Dermatology

Labial Lentigo (labial melanotic macule)

Are You Confident of the Diagnosis?

There is significant terminologic confusion regarding labial melanotic macules. They have been called ephelides, lentigines, melanosis, solitary labial lentigines, and oral melanotic macules. To further complicate matters, pigmented (melanotic) macules also can occur on the genital labia or oral labia.

Traditionally, labial melanotic macules refer to oral labial lesions and represent a distinct clinicopathologic entity. Unlike (oral) labial melanotic macules, pigmented macules on genital labia are not a distinct entity and can represent a range of conditions—including melanocytic nevi, lentigines, melanocytic nevi with architectural disorder and atypia of melanocytes (dysplastic nevi), atypical melanocytic nevi of the genital type (AMNGT), and melanomas.

What you should be alert for in the history

History should include onset, number of lesions (solitary or multiple), distribution (eg, other mucosal sites, skin, nails), lesional change, family history, UV exposure, history of preceding lesions or trauma (including prior procedures), and a complete review of systems.

Characteristic findings on physical examination

Labial melanotic macules typically present as solitary, symmetric, asymptomatic, well-defined, brown or black macules on the medial third of the lower lip (Figure 1).

Figure 1.

Labial lentigo

Sometimes, lesions may be multiple, located on the upper lip, have variegated pigmentation, or have a history of color change—lending to confusion with other pigmented lesions. To rule out other possible entities, be sure to perform a complete skin examination, checking for lesions involving the mouth, eyes, genitals, skin, or nails. Palpation of the lip for evaluation of deeper involvement is advised.

Expected results of diagnostic studies

Dermoscopy of labial melanotic macules reveals homogeneous pigmentation that may be structureless or contain partial linear or curvilinear streaks in a regular parallel pattern that gradually fades towards the periphery.

While histology is nonspecific, labial melanotic macules generally have increased melanin in melanocytes, basal layer keratinocytes, and melanophages in the dermal papillae. A mild degree of acanthosis without elongation of rete ridges may be present. Nuclear atypia is absent. Melanocyte count is normal (Figure 2, Figure 3).

Figure 2.

Labial melanotic macule (low power); mild acanthosis without elongation of rete ridges.

Figure 3.

Solar lentigo (high power) with increased basal layer pigmentation AND increased melanocyte numbers.

Diagnosis confirmation

Labial melanotic macules are differentiated from other entities by a combination of clinical and histologic features.

While ephelides and Peutz-Jeghers syndrome are histologically similar to labial melanotic macules, ephelides present as brown macules in childhood that darken on sun exposure and the macules of Peutz-Jeghers syndrome are typically multiple, more widespread (ie, oral mucosa, lips, eyes, nose, hands, feet), and are associated with intestinal polyposis (hamartomas).

Both lentigo simplex and solar lentigines have increased basal layer pigmentation and increased melanocyte concentration. Lentigines also have elongated rete ridges and often present with irregularly shaped borders (Figure 4, Figure 5).

Figure 4.

Solar lentigo (low power) with elongated rete ridges.

Lentigo maligna presents as an irregular brown or black macule with flattened rete ridges and atypical melanocytes on histology.

Melanocytic nevi are uncommon on the oral mucosa, where they most commonly occur on the hard palate or buccal mucosa. Intramucosal nevi are the most common oral nevi and contain nests of melanocytes in the dermis. Compound nevi have melanocyte nests in both the epithelium and dermis. Blue nevi have spindle-shaped melanocytes deeper in the dermis. Junctional melanocytic nevi are the least common intraoral nevi and are composed of nests of nevomelanocytic cells at the dermal-epidermal junction.

Superficial spreading melanoma is uncommon on the oral mucosa, constituting only approximately 1% of all superficial spreading melanomas and occuring approximately 3 times more frequently in men than women. These usually present as brown or black unevenly pigmented lesions with irregular margins, can become ulcerative or nodular, and have histologic features of melanoma.

Oral melanoacanthoma presents as an asymptomatic, slightly-elevated, well-defined, solitary, pigmented plaque on the buccal, palatal, gingival, or labial mucosa that is often associated with local trauma. It is a rare benign proliferation of normal melanocytes and keratinocytes with acanthosis and basal layer hyperpigmentation.

Addison's disease presents with pigmented oral mucosal macules, diffuse pigmentation in other sites (eg, lateral aspects of tongue, buccal mucosa, skin), other manifestations of adrenal insufficiency (fatigue, weakness, nausea, vomiting, changes in bowel habits, weight loss), and increased pigmentation in the basal and upper epidermal layers on histology.

Laugier-Hunziker disease is an acquired benign disorder with multiple pigmented labial macules, melanonychia striata, and possible genital mucosal involvement. Lesions have increased basilar pigmentation and number of melanophages in the chorion.

Amalgam tattoos appear as blue or black macules usually on gums or alveolar mucosa that contain irregularly shaped granules within macrophages or dermal collagen.

Venous hemangiomas (venous lakes) are blanchable blue macules composed of numerous blood vessels. Dermatoscopic examination is helpful in differentiating these.

There also are multiple inherited syndromes in which mucosal pigmented lesions may occur, including myxoma syndromes (ie, Carney syndrome [LAMB syndrome, NAME syndrome]), and LEOPARD syndrome. Typically, these syndromes have an autosomal dominant inheritance pattern, present with multiple widespread pigmented lesions, and are associated with internal organ involvement and increased risk of cancers.

Who is at Risk for Developing this Disease?

Labial melanotic macules most commonly present in women. Ultraviolet light exposure is thought to be a risk factor.

What is the Cause of the Disease?

Etiology

Pathophysiology

As labial melanotic macules almost always occur on the central third of the lower lip, a site receiving maximum sun exposure, ultraviolet radiation may play a role in their development. In one study, upper lip lesions occurred following tanning bed use in 2 of 4 patients. There are also two case reports of labial melanotic macules following application of topical tacrolimus, thought possibly secondary to its activation of melanocytes or its immunosuppressive activity.

Systemic Implications and Complications

Patients with multiple lesions that are histologically consistent with labial melanotic macules should be evaluated for other possible conditions, like HIV or Peutz-Jeghers syndrome. Of note, skin lesions of Peutz-Jeghers syndrome usually fade after puberty while mucosal lesions may persist. In some patients with HIV, oral melanotic macules may be an early sign of HIV infection. While most of these patients have multiple macules on the buccal mucosa, some may have labial, gingival, or palatal lesions. Screening for risk factors for HIV, particularly in patients with multiple mucosal lesions, is advisable.

Treatment Options

Table I. Reported Treatment Options for Labial Melanotic Macules

Table 1.

Reported Treatment Options for Labial Melanotic Macules
Medical Management Surgical Procedures Physical Modalities
Monitor for change Excisional surgery (by traditional, punch, or shave methods) Laser treatment
Sun protection   Cryosurgery

Optimal Therapeutic Approach for this Disease

Treatment of labial melanotic macules is not necessary, given their benign nature with apparently no reported cases of malignant transformation. As histology for labial melanotic macules is nonspecific and other entities may present similarly, patients should monitor lesions, seek medical attention for any lesional change, and practice good sun protection. A paucity of published data exists regarding cosmetic treatment of labial melanotic macules, which is often debatable. Reported options for elective cosmetic augmentation include surgical excision (including by traditional, punch, or shave methods), laser therapy, and cryotherapy.

Perhaps considered the most invasive modality, an advantage of excisional surgery is the prospect of complete removal for histologic evaluation. This may alleviate concerns about misdiagnosis of significant pathology due to the potential biopsy sampling error or fear that other cosmetic modalities may mask detection of possible lesional change.

Cryosurgery is a relatively simple and inexpensive treatment option. However, only one published article is available regarding its use in labial melanotic macules. In this study, fifteen patients with labial melanotic macules were pretreated with topical 4% lidocaine gel, then treated with simple cryosurgery via direct cotton swab application of liquid nitrogen for 10 to 15 seconds.

Patients experienced slight erythema immediately after treatment, whitish slough within 3 to 4 days, and disappearance of melanotic macules at 1 week post-treatment. Reported patient acceptance of the procedure was good and healing was uneventful without postoperative pain, hemorrhage, infection, or scarring. Six patients had repigmentation 2 to 18 months post-cryosurgery and were retreated with the same method.

Laser therapy, although the most expensive modality, has shown favorable cosmetic results. The Q-switched lasers that target pigment (694nm, 755nm, and 1064nm) are all reasonable options for laser therapy. Multiple small studies report good response of labial melanotic macules to Q-switched lasers. In one retrospective study, 9 patients were treated by Q-switched ruby laser (694nm, 25 to 40nsec, 4mm spot, 10J/cm2) and followed for a maximum of 5.5 years. The benign nature of the lesions was assessed by dermoscopy and, in one case, by biopsy. Three patients achieved complete clearance after one treatment session, while a second treatment was needed in six patients. There were no reported recurrences, scars, or pigment alterations.

In a second study, 8 patients were treated by Q-switched ruby laser (694nm, 20 nsec, 5mm spot, 6.5J/cm2) with clearance in 5 patients after a single pulse and 3 patients requiring a second treatment session. No side effects or recurrence were reported over the 24-month follow-up period. In a third study, three patients with “labial lentigos” had dramatic clearing after one to two treatments with a Q-switched ruby laser (694nm, 10J/cm2). The use of other lasers is mentioned sparingly in the literature. In a study of six Japanese patients with labial melanosis, including “labial lentigo” and Peutz-Jeghers syndrome, rapid clearance without mucosal textural changes or recurrence was accomplished with a pulsed ruby laser (695nm, 1 to 2msec pulse).

Patient Management

Reassure patients that labial melanotic macules are benign lesions for which treatment is not necessary unless there is lesional change. As such, advise patients to seek medical attention should they note lesional change. While stable lesions can be left alone, all progressive or changing lesions should be biopsied.

Educate all patients about the importance of sun protection, the appropriate use of sunscreen, and the ABCDE criteria (Asymmetry, irregular Border, uneven Color, Diameter > 6mm, lesional Evolution/change) of routine skin self-examinations for concerning pigmented lesions.

Inform patients that multiple modalities exist for elective cosmetic augmentation (eg, excision, cryosurgery, lasers), but these are not without potential risks (eg, out-of-pocket financial costs, ulceration, scarring, post-inflammatory dyspigmentation, infection, lack of efficacy, recurrence, and possible masking of lesional change if not fully removed).

Lesional photography is a useful tool for monitoring change, with a photo given to the patient to follow for change. Any lesion with a papular component should be biopsied, as this no longer represents a labial melanotic macule.

Unusual Clinical Scenarios to Consider in Patient Management

As differential diagnosis for labial melanotic macules includes more concerning entities, it is important to rule out other potential etiologies, including any of the aforementioned syndromes and high-risk lesions like melanoma. Of note, there have been increasing numbers of desmoplastic melanomas on the lips of younger people. Although these characteristically present as non-healing lesions, any atypical pigmented lesion warrants concern and consideration of biopsy.

What is the Evidence?

Ho, KKL, Dervan, P, O'Loughlin, S, Powell, FC. "Labial melanotic macule: a clinic histopathological and ultrastructural study". J Am Acad Dermatol. vol. 28. 1993. pp. 33-9.

(Nice review of a number of cases with histological analysis.)

Gaeta, GM, Satriano, RA, Baroni, A. "Oral pigmented lesions". Clin Dermatol. vol. 20. 2002. pp. 286-8.

(Discusses the various pigmented lesions encountered in the oral mucosa. Discusses labial melanotic macules.)

Muller, S. "Melanin-associated pigmented lesions of the oral mucosa: presentation, differential diagnosis, and treatment". Dermatol Ther. vol. 23. 2010. pp. 220-9.

(Another review of oral pigmented lesions. Reviews labial melanotic macules and is a nice overview.)

Mannone, F, de Giorgi, V, Cattaneo, A, Massi, D, de Magnis, A, Carli, P. "Dermoscopic features of mucosal melanosis". Dermatol Surg. vol. 30. 2004. pp. 1118-23.

(Attempts to determine the dermoscopic features of labial melanotic macules that differentiate them from other pigmented lesions.)

Raulin, C, Greve, B, Hartschuh, W, Werner, S. "Benign melanosis of the lip". Treatment with the Q-switched ruby laser. Hautarzt. vol. 52. 2001. pp. 116-9.

(Report of a case of successful therapy of labial melanotic macules treated with a ruby laser.)

Gupta, G, MacKay, IR, MacKie, RM. "Q-switched ruby laser in the treatment of labial melanotic macules". Lasers Surg Med. vol. 25. 1999. pp. 219-22.

(Similar report as to the above reference; adds to the literature on the use of Q-switched ruby lasers for this entity.)

Ashinoff, R, Geronemus, RG. "Q-switched laser treatment of labial lentigos". J Am Acad Dermatol. vol. 27. 1992. pp. 809-11.

(Similar report as to the above reference; adds to the literature on the use of Q-switched ruby lasers for this entity.)
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