Pigmented macular 
lip lesion - Clinical Advisor

Pigmented macular 
lip lesion


  • Labial melanotic macule?

An active-duty airman aged 30 years presented for an assessment of intermittent abdominal cramps. Physical examination revealed five macular, brown, hyperpigmented lesions on his lower lip. The first lesion appeared two years earlier and remained asymptomatic except for a slight increase in size. The four similar lesions developed at different stages during this time period.

The man is a nonsmoker with a fair amount of sun exposure. No known heavy-metal exposure was reported. Family history was negative for skin or GI cancer. The patient took daily doxycycline for malaria prophylaxis during his recent deployment. 

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A deep 4-mm complete excisional punch biopsy of the largest macule confirmed the suspected diagnosis of labial melanotic macule (LMM). LMMs are chiefly noted on the vermilion border of the lower lip. They are usually well-defined, solitary, uniformly tan-to-brown macules...

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A deep 4-mm complete excisional punch biopsy of the largest macule confirmed the suspected diagnosis of labial melanotic macule (LMM). LMMs are chiefly noted on the vermilion border of the lower lip. They are usually well-defined, solitary, uniformly tan-to-brown macules that, once developed, remain unchanged in size and color, rarely exceeding 5 mm in diameter. Young women are most frequently affected, with a mean age range between 27.5 and 34.9 years, and patients appear to be almost exclusively white.1,2

Mucosal melanotic macule is a broader term encompassing lesions of the mouth as well as the lip. Oral melanotic macules may have more of a predilection toward malignant melanoma than LMM. These macules, noted on gingival, buccal or palatal mucosa, usually present in patients older than age 40 and may be larger, reaching up to 1 cm in diameter. A lingual macule is a specific type of oral lesion noted on the tongue at birth and proportionally grows to between 2 and 5 mm.1

Specific terminology for LMM can be variable and confusing. Such terms as ephelis and lentigo are typically used to describe these lip lesions, both of which are synonymous with the term freckle. The phrase labial melanotic macule was first suggested by Weathers et al in oral pathology literature, and although LMMs histologically resemble ephelides, they do not usually darken with sun exposure or fade in the winter months, nor are they found on mucous membranes.3,4 Microscopic examination of lentigines will reveal elongated rete ridges not seen with LMM.2

LMM histopathology reveals increased melanin pigment in the basal cell layer (and possibly the lamina propria) along with occasional pigment incontinence. When coupled with elongation of the rete ridge, nuclear atypia or an increased number of melanocytes would suggest malignant melanoma or lentigo, respectively.1,4 While LMMs are considered benign, and diagnoses can most often be made clinically, a punch biopsy is a simple enough procedure to reassure the patient and provide the definitive diagnosis.

The differential diagnoses to consider for mucosal melanotic macules fall into two categories: (1) melanocytic lesions, and (2) nonmelanocytic lesions.

Of the melanocytic lesions, mucosal melanoma is the most important to recognize, as it is invasive at discovery 85% of the time due to delay in diagnosis. Lesions usually present on the palate and gingival surfaces and have a racial predilection for adult Asians and blacks.5 Any lesions with pigmentation patterns that have changed over time suggest melanoma. The ABCDs should be noted: Asymmetry, Borders (irregular), Color (variable), Diameter (enlarging), and satellite lesions. Fortunately, primary oral melanoma is rare, accounting for approximately 0.2% to 8% of all melanomas.1

Physiologic or ethnic/racial pigmentation is symmetric and diffuse and usually presents at birth but can appear in persons of any age with no gender predilection. This pigmentation is most commonly found on the gingival mucosa. A related type, known as postinflammatory pigmentation, is usually seen after mucosal reaction to injury and usually fades with time.

Abnormal melanin pigmentation has also been related to cigarette smoking, resulting in smoking-associated melanosis (smoker’s melanosis). A component in tobacco smoke stimulates melanocytes. Gingival pigmentation in children has been linked to passive smoking from parents and other adults who smoke.6 Cessation of smoking improves this condition, with resolution ranging from months to years.

Systemic conditions associated with mucosal melanotic macules include Addison’s disease, Laugier-Hunziker syndrome, and Peutz-Jeghers syndrome. These conditions must be considered in patients with numerous oral pigmentations. Addison’s disease (primary adrenal insufficiency) results in reduced cortisol production by the adrenal gland, resulting in increased pituitary adrenocorticotropic hormone and melanocytic-stimulating hormone as part of a negative feedback mechanism. This leads to diffuse pigmentation of the skin, including irregular and patchy darkening of the oral mucosa (gums). Other presenting symptoms indicative of systemic involvement include weakness, weight loss, nausea, vomiting and hypotension.

Laugier-Hunziker syndrome is a rare acquired benign disorder that involves pigmentation of the oral mucosa to include the lips, as well as finger macules and subungual melanocytic streaks. Although there is virtually no systemic involvement, the syndrome is usually listed under systemic pigmentation disorders.1,6 Peutz-Jeghers syndrome is an inherited autosomal-dominant condition that presents with more speckled extensive pigmentation and is associated with GI polyposis later in life. The polyps have limited neoplastic potential and are usually found in the small intestine, resulting in potential systemic signs and symptoms of abdominal pain, rectal bleeding and diarrhea.

The nonmelanocytic lesion differential is smaller. Amalgam tattoo is iatrogenic and the most common pigmentation of the oral mucous membrane.6 It is mainly found in adult patients in the soft tissue next to teeth restored with amalgam alloy from chronic low-grade frictional contact or traumatic implantation. Amalgam tattoo is typically seen on mandibular gingival mucosa but may also be seen on the buccal mucosa, palate and tongue.5 Observation is all that is needed, but elective removal for cosmoses may be performed.

Drug-induced oral pigmentation usually occurs after months of chronic use and usually resolves once the medication is discontinued. Some of the more common causative agents are tetracyclines and antimalarial drugs.6 All of these pigment changes can also be seen on sun-exposed areas. Systemic exposure to such heavy metals as silver, gold, bismuth and mercury may also be responsible for mucocutaneous discoloration.

The patient in this case had concerning multiple lesions with systemic GI symptoms and a history of prolonged doxy­cycline malaria prophylaxis during deployment. His screening bloodwork was negative. A colonoscopy was normal, and the excisional punch biopsy of the lesion was not only diagnostic but curative as well. The patient was given the option of cryotherapy or observation for his remaining lesions.

Norman D. Zellers, MSPAS, PA-C, is a physician assistant and Ceasar A. Valle, MD, MBA, is a flight surgeon and pediatrician at the Los Angeles Air Force Base in El Segundo, Calif. The authors have no relationships to disclose relating to the content of this article.


1. Dohil MA, Billman G, Pransky S, Eichenfield LF. The congenital lingual melanotic macule. Arch Dermatol. 2003;139:767-770.

2. Spann CR, Owen LG, Hodge SJ. “The labial melanotic macule.” Arch Dermatol. 1987;123:1029-1031.

3. Weathers DR, Corio RL, Crawford BE et al. “The labial melanotic macule.” Oral Surg Oral Med Oral Pathol. 1976;42:196-205.

4. Pais S, Hegde SK, Bhat SS. “Oral melanotic macule — a case report.” J Indian Soc Pedod Prev Dent. 2004;22:73-75.

5. Flint PW, Haughey BH, Lund VJ et al. Cummings Otolaryngology: Head & Neck Surgery. 5th ed. Philadelphia, Pa.: Mosby; 2010:1241-1244.

6. Regezi JA, Sciubba JJ, Jordan RCK. Oral Pathology: Clinical Pathology Correlations. 5th ed. St Louis, Mo.: Saunders; 2008:127-139.

All electronic documents accessed January 9, 2012.

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