Practical Dermatology
Basic Concepts in Skin Biopsy. Part I
La biopsia cutánea: bases fundamentales. Parte I
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Part I" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "12" "paginaFinal" => "20" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Llamas-Velasco, B.E. Paredes" "autores" => array:2 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Llamas-Velasco" "email" => array:1 [ 0 => "mar.llamasvelasco@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "B.E." 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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" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Exposed internal jugular vein during surgery to remove a cervical sentinel lymph node.</p>" ] ] ] "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, which must nonetheless be done thoughtfully, not mechanically.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></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"><span class="elsevierStyleSup">1</span></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"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">3</span></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.</p><p id="par0015" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">5</span></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"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">3</span></a> Dermatologists themselves, therefore, should do these procedures in the interest of avoiding diagnostic and therapeutic delays.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">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"><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. In this first paper we will cover the following points:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0035" class="elsevierStylePara elsevierViewall">Functions of skin biopsy: the role of clinical information and technical aspects of the procedure</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0040" class="elsevierStylePara elsevierViewall">The biopsy: processing the specimen</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3.</span><p id="par0045" class="elsevierStylePara elsevierViewall">Complications of dermatologic surgery</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4.</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. 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.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">8</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">9</span></a> and the procedure may also strengthen good physician–patient relations by re-establishing confidence that a correct diagnosis has been made.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Finally, skin biopsies are sometimes required for monitoring purposes, to obtain objective evidence of clinical course, response to treatment, and possible side effects.</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, 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.</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. However, the situation is quite different when inflammatory dermatoses or rare neoplastic lesions are involved.<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; 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"><span class="elsevierStyleSup">4</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">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).</p><p id="par0090" class="elsevierStylePara elsevierViewall">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.</p><p id="par0095" class="elsevierStylePara elsevierViewall">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"><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.</p><p id="par0105" class="elsevierStylePara elsevierViewall">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"><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, as follows:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1.</span><p id="par0115" class="elsevierStylePara elsevierViewall">Tangential cut, with scissors.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2.</span><p id="par0120" class="elsevierStylePara elsevierViewall">Curettage, with a spoon-shaped curette.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3.</span><p id="par0125" class="elsevierStylePara elsevierViewall">Shave biopsy.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">4.</span><p id="par0130" class="elsevierStylePara elsevierViewall">Punch biopsy, with a circular blade.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">5.</span><p id="par0135" class="elsevierStylePara elsevierViewall">Elliptical biopsy, which may be either incisional or excisional, according to whether the lesion is partially or completely removed.</p></li></ul></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Tangential Cut, With Scissors</span><p id="par0140" class="elsevierStylePara elsevierViewall">This 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.</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. 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.</p><p id="par0150" class="elsevierStylePara elsevierViewall">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"><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. 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"><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.</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,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> using either a blade (mounted or not on a scalpel handle) or a disposable curette.</p><p id="par0165" class="elsevierStylePara elsevierViewall">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.</p><p id="par0170" class="elsevierStylePara elsevierViewall">A shave biopsy is indicated for superficial lesions that are usually exophytic, and excellent cosmetic results can be obtained<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> with no need for sutures.</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.</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. Small diameters (eg, 2<span class="elsevierStyleHsp" style=""></span>mm), which are used only exceptionally, are reserved for cosmetically sensitive sites such as the face. A punch of 4<span class="elsevierStyleHsp" style=""></span>mm is usually large enough.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Smaller sizes are challenging to the diagnosing dermatopathologist, leading some authors to suggest punches of 6<span class="elsevierStyleHsp" style=""></span>mm, particularly if complementary microbiologic procedures and/or direct immunofluorescence are foreseen, as these will require division of the material.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,11</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">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.</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, 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"><span class="elsevierStyleSup">16</span></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.</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. 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"><span class="elsevierStyleSup">17</span></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"><span class="elsevierStyleSup">18</span></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.</p></span></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">The Biopsy: 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. Tissue that is to be stained with hematoxylin–eosin should be fixed in a 10% formol solution (4% formaldehyde in water) for about 24<span class="elsevierStyleHsp" style=""></span>hours, though the time required can vary according to the thickness of the specimen.</p><p id="par0205" class="elsevierStylePara elsevierViewall">If possible, use transparent containers for transport so that the contents can be seen easily.</p><p id="par0210" class="elsevierStylePara elsevierViewall">Ideally the formol-to-volume ratio should be 20:1, or at least 5:1<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></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.</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. 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.</p><p id="par0220" class="elsevierStylePara elsevierViewall">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 24<span class="elsevierStyleHsp" style=""></span>hours, 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"><span class="elsevierStyleSup">19</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">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.</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 0.5% Karnovsky solution (0.5% glutaraldehyde, 2% paraformaldehyde in a 0.2<span class="elsevierStyleHsp" style=""></span>M cacodylate buffer at a pH of 7.3) and later fixed in osmium tetroxide in the same buffer solution.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></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"><span class="elsevierStyleSup">20</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">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.</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, the dermatologist should explain the reasons for the biopsy, the surgical technique that will be used, and the possible side effects.</p><p id="par0245" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">21</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">21</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">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.</p><p id="par0260" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">14</span></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"><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% 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"><span class="elsevierStyleSup">1</span></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"><span class="elsevierStyleSup">22</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">Several antiseptics can be used in combination.</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, to which epinephrine (1:100<span class="elsevierStyleHsp" style=""></span>000) 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.</p><p id="par0280" class="elsevierStylePara elsevierViewall">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"><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. 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"><span class="elsevierStyleSup">22</span></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"><span class="elsevierStyleSup">22</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">Prophylaxis should cover the usual skin flora, mainly gram-positive microorganisms (staphylococci and streptococci). Oral cephalexin (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) is the treatment of choice, although it is also possible to use amoxicillin (2<span class="elsevierStyleHsp" style=""></span>g orally) or cloxacillin (2<span class="elsevierStyleHsp" style=""></span>g orally). In allergic patients, use erythromycin (1<span class="elsevierStyleHsp" style=""></span>g orally before surgery and 500<span class="elsevierStyleHsp" style=""></span>mg afterwards), azithromycin (500<span class="elsevierStyleHsp" style=""></span>mg orally), clarithromycin (500<span class="elsevierStyleHsp" style=""></span>mg orally), or clindamycin (600<span class="elsevierStyleHsp" style=""></span>mg orally).<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The presurgical dose should be given 30–60<span class="elsevierStyleHsp" style=""></span>minutes beforehand.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></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"><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.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">21</span></a> or on sites at higher risk of infection or where functional consequences could be significant (eg, the hand).<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, 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.</p><p id="par0310" class="elsevierStylePara elsevierViewall">In a recent review, Bassas et al.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></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"><span class="elsevierStyleSup">25,26</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">27</span></a> suspending therapy does not seem to be necessary.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25,28</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. 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"><span class="elsevierStyleSup">6</span></a></p><p id="par0325" class="elsevierStylePara elsevierViewall">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.</p><p id="par0330" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">29,30</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. 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>).</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, 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"><span class="elsevierStyleSup">31</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">32</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">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 6<span class="elsevierStyleHsp" style=""></span>mm 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"><span class="elsevierStyleSup">33,34</span></a></p><p id="par0350" class="elsevierStylePara elsevierViewall">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.</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.</p></span></span>" "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" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">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.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">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.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as. Llamas-Velasco M. Paredes BE. La biopsia cutánea: bases fundamentales. Parte I. Actas Dermosifiliogr. 2012;103:12-20.</p>" ] ] "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" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Hematoxylin–eosin, original magnification ×20. Dermatofibrosarcoma protuberans extending to the deep margin of the excisional biopsy.</p>" ] ] 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" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">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.</p>" ] ] 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" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Scissors are used to make a tangential cut biopsy of a fibroma.</p>" ] ] 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" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">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.</p>" ] ] 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" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Exposed internal jugular vein during surgery to remove a cervical sentinel lymph node.</p>" ] ] 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" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Exposure of the fascia covering the flexor tendons of the hand during excision of a melanoma.</p>" ] ] 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" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Hematoxylin–eosin, original magnification ×40. Incipient juvenile xanthogranuloma.</p>" ] ] 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" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Hematoxylin–eosin, original magnification ×100. Perivascular lymphocytic infiltrate with leukocytoclasia. Leukocytoclastic vasculitis was suspected and later confirmed after additional biopsies.</p>" ] ] 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" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A, Hematoxylin–eosin, original magnification ×100. A, Actinic porokeratosis. B, Periodic acid–Schiff stain, original magnification ×100.</p>" ] ] 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" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A, Hematoxylin–eosin, original magnification ×400. Long and oval-shaped structures, bluish in color, corresponding to <span class="elsevierStyleItalic">Malassezia</span> 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.</p>" ] ] 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" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Sites of Common Skin Diseases.</p>" ] ] ] "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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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 5 | 7 | 12 |
| 2024 Octubre | 156 | 58 | 214 |
| 2024 Septiembre | 188 | 55 | 243 |
| 2024 Agosto | 229 | 70 | 299 |
| 2024 Julio | 205 | 59 | 264 |
| 2024 Junio | 207 | 40 | 247 |
| 2024 Mayo | 200 | 59 | 259 |
| 2024 Abril | 174 | 40 | 214 |
| 2024 Marzo | 213 | 52 | 265 |
| 2024 Febrero | 223 | 50 | 273 |
| 2024 Enero | 156 | 46 | 202 |
| 2023 Diciembre | 145 | 25 | 170 |
| 2023 Noviembre | 180 | 51 | 231 |
| 2023 Octubre | 171 | 42 | 213 |
| 2023 Septiembre | 157 | 49 | 206 |
| 2023 Agosto | 130 | 33 | 163 |
| 2023 Julio | 181 | 44 | 225 |
| 2023 Junio | 145 | 30 | 175 |
| 2023 Mayo | 154 | 44 | 198 |
| 2023 Abril | 170 | 36 | 206 |
| 2023 Marzo | 137 | 63 | 200 |
| 2023 Febrero | 114 | 36 | 150 |
| 2023 Enero | 126 | 45 | 171 |
| 2022 Diciembre | 100 | 53 | 153 |
| 2022 Noviembre | 43 | 24 | 67 |
| 2022 Octubre | 36 | 46 | 82 |
| 2022 Septiembre | 32 | 45 | 77 |
| 2022 Agosto | 34 | 44 | 78 |
| 2022 Julio | 31 | 41 | 72 |
| 2022 Junio | 31 | 29 | 60 |
| 2022 Mayo | 115 | 49 | 164 |
| 2022 Abril | 154 | 46 | 200 |
| 2022 Marzo | 163 | 85 | 248 |
| 2022 Febrero | 154 | 72 | 226 |
| 2022 Enero | 185 | 68 | 253 |
| 2021 Diciembre | 108 | 50 | 158 |
| 2021 Noviembre | 134 | 60 | 194 |
| 2021 Octubre | 182 | 91 | 273 |
| 2021 Septiembre | 119 | 55 | 174 |
| 2021 Agosto | 144 | 86 | 230 |
| 2021 Julio | 84 | 45 | 129 |
| 2021 Junio | 107 | 63 | 170 |
| 2021 Mayo | 128 | 59 | 187 |
| 2021 Abril | 259 | 121 | 380 |
| 2021 Marzo | 254 | 55 | 309 |
| 2021 Febrero | 144 | 65 | 209 |
| 2021 Enero | 112 | 35 | 147 |
| 2020 Diciembre | 94 | 41 | 135 |
| 2020 Noviembre | 64 | 23 | 87 |
| 2020 Octubre | 39 | 12 | 51 |
| 2020 Septiembre | 76 | 32 | 108 |
| 2020 Agosto | 57 | 26 | 83 |
| 2020 Julio | 46 | 30 | 76 |
| 2020 Junio | 61 | 56 | 117 |
| 2020 Mayo | 62 | 29 | 91 |
| 2020 Abril | 60 | 30 | 90 |
| 2020 Marzo | 38 | 31 | 69 |
| 2020 Febrero | 8 | 3 | 11 |
| 2020 Enero | 6 | 3 | 9 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Noviembre | 4 | 3 | 7 |
| 2019 Octubre | 0 | 2 | 2 |
| 2019 Agosto | 4 | 4 | 8 |
| 2019 Julio | 4 | 8 | 12 |
| 2019 Junio | 4 | 28 | 32 |
| 2019 Mayo | 6 | 27 | 33 |
| 2019 Abril | 2 | 12 | 14 |
| 2019 Marzo | 2 | 10 | 12 |
| 2019 Febrero | 4 | 2 | 6 |
| 2019 Enero | 10 | 0 | 10 |
| 2018 Diciembre | 11 | 7 | 18 |
| 2018 Noviembre | 4 | 0 | 4 |
| 2018 Octubre | 10 | 0 | 10 |
| 2018 Septiembre | 11 | 0 | 11 |
| 2018 Junio | 0 | 4 | 4 |
| 2018 Mayo | 0 | 9 | 9 |
| 2018 Abril | 0 | 1 | 1 |
| 2018 Marzo | 3 | 3 | 6 |
| 2018 Febrero | 97 | 14 | 111 |
| 2018 Enero | 136 | 12 | 148 |
| 2017 Diciembre | 152 | 14 | 166 |
| 2017 Noviembre | 154 | 20 | 174 |
| 2017 Octubre | 139 | 16 | 155 |
| 2017 Septiembre | 111 | 8 | 119 |
| 2017 Agosto | 150 | 22 | 172 |
| 2017 Julio | 136 | 10 | 146 |
| 2017 Junio | 137 | 16 | 153 |
| 2017 Mayo | 128 | 28 | 156 |
| 2017 Abril | 190 | 16 | 206 |
| 2017 Marzo | 120 | 49 | 169 |
| 2017 Febrero | 128 | 21 | 149 |
| 2017 Enero | 125 | 11 | 136 |
| 2016 Diciembre | 155 | 26 | 181 |
| 2016 Noviembre | 201 | 19 | 220 |
| 2016 Octubre | 227 | 22 | 249 |
| 2016 Septiembre | 281 | 19 | 300 |
| 2016 Agosto | 290 | 12 | 302 |
| 2016 Julio | 135 | 16 | 151 |
| 2016 Junio | 9 | 24 | 33 |
| 2016 Mayo | 8 | 39 | 47 |
| 2016 Abril | 8 | 1 | 9 |
| 2016 Marzo | 6 | 9 | 15 |
| 2016 Febrero | 8 | 2 | 10 |
| 2016 Enero | 7 | 2 | 9 |
| 2015 Diciembre | 6 | 0 | 6 |
| 2015 Noviembre | 51 | 5 | 56 |
| 2015 Octubre | 84 | 3 | 87 |
| 2015 Septiembre | 86 | 4 | 90 |
| 2015 Agosto | 43 | 5 | 48 |
| 2015 Julio | 287 | 14 | 301 |
| 2015 Junio | 237 | 19 | 256 |
| 2015 Mayo | 226 | 16 | 242 |
| 2015 Abril | 215 | 12 | 227 |
| 2015 Marzo | 242 | 12 | 254 |
| 2015 Febrero | 207 | 15 | 222 |
| 2015 Enero | 158 | 19 | 177 |
| 2014 Diciembre | 157 | 15 | 172 |
| 2014 Noviembre | 183 | 14 | 197 |
| 2014 Octubre | 262 | 17 | 279 |
| 2014 Septiembre | 162 | 11 | 173 |
| 2014 Agosto | 146 | 21 | 167 |
| 2014 Julio | 157 | 23 | 180 |
| 2014 Junio | 200 | 17 | 217 |
| 2014 Mayo | 258 | 24 | 282 |
| 2014 Abril | 214 | 22 | 236 |
| 2014 Marzo | 196 | 24 | 220 |
| 2014 Febrero | 178 | 28 | 206 |
| 2014 Enero | 171 | 19 | 190 |
| 2013 Diciembre | 101 | 15 | 116 |
| 2013 Noviembre | 89 | 28 | 117 |
| 2013 Octubre | 54 | 18 | 72 |
| 2013 Septiembre | 31 | 26 | 57 |
| 2013 Agosto | 32 | 23 | 55 |
| 2013 Julio | 21 | 26 | 47 |
| 2013 Junio | 23 | 27 | 50 |
| 2013 Mayo | 31 | 50 | 81 |
| 2013 Abril | 18 | 32 | 50 |
| 2013 Marzo | 25 | 15 | 40 |
| 2013 Febrero | 59 | 11 | 70 |
| 2013 Enero | 69 | 10 | 79 |
| 2012 Diciembre | 40 | 9 | 49 |
| 2012 Noviembre | 2 | 2 | 4 |
| 2012 Octubre | 1 | 8 | 9 |
| 2012 Septiembre | 0 | 6 | 6 |
| 2012 Agosto | 1 | 0 | 1 |
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