Lentigo Maligna

Review of Salient Characteristics and Management

Joseph R. Kallini; Supriya K. Jain; Amor Khachemoune

Disclosures

Am J Clin Dermatol. 2013;14(6):473-480. 

In This Article

4 Diagnosis

The preferred method for diagnosing lentigo maligna is excisional biopsy. If limited by the size of the lesion, shave and punch biopsies can also be utilized, but these techniques have a greater risk of sampling error. Another technique is a fusiform incisional biopsy measuring at least 5 mm in depth and spanning the center of the tumor.[6] Biopsy of the darkest portion of the lesion yields a more definitive diagnosis.

4.1 Histopathology

Lentigo maligna has traditionally been challenging to diagnose, since it is difficult to distinguish non-malignant atypical melanocytic hyperplasia from melanoma in situ in chronically sun-damaged skin.[7] As such, the histological differential for this lesion is broad and includes solar lentigo, early lesions of seborrheic keratosis, lichen planuslike keratosis, pigmented actinic keratosis, and melanocytic nevus. Debate also exists in the characterization of lentigo maligna as a 'melanoma in situ.' Some pathologists believe that lentigo maligna is a melanoma precursor, while others call it a true melanoma in situ on the basis of the number of atypical melanocytes and their pattern of arrangement within the basal epidermis.[8]

The most reproducible histological parameter that is used to confirm a diagnosis of lentigo maligna is proliferation of atypical melanocytes at the epidermal–dermal junction in small nests or single cells, coupled with underlying photodamage. Disagreement exists about the utility of several additional histological features in diagnosing lentigo maligna, given the overlap between suninduced changes to the skin. These histological characteristics include bridging of rete pegs, epidermal atrophy, extension of melanocytes into periadnexal structures, extensive underlying solar necrosis, melanocyte atypia, the presence of an inflammatory dermal infiltrate, and non-uniform pigmentation or distribution of melanocytes.[9] A multi-center comparative study examining melanocytes in sun-exposed skin identified a high density and confluence of melanocytes, superficial follicular extension, and moderate cytologic atypia. That study suggested that melanocytes along the follicular epithelium and increased melanocyte density and confluence cannot by themselves be diagnostic of lentigo maligna. The presence of other histological criteria, such as nesting, vertical stacking, or pagetoid spread, help to more accurately distinguish lentigo maligna from the melanocytic features of sun-damaged skin. Furthermore, the extent of pagetoid spread can differentiate lentigo maligna from malignant melanoma: minimal pagetoid spread into the epidermis distinguishes lentigo maligna from superficial spreading melanoma.[10]

4.2 Staining Techniques

Hematoxylin and eosin (H&E) staining is one method that has been employed to help evaluate the surgical margins of lentigo maligna via light microscopy. It has been reported that H&E evaluation of lentigo maligna is 100 % sensitive and 90 % specific. Excellent-quality sections and experienced reviewers are critical to the success of this technique, which has been shown to yield greater than 90 % survival at 5-year follow-up.[11]

Several immunohistochemical stains are used to aid diagnosis of lentigo maligna in frozen sections during Mohs micrographic surgery and other surgical techniques. The advent of immunostaining has substantially decreased the skepticism regarding Mohs micrographic surgery— once a controversial approach for treating lentigo maligna. The immunostains most commonly used include HMB-45, MART-1, Melan-A, Mel-5, and S-100. These immunostains are regarded as advantageous to the traditional H&E approach because they better distinguish lentigo maligna from benign melanocyte proliferation on chronically sundamaged skin. Immunohistochemistry also better differentiates residual lentigo maligna from benign post-excisional melanocytic scarring.[12]

MART-1/Melan-A is currently regarded by several groups as the most beneficial in identifying atypical melanocytes in frozen sections. Studies of MART-1 in melanoma chemosurgery have shown that it is typically crisp and with less background staining than MEL-5 and preferable to HMB-45 for better staining consistency.[11]

However, MART-1 has many disadvantages. MART-1 is reported to have superb sensitivity but a lack of specificity, with the implication of incorrectly extending surgical margins into normal tissue. This is due to the fact that most epidermal melanocyte cell surfaces, whether benign or malignant, possess the MART-1 antigen. One group demonstrated that MART-1 stained all pigmented actinic keratoses in their study.[13] Another group found it useful in distinguishing 66 out of 68 pigmented actinic keratoses from melanoma in situ.[14] MART-1 also fails to distinguish benign melanocyte proliferation from melanocyte atypia and follicular involvement characteristic of melanoma in situ. Characteristics typical of photodamaged skin may be wrongly interpreted as a positive margin when using MART-1 immunohistochemistry.

Similarly, it has been shown that another stain, Mel-A, also fails to distinguish between lentigo maligna and chronically sun-damaged skin. One group advocates for the use of control biopsies between the lesion and uninvolved sun-damaged skin of individual patients to account for varying melanocytic characteristics.[13]

Furthermore, the drawback of immunohistochemistry is the time constraint. This technique was intended for permanent sections rather than frozen sections. MART-1, in particular, has required a 1-hour protocol (developed by Bricca) to ensure greater specificity of detecting lentigo maligna.[15] Fortunately, newer studies have found that a 19-minute protocol is equivalent to that obtained from MART-1-stained permanent sections.[16]

4.3 The Wood's Lamp

Because the true margins of the lesion can extend far past the visible margins, several techniques have been developed to improve margin delineation over visual inspection. The Wood's lamp takes advantage of the property of ultraviolet light to be preferentially absorbed by epidermal melanin, distinguishing it from the surrounding uninvolved tissue. The ability of the Wood's lamp to amplify these differences in pigmentation makes it especially invaluable in delineating the borders of lentigo maligna, as was the case in the patient presented in Fig. 3.[17]

Figure 3.

Lentigo maligna melanoma. This lentigo maligna melanoma extended beyond what was visible to the naked eye. Use of a Wood's lamp allowed accurate margins to be determined in this case

4.4 Dermatoscopy

Dermatoscopy is the process of viewing skin lesions through a dermatoscope, which is an instrument that magnifies the skin (usually by 10 times) and illuminates non-polarized light upon the lesion being examined. Tanaka has identified four key criteria that are diagnostic for lentigo maligna on dermatoscopy: asymmetrical pigmented follicular openings (which usually develop into rhomboid structures, as seen in Fig. 4), linear pigmented lines forming rhomboidal structures, annular–granular structures, and a gray pseudo-network (perifollicular slate-gray dots and granules).[18] Two of these characteristics, annular–granular structures and the gray pseudo-network, are also present in regressive areas of solar lentigo/initial seborrheic keratosis, lichen planus-like keratosis, and pigmented actinic keratosis. As such, asymmetrical pigmented follicular openings and rhomboidal structures are regarded as the more specific dermatoscopy criteria. Circles within circles and atypical blood vessels have separately been identified as diagnostic features of lentigo maligna.[19]

Figure 4.

Lentigo maligna under dermoscopy. The dark rhomboidal structures near hair follicles is highly specific for lentigo maligna when viewed under dermoscopy. Reproduced with permission from Tanaka et al. [18]

One group recently identified a 'zig-zag' pattern of incomplete rhomboidal structures of ''brown to bluish gray dots and lines arranged in an angulated linear pattern'' seen in lentigo maligna. Though the zig-zag pattern is not pathognomonic for lentigo maligna, as it can also appear in pigmented actinic keratosis, the presence of a rough texture in the latter helps distinguish the two lesions.[20]

Digital epiluminescence microscopy, also known as digital dermatoscopy and video dermatoscopy, is a technique in which digital images are captured and stored so they can be compared with images captured at future visits. This tool can provide 30-fold magnification of the lesion in question. One study found that use of digital epiluminescence microscopy during surgical excision of lentigo maligna greatly reduced the border size of excised samples, compared with visual inspection. The superior magnification of digital epiluminescence microscopy can differentiate the rete ridge pattern at the dermoepidermal junction of lentigo maligna from the atrophic, flat rete ridges of benign melanocytes.[21]

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