Although new technologies are becoming available to aid in diagnosis, the skin biopsy continues to be the fundamental tool of the dermatologist to evaluate the nature of a pigmented lesion. There are 3 major techniques for the biopsy of a pigmented lesion: shave biopsy, punch/incisional biopsy, and excisional biopsy. This article discusses when to biopsy a pigmented lesion and reviews the different biopsy techniques, with reference to specific clinical scenarios.
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The skin biopsy is the fundamental procedure all dermatologists should be familiar with when approaching patients with pigmented lesions.
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When deciding to perform a skin biopsy of a pigmented lesion it is important to decide which type of biopsy is appropriate: shave, incisional or excisional.
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Determining which type of biopsy to perform should be guided by clinical suspicion and informed by area on the body.
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For pigmented lesions, partial biopsies are not recommended.
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While complete excision of a pigmented lesion allows the pathologist to fully evaluate the depth and margins of a suspicious lesion, this may not always be practical. In such cases, the dermatologist must always remember that a biopsy is a diagnostic tool and additional tissue can always be taken at a later time if needed.
Introduction
The rate of melanoma has increased significantly in the last several decades. It is not clear whether this is a true increase in the incidence of the biologic process or a function of improved diagnostic acumen amongst dermatologists and dermatopathologists. Early-stage lesions comprise most newly diagnosed melanomas, suggesting that the increase may be because of an uptick in biopsy rates. However, given that melanoma continues to claim several thousand lives annually, an argument can be made that melanocytic lesions are still not biopsied enough. Although new technologies are becoming available to aid in diagnosis, the skin biopsy continues to be the fundamental tool of the dermatologist to evaluate the nature of a pigmented lesion.
When a decision to biopsy is made, the method by which to do it can represent a challenging dilemma. There are 3 major techniques for the biopsy of a pigmented lesion: shave biopsy, punch/incisional biopsy, and excisional biopsy. Each has its advantages and drawbacks and which the clinician chooses is based on many factors, including, but not limited to, the morphologic characteristics and anatomic site of the pigmented lesion, the clinician’s level of suspicion regarding the aggressiveness of the lesion, the clinician’s level of comfort with each technique under varying circumstances, and the cosmesis of the resultant defect.
This article discusses when to biopsy a pigmented lesion and reviews the different biopsy techniques. Specific clinical scenarios are discussed. When approaching a pigmented lesion, the most important end point is realizing that a biopsy is needed and then choosing the technique that provides an accurate diagnosis.
Lesion evaluation
Before performing a biopsy, the first step for the clinician is determining whether a pigmented lesion is suspicious enough to warrant removal. There are multiple factors that influence the clinician’s decision regarding the biologic behavior of a pigmented lesion. The most widely known are probably best encapsulated by the ABCDE criteria. Lesions that are asymmetric (A) warrant a heightened level of suspicion, as do lesions with irregular borders (B), multiple colors (C), or a diameter (D) greater than 6 mm. The evolution of the lesion (E), or how it is changing, is one of the newly added criteria, although it can lead to diagnostic challenges, especially in children whose nevi are often growing as they are.
In general, the dermatologist has few tools other than their clinical experience to evaluate the malignant potential of a pigmented lesion in vivo. The most widely used is dermoscopy, which has gained significant traction in recent years. As a technique, it requires a hand-held device that allows for closer inspection of the structural pattern of a lesion. Although there are multiple published criteria and methods for evaluation of pigmented lesions with dermoscopy, many of the criteria are still in flux and subject to interpreter variability. Another tool used at some academic medical centers for diagnosis of melanoma is confocal microscopy. However, the science is still in its early stages; it is time-consuming, the machinery is expensive, and few operators are trained on its interpretation. MelaFind (Mela Sciences, Irvington, NY, USA) is a new technology that received approval by the United States Food and Drug Administration in 2011. The device evaluates a pigmented lesion and uses a series of algorithms to guide the dermatologist in the decision to perform a biopsy. It is used as an adjunct in the overall clinical picture because it is still at the discretion of the physician to biopsy MelaFind-negative and nonevaluable lesions. Thus, in general, the decision to biopsy a pigmented lesion rests principally on the clinician’s experience.
When deciding whether to biopsy, Bolognia has said that the first step is visualizing the gross configuration of the tumor as well as a cross-section of the skin that contains the tumor cells. Thus, an important part of the physical examination is palpation of the suspicious lesion. Because a melanoma with invasion feels thicker than a melanoma in situ, palpation can aid in the selection of the biopsy method. For example, a pigmented nodule is not appropriately sampled by means of a simple shave biopsy, in which the lesion is removed at a level even with the skin; this misses the depth of a melanoma and results in inappropriate management of the patient.
Patients with numerous nevi are especially challenging for the clinician. In this scenario, it is important to assess whether the patient has a signature nevus, which can range from nevi that present as couplets to darkly pigmented nevi that are otherwise benign. For these patients, or patients with greater than 50 nevi (and thus an increased risk for melanoma), regular total body skin examinations with biopsy of the most unusual appearing nevus on an annual basis should be considered.
Lesion evaluation
Before performing a biopsy, the first step for the clinician is determining whether a pigmented lesion is suspicious enough to warrant removal. There are multiple factors that influence the clinician’s decision regarding the biologic behavior of a pigmented lesion. The most widely known are probably best encapsulated by the ABCDE criteria. Lesions that are asymmetric (A) warrant a heightened level of suspicion, as do lesions with irregular borders (B), multiple colors (C), or a diameter (D) greater than 6 mm. The evolution of the lesion (E), or how it is changing, is one of the newly added criteria, although it can lead to diagnostic challenges, especially in children whose nevi are often growing as they are.
In general, the dermatologist has few tools other than their clinical experience to evaluate the malignant potential of a pigmented lesion in vivo. The most widely used is dermoscopy, which has gained significant traction in recent years. As a technique, it requires a hand-held device that allows for closer inspection of the structural pattern of a lesion. Although there are multiple published criteria and methods for evaluation of pigmented lesions with dermoscopy, many of the criteria are still in flux and subject to interpreter variability. Another tool used at some academic medical centers for diagnosis of melanoma is confocal microscopy. However, the science is still in its early stages; it is time-consuming, the machinery is expensive, and few operators are trained on its interpretation. MelaFind (Mela Sciences, Irvington, NY, USA) is a new technology that received approval by the United States Food and Drug Administration in 2011. The device evaluates a pigmented lesion and uses a series of algorithms to guide the dermatologist in the decision to perform a biopsy. It is used as an adjunct in the overall clinical picture because it is still at the discretion of the physician to biopsy MelaFind-negative and nonevaluable lesions. Thus, in general, the decision to biopsy a pigmented lesion rests principally on the clinician’s experience.
When deciding whether to biopsy, Bolognia has said that the first step is visualizing the gross configuration of the tumor as well as a cross-section of the skin that contains the tumor cells. Thus, an important part of the physical examination is palpation of the suspicious lesion. Because a melanoma with invasion feels thicker than a melanoma in situ, palpation can aid in the selection of the biopsy method. For example, a pigmented nodule is not appropriately sampled by means of a simple shave biopsy, in which the lesion is removed at a level even with the skin; this misses the depth of a melanoma and results in inappropriate management of the patient.
Patients with numerous nevi are especially challenging for the clinician. In this scenario, it is important to assess whether the patient has a signature nevus, which can range from nevi that present as couplets to darkly pigmented nevi that are otherwise benign. For these patients, or patients with greater than 50 nevi (and thus an increased risk for melanoma), regular total body skin examinations with biopsy of the most unusual appearing nevus on an annual basis should be considered.
Anesthesia
Depending on the biopsy method, the tools for biopsy vary slightly. However, universal to all biopsies is the selection of anesthesia. Typically, 1% lidocaine with epinephrine at 1:100,000 is used to achieve local anesthesia. However, it is possible to use concentrations as dilute as 1:500,000. The epinephrine provides for vasoconstriction, thereby minimizing the risk of bleeding, although it takes 7 to 10 minutes to achieve its full effect. The duration of action is 1 to 2 hours. Some patients report an allergy to lidocaine, although this is usually more likely a reflection of the sympathomimetic effects of epinephrine, leading to tachycardia. If there is a true allergy to lidocaine (and thus other amide anesthetics), an ester anesthetic such as procainamide can be used. Depending on the size of the lesion to be biopsied, it is also possible to use saline alone for anesthesia.
The area to be biopsied should be injected using a 30-gauge, 1.27-cm (half-inch) needle and infiltrated with the anesthetic until a raised bleb is visible on the skin surface. When infiltrating the skin with anesthesia, it is preferable to insert the needle adjacent to the lesion so as not to disrupt the epidermis of the pigmented lesion itself. If the lesion is greater than 1.0 cm, a ring block technique can be used. In this method, anesthesia is placed peripherally and allowed to diffuse to the center of the lesion. Techniques for minimizing discomfort include warming the anesthetic, injecting slowly, alkalinizing the lidocaine with sodium bicarbonate, and inserting the needle in areas already anesthetized to minimize the number of needlesticks the patient feels.
In children, it is advisable to pretreat the area with topical anesthetic such as eutectic mixture of local anesthetics (EMLA) or a 4 or 5% lidocaine cream for 45 minutes under occlusion with either a bandage or Tegaderm clear dressing. Doing so prevents the patient from feeling the needlestick for additional anesthesia. Depending on the age of the child and their weight, the patient can be placed in a papoose or the parent can hold the child in their lap. It is critical when performing biopsies on children that arms and legs are immobilized as well as the head, if needed. It is important to discuss the biopsy at length with the parent because children often react at the sight of a needle regardless of the amount of pain felt, which can be difficult for a parent to witness. Other modes of pretreating a biopsy area before injection include ice packs, cryogen (which should be sprayed at a distance), or Medi-First cold spray.
In pregnant women, biopsies should be performed without epinephrine. In the first trimester, total amount of lidocaine should be minimized and should not exceed 10 mL. If an excision is performed, patients should be alerted that the scar may spread (depending on the area) because of stretch and that healing time is slightly prolonged.
Equipment
The tools required for the biopsy of a pigmented lesion depend, in part, on the method chosen (see later discussion). However, most tools are present in the dermatologist’s outpatient office. The most commonly used pieces of equipment include a disposable scalpel with a number 15 blade, Webster needle holder, Adson type forceps, Iris scissor, skin hook, Dermablade, punch biopsy tool, suture, aluminum chloride, electrocautery, gauze, and a cotton-tipped applicator. We do not recommend the use of an iron-based solution (eg, Monsel) for coagulation after biopsy of a pigmented lesion because the solution can leave residual pigment (the so-called “Monsel tattoo”) in the area. Thus, if a second biopsy or additional tissue is required, light-brown exogenous pigment is seen on permanent section of the tissue, which could make evaluation difficult.
How to biopsy: the guidelines
Many different national organizations have issued guidelines on the biopsy of a suspicious pigmented lesion. In 2002, the British Association of Dermatologists issued their evidence-based guidelines for the management of cutaneous melanoma, and this was updated in 2010. Their guidelines indicate that excisional biopsy of clinically suspicious lesions is almost always preferable to any other technique. However, they note that their guidelines are just that, and each clinical scenario relies on decision making that takes into account many factors. Similarly, the American Academy of Dermatology has recently issued a position statement on the management of melanoma, recommending that a narrow excisional biopsy with 1-mm to 3-mm margins is required to clear the subclinical component of most atypical melanocytic lesions and is therefore preferable in almost all scenarios.
Biopsy techniques
Shave Biopsy (Saucerization Technique)
Method
The shave biopsy technique is the most commonly performed to evaluate pigmented lesions. The equipment needed is shown in Fig. 1 . First, the border of the lesion is clearly delineated. A woods lamp (365 nm) can be useful in finely demarcating the lesion; pigment is visualized as a darker area when compared with normal, unaffected background skin. The area is then anesthetized with lidocaine and epinephrine. A disposable scalpel with a number 15 blade or flexible razor blade is then used to remove the lesion, usually with a 1-mm margin of normal surrounding skin.
The advantage of the flexible razor blade over a number 15 scalpel blade is that the diameter of the biopsy can be altered by curving the blade; a greater curvature decreases the diameter of the sampling. Ideally, the lesion should be completely removed so that the depth can be evaluated. This strategy can be accomplished by angling the blade deeper toward the subcutis. If residual pigment remains in the dermis and it is appreciated immediately after performing the biopsy, the lesion should be either reshaved to make sure all the pigment is removed or completely excised. A razor blade is best used in areas of thick skin such as the back or nonfacial areas. A disadvantage of this blade is that it can leave a depressed scar if angled too much and the scar can be hypopigmented after biopsy.
A disposable scalpel with a number 15 blade is helpful when cosmesis is an issue because the scalpel can be used to remove a lesion at the level of the skin. In this scenario, the tip of the needle used for injection can be placed into the lesion and pulled upwards; this holds the lesion in place and provides for countertraction while the scalpel is used to remove the suspicious area. A scalpel with a number 15 blade is ideal to use on the face, the ears, and areas of thin skin such as the dorsal hand.
When performing a shave biopsy of a pigmented lesion, it is best to remove the diameter of the lesion completely, otherwise the biopsy is considered a partial biopsy and the true nature of the lesion cannot be ascertained with accuracy by the examining pathologist. If a lesion is large and biopsy of the entire area would leave a significant scar, it is best to biopsy the darkest or most unusual part of the lesion and note that the biopsy is partial for the dermatopathologist. If the lesion is benign, the area not biopsied should continue to be monitored on a regular basis.
After biopsy, hemostasis is usually achieved using 35% to 50% aluminum chloride, which deposits small crystal plugs into blood vessels. The area is then allowed to heal by secondary intention. Patients are instructed to keep the area moist and coated with Vaseline daily and then covered with a bandage. We do not recommend the use of antibiotic ointments, because there is significant risk for allergic contact dermatitis and the potential for wound infection is low given that the dermis is usually not broken. In addition, recent studies suggest a selection bias toward methicillin-resistant Staphylococcus aureus by these antibiotic ointments.
Patients should be advised that the biopsy site looks red initially followed by the appearance of yellow fibrinous tissue, which is normal and not a sign of infection. In addition, patients should be informed that biopsies on the lower extremities may take up to 1 month or longer to heal completely because of the poor circulation in the area. This situation is especially true in obese and vasculopathic patients. We also instruct patients to allow shower water to flow over the wound gently rather than allowing it to hit the area directly because water leaving most shower heads does so at a force of 5.6 kilograms per square centimeter and can slow wound healing. Patients are instructed to use mild soap to clean the area and refrain from swimming in chlorinated pools while the biopsy site is healing. We also advise against the use of hydrogen peroxide on biopsy sites because this too impedes healing.
Given that this method is usually selected for small lesions, it tends to provide good cosmetic outcome, especially if used off the face. The defect created is usually circular in shape and shallow so that a significant scar is not evident if the procedure is performed well. Also, because scars contract as they fibrose, the patient can be reassured from the outset that the cosmetic defect will likely be smaller than the pigmented lesion with respect to size.
Controversies
This method of sampling pigmented lesions offers many benefits but also has some disadvantages. In terms of advantages, the procedure is quick. Typically, this procedure can be performed within a few minutes, thus allowing for little patient anxiety and good in-office flow. The training to adequately perform this procedure is not unduly burdensome, and most dermatology residents are proficient early in their careers. The procedure may even be learned using common household fruits instead of human skin. It is also inexpensive to perform because sutures are not required. Nondermatologists are capable of performing this procedure accurately, which is especially important in areas in which primary care physicians provide most of the dermatologic care without training in skin surgery. In addition, in a patient who has multiple suspicious melanocytic lesions, the shave biopsy might be preferable because performing multiple excisional biopsies can become laborious for both provider and patient. Finally, most providers cannot interrupt their clinic to perform a surgery and must reschedule the patient. There is a significant potential of loss to follow-up in such a scenario. The patient may be too fearful to undertake a cutaneous surgery or scheduling difficulties may not allow for a return visit in the immediate future. In such cases, the saucerization method might at least allow for immediate diagnostic testing.
The biggest problem with this technique arises when the procedure is inadequately selected or the operator is inexperienced. For example, larger lesions are more difficult to completely sample and may best be sampled by other means (see later discussion). Lesions with deep pigment are also difficult to completely evaluate, and a major criticism of this technique has been the potential for transection at the base of the specimen, thereby losing the ability to accurately evaluate the depth of the lesion. A retrospective study of 223 patients showed that shave biopsy specimens left a positive deep margin in 22 patients. This problem becomes especially important when the depth of the lesion affects prognosis and additional intervention (ie, what margins to undertake with a wide excision or whether a sentinel node biopsy is needed). In this regard, a recent retrospective study of 139 patients with melanoma showed that 18 patients had a thicker Breslow depth as determined by excision compared with initial shave biopsy of the lesion. Seven of these patients required additional surgery after the initial wide local excision because of the discrepancy. A more recent study, with a bigger sample size of 600 patients, noted that the initial shave biopsy accurately predicted the lesion depth and thus the correct treatment strategy in 97% of patients. Thus, when properly performed in the right setting, the shave technique may yield the accurate melanoma depth in 97% of patients, but it may be incorrect in as much as 10%. The most worrisome scenario could occur if a biopsy is performed too superficially and the pathologist notes that there are atypical features but does not interpret them as a melanoma. Here, it is possible that the deeper portions of the specimen would have resulted in pathologic interpretation as melanoma and the lesion is being undercalled without this additional tissue. Thus, if the pathologist notes that a lesion has significant atypia and it extends to the base of the specimen, it is advisable to have it definitively sampled.
Incisional or Punch Biopsy
Technique
There are several settings in which an incisional biopsy may be useful. For example, as congenital nevi age, there are often areas that become cobblestoned, bleed from irritation, or become darker. An incisional biopsy using a punch biopsy tool is helpful to sample a portion of the larger lesion. Similarly, in a nevus spilus, areas of hyperpigmentation can become darker and may require sampling. Incisional biopsies have been recommended in other circumstances, including extensive or large pigmented lesions with unclear margins, extensive facial lentigo maligna, pigmented lesions in acral areas, and pigmented lesions in mucosal areas.
The tools needed to complete a punch biopsy are shown in Fig. 2 . As with the shave biopsy, the portion of the lesion to be biopsied is clearly marked. We recommend the use of a camera to photograph exactly where in the lesion the biopsy is taken from. Anesthesia is again provided with 1% lidocaine with epinephrine.
