Punch biopsy is typically performed under local anesthetic&#59; the skin to be biopsied is pinched between two fingers&#44; parallel to the skin tension lines&#44; and the punch is applied perpendicularly&#46; When the punch is rotated&#44; the blade cuts a cylindrical specimen&#44; which can then be pulled up out of the skin&#44; though scissors may be required to separate it from the base&#46; The resulting wound can be sutured if necessary&#44; although the wound may sometimes be left to heal by secondary intention&#44; especially when a small diameter punch has been used&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Elliptical Biopsy</span><p id="par0190" class="elsevierStylePara elsevierViewall">The main reason for choosing to perform an elliptical biopsy is to fully excise a tumor&#44; whether benign or malignant&#46; This procedure is also highly useful in non-neoplastic dermatoses such as panniculitis&#44; scarring alopecia&#44; and vasculitis &#40;especially in conditions affecting larger vessels&#44; such as polyarteritis nodosa or thrombophlebitis&#44; in which an excessively superficial biopsy could lead to diagnostic error&#41;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; An elliptical biopsy is also called for when ulceration is present and it will be useful to compare healthy and diseased skin&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0195" class="elsevierStylePara elsevierViewall">The endpoints of the incision should be noted on the skin with a sterile marker&#46; After injection of local anesthetic into the area&#44; an incision is made perpendicular to the surface and deep enough to reach subcutaneous tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The angle between the first and second incision should not exceed 30&#176; and the width between the 2 cuts should be no more than a third the length in the interest of preventing excessive tension once the wound is closed&#46; The incisions should follow the skin tension lines and aesthetic units should be respected&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Other than taking care to follow these basic principles&#44; the operator should consult more specialized literature for information on such surgical techniques as flap and graft repairs of biopsy sites&#46;</p></span></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">The Biopsy&#58; Processing the Specimen</span><p id="par0200" class="elsevierStylePara elsevierViewall">The tissue sample should be removed carefully with forceps or a hypodermic needle to avoid damage&#46; Tissue that is to be stained with hematoxylin&#8211;eosin should be fixed in a 10&#37; formol solution &#40;4&#37; formaldehyde in water&#41; for about 24<span class="elsevierStyleHsp" style=""></span>hours&#44; though the time required can vary according to the thickness of the specimen&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">If possible&#44; use transparent containers for transport so that the contents can be seen easily&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Ideally the formol-to-volume ratio should be 20&#58;1&#44; or at least 5&#58;1<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#59; therefore&#44; a variety of collection containers must be on hand in the clinic&#46; To avoid confusion&#44; each biopsy should be placed in a separate&#44; properly labeled receptacle&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Tumor excision biopsies must be inspected to ensure they are complete and that the borders of the lesion are included&#46; One side of the prepared specimen should be marked&#44; usually by placing a suture to designate the cephalad border&#44; trying to leave the strand loose enough so that the specimen remains undamaged when the suture is removed&#59; otherwise evaluation may be difficult&#46; Once the suture is removed in the laboratory&#44; the specimen is marked again and cut into cross-sections&#46; If there is residual lesion&#44; it will be possible to verify its exact location&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">When material is to be used for immunofluorescence&#44; the specimen must be divided into 2 parts&#46; One will be processed as already described&#44; by fixing it in formol&#46; The other portion will be wrapped in gauze moistened with normal saline solution and placed in an appropriate receptacle&#44; which does not need to be filled with saline since it is only necessary to keep the tissue moist&#46; If transporting the specimen to an external laboratory will take more than 24<span class="elsevierStyleHsp" style=""></span>hours&#44; it should be placed inside a larger&#44; isothermal carrier packed with dry ice&#46; The specimen might also be placed in Michel&#39;s transport medium &#40;an ammonium sulfide&#44; N-ethylmaleimide&#44; and magnesium sulfate solution&#41;&#44; which will preserve the specimen well for as long as 10 days&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">For diagnosis on the basis of frozen specimen sections&#44; as in Mohs micrographic surgery&#44; the tissue is preserved in a special medium&#44; usually an optimum cutting temperature &#40;OCT&#41; medium composed of water-soluble glycols and resins&#59; the specimen is embedded and then frozen for cryostat sectioning&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">A specimen to be studied by electron microscopy must be placed for 2<span class="elsevierStyleHsp" style=""></span>hours in a 0&#46;5&#37; Karnovsky solution &#40;0&#46;5&#37; glutaraldehyde&#44; 2&#37; paraformaldehyde in a 0&#46;2<span class="elsevierStyleHsp" style=""></span>M cacodylate buffer at a pH of 7&#46;3&#41; and later fixed in osmium tetroxide in the same buffer solution&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In this technique&#44; the specimen must be dried before cutting into thin sections for staining &#40;eg&#44; with uranyl acetate&#41;&#59; this treatment is useful&#44; for example&#44; for immune phenotyping of amyloidosis in abdominal fat biopsies&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">When obtaining specimens for microbiology&#44; a sterile receptacle should be used and the tissue wrapped in gauze soaked in normal saline &#40;ie&#44; a nonbacteriostatic solution&#41;&#46; Samples for viral culture can be transported in a liquid medium&#46; Contact the microbiology laboratory for specific instructions if in doubt&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient Considerations and Complications of Dermatopathologic Surgery</span><p id="par0240" class="elsevierStylePara elsevierViewall">As a well informed patient is more cooperative&#44; the dermatologist should explain the reasons for the biopsy&#44; the surgical technique that will be used&#44; and the possible side effects&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Dermatologic surgery does not usually lead to life-threatening complications&#44; although anaphylactic reactions or arrhythmias may occur&#59; therefore&#44; it is important to be ready to perform basic resuscitation maneuvers if need be&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Most complications involve bleeding&#44; infection and unsightly scars or changes in pigmentation&#46; In taking the medical history&#44; therefore&#44; it is important to note predisposing factors such as malnutrition&#44; advanced age&#44; metabolic disease or genodermatoses&#44; medication&#44; smoking or alcohol intake&#44; or previous therapeutic procedures&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">The possibility of doing a shave biopsy should be discussed&#44; particularly if a melanocytic tumor is suspected&#44; considering the cosmetic advantages of this technique but also the medical disadvantages&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">The possibility of injuring delicate anatomical structures&#44; such as large vessels&#44; nerves or articular capsules might constitute a relative contraindication&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Particular care must be taken when working near large pulsatile vessels in the trunk or head and neck &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46; The presence of structures deep to the biopsy site &#40;such as neurovascular bundles and even spinal fluid&#41; must also be taken into consideration &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46; Thorough knowledge of the anatomy of the biopsy site is therefore essential&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Disinfection of the Site</span><p id="par0265" class="elsevierStylePara elsevierViewall">Alcohol reduces skin flora by 75&#37; within a minute of application and is usually adequate for disinfection&#44; but it is mainly effective against gram-positive microorganisms&#46; A povidone&#8211;iodine solution&#39;s effect is slower than that of alcohol&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> but its antibacterial spectrum is broader&#44; as it acts against some gram-negative microorganisms as well as gram-positive ones&#46; Chlorhexidine&#44; which is also effective against both types&#44; has a rapid onset of effect that lasts for several hours&#46; This disinfectant should not be used near the eye to avoid irritation&#44; but it is the most effective antiseptic agent both for prevention and for application on the surgical field&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">Several antiseptics can be used in combination&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Anesthesia</span><p id="par0275" class="elsevierStylePara elsevierViewall">The biopsy site can be adequately anesthetized with an infiltration anesthetic such as lidocaine&#44; to which epinephrine &#40;1&#58;100<span class="elsevierStyleHsp" style=""></span>000&#41; can be added to prolong the effect and curb bleeding&#59; mepivacaine and bupivacaine are possible alternatives&#46; The local anesthetic can also be combined with the use of a cryogen or topical anesthetic&#44; for example&#44; EMLA cream &#40;an eutectic mixture of prilocaine and lidocaine&#41; or 4&#37; lidocaine cream&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">No product is risk-free and there have been reports of erythema&#44; contact urticaria&#44; irritative dermatitis&#44; and more rarely&#44; methemoglobinemia and purpura in association with EMLA cream&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Prophylactic Antibiotic Therapy</span><p id="par0285" class="elsevierStylePara elsevierViewall">Wound infection is one of the factors that can delay healing&#46; Presurgical antibiotic therapy to prevent endocarditis is not recommended in patients undergoing surgery on clean&#44; noninflamed skin under any circumstances&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> However&#44; prophylaxis is recommended for high-risk patients &#40;those with prosthetic valves or a history of endocarditis or complex cyanotic congenital heart disease&#41; when surgery will affect mucosas&#44; central areas of the face&#44; or genitalia&#59; prophylaxis is also recommended before Mohs micrographic surgery involving evaluation of fresh tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">Prophylaxis should cover the usual skin flora&#44; mainly gram-positive microorganisms &#40;staphylococci and streptococci&#41;&#46; Oral cephalexin &#40;2<span class="elsevierStyleHsp" style=""></span>g before surgery and 500<span class="elsevierStyleHsp" style=""></span>mg 6<span class="elsevierStyleHsp" style=""></span>hours later if indicated&#41; is the treatment of choice&#44; although it is also possible to use amoxicillin &#40;2<span class="elsevierStyleHsp" style=""></span>g orally&#41; or cloxacillin &#40;2<span class="elsevierStyleHsp" style=""></span>g orally&#41;&#46; In allergic patients&#44; use erythromycin &#40;1<span class="elsevierStyleHsp" style=""></span>g orally before surgery and 500<span class="elsevierStyleHsp" style=""></span>mg afterwards&#41;&#44; azithromycin &#40;500<span class="elsevierStyleHsp" style=""></span>mg orally&#41;&#44; clarithromycin &#40;500<span class="elsevierStyleHsp" style=""></span>mg orally&#41;&#44; or clindamycin &#40;600<span class="elsevierStyleHsp" style=""></span>mg orally&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The presurgical dose should be given 30&#8211;60<span class="elsevierStyleHsp" style=""></span>minutes beforehand&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The decision to prescribe prophylaxis for patients who have recently &#40;within the past 2 years&#41; been implanted with a prosthesis should be made on a case-by-case basis after discussion between the dermatologist and surgeon&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Similar infection rates have been reported in patients using bacitracin or mupirocin cream on the biopsy site and those using petroleum jelly&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">If oral antibiotics are prescribed&#44; they should be reserved for cases in which there will be flap or graft repair in the area around the nose&#44; the wound closure will be subject to tension&#44; or the surgeon will be acting on infected lesions<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> or on sites at higher risk of infection or where functional consequences could be significant &#40;eg&#44; the hand&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Anticoagulant and Antiplatelet Therapy</span><p id="par0305" class="elsevierStylePara elsevierViewall">Important factors to take into account are whether the patient is taking oral anticoagulants or has a systemic disease that increases the risk of coagulation disorders&#44; thrombocytopenia&#44; or immune system compromise&#46; The presence of diabetic angiopathy&#44; lower limb edema or chronic venous insufficiency should also be taken into account&#44; particularly when the biopsy site is on the lower extremities&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">In a recent review&#44; Bassas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> concluded that warfarin therapy should not be suspended before dermatologic surgery&#44; although the surgical technique should be planned carefully&#44; with strict hemostatic measures&#44; and there should be adequate postoperative follow-up&#46; An international normalized ratio between 2&#46;5 and 3 would be acceptable in patients treated with warfarin who are candidates for dermatologic surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">Less is known about the use of antiplatelet therapy &#40;with acetylsalicylic acid or other cyclooxygenase inhibitors&#41;&#46; Although it seems that combined use of clopidogrel and acetylsalicylic acid increases the risk of complications in Mohs surgery&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> suspending therapy does not seem to be necessary&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;28</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Selecting the Biopsy Site</span><p id="par0320" class="elsevierStylePara elsevierViewall">Inflammatory skin diseases have successive phases&#46; For that reason it is not always possible to perform biopsies during an acute episode&#44; when the most information will be obtained because the later changes present in advanced lesions are often nonspecific and do not contribute to the diagnosis &#40;and may even make it more difficult&#41;&#46; The patient does not always seek care as soon as lesions appear&#44; however&#44; and biopsy is sometimes delayed&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">Certain biopsies can be avoided&#44; such when cutaneous mastocytosis is suspected after Darier&#39;s sign is elicited&#59; in this disease&#44; degranulating mast cells are barely discernible even with immunohistochemistry&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">Bullous dermatoses &#40;bullous pemphigoid&#44; pemphigus vulgaris&#44; dermatitis herpetiformis&#44; etc&#41; often begin with an urticarial rash that has a histologic pattern of eosinophilic spongiosis affecting the epidermis and papillary dermis&#46; This pattern can also be seen in other conditions&#58; allergic contact eczema&#44; nummular eczema&#44; dermatitis medicamentosa&#44; bites from insects and other arthropods&#44; scabies&#44; urticaria&#44; incontinentia pigmenti&#44; and Leiner disease &#40;toxic erythema&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a> Bear in mind that after the site has been treated with corticosteroid creams the eosinophil count will decrease and diagnosis may become more difficult&#46; When diagnosing blistering diseases&#44; examination of the site of cleavage can be useful&#46; If biopsy has been delayed&#44; the only observations may be erosion and ulceration&#44; or repair processes or signs of bacterial colonization&#46; Histologic findings vary according to the phase when the biopsy is performed in certain diseases &#40;leukocytoclastic vasculitis&#44; juvenile xanthogranuloma &#91;<a class="elsevierStyleCrossRef" href="#fig0035">Fig&#46; 7</a>&#93; or pityriasis lichenoides et varioliformis acuta&#41; and may initially be nonspecific &#40;<a class="elsevierStyleCrossRef" href="#fig0040">Fig&#46; 8</a>&#41;&#46; Several biopsies may therefore be required before a precise diagnosis can be made&#46; For annular lesions &#40;eg&#44; granuloma annulare&#44; dermatomycosis&#44; erythema chronicum migrans&#44; erythema annulare centrifugum&#44; cutaneous lupus erythematosus&#44; porokeratosis and others&#41;&#44; tissue must be sampled from the active border &#40;<a class="elsevierStyleCrossRef" href="#fig0045">Fig&#46; 9</a>&#41;&#46;</p><elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="fig0040"></elsevierMultimedia><elsevierMultimedia ident="fig0045"></elsevierMultimedia><p id="par0335" class="elsevierStylePara elsevierViewall">From either a clinical or histologic perspective&#44; an etiologic diagnosis is hard to achieve in erythroderma&#44; also known as exfoliative dermatitis&#46; When taking the medical history&#44; questions about medication and substance use must be included as well as investigation of previous skin diseases&#46; A thorough physical examination should include palpation to detect masses&#44; organomegaly&#44; and lymphadenopathy&#46; Even so&#44; several biopsy procedures are necessary for diagnosis in over half the cases&#44; and the diagnosis usually rests on a combination of histopathologic and clinical factors&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">Whenever possible&#44; the operator should take samples from several representative sites on the trunk or proximal extremities&#44; given that skin on the distal lower extremities nearly always shows a degree of inflammatory infiltrate and changes related to superimposed stasis dermatitis&#59; moreover&#44; surgical wounds in distal areas will heal more slowly&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">For the accurate diagnosis of panniculitis lesions&#44; biopsy plays a crucial role&#46; Deep incisional biopsies are required to ensure taking an adequate sample of adipose tissue&#46; If the operator chooses to do a punch biopsy&#44; the blade should be at least 6<span class="elsevierStyleHsp" style=""></span>mm in diameter&#46; To interpret the findings&#44; it will be important to know the location or distribution of the infiltrate &#40;predominantly lobular or septal&#41;&#44; the predominating cell populations&#44; and the presence or absence of vasculitis&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#44;34</span></a></p><p id="par0350" class="elsevierStylePara elsevierViewall">To study pigmentation changes&#44; particularly postinflammatory hypopigmentation or vitiligo&#44; the operator should take a sample that contains both lesional and healthy skin &#40;for comparison within the same specimen&#41;&#46; Specific stains&#44; such as Masson&#8211;Fontana stain&#44; and immunohistochemical analysis &#40;eg&#44; with S-100&#44; Melan-A&#41; can help pinpoint the diagnosis&#46; Periodic acid&#8211;Schiff &#40;PAS&#41; staining should also be performed to rule out or identify fungal infections &#40;mainly pityriasis versicolor&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0050">Fig&#46; 10</a>&#41;&#46; PAS staining can also help identify hyphae and spores when pigmentation changes are present in patients who have been treated with antifungal agents&#46;</p><elsevierMultimedia ident="fig0050"></elsevierMultimedia></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interests</span><p id="par0355" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "identificador" => "xres95625"
          "titulo" => "Abstract"
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          "identificador" => "xpalclavsec82783"
          "titulo" => "Keywords"
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        2 => array:2 [
          "identificador" => "xres95624"
          "titulo" => "Resumen"
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          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
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          "identificador" => "sec0010"
          "titulo" => "Functions of Skin Biopsy"
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            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Clinical Information"
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            1 => array:3 [
              "identificador" => "sec0020"
              "titulo" => "Technical Aspects of Biopsy Procedures"
              "secciones" => array:5 [
                0 => array:2 [
                  "identificador" => "sec0025"
                  "titulo" => "Tangential Cut&#44; With Scissors"
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                1 => array:2 [
                  "identificador" => "sec0030"
                  "titulo" => "Curettage"
                ]
                2 => array:2 [
                  "identificador" => "sec0035"
                  "titulo" => "Shave Biopsy"
                ]
                3 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Punch Biopsy"
                ]
                4 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "Elliptical Biopsy"
                ]
              ]
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "The Biopsy&#58; Processing the Specimen"
        ]
        7 => array:3 [
          "identificador" => "sec0055"
          "titulo" => "Patient Considerations and Complications of Dermatopathologic Surgery"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Disinfection of the Site"
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            1 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Anesthesia"
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            2 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Prophylactic Antibiotic Therapy"
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            3 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Anticoagulant and Antiplatelet Therapy"
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          ]
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        8 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Selecting the Biopsy Site"
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        9 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflicts of Interests"
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        10 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2011-02-13"
    "fechaAceptado" => "2011-05-08"
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          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Skin biopsy"
            1 => "Pathology"
            2 => "Dermatopathology"
            3 => "Histological preparation"
            4 => "Technique"
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          "clase" => "keyword"
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            0 => "Biopsia cut&#225;nea"
            1 => "Anatom&#237;a patol&#243;gica"
            2 => "Dermatopatolog&#237;a"
            3 => "Preparaci&#243;n histocitol&#243;gica"
            4 => "T&#233;cnica"
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim of these reviews is to describe the reasons for performing skin biopsy&#44; to provide indications for the choice of area to be biopsied and the preparation of the sample&#44; and to summarize the various complications of dermatologic surgery&#46; In addition&#44; we present a guide for selecting the biopsy technique based on the suspected diagnosis and on the area to be biopsied&#46; Finally&#44; the various artifacts that can complicate interpretation of results are described&#44; together with the methods used to prevent their appearance insofar as is possible&#46; The aim of this guide is to improve the diagnostic yield of biopsies and to highlight the importance of a correct clinical&#8211;histological correlation&#46;</p>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">En estas revisiones se pretende abarcar las diversas funciones de la biopsia cut&#225;nea&#44; ciertas nociones b&#225;sicas acerca de la elecci&#243;n del &#225;rea a biopsiar y de la forma de procesar la muestra&#44; as&#237; como las diversas complicaciones de la cirug&#237;a dermatol&#243;gica de una manera breve&#46; Adem&#225;s&#44; se ofrece una gu&#237;a del m&#233;todo a elegir para la realizaci&#243;n de la biopsia en funci&#243;n tanto del diagn&#243;stico de sospecha&#44; como de algunas localizaciones que ofrecen mayores dificultades&#46; Por &#250;ltimo se analizan diversos artefactos que pueden dificultar la interpretaci&#243;n de las lesiones ofreciendo pautas para evitarlos en lo posible&#46; Con esta gu&#237;a b&#225;sica pretendemos mejorar la rentabilidad de la biopsia y resaltar la importancia de realizar una correcta correlaci&#243;n cl&#237;nico-histol&#243;gica&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#46; Llamas-Velasco M&#46; Paredes BE&#46; La biopsia cut&#225;nea&#58; bases fundamentales&#46; Parte I&#46; Actas Dermosifiliogr&#46; 2012&#59;103&#58;12-20&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Hematoxylin&#8211;eosin&#44; original magnification &#215;40&#46; Incipient juvenile xanthogranuloma&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t">Epidermis and papillary dermis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Melanocytic nevus&#44; age spots&#44; seborrheic keratosis&#44; fibroepithelial polyps&#44; common wartSuperficial basal cell carcinoma&#44; melanoma in situ&#44; mycosis fungoides&#44; actinic keratosis&#44; Paget disease &#40;mammary and extramammary&#41;Contact dermatitis &#40;allergic and irritant&#41;&#44; atopic dermatitis&#44; seborrheic dermatitis&#44; plaque psoriasis&#44; scabies&#44; lichen ruber planus&#44; Gibert pityriasis rosacea&#44; vesiculobullous dermatoses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">Papillary and reticular dermis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Melanocytic nevus&#44; neurofibroma&#44; hemangioma&#44; glomangioma&#47;glomus tumor&#44; sebaceous nevi &#40;hamartomas of the sebaceous follicle&#41;&#44; follicular cystsBasal cell carcinoma &#40;solid&#44; sclerodermiform&#41;&#44; melanoma&#44; squamous cell carcinomaPhotoallergic dermatitis&#44; phototoxic dermatitis&#58; polymorphic light eruption&#44; scleroderma&#44; morphea&#44; scabietic nodules&#44; leukocytoclastic vasculitis&#44; cutaneous lupus erythematosus&#44; urticaria&#44; granuloma annulare&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Reticular dermis and subcutaneous tissue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blue nevus&#44; lipoma&#44; dermatofibroma&#44; epidermoid or trichilemmal cystsMelanoma&#44; cutaneous lymphoma&#44; dermatofibrosarcoma protuberans&#44; metastasis &#40;melanoma&#44; breast cancer&#44; etc&#46;&#41;Panniculitis&#44; sarcoidosis&#44; rheumatoid nodules&#44; nodular vasculitis&#44; polyarteritis nodosa&#44; thrombophlebitis&#44; granuloma annulare&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Sites of Common Skin Diseases&#46;</p>"
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                      "Revista" => array:6 [
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2011.05.005

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2024 June	207	40	247
2024 May	200	59	259
2024 April	174	40	214
2024 March	213	52	265
2024 February	223	50	273
2024 January	156	46	202
2023 December	145	25	170
2023 November	180	51	231
2023 October	171	42	213
2023 September	157	49	206
2023 August	130	33	163
2023 July	181	44	225
2023 June	145	30	175
2023 May	154	44	198
2023 April	170	36	206
2023 March	137	63	200
2023 February	114	36	150
2023 January	126	45	171
2022 December	100	53	153
2022 November	43	24	67
2022 October	36	46	82
2022 September	32	45	77
2022 August	34	44	78
2022 July	31	41	72
2022 June	31	29	60
2022 May	115	49	164
2022 April	154	46	200
2022 March	163	85	248
2022 February	154	72	226
2022 January	185	68	253
2021 December	108	50	158
2021 November	134	60	194
2021 October	182	91	273
2021 September	119	55	174
2021 August	144	86	230
2021 July	84	45	129
2021 June	107	63	170
2021 May	128	59	187
2021 April	259	121	380
2021 March	254	55	309
2021 February	144	65	209
2021 January	112	35	147
2020 December	94	41	135
2020 November	64	23	87
2020 October	39	12	51
2020 September	76	32	108
2020 August	57	26	83
2020 July	46	30	76
2020 June	61	56	117
2020 May	62	29	91
2020 April	60	30	90
2020 March	38	31	69
2020 February	8	3	11
2020 January	6	3	9
2019 December	4	0	4
2019 November	4	3	7
2019 October	0	2	2
2019 August	4	4	8
2019 July	4	8	12
2019 June	4	28	32
2019 May	6	27	33
2019 April	2	12	14
2019 March	2	10	12
2019 February	4	2	6
2019 January	10	0	10
2018 December	11	7	18
2018 November	4	0	4
2018 October	10	0	10
2018 September	11	0	11
2018 June	0	4	4
2018 May	0	9	9
2018 April	0	1	1
2018 March	3	3	6
2018 February	97	14	111
2018 January	136	12	148
2017 December	152	14	166
2017 November	154	20	174
2017 October	139	16	155
2017 September	111	8	119
2017 August	150	22	172
2017 July	136	10	146
2017 June	137	16	153
2017 May	128	28	156
2017 April	190	16	206
2017 March	120	49	169
2017 February	128	21	149
2017 January	125	11	136
2016 December	155	26	181
2016 November	201	19	220
2016 October	227	22	249
2016 September	281	19	300
2016 August	290	12	302
2016 July	135	16	151
2016 June	9	24	33
2016 May	8	39	47
2016 April	8	1	9
2016 March	6	9	15
2016 February	8	2	10
2016 January	7	2	9
2015 December	6	0	6
2015 November	51	5	56
2015 October	84	3	87
2015 September	86	4	90
2015 August	43	5	48
2015 July	287	14	301
2015 June	237	19	256
2015 May	226	16	242
2015 April	215	12	227
2015 March	242	12	254
2015 February	207	15	222
2015 January	158	19	177
2014 December	157	15	172
2014 November	183	14	197
2014 October	262	17	279
2014 September	162	11	173
2014 August	146	21	167
2014 July	157	23	180
2014 June	200	17	217
2014 May	258	24	282
2014 April	214	22	236
2014 March	196	24	220
2014 February	178	28	206
2014 January	171	19	190
2013 December	101	15	116
2013 November	89	28	117
2013 October	54	18	72
2013 September	31	26	57
2013 August	32	23	55
2013 July	21	26	47
2013 June	23	27	50
2013 May	31	50	81
2013 April	18	32	50
2013 March	25	15	40
2013 February	59	11	70
2013 January	69	10	79
2012 December	40	9	49
2012 November	2	2	4
2012 October	1	8	9
2012 September	0	6	6
2012 August	1	0	1

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