Superficial spreading in lentigo maligna

Case Presentation

A 61-year-old white female with a past medical history of atrial fibrillation presents with a brown spot on her right ear of unknown duration. On physical exam, there is a 3 mm brown macule with perifollicular irregular dotted pigmentation on the right helical rim (Figures 1 and 2).

Figure 1 and Figure 2

ANSWER

1. Treat with bleaching cream for two weeks, then reassess

Figure 1 and Figure 2

ANSWER

3. Lentigo maligna/lentigo maligna melanoma

Figure 1 and Figure 2

ANSWER

True

Figure 1 and Figure 2

ANSWER

4.  Depth of invasion (Breslow depth or stage)

Figure 1 and Figure 2DISCUSSION 

Melanoma is a malignant tumor originating from melanocytes (most often cutaneous) and responsible for the largest number of skin cancer mortalities worldwide (1,2). The incidence of melanoma has been rising over the past 40 years most in Caucasians, while it has a lower incidence in darker skinned populations (1,3).

There are a number of independent risk factors that make patients susceptible to cutaneous melanoma, including genetic factors such as family history of cutaneous melanoma, light skin color, tendency to burn or inability to tan, red hair color due to mutations in variants of MC1R (melanocortin 1 receptor) alleles, and rare heritable conditions such as Familial Atypical Mole syndrome and Xeroderma Pigmentosa; environmental factors such as sun exposure, history significant for sunburns, tanning bed use, exposure to PUVA (psoralen and ultraviolet A) therapy and phenotypic expressions, such as many melanocytic nevi and solar lentigines (1,4,5).

The major subtypes of primary cutaneous melanoma include superficial spreading, nodular, lentigo maligna, and acral lentiginous melanoma. The most common type, superficial spreading (~57%), typically is diagnosed between ages 40 and 60 and arises de novo or in about one third of cases in a nevus previously present (1,6). Superficial spreading melanoma in situ is often <5 mm in diameter and presents as an asymptomatic brown to black macule with irregular color and borders (1). Nodular melanomas are the second most common subtype (~21%), (1,7).  Of note, nodular melanomas are the most aggressive subtype with early evolution into the vertical (invasive) growth phase (7). Lentigo maligna is a melanocytic neoplasm arising on sun-exposed skin of the head and neck, of middle-aged and elderly individuals. It represents the in situ phase of and can lead to development of lentigo maligna melanoma (~8%) (8). Acral lentiginous melanoma is an uncommon subtype of melanoma mostly occurring on the palms, soles, and nail beds, and is frequently diagnosed at advanced stages with poor prognosis compared to other subtypes (9). Melanoma in situ is characterized by malignant melanocytes localized to the epidermis during a noninvasive radial growth phase (T0 stage), and can progress if untreated to invasive and metastatic disease (10). 

In the clinical setting, melanomas are diagnosed with visual examination and dermoscopy. Clinical diagnosis of melanomas is simplified by the ABCDE’s proposed, including asymmetry, border irregularity, color variegation, diameter larger than 5 and evolving lesion (1,11). The “ugly duckling” sign allows for differentiation between the characteristic single lesion of a melanoma and surrounding benign nevi (1,12). 

Dermoscopy has been shown to increase accuracy of diagnosis of melanoma by 50% (1,13). Dermoscopic findings of melanoma include asymmetry, multiple colors, various patterns, atypical networks, streaks, atypical dots or globules, irregular blood vessels, regression structures, and blue-white veil (1).  For lentigo maligna or lentigo maligna melanoma on dermoscopy, diagnostic findings include asymmetrical pigmented follicular openings, rhomboidal structures, annular-granular structures and gray pseudo-network (14,15).  To diagnose lentigo maligna or lentigo maligna melanoma, 4 criteria in combination have a sensitivity of 89% and a specificity of 96%: asymmetric pigmented follicular openings, dark rhomboidal structures, slate gray dots, and slate gray globules (16,17).

The histopathologic diagnosis of melanoma can be very challenging and is best referred to a dermatopathology specialist. Histopathology of melanoma can show melanocytes both solitary and in nests within the epidermis that are asymmetric and poorly circumscribed, varying in shape, size, and distance from one another. In melanoma in situ, atypical melanocytes remain above the dermal-epidermal junction (1). In addition to H&E staining, special stains for various antigens, including HMB45, tyrosinase, and Melan-A/MART-1, and S100, melanocytic differentiation markers that assist in identifying melanocytes and delineating the extent of a melanoma (1,18). Genomic hybridization studies and Fluorescence in situ hybridization (FISH) play a minor supportive role in the diagnosis of melanoma (1,19).

Cutaneous melanoma staging, using the TNM parameters per the American Joint Committee on Cancer (AJCC), should be reported using primary tumor thickness, presence of ulceration, mitoses, lymph node spread, and distant metastases, which all have independent prognostic significance (20,21). T is determined by Breslow depth, primary tumor mitotic rate, and histopathologic findings of ulceration (1,22). Breslow depth, or vertical tumor thickness, is the most important factor in determining prognosis in cutaneous melanoma (1,21,22,23). It is measured in millimeters from the uppermost part of the granular cell layer of the epidermis to the lowest area of tumor infiltration (1). Studies have found that tumor thickness tends to be increased in older individuals diagnosed with melanoma (1,24). N refers to the number of metastatic lymph nodes, the presence of microscopic versus macroscopic nodal tumor load, and presence or absence of satellite or in-transit metastases (1). M involves the anatomic location of distant metastases and serum lactate dehydrogenase (LDH) level, which reflect liver involvement (1,25). Melanoma in situ is considered Stage 0, localized disease by Stages I and II, regional nodal and/or intralymphatic metastases by Stage III, and distant metastases by Stage IV (1).  Stages I and II have more favorable prognoses than subsequent stages.

Management of a primary melanoma includes surgical excision by a margin selected based upon tumor depth (Table 2). Early stage diagnosis and surgical excision are the best methods to cure disease (2). For melanoma in situ, excision with 0.5 to 1 cm margin is recommended (26).  For invasive melanomas greater than 1 mm, sentinel lymph node biopsy is considered an option that offers prognostic value although its therapeutic value is unclear. Complete lymph node dissection is recommended if lymph node metastasis is diagnosed and allows for determination of staging and prognosis. For patients with distant metastatic melanoma, the 5-year survival rate is approximately 10% and the median survival time is close to 9 months (1,27). Systemic therapy, including immunotherapy, BRAF inhibitors and combination protocols have advanced greatly in recent years with significant survival impact seen (2).

Table 1. TNM Classification for Melanoma Staging

Adapted from Bolognia, J, Jorizzo, JL, and Schaffer JV. (2012). Dermatology. Philadelphia: Elsevier Saunders.

Table 2. Tumor margins for excision

ADAPTED FROM

Bolognia, J, Jorizzo, JL, and Schaffer JV. (2012). Dermatology. Philadelphia: Elsevier Saunders.

Coit DG, Thompson JA, Albertini MR, et al. Melanoma, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2016 Nov.

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