FIGURE 8-3  Full-thickness biopsy of a deep nodular melanoma. The nodular growth pattern predicted a deeper melanoma. (Copyright Richard P. Usatine, MD.)

FIGURE 8-5  A shave biopsy of an intact blister in a patient with suspected bullous pemphigoid. (Copyright Richard P. Usatine, MD.)

incision rather than removing an elliptical portion of the skin (see Chapter 12, Cysts and Lipomas).

CHOICE OF SITE TO BIOPSY

When the decision has been made to biopsy a lesion, along with choosing the method of biopsy, the clinician must also choose the site (exact spot in the lesion) that will be biopsied.

If a “rash” or inflammatory process is present, select a “fresh” lesion that has recently appeared rather than one that has been present longer. Oftentimes, older lesions have been excoriated or secondarily infected, obscuring the primary pathology. Choose a lesion on the upper body rather than the lower body whenever possible (Figure 8-4). The histology may be easier to interpret and the healing should be more rapid. Biopsies of the lower legs are more likely to get infected or have delayed healing. Also avoid the axilla and groin

if possible because these areas are more prone to infections.

If a vesicular-bullous reaction is present, it is best to biopsy an intact bulla with some normal tissue (Figure 8-5). It is helpful for the pathologist to examine the edge of the bulla to characterize the exact etiology of the disease process.

If lesions are scattered throughout the body, choose a site where aesthetic considerations are less of a concern (e.g., avoid the face) and where scarring is less likely. The sternum, shoulders, upper back, and areas of skin tension are more likely to scar. Also, choose a lesion on the upper body rather than the lower body whenever possible.

When direct immunofluorescence (DIF) testing is to be done, biopsies are usually taken from perilesional skin (Figure 8-6). That means the biopsy will not include

FIGURE 8-4  Erythroderma in a 19-year-old woman from head to toe. A 4-mm punch biopsy was performed on her arm rather than the leg.

(Copyright Richard P. Usatine, MD.)

FIGURE 8-6  A shave biopsy was performed of an intact blister including perilesional skin in a patient with suspected bullous pemphigoid. The specimen shows that the blister remained intact and there is sufficient perilesional skin to the left of the blister to cut from the specimen and send separately for direct immunofluorescence. (Copyright Richard P. Usatine, MD.)

the bulla or erosion at all. The specimen is generally obtained with a shave or punch biopsy next to the visible pathology. DIF studies are especially helpful for autoimmune bullous diseases because antibodies will light up in the skin (Figure 8-7). They do not have to be done on the initial biopsy but may be performed to clarify and add data to a standard biopsy for hematoxylin and eosin (H&E) staining. There are only a few autoimmune diseases in which lesional skin is preferred (see Table 8-1). A 4-mm punch is adequate. It must be sent to the lab in special Michel’s media (or on salinesoaked gauze). This media should be kept in the refrigerator and can expire. If the cap is on tight and the media has just expired, it is probably still usable. See Table 8-1 for more information on the DIF biopsy.

If a basal cell carcinoma is suspected, it is often easy to shave off the whole lesion. If the lesion is large, almost

FIGURE 8-7  Immunofluorescence microscopy of a skin biopsy displays prominent intercellular “fish-net” deposition of C3 as well as a suprabasilar cleft within the epidermis. This confirms the diagnosis of pemphigus vulgaris. (Courtesy of Robert Law, MD.)

any area can be biopsied but it is better to select a raised-up border rather than an ulcerated portion. Biopsying the latter may inaccurately provide a pathology specimen that shows only inflammation and reparative debris if not sampled deeply enough. Curettement and punch methods can also be used. An advantage with curettement is that if the tissue is necrotic, it feels “soft” with curetting and also has a classic appearance. The appearance and feel can confirm the initial impression, and treatment can be performed immediately (electrodesiccation and curettage ×3) (see Chapter 14,

Electrosurgery).

If a squamous cell carcinoma is suspected, and the lesion is too large to shave off in its entirety, biopsy centrally and try to obtain a deep sample so the pathologist can determine the extent of invasion. Peripheral areas may only involve actinic change, missing the most advanced pathology. A broad deep shave is usually adequate for a biopsy. A second biopsy/excision may be needed if the pathologist reports that there is squamous dysplasia and a SCC cannot be ruled out.

If a melanoma is suspected, it is best to provide a specimen with adequate depth. Unfortunately choosing the darkest and most raised area does not guarantee the correct diagnosis. Although a full elliptical excision has been considered the gold standard, in some circumstances this is not desirable, for instance, in a large pigmented lesion on the face. In cases of suspected lentigo maligna melanoma on the face, a broad shave provides a better sample than a few punch biopsies and is less deforming that a large full-thickness biopsy. It is also just not practical to perform an elliptical excision on every potentially malignant pigmented lesion. It may be better in some instances to sample the whole lesion with a broad deep shave than to do one or more punch biopsies. Of course, sooner or later, an unsuspecting melanoma may be biopsied with a shave that misses the true depth of the lesion. Note, however, that it is far better to biopsy a lesion—regardless of the method—and find a melanoma early than to delay and procrastinate, thus missing an opportunity for early detection and treatment.4 Suspected early thin melanomas can easily be biopsied with a deep shave technique.

When sampling a suspected thick nodular melanoma, a deep sample will be needed to find the Breslow level and plan the definitive surgery. Dermoscopy (see Chapter 32) is a tool that can help you choose the most suspicious area to biopsy in a large lesion if it is impractical to biopsy the whole lesion. Fortunately, nonexcisional biopsies do not negatively influence melanoma patient survival and, in general, do closely correlate with the true depth of the lesion.5,6

Documentation of Biopsy Site

With all biopsies (especially if multiple lesions are obtained), record a detailed description of the biopsy site and, if possible, include a diagram or photo in the medical record. Biopsy sites may heal quickly and can be difficult to find later when definitive treatment is necessary. Photos can aid in identifying correct locations. If it is not easy to place photographs in the medical record, make sure the camera is set to record the correct date of the photo. Then the prebiopsy photo can be found by searching the electronic files by date. Some clinicians photograph the patient label at the same time to make it easier to locate a preop photo. Adequate privacy protection is necessary to ensure that photo storage options are HIPAA compliant (password protected and data encryption) if a computer is used.

IS IT CANCER?

Pigmented Lesions: Melanoma and Its Differential Diagnoses

Early detection and prompt removal of melanoma can be lifesaving. The early signs of melanoma are summarized as ABCDE, where A = asymmetry, B = borders (irregular), C = color (variegated), D = diameter (greater than 6 mm), and E = evolving and elevation (Figure 8-8).7 Some have suggested adding an F for a change in feeling since some melanomas present with onset of pruritus in a nevus. However, not all melanomas show these signs and not all lesions with these signs are

melanomas. The dermatoscope can be used to increase your sensitivity and specificity for detecting melanoma (see Chapter 32, Dermoscopy). Whether or not a dermatoscope is used, it is incumbent on the clinician to biopsy any suspicious pigmented lesion. We cannot overemphasize that patient history is of utmost importance in the evaluation of any lesion and should never be taken lightly. If a patient is concerned that a pigmented lesion has changed, most often it deserves a biopsy/removal.

Pigmented lesions highly suggestive of melanoma should be biopsied for depth because treatment is primarily based on that parameter. Other considerations needed to select the proper treatment include whether there is neural or vascular involvement and whether ulceration is present. Some suggest that all suspected melanomas be biopsied using the excisional technique (fullthickness excision with suture closure). This practice presents several problems: (1) How much free margin should be obtained? Most commonly, a simple excision with a margin of 5 mm (melanoma in situ) to 1 cm (up to 1 mm of invasion with no other warning signs on pathology) is needed for treatment. If the invasion is greater than 1.5 mm, a 2-cm margin is recommended.8,9 So, should the excisional biopsy always have a 1-cm margin? Most lesions will not be a melanoma. Should the excision then just remove the lesion with no free margins? Using excision as the primary approach for biopsying a suspicious lesion will not only cost more and, in many cases, remove an excess amount of normal tissue, but will most likely require that the patient have a second surgery if a melanoma is found. (2) Full surgical excision takes significant time and skills. Many primary care clinicians are not prepared to excise all suspicious lesions. Referral for a biopsy takes time, increases the cost, and may not be readily available. Patients also may not comply with seeing another physician. The optimal time to biopsy is when the lesion is first evaluated. A shave or a punch biopsy takes only a few minutes and then therapy can be based on the results. This approach saves time and limits costs, while reducing unnecessary scarring, infected wounds, and return visits to the office. Survival time does not appear to be influenced by the method of biopsy.5

If a melanoma is truly suspected, a deep shave biopsy may indeed be the ideal method of sampling (Figure 8-8B). A punch biopsy can have significant sampling errors and false-negative results unless the whole lesion is removed or multiple biopsies are obtained from larger lesions. The object is to detect melanoma early and save lives. If a larger lesion is atypical in appearance, the entire lesion will need to be removed but the initial biopsy will at least help determine required margins for excision, or if a referral is indicated. A punch biopsy may be used as long as a negative (nonmalignant) biopsy of a suspicious lesion larger than the initial punch is followed up with an excision in which all the remaining tissue is excised and examined (Figure 8-9).

Pigmented lesions that are unusual and are considered to have a low, but definite, possibility of malignancy or dysplasia (atypia) also require prompt biopsy. If these lesions are small (up to 6 to 7 mm), a saucer-type shave excision with narrow margins (1 to 2 mm) is the method of choice. Very small lesions, those less than 3 mm in diameter, can often be adequately excised by using the deep shave technique or a 4-mm punch to remove the entire lesion. Large lesions (those greater than 2 cm in diameter), with a low level of suspicion, may be investigated by doing a 4-mm punch biopsy in the area of highest suspicion (i.e., the blackest area or the area of greatest elevation) or with frank excision (Figure 8-10).

Lentigo Maligna

Lentigo maligna (LM) is one type of melanoma in situ. Flat, macular lesions suspected of being lentigo maligna (Figure 8-11) present a problem because many of these lesions are very large (often over 2 cm in diameter) and frequently are present on the face in 50 to 70 year olds. They are interesting because the radial growth phase may last for years and the vertical (invasive) phase may never develop. Excisional biopsy is preferred for small lesions, but this method may be impractical for large lesions. A broad shave biopsy of suspected LM or lentigo maligna melanoma (LMM) should provide a better tissue sample than one or more punch biopsies and will not cause the cosmetic deformities of a large full-thickness biopsy (Figure 8-11).

FIGURE 8-10  A seborrheic keratosis that has all five ABCDE criteria. A shave or punch biopsy should be adequate to confirm that this is benign. Dermoscopy would also be helpful and might prevent the need for a biopsy. (Copyright Richard P. Usatine, MD.)

FIGURE 8-12  Compound dysplastic melanocytic nevus (nevus with architecture disorder). (Copyright Richard P. Usatine, MD.)

Atypical Moles (Dysplastic Nevi)

Terminology can be confusing. Atypical and dysplastic are often used interchangeably in dermatologic communication. The current recommended NIH nomenclature, however, is “nevus with architectural disorder” (Figure 8-12). See Box 8-1 for further clarification.

FIGURE 8-11  Lentigo maligna that is best biopsied with a broad shave of the whole pigmented area. (Courtesy of the Skin Cancer Foundation, New York, NY.)

Many benign lesions are so characteristic that a biopsy is not necessary. On the other hand, early melanoma can be exceedingly difficult to diagnose (some lesions are not even pigmented). Considering this, and also taking into consideration that the morphology of benign pigmented lesions can be remarkably varied, it is best to be cautious when dealing with atypical pigmented lesions. Biopsies should be performed on all questionable pigmented lesions. Another very basic premise that should be closely adhered to is that any nevus that the patient reports to have changed should be considered for biopsy despite the clinical appearance. Also keep in mind that normal benign nevi can go through an evolution over time.

Although benign, atypical nevi have clinical, histologic, and biologic behavior distinct from common nevocellular nevi. Two percent to 8% of the population have nevi that fit the definition of atypical moles. Clinically, these nevi are large (5 to 12 mm in diameter), are characteristically multicolored (with shades of brown, tan, or pink), and have irregular borders that tend to be indistinct (Figure 8-12). They usually have a flat macular component, are frequently multiple, and are most common on the trunk. In contrast to common nevi, atypical moles usually begin to appear during adolescence and continue to appear during young adult life.

The clinical approach to multiple atypical moles has evolved since their first description. There still remains a difference of opinion as to their proper management. Atypical moles may not all require biopsy, such as in patients with more than 100 of these moles. Any pigmented lesion that the physician is uncertain about or that has changed, however, should still undergo biopsy. One of the most common reasons for lawsuits is missing a melanoma.

Patients with a few atypical moles can also be divided into those with a personal history or a first-degree relative with a history of melanoma, and those without

BOX 8-1  Nevus with Architectural Disorder (Dysplastic Nevus)

We use the recommended NIH nomenclature of nevus with architectural disorder. If there is atypia, it is graded as either mild or severe (we do not use moderate). If there is severe atypia and the lesion has not been excised, a comment on the report will recommend conservative excision. There will also be a comment indicating that this lesion may be part of the familial mole melanoma syndrome.

Atypical Melanocytic Hyperplasia

Lesions that have intraepidermal spread that falls short of melanoma in situ are classified as atypical melanocytic hyperplasia. The atypia is not graded, because it is the pattern that is of concern. The report will include a comment that AMH may represent an evolutionary precursor to melanoma and recommend that the lesion be conservatively excised.

Atypical Compound Nevus

Lesions that have atypia in both the junctional and dermal components, but in the absence of diagnostic melanoma, are classified as atypical compound nevi. Often, we will perform immunomarkers to determine proliferative activity to exclude nevoid melanoma on these lesions. For lesions designated as atypical compound nevi (ACN), we recommend conservative excision. Please note that we do not use the terms atypical compound nevus and nevus with architectural disorder (dysplastic nevus) synonymously. Dysplastic nevi have atypia only at the junction, not ascending cells (AMH) and not dermal atypia (ACN).

Margin Assessment

Margin examination may be requested; however, only the Mohs technique allows examination of 100% of the margin. For all other types of biopsies and excisions, margins are sampled only. The greater the sampling, the higher the degree of confidence in the margin assessment. To increase the degree of sampling, larger specimens may be sectioned during grossing and then step sectioned to view multiple cuts on the slide. We report that the “examined margins are negative” or that the lesion extends to the deep or a lateral margin. Note, however, that while a positive margin is positive, a negative margin does not ensure that the lesion has been completely removed. For example, if you do a shave excision of a BCC, we will say on the report that the examined margins are negative. This means that on the two dimensions that can be examined on a slide, the margins are negative, not necessarily that the lesion has been fully removed. If a specimen is oriented (tagged), we will use color-coded inks. In the event a margin is positive, we will be able to describe which margin is positive.

Source: Courtesy of Terry L. Barrett, MD.

such a history (sporadic atypical moles). Patients with sporadic atypical moles are probably not at as great a risk for developing melanoma.10,11

Benign Nevi

Many will request mole removal purely for cosmetic reasons.

Alternatively, the lesions may be in areas of repeated trauma (e.g., from shaving, combing, irritation from

FIGURE 8-13  Intradermal nevus that is pearly with telangiectasias and spotty pigmentation. A shave biopsy was performed to rule out BCC and to obtain a good cosmetic result. (Copyright Richard P. Usatine, MD.)

clothes or jewelry). Shave biopsy is the treatment of choice for most totally benign-appearing nevi, and the lesion should still be sent for histological examination. In Figure 8-13, the raised lesion could be a benign nevus or a BCC. If the history suggests a nevus, a shave biopsy would be the method of choice. Removal of some nevi on the face may yield a better cosmetic result when accomplished by punch or meticulous excision when large. Size, location, age of the patient, history, and type of skin all are factored into the decision. Nevi with a deeper intradermal component tend to recur or become pigmented after shave removal especially in younger patients. A shave can still be performed but the patient should be forewarned as a part of informed consent that regrowth or pigment changes may still require full-depth excision later. For nevi with hair a shave biopsy is often too superficial to remove the deeper root of the hair follicle. In this instance, to reduce potential scarring from an excision, a shave can be performed and if hair does regrow, simple epilation techniques can remove it. It is again important to inform the patient of the potential for hair growth.

Seborrheic Keratoses

Most seborrheic keratoses will not need a biopsy. However, because some of these lesions mimic malignant tumors such as melanomas when they are darkly pigmented, biopsy should be performed if any doubt exists (Figure 8-10). Dermoscopy (see Chapter 32) can help make this distinction and avoid a biopsy in many cases. When performing a biopsy on seborrheic keratoses, care should be taken to avoid unnecessarily deep or destructive techniques. Seborrheic keratoses are epidermal lesions. Shave biopsy is the biopsy technique of choice unless the suspicion of melanoma is high. Treatment with cryotherapy without biopsy is very acceptable for lesions in which the clinical diagnosis is certain. However, lesions that fail to resolve after 6 weeks should be evaluated and a biopsy considered.

FIGURE 8-14  A cutaneous horn arising in a squamous cell carcinoma on the face. (Copyright Richard P. Usatine, MD.)

Nonpigmented Lesions Suspicious for Cancer

Actinic Keratoses

Actinic keratoses can be very superficial or hypertrophic. They are considered a precancerous lesion and as such, should be treated or biopsied. Thinner obvious lesions can be treated with topical agents, cryotherapy, or electrodesiccation without biopsy initially. If lesions persist after treatment, or if there is concern about a cancer at the base, then a shave biopsy or curettement is indicated. With high-risk lesions such as those with a cutaneous horn, a deeper saucer-type shave is best to provide the pathologist with enough tissue to discern invasion (Figure 8-14).

Keratoacanthomas

The history and clinical appearance of keratoacanthomas (KAs) are quite distinct. They grow rapidly in a matter of months and appear most like a BCC with central keratin plug (Figure 8-15). It is considered a

variant of SCC. If suspected, smaller lesions (8 to 10 mm) can be removed with a deep saucer-type shave followed by electrodesiccation and curettage (×3). For larger lesions, full-thickness excision is the best method of biopsy/removal.

Basal Cell Carcinoma

The majority of BCCs are relatively small (less than 1 cm), raised tumors on the face, head, neck, or exposed parts of the trunk and extremities. Nearly any method can be used to biopsy these lesions if their exact nature is uncertain. With curettement, the typical soft necrotic tissue can be identified so treatment with electrodesiccation and curettage (ED&C) can be immediately performed (see Chapter 14, Electrosurgery, and Chapter 34,

Diagnosis and Treatment of Malignant and Premalignant Lesions). Shave biopsy can be used for most of these tumors and has the advantage of not producing a deeper or full-thickness wound should the lesion prove not to be a cancer (Figure 8-16). A punch biopsy of the raised “pearly border” can also be performed. Although data on this issue is not available, some clinicians will not use ED&C on a BCC that was diagnosed with a punch biopsy. If an excisional biopsy is planned because the diagnosis of BCC is likely, then 3 to 5 mm of clear margin should be included in the specimen to reduce the likelihood that further excisions will be needed (see Chapter 11, The Elliptical Excision).

Sclerosing (morpheaform, aggressive) BCCs are flat and more difficult to diagnose clinically and histopathologically. Therefore, a punch specimen is usually preferred, although a deeper shave often will be adequate to make the diagnosis. However, as seen in Figure 8-17, these lesions are most often flat and difficult to biopsy with the shave technique. It is difficult to discern margins of the abnormality clinically and for all but the smallest of lesions, excision will be needed for treatment. These lesions are fibrotic and often do not lend themselves to curettement. They also have a higher recurrence rate.

Pigmented BCCs can appear very much like melanomas (Figure 8-18). In these instances, a biopsy for depth may be indicated.

FIGURE 8-15  A keratoacanthoma with a pearly raised border and a keratin-like volcanic core. (Copyright Richard P. Usatine, MD.)

FIGURE 8-16  A razor blade being used for a shave biopsy of a nodular BCC. (Copyright Richard P. Usatine, MD.)