Melanoma
Thomas S. Bander
Andrés Már Erlendsson
Cristian Navarrete-Dechent
Saud Aleissa
Kishwer S. Nehal
Anthony M. Rossi
BACKGROUND
Patients commonly seek the expertise of dermatologists to evaluate and treat pigmented lesions. Given the increasing incidence of melanoma and the potential for cure with early detection, such visits serve as an important opportunity to rule out malignancy and provide education about future risk. These interventions are especially important in otherwise healthy patients who may be seeking cosmetic treatment. Numerous treatment options are available for benign pigmented lesions; however, these should be approached with caution until their malignant counterparts have been excluded. Whether a patient presents for a routine skin check or treatment of a “dark spot” on the face, clinicians must utilize their diagnostic expertise before pursuing a treatment that may delay melanoma detection. This chapter will focus on the diagnosis and treatment of melanoma from a cosmetic perspective, structured around 2 common clinical scenarios. We will review the differential diagnosis and clinical tools we use to arrive at the correct diagnosis and then discuss cosmetic considerations in the treatment of melanoma.
PRESENTATION
Patient 1: A 45-year-old woman presents with a dark brown papule on her left chest. She is bothered by its appearance and interested in laser treatment. She has other similar-appearing lesions in less conspicuous locations on her trunk and extremities. She had intermittent sunburns as a child but now wears sunscreen regularly.
Patient 2: A 65-year-old woman presents with a dark brown macule on her right cheek. She is bothered by its appearance and interested in removal. She has a history of severe sun exposure and has had multiple basal cell carcinomas on her face.
DIAGNOSIS
Clinical Diagnosis
Visual Inspection
Clinical evaluation of pigmented lesions includes visual inspection, palpation, dermoscopy, and reflectance confocal microscopy (RCM). Although the definitive diagnosis ultimately depends on histologic evaluation, clinicians must determine which lesions to biopsy. This decision may be complex, especially in cosmetically sensitive locations. Clinical expertise in the evaluation of pigmented lesions increases early detection of melanoma and prevents unnecessary procedures and their resulting costs and scars.
Morphologic analysis of pigmented lesions has historically been performed with visual inspection, using the ABCDE rule or the ugly duckling sign. The ABCDE mnemonic is widely recognized by dermatologists, primary care physicians, and patients as a checklist for characteristics concerning for melanoma (Table 13.3.1). The ugly duckling sign is another morphologic descriptor of potentially concerning pigmented lesions. This heuristic accounts for lesions that may look atypical when viewed in isolation but are less concerning in the context of other similar-appearing lesions. Rather than sample every atypical-appearing lesion, the clinician identifies only those that are morphologically different from their neighbors.
A 365-nm Wood lamp, or blacklight, can assist in the identification of pigmented lesions. This wavelength is strongly absorbed by melanin, resulting in a clearer distinction between pigmented lesions and surrounding photodamaged skin (Figure 13.3.1). Although it cannot distinguish benign from malignant, better visualization of the lesion size and border can improve morphologic analysis.
TABLE 13.3.1 ABCDE Mnemonic for Clinical Features of Pigmented Lesions Concerning for Melanoma | ||||||||||
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Dermoscopy
Early detection of melanoma depends on the identification of subtle morphologic features, and recent evidence has revealed that visual inspection alone is insufficient for the evaluation of these features. Dermoscopy refers to the use of a handheld microscope at the skin surface to improve diagnostic accuracy. For experienced users, the magnification and lighting reveal colors and structures that correlate with histologic features of either benign or malignant lesions (Figures 13.3.2 and 13.3.3).
Although most benign melanocytic lesions are symmetric with a single dermoscopic pattern, melanomas have an asymmetric combination of disorganized patterns. There are also melanoma-specific pigment and vascular structures (Table 13.3.2). These features have been combined into formalized algorithms for dermoscopic diagnosis, including the Menzies method, 7-point checklist, chaos and clues method, or the 2-step algorithm (the authors’ preferred method).
The classic and revised 2-step algorithms first instruct users to differentiate melanocytic lesions from nonmelanocytic lesions before distinguishing melanoma from benign lesions.1,2 The top-down 2-step algorithm is a more recent modification that recommends first establishing a diagnosis based on classic features of a benign nevus, dermatofibroma, intradermal nevus, basal cell carcinoma, squamous cell carcinoma, seborrheic keratosis, angioma, angiokeratoma, sebaceous hyperplasia, or clear cell acanthoma.3 If such a clear-cut diagnosis cannot be made, step 2 helps clinicians rule out melanoma by identifying melanoma-specific structures or patterns (Figures 13.3.4 and 13.3.5).
 FIGURE 13.3.1 A, A 70-year-old man with ill-defined light and dark brown patches recurring near scars from previous excision of lentigo maligna. B, Wood lamp (365 nm) examination demarcates the borders of the pigmented lesions. |
A recent Cochrane review revealed improved sensitivity and specificity with dermoscopy in addition to visual inspection (Table 13.3.3). In a population with 12% melanoma prevalence, evaluation of 1000 lesions with dermoscopy in addition to visual inspection would result in 19 fewer overlooked melanomas and prevent 176 avoidable biopsies compared with visual inspection alone.4
 FIGURE 13.3.2 Dermoscopic patterns of nevi. Rows 1 and 2 are benign patterns. Row 3 requires context, and melanoma should be in the differential. (Courtesy of Ralph B. Braun. From Dermoscopedia website. www.dermoscopedia.org. Accessed August 21, 2019.) |
 FIGURE 13.3.3 Melanoma-specific dermoscopic structures. Identification of such structures in a pigmented lesion should raise threshold for biopsy to rule out melanoma. (Courtesy of Ralph B. Braun from Dermoscopedia [www.dermoscopedia.org].) |
TABLE 13.3.2 Melanoma-Specific Dermoscopic Structures | ||||
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Reflectance Confocal Microscopy
Noninvasive imaging with RCM is also a valuable addition to the dermatologist’s armamentarium. RCM utilizes backscattering of laser light to provide in vivo images with near-histologic resolution. Endogenous grayscale contrast is provided by differential reflectance of nuclei, which appear dark, and cytoplasm (keratin, melanin, collagen, and organelles), which appears bright (Figures 13.3.6 and 13.3.7). Melanin is especially refractile, making RCM a promising modality for evaluation of melanocytic lesions.
RCM is increasingly used in the diagnosis and management of melanoma (Table 13.3.4). RCM has demonstrated excellent accuracy for diagnosis of melanocytic lesions, but further study is needed to compare RCM with dermoscopy.5 There are limitations to its use in every patient with a pigmented lesion (Table 13.3.5): the time for image acquisition is not practical in every clinic setting, it can be challenging to differentiate inflammatory cells from neoplastic cells, and the depth is limited to the papillary dermis (about 200 µm). Despite these limitations, the authors use RCM for lesions whose diagnosis is equivocal on visual inspection and dermoscopy. Its increased specificity has the potential to reduce unnecessary biopsies, which we find especially useful for pigmented lesions on cosmetically sensitive locations.6
Biopsy Technique
The addition of dermoscopy and RCM has significantly improved the diagnostic accuracy of pigmented lesions, but histologic confirmation remains the gold standard for diagnosis (Figures 13.3.6, 13.3.7, 13.3.8). An ideal biopsy of a pigmented lesion samples the entire clinical lesion, with excisional biopsy, punch biopsy, or shave/saucerization with clinical margins of 1 to 3 mm to a depth below the anticipated extent of the lesion.7,8,9 Partial sampling is reasonable for large lesions or those in cosmetically sensitive locations; however, the potential for sampling error should be considered. If prebiopsy suspicion for melanoma is high, a negative partial biopsy should be questioned and repeat biopsy
pursued. Importantly, there is no evidence to suggest that a partial sample worsens prognosis. Multiple shave or punch biopsies of different clinical morphologies may be helpful in large lesions, especially on the head and neck.
pursued. Importantly, there is no evidence to suggest that a partial sample worsens prognosis. Multiple shave or punch biopsies of different clinical morphologies may be helpful in large lesions, especially on the head and neck.
 FIGURE 13.3.4 A, A 55-year-old woman with ill-defined light brown patch on left nasal sidewall that is difficult to detect clinically. Inset: Features concerning for lentigo maligna become clear with dermoscopy given presence of asymmetric follicular openings (thin arrows), gray dots/granules (thick arrows), circle-within-a-circle/isobar structures (red arrow), rhomboidal structures (circles), and polymorphous vessels with milk red areas (star). Biopsy confirmed lentigo maligna. B, Surgical defect after staged excision with radial sections. Histologic margins were clear after 2 stages. C and D, Four-month follow-up after repair with advancement flap and full-thickness skin graft. (Photos C and D courtesy of Dr. Joseph Disa.) |
Selection of biopsy technique should factor in the size, location, and biology of the suspected lesion as well as the patient’s propensity for hypertrophic or keloid scarring. Excisional biopsies oriented along relaxed skin tension lines provide the most complete and reliable sample for histologic examination, and the resulting linear scars may be preferred on the trunk and extremities. Shave or saucerization biopsies that extend to deep dermis can achieve similar tissue sampling, provided a small margin of normal skin is included. The resulting circular scars are smaller and may be preferred in concave locations, such as the temples, medial canthi, and skin folds. Furthermore, saucerization is faster and requires no downtime after the procedure for the patient. In general, these 2 methods are preferable to punch biopsies because of decreased sampling error.
Histopathology
Histologic assessment of pigmented lesions includes architectural and cytological evaluation. Compared with benign counterparts, melanoma is asymmetrical and poorly circumscribed with melanocytic nests and single cells variably scattered along the dermal-epidermal junction and adnexal epithelium in the case of melanoma in situ. These atypical melanocytes are considered invasive when they extend into the dermis. Individual melanocytes have pleomorphic nuclei or mitotic figures and may extend beyond their normal location in the basal layer to the upper epidermis, which is termed pagetoid spread (Figures 13.3.6, 13.3.7, 13.3.8).
 FIGURE 13.3.5 Benign brown lesions on sun-damaged skin. A, Well-demarcated brown papule. B, Dermoscopic features consistent with seborrheic keratosis: milialike cysts (thin arrows), comedolike openings (thick arrows), and gyri and sulci (red arrows). Cosmetic treatment may be considered. C, Dark brown, gray, and red macule with gritty scale. D, Dermoscopic features consistent with pigmented actinic keratosis: gray rhomboidal pseudonetwork (black arrow), white ringlike structures within hair follicles surrounding central yellow keratin core (thin black arrow), and rosettes (red arrow). (Images C and D courtesy of Dr. Alvaro Abarzúa-Araya.) |
TABLE 13.3.3 Sensitivity and Specificity for Diagnosis of Equivocal Melanocytic Lesions Based on Cochrane Meta-analyses | ||||||||||||||||||
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The ultimate diagnosis is based on routine formalin-fixed, paraffin-embedded, hematoxylin and eosin-stained sections; however, diagnostically challenging cases may benefit from use of ancillary studies. Immunohistochemical stains, such as S100, HMB45, MART-1/Melan-A, Sox10, and MITF, may improve diagnostic accuracy in certain situations, but no single stain can reliably differentiate benign from malignant. Molecular studies, such as fluorescent in situ hybridization and comparative genomic hybridization, identify genetic aberrations associated with malignancy. This additional information may be used in context with other clinical and histologic features to better classify pigmented lesions. Gene expression profiling is promising technology that requires further study for use in distinguishing benign from malignant melanocytic lesions. Given the complexity of melanoma
diagnosis and the risks of misdiagnosis, evaluation by pathologists with experience in melanocytic lesions is recommended.
diagnosis and the risks of misdiagnosis, evaluation by pathologists with experience in melanocytic lesions is recommended.
 FIGURE 13.3.6 A, A 64-year-old man with lentigo maligna melanoma (Breslow depth 1.0 mm) on right lateral canthus. Clinical size (1.5 × 1.9 cm), asymmetry, presence of multiple colors (light brown, dark brown, gray, blue, and pink), and history of change over time prompted biopsy. B, Dermoscopic image with annular-granular pattern (thin black arrows), gray dots/granules (thin red arrows), asymmetric follicular openings (thick black arrows), rhomboidal structures (circles), and central homogenous structureless gray-blue area with obliteration of hair follicles (star). Inferior pink area corresponds to initial punch biopsy that demonstrated lentigo maligna. Repeat excisional biopsy of the entire lesion revealed invasion to 1.0 mm depth, likely corresponding to the gray-blue structureless area. C, Reflectance confocal microscopy image with large, plump, hyperreflective atypical melanocytes (thin arrows), some with dendrites (thick arrows), surrounding hair follicles (circles) at the dermoepidermal junction, consistent with lentigo maligna. D, Large, atypical melanocytes with irregular nests and single units arranged asymmetrically at the dermoepidermal junction and extending into dermis. E, Surgical defect after staged excision with radial sections. Histologic margins were clear after 2 stages. F, Three-month follow-up after repair with advancement flap. (Photo F courtesy of Dr. Joseph Disa.) |
Consensus national guidelines recommend that all pathology reports with a diagnosis of melanoma include the size of the specimen, tumor thickness (Breslow depth), presence or absence of ulceration, mitotic rate (per mm2), peripheral and deep margin status, and presence or absence of microsatellitosis in all cases. These features are crucial for accurate staging. Additional information, such as gross description, histologic subtype, or presence of lymphovascular invasion, perineural invasion, regression, tumor-infiltrating lymphocytes, or vertical growth phase, may also be included, as they may have prognostic significance.
 FIGURE 13.3.7 A, A 60-year-old woman with a subtle light brown macule on nasal tip. B, Dermoscopic image at initial presentation had features concerning for lentigo maligna, including asymmetric follicular openings (thin arrows) and possible early rhomboidal structures (thick arrows). Patient initially opted for close monitoring, but these features became more prominent 6 mo later with change in color to dark brown and gray (star). Biopsy revealed lentigo maligna melanoma (Breslow depth 0.2 mm). C, Large, hyperreflective melanocytes (arrows) distributed asymmetrically around follicular openings (circles). D, Large, atypical melanocytes with irregular nests and microinvasion into papillary dermis. E, Surgical defect after staged excision with radial sections. The marked clockface helped orient pathology specimen. Histologic margins were clear after 2 stages. F, Four-month follow-up after repair with paramedian forehead flap. (Photo F courtesy of Dr. Joseph Disa.) |
TABLE 13.3.4 Clinical Uses of Reflectance Confocal Microscopy for Diagnosis and Treatment of Pigmented Lesionsa | ||||||||||||||
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Subtypes
There are 4 main subtypes of melanoma: superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma (LMM), and acral lentiginous melanoma. The subtypes are characterized by varied epidemiology, risk factors, and clinical presentations but do not have prognostic implications independent of other factors.
Superficial Spreading Melanoma
Superficial spreading melanoma is the most common type of cutaneous melanoma in light-skinned individuals and constitutes about 70% of all melanomas. It can present on any anatomic site but is most commonly found on the trunk in men and the legs of women. About a third of this subtype arise in a preexisting nevus with the remainder arising on previously uninvolved skin.
Nodular Melanoma
Nodular melanoma is the second most common type of cutaneous melanoma in light-skinned patients and constitutes about 15% to 20% of all melanomas. It typically presents as a blue or black nodule that develops rapidly over months and is characterized by its predominant vertical growth phase. Because it is thought to lack a preceding horizontal growth phase, nodular melanoma is often diagnosed at a more advanced stage and has a poorer prognosis.
TABLE 13.3.5 Advantages and Limitations of Reflectance Confocal Microscopy (RCM)
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