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Lentigo
Updated: Apr 16, 2019
Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD

Overview

Background
A lentigo is a small, sharply circumscribed, pigmented macule surrounded by normal-appearing skin. Histologic findings may
include hyperplasia of the epidermis and increased pigmentation of the basal layer. A variable number of melanocytes are
present; these melanocytes may be increased in number, but they do not form nests. Lentigines may evolve slowly over
years, or they may be eruptive and appear rather suddenly. Pigmentation may be homogeneous or variegated, with a color
ranging from brown to black.

Multiple clinical and etiologic varieties exist. The distinction of a lentigo from other melanocytic lesions (eg, melanocytic nevi,
melanoma) and its role as a marker for ultraviolet damage and systemic syndromes is of major significance.

A case-controlled study in France comparing 145 adults with multiple solar lentigines on the upper back and 145 matched
control subjects found that multiple solar lentigines on the upper back and shoulders of adults may serve as clinical markers
of past severe sunburn and may be used to identify a population at higher risk of developing cutaneous melanoma.[1]

The concept of “unstable solar lentigos” evident as irregularly pigmented macules on the background of chronic sun damage
has been considered alongside the idea that they may have malignant potential.[2]

Note the images below.

Woman with solar lentigo.

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Close-up view of a woman with solar lentigo.

Pathophysiology
Long-term exposure to ultraviolet radiation and pollution as one ages may induce the common solar lentigo.[3] Depending
on the type of lentigo present, a solitary lesion or multiple lesions can occur anywhere on the body. Some lentigines have
associated systemic manifestations that accompany the skin lesions, such as the LEOPARD syndrome.

A Japanese microarray analysis evaluation of solar lentigo in 16 adults demonstrated up-regulation of genes related to
inflammation, fatty-acid metabolism, and melanocytes and down-regulation of cornified envelope-related genes.[4] The
researchers suggested solar lentigo may be induced by the mutagenic effect of repeated past UV light exposures, leading to
characteristic enhancement of melanin production.

Little is known about the genetic basis of human solar lentigines, which were analyzed for potential FGFR3 and PIK3CA
mutations. FGFR3 mutations were detected in 5 (17%) of 30 solar lentigines, and PIK3CA mutations were detected in 2
(7%) of 28 solar lentigines, suggesting that FGFR3 and PIK3CA mutations are involved in their pathogenesis and further
substantiating previous speculations that UV exposure may be a causative factor for FGFR3 and PIK3CA mutations in
human skin.[5] Lentigines, which develop earlier and are more pronounced in Japanese than in German women, have been
found to correlate with variants in the SLC45A2 gene.[6] Extensive lentigo simplex, linear epidermolytic nevus, and
epidermolytic nevus comedonicus were linked with a somatic mutation in KRT10.[7]

The LEOPARD syndrome may be associated with a mutation in the PTPN11 gene at Thr468Met.[8]

Etiology
The cause of lentigo formation depends on the type of lesion, as follows:

The cause of lentigo simplex is unknown. Case reports have described simple lentigines developing in children after
use of topical tacrolimus for atopic dermatitis.[9]

Solar lentigo and ink-spot lentigo are associated with sun exposure in fair-skinned people.

PUVA lentigines[10, 11, 12] are associated with PUVA therapy in patients with psoriasis.

Radiation lentigo is caused by local high-dose irradiation.[13]

Genetic factors may be involved in other forms of lentigines, including XP, LEOPARD syndrome, Peutz-Jeghers
syndrome, and inherited patterned lentiginosis.

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Epidemiology
Frequency

United States

In America, solar lentigines are observed in as many as 90% of whites older than 60 years and in 20% of whites younger
than 35 years. Psoralen plus UVA (PUVA) lentigines are noted in almost one half of individuals with psoriasis who receive
PUVA therapy for at least 5 years. They may also be evident in resolving psoriatic plaques in individuals, including children,
who did not receive UV therapy.[14]

Lentigo simplex is the most common form of lentigo, but its frequency has yet to be determined. Alper and Holmes[15] noted
multiple lentigines in 91 (18.5%) of 492 black newborns and 1 (0.04%) of 2682 white newborns; however, histologic
confirmation of these lesions was lacking.

International

Lentigines are observed worldwide. The incidence depends on the type of lesion.

Seborrheic keratosis and lentigo solaris were found to be increased on the driver side of the face in an evaluation of truck
drivers in Turkey assessing the effects of UV light.[16]

Race

Solar lentigines are more abundant in fair-skinned whites than in dark-skinned individuals, in whom the disease is distinctly
uncommon because they have a greater amount of natural pigment that provides some degree of photoprotection.
Lentigines, prominent skin signs of aging, develop earlier and are more pronounced in Japanese than in German women.[6]

Inherited patterned lentiginosis can occur in blacks, particularly those with mixed American Indian heritage and those with
relatives with red hair.[17]

Ephelides, PUVA lentigines, tanning-bed lentigines, vulvar lentigines, ink-spot lentigines,[18] oral and labial melanotic
macules, and Laugier-Hunziker syndrome are also more common in people with light skin than in those with dark skin. Ink-
spot lentigo occurs in patients of Celtic ancestry.

Acral lentigines are more common in dark-skinned individuals, but they may also be present in light-skinned individuals.

Sex

PUVA lentigines are more common in men than in women. Tanning-bed lentigines and oral and labial melanotic macules are
more common in women than in men.

Age

Lentigines can appear in both children and adults; however, children are more likely to have genetically associated lesions
such as those of Peutz-Jeghers syndrome.

Adults are more likely to acquire lesions due to chronic exposures, which cause solar lentigo for example.

Prognosis
Lentigines are benign by nature.

In patients in whom lentigines are associated with systemic abnormalities or complications, the prognosis may depend on
the severity of the associated conditions.

Treatments with cryosurgery, lasers, and/or topical creams have been successful (see Medical Care).

Patient Education
Patients should be advised about the risks of sun exposure and the use of tanning beds.
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Presentation

History
The initial appearance of lentigines varies widely and depends on the following:

Race

History of exposures

Genetic predisposition

Other factors, depending on the type of lentigo

Physical Examination
The physical appearance and morphology of lentigines depend on the type of lesion.

Lentigo simplex

Lentigo simplex (eg, simple lentigo, juvenile lentigo) is the most common form of lentigo. Lentigo simplex is not induced by
sun exposure, and it is not associated with systemic disease. Clinically, the lesions are round or oval asymptomatic macules
that are 3-15 mm in diameter. Their margins can be either jagged or smooth. Pigmentation is evenly distributed, with a color
ranging from brown to black. The lesions are few in number and may occur anywhere on the skin or mucous membranes.
The lesions usually appear first in early childhood, but they can also be present at birth or develop later.

Multiple dysplastic nevi and lentigines were reduced in number in a patient with familial gastrointestinal stromal tumors
syndrome after treatment with imatinib mesylate.[19] The effect of effect of imatinib on pigmentation is not well understood.

Solar lentigo

Solar lentigo (eg, actinic lentigo, senile lentigo, sun spot, liver spot) is the most common benign sun-induced lesion that
occurs in sun-exposed areas. Solar lentigo most commonly appears on the face, arms, dorsa of the hands, and upper part
of the trunk. The spots initially are smaller than 5 mm in diameter. The surface of the lesions is either flat or depressed, and
it may be split by fine wrinkles.

The lesions are usually brown, but the color may range from yellow-tan to black. Older lesions are often dark brown or
brownish black. Solar lentigines slowly increase in number and in size. Many lesions eventually coalesce to form larger
patches. Although these lesions are most common in individuals aged 30-50 years, they are now seen in younger
individuals because of their increased exposure to sun tanning and the use of artificial sources of UV light. Although they
are often called liver spots, they are not a manifestation of systemic disease.

In vivo reflectance confocal microscopy may show solar lentigines having increased melanin and hemoglobin levels and a
higher rate of epidermal proliferation. Deformation and the number of the hyperrefractive dermal papillary rings may
increase significantly over the 5-year time span, with the lentigo size enhanced and color darkened.[20]

Ink-spot lentigo

Ink-spot lentigo (ie, reticulated black solar lentigo) can be distinguished by a wiry or beaded, markedly irregular outline;
these lesions occur in patients of Celtic ancestry. The benign lesions have a reticulated pattern, and most lesions resemble
a spot of ink. The distribution is limited to sun-exposed areas of the body, similar to that of solar lentigo; however, in contrast
to solar lentigines, patients usually have only 1 ink-spot lentigo. The most common presentation includes 1 ink-spot lentigo
among an extensive number of solar lentigines.

These lesions can also be distinguished from the darkly pigmented PUVA lentigo by their more reticulated or beaded pattern
and multiple central and peripheral skip areas. Ink-spot lentigines can initially suggest melanoma because of their dark
color, irregular border, and limited number; however, further investigation, which may include biopsy, reveals the
characteristic features of these benign lesions.

PUVA lentigo
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PUVA lentigo is a persistent, pale brown macule appearing 6 months or longer after the start of PUVA therapy for psoriasis.
The lesions resemble solar lentigines, but they often have more irregular borders and may mimic ephelides. The occurrence
of lesions is closely associated with greater cumulative doses of PUVA, and the lesions may occur on all treatment sites.
The most common areas include the upper part of the chest and back, groin, buttocks, glans penis, and penile shaft. The
axillae, palms, soles, and gluteal cleft are spared. The lesions vary from 3-8 mm in diameter, but stellate lesions can be as
large as 3 cm in diameter. The lentigines may persist for 3-6 months after therapy is discontinued. In contrast, stellate
lesions can persist longer than 2 years.

Radiation lentigo

Radiation lentigo resembles UV-induced lentigo, but it often includes other histopathologic signs of long-term cutaneous
radiation damage such as epidermal atrophy, subcutaneous fibrosis, keratosis, and telangiectasias. The presence of a
radiation lentigo is considered an indicator of a prior cutaneous exposure to a large single dose of ionizing radiation (eg,
exposure during the Chernobyl nuclear accident). These lesions have not been shown to occur after local fractionated
radiation therapy. Radiation lentigines are persistent and typically occur 4 months or longer after the initial exposure. The
malignant potential of the lesions is unknown; however, the induction of melanoma by ionizing radiation has never been
proven.

Tanning-bed lentigines

Tanning-bed lentigines[21, 22, 23] usually occur in women with a history of tanning-bed use. Tanning-bed lentigines are
similar to PUVA lentigines, except psoralens are not involved. The site of tanning-bed lentigines is primarily acral despite
whole-body exposure. The most common areas include the anterior aspects of the arms and legs, but they can also occur
on the neck and chest. The size of the lesions varies. The lesions are usually 2-5 mm in diameter, with color ranging from
dark brown to black. Some lentigines may coalesce and enlarge. Pigmentation of the lesions may be uneven, with irregular
or stellate shapes. The lesions can appear abruptly after intense tanning, or they can appear after prolonged (eg, 1 y)
regular use of tanning beds. The malignant potential of the lesions is unknown.

Oral and labial melanotic macules

Oral and labial melanotic macules are similar to each other. Labial lesions almost always occur on the vermilion of the lower
lip, and their color ranges from brown to blue to blue-black. Occasionally, variegated pigmentation occurs. The lesions are
usually solitary, symmetric, and asymptomatic. Oral lesions can appear on the gingiva, buccal mucosa, palate, and tongue.
Usually, oral and labial lesions have a diameter smaller than 4 mm. The individual's age at onset ranges from 25-71 years.

The differential diagnosis should include Laugier-Hunziker syndrome and Peutz-Jeghers syndrome. The absence of
systemic features and involvement at other sites should assist in differentiating oral and labial melanotic macules from these
syndromes. Both oral and labial melanotic macules are benign; however, lesions suggestive of malignancy should be
examined at biopsy.

Vulvar and penile lentigo

Vulvar and penile lentigo are benign lesions similar to labial melanotic macules. In men, the most common sites are the
glans penis, corona, corona sulcus, and penile shaft. The lesions vary in color from tan to brown to dark brown, and they
have irregular borders and skip areas. Individual lesions may have a diameter as large as 15 mm. In women, the lesions
appear anywhere on the genital mucosa as a mottled, pigmented patch with skip areas. The diameter can be 5-15 mm or
larger. The lesions may also occur in episiotomy scars after childbirth. Lentigines involving the external genitalia are also
reported in LAMB syndrome.

Lentigines profusa

Lentigines profusa (ie, generalized lentigines) is characterized by numerous lentigines without signs of associated
abnormalities or triggering factors. The clinical appearance of lentigines profusa resembles that of ephelides, but its
distribution is widespread. Usual areas of involvement include the extremities, trunk, palms, and genitalia. Mucosal surfaces
such as the conjunctiva can also be affected, but the buccal mucosa may be spared. The macules vary from 1 mm to 2 cm
in diameter. The color of the macules ranges from dark brown to black.

Lentigines profusa appears similar to the cutaneous manifestations of LEOPARD, LAMB, and NAME syndromes; however,
a notable exception is the absence of the variety of the physical anomalies and defects associated with these syndromes.

Agminated lentiginosis

Agminated (segmental, unilateral, partial unilateral) lentiginosis is characterized by numerous lentigines confined to a body
segment, with a sharp demarcation at the midline. The distribution frequently corresponds to one or more dermatomes. Less
commonly, the lesions can be distributed unilaterally, bilaterally, in a checkerboard pattern, or in midline clusters. Usually,
the disease appears in early childhood, although the lentigines may also be noted at birth. These lesions have been
associated with numerous diseases. Clinically, the lesions appear as circumscribed, tan or dark brown macules on healthy
background skin.

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Xeroderma pigmentosum

Xeroderma pigmentosum (XP) is an autosomal-recessive condition involving abnormalities that stem from an inability of
cells to repair DNA damage induced by exposure to UV light and certain chemicals. Clinically, patients have skin atrophy
and progressive pigmentary changes. Subsequently, neoplastic changes occur on the skin, often in childhood; squamous
cell and basal cell carcinomas are the most common malignancies. Other cancers, such as melanoma, may appear as well.
All of these neoplastic changes evolve on sun-exposed areas, particularly the head, neck, and face.

XP is diagnosed in young children, who are typically healthy. Children should avoid sun exposure because the acceleration
of skin changes leads to the formation of neoplasms. Ocular and neurologic defects are also associated with XP. See the
image below.

Thirteen-year-old Greek adolescent with xeroderma pigmentosum.

LEOPARD syndrome

LEOPARD syndrome (lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis,
abnormal genitalia, retardation of growth, and deafness syndrome) (ie, multiple lentigines syndrome) is a complex
dysmorphogenetic disorder that is transmitted as an autosomal-dominant trait with variable penetrance. A mutation of the
PTPN11 gene may be documented.[24] The diagnosis can be difficult because most patients have only 3-5 of the criteria.
Lentigines are the most common feature of the syndrome, although they do not have to be present to diagnose LEOPARD
syndrome.

In the absence of lentigines, the diagnosis can be made if the patient has 3 features of the disease and an immediate
relative with the disease. Lentigines are present at birth and increase in number until puberty. The intensity of the
pigmentation varies. The lesions are numerous on the neck and trunk, but they can also be widespread and involve the
genitalia, palms, soles, and scalp. Lentigines spare some parts of the face and may be limited to one side of the body in
some cases.

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is an autosomal-dominant condition with a high degree of penetrance and is characterized by
gastrointestinal polyps and pigmented macules. The polyps are benign hamartomas that can affect the entire bowel, most
characteristically the jejunum. These polyps result in recurrent perirectal bleeding and abdominal pain. Patients are often
first seen with bleeding or with intussusception that manifests as an obstruction, abdominal pain, rectal prolapse, vomiting,
and/or currant jelly–like stool.

Lentigines are brown-to-black-to-blue macules that usually arise in early childhood. Their size ranges from 1-12 mm in
diameter. Hyperpigmented macules occur in more than 95% of patients, and they have a characteristic distribution around
the mouth, on the lips, and on the buccal mucous membranes; they can also be scattered around the nose and face.
Additionally, lesions appear on the fingers and toes on both the palmar and volar surfaces. Lesions are characteristically
absent on the flexor and extensor surfaces of the rest of the body. The buccal mucosal macules are important because they
persist, whereas the other macules may fade with age. A relationship between the extent of melanosis and the extent of
polyposis has not been found.

Almost all women have unusual sex cord tumors that are small, bilateral, asymptomatic, and multifocal. Gonadal tumors are
also noted in men. Women have an increased risk of breast cancer, either unilateral or bilateral in presentation.

Laugier-Hunziker syndrome
Laugier-Hunziker syndrome is characterized by a variable number of pigmented macules that most commonly appear on the
lower lip; buccal mucosa; hard palate; and, occasionally, tips of the fingers. Other locations include the labial commissure,
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tongue, gums, floor of the mouth, neck, thorax, abdomen, nails, and soles. The lentigines may be numerous and confluent,
but they rarely occur in a linear pattern. The lesions mostly occur on the nails. Their borders are smooth and well defined.
The color of the lesions can vary from gray to brown, blue, or black. Although the syndrome has a chronic course without
remission, individuals are generally asymptomatic.

This syndrome differs from Peutz-Jeghers syndrome because of the absence of intestinal polyps. Laugier-Hunziker
syndrome occurs in individuals aged 20-50 years and in both sexes, whereas isolated labial melanotic macules affect
younger patients and are usually solitary. Pigmentation of the oral mucosa and nails is reported to occur in patients taking
the antiretroviral medication zidovudine. The clinical and drug histories are important in differentiating this phenomenon from
Laugier-Hunziker disease.

Myxoma syndrome

The myxoma syndrome is associated with mucocutaneous lentigines along with various additional abnormalities. Some
constellations of abnormalities have been given specific names. They may all be part of a spectrum of manifestations of the
same disorder.

LAMB syndrome

LAMB (lentigines, atrial myxomas, mucocutaneous myxomas, and blue nevi) syndrome is one of the myxoma syndromes.
The lentigines most commonly occur on the lips, face, sclera, and vulva. The lesions are brown and can be as large as 1 cm
in diameter. The mucocutaneous myxomas appear as papules or dermal nodules at various sites on the body, including the
breasts, shoulders, oral mucosa, and tongue. Cardiac myxomas are rare in children and usually occur in the form of atrial
myxomas, which are clinically evident as intermittent embolic episodes and valvular obstructions. An association with benign
thyroid nodules is noted.

NAME syndrome

NAME (nevi, atrial myxoma, myxoid neurofibroma, and ephelides) syndrome is another myxoma syndrome. This possible
variant of LAMB syndrome involves multiple, flat, pigmented macules. The lesions begin at birth and are accentuated in the
summer. The color of the lesions varies from pale to dark brown. The most commonly involved areas are the neck, trunk,
and thighs. The palms and soles are sometimes affected.

Carney syndrome

Carney syndrome is an autosomal dominant multiple neoplasia syndrome involving cardiac, cutaneous, and mammary
myxomatous masses; lentigines; blue nevi; endocrine disorders; and testicular tumors.[25] Often, multicentric and bilateral
organ involvement is present; this usually occurs in young patients. The cutaneous myxomas are often observed on the
eyelids and other sites such as the nipples, scalp, face, oral mucosa, ears, neck, trunk, limbs, and perineum. Cardiac
myxomas are either single or multiple and often result in fibrosis or calcification.

Two types of pigmented macules exist: blue nevi and lentigines. Lentigines are brown to black and 0.2-2 mm in diameter;
they have irregularly shaped, jagged margins. They are widespread throughout the body and may coalesce to form brown
patches. The lesions can be found on the face, eyelids, ears, vermilion borders of the lips, conjunctiva, vulva, extremities,
and glans penis. Unlike Peutz-Jeghers syndrome, Carney syndrome infrequently involves buccal lesions. Endocrine
involvement includes calcifying pigmented neuroectodermal tumors, pituitary adenomas with acromegaly and gigantism,
and adrenocortical disease leading to Cushing syndrome.

Testicular tumors feature Sertoli cell tumors, Leydig cell tumors, and adrenocortical rest tumors. Mammary involvement
includes gynecomastia and myxomatous enlargement of the stroma.

Inherited patterned lentiginosis

Inherited patterned lentiginosis can occur in blacks. This form is characterized by hyperpigmented macules on the face and
lips. At times, additional lesions are seen on the elbows, knees, buttocks, and palmoplantar surfaces. Lesions are not
present on the oral mucosa, and they are not associated with organ involvement or an apparent risk of cancer. The
inheritance pattern appears to be autosomal dominant. Light-skinned African American families, some of whom have a
mixed American Indian heritage and those with relatives with red hair, are particularly affected. See the image below.

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Ephelides (ie, freckles) on the forearm of a 26-year-old redheaded patient.

Nevus spilus

The nevus spilus is a both a lentigo and melanocytic nevus, a unique neoplasm that has only a slight potential to develop
into melanoma.[26] It is evident as multiple pigmented macules or papules within a congenital or acquired pigmented patch.

Complications
Some lentigines have associated systemic manifestations that accompany the skin lesions (see Physical Examination).

DDx

Diagnostic Considerations
Consider melanoma and lentigo maligna melanoma.

Ephelides (ie, freckles) are light brown macules that occur on the sun-exposed areas of the face, dorsum of the hands, and
forearms. These lesions are more common in individuals with light hair, especially red hair, and light skin, but they can also
occur in people with dark hair and skin. They usually appear in the summer months, and they may persist throughout life.
Examination of the skin with a Wood lamp may reveal ephelides that are not evident in ordinary light. The distribution is
symmetric, and the lesions may be either sparse or dense. The color of the lesions tends to deepen after sun exposure,
ranging from pale yellow to brown or even black. The borders are well defined and irregular, and the lesions can have a
diameter as large as 5 mm. In people with natural ephelides, a single UVB exposure can induce the formation of additional
ephelides.

Diagnostic key points for lentigo are noteworthy to distinguish it from lentigo maligna, the former having findings that include
annular-granular structures and a gray pseudonetwork.[27] However, pigmented actinic keratosis, lichen planus–like
keratosis, and lentigo maligna may be challenging to clinically distinguish, making the differential diagnosis difficult.[28] The
distinction between lentigo maligna and solar lentigo may be challenging. Digital epiluminescence microscopy–specific
criteria may facilitate distinction.[29] Spontaneous hair repigmentation of physiologically white or gray hair is rare
occurrence and may portend lentigo maligna in elderly individuals.[30]

Large cell acanthoma may be a variant of solar lentigo.[31]

Differential Diagnoses
Actinic Keratosis

Ephelides (Freckles)

Seborrheic Keratosis

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Workup

Workup

Other Tests
Dermoscopic evaluation of a few lichenoid regressing solar lentigines showed a pattern similar to that of lichenoid
regressing seborrheic keratosis.[32]

Histologic Findings
Lentigo simplex is characterized by a slight-to-moderate elongation of the rete ridges with melanocyte proliferation in the
basal layer, increased melanin in both the melanocytes and the basal keratinocytes, and the presence of melanophages in
the upper dermis. Lentigines profusa and agminated lentigo are similar in appearance.

Solar lentigines have elongated rete ridges and a proliferation of pigmented basaloid cells, which form buds and strands.
These rete ridges may appear flattened.[33] Ink-spot lentigines are also similar to solar lentigines, except the rete ridges in
ink-spot lentigines appear less blunted and more tortuous. No atypia of the melanocytes is present. The solar lentigo has an
increased number of melanophages compared with unaffected skin from the same subject.[34] These melanophages were
demonstrated to be factor XIIIa-positive dermal dendrocytes.

The melanocytes of PUVA lentigines are increased in number and hypertrophic; they frequently demonstrate cellular atypia.
Elongation of the rete ridges and increased pigmentation in the basal cell region is present with transepidermal pigment cell
excretion.

Radiation lentigines show increased melanin deposition in basal keratinocytes, cellular or nuclear atypia, increased number
of melanocytes, and reduction of rete ridges.

Oral and labial melanotic macules show epithelial hyperplasia with somewhat irregular widening and elongation of the rete
ridges. Melanin is increased in the melanocytes and keratinocytes of the basal layer and in the melanophages in the dermal
papillae; this increase in melanin indicates pigment incontinence. Vulvar and penile lentigines have similar histologic
features except for a slight increase in dendritic melanocytes along the basal layer of the epidermis.

Tanning-bed lentigines resemble PUVA lentigines with the increased density of melanocytes, some of which show mild
nuclear atypia. Ultrastructurally, these lesions are similar to those of other forms of lentigo.

Ephelides have an increase in pigment content in the basal cell layer, with neither elongated rete ridges nor increased
number of melanocytes.

The myxoma syndromes (ie, LAMB, NAME, and Carney syndromes) show basal layer and, sometimes, spinous layer
hyperpigmentation with or without elongation of the rete ridges and melanocytic hyperplasia. Melanocytes may have large
dendritic processes, and melanophages may be observed in the upper dermis.

In Peutz-Jeghers syndrome, the lentigines also show marked hyperpigmentation of the basal layer. LEOPARD syndrome
involves increased pigment content of the epidermis with an increased number of melanocytes. The melanocytes are filled
with melanosomes and are distributed singly or in the form of micronests.

Treatment

Medical Care
Noninvasive topical creams are also used. After several months of application, tretinoin cream and hydroquinone cream can
lighten lentigines.

The efficacy and safety of cryotherapy and trichloroacetic acid (TCA) were compared for the treatment of solar lentigo.[35]
Cryotherapy was more effective than TCA 33% solution in the treatment of solar lentigines of the back of the hands,

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particularly in lighter-complexioned individuals. For darker-complexioned people, TCA 33% may be preferred, although
postinflammatory hyperpigmentation remains a risk for both modalities.

A triple combination cream with fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05% as adjuvant to
cryotherapy for solar lentigines on the dorsal hands was found to be effective.[36]

The effect of a bleaching solution containing 2% mequinol (4-hydroxyanisole, 4HA) and 0.01% tretinoin (Solagé) applied
twice daily for 3 months on solar lentigines present on the back of one hand demonstrated a significant lightening effect after
2 months of treatment and was maintained at least 2 months after stopping treatment.[37]

Skin-lightening products commercially available target natural melanin production, many as competitive inhibitors of
tyrosinase.[38] Phalaenopsis orchid extract may be useful as a novel treatment of solar lentigines.[39]

A weak but significant whitening effect on solar lentigos was documented using L-ascorbate-2-phosphate trisodium salt in
Japanese women.[40]

Surgical Care
Treatment of solar lentigines with a focal medium-depth chemical peel may be clinically superior to treatment with
cryosurgery, owing to the paucity of adverse effects (eg, hypopigmentation, pain) associated with chemical peels.[41]

Cryosurgery[42] is a simple treatment for isolated lentigines. Many consider the first-line therapy for solar lentigines to be
ablative therapy with cryotherapy.[43] This procedure is often successful because of the susceptibility of melanocytes to
freezing with liquid nitrogen. Squamous cells resist injury at -20°C, whereas melanocytes freeze at -4 to -7°C.

Lasers are effective in the treatment of various lentigines. The development of short-pulsed, pigment-specific lasers to
selectively destroy the pigment within the solar lentigo has led to significant clinical improvement, a low risk of adverse
effects, and high patient acceptance.[44] The frequency-doubled, Q-switched Nd:YAG laser,[45] the HGM K1 krypton laser,
and the 532-nm diode-pumped vanadate laser are all used with success.[46] Use of a low-fluence 1,064-nm Q-switched
neodymium-doped yttrium aluminum garnet (QS Nd:YAG) laser is another choice.[47]

Treatment with Q-switched Nd:YAG laser may work better than fractional carbon dioxide laser for solar lentigines,[48] with
repetitive low-fluence 1064-nm Q-switched Nd:YAG laser being a safe and effective approach for them.[49]

Intense pulsed-light (IPL) treatment is another option.[50]

Prevention
The application of sunscreen helps decrease the rate of appearance and the darkening of solar lentigines. Summer
darkening can be avoided by use a SPF-30 day skin cream.[51] Limiting one's exposure to sun tanning and the use of
artificial sources of UV light may help prevent solar lentigines.

Limiting one's exposure to sun tanning and the use of artificial sources of UV light may help prevent solar lentigines.

Individuals of Celtic ancestry might limit their exposure to the sun to help prevent ink-spot lentigines.

The avoidance of a large single dose of ionizing radiation may prevent radiation lentigines.

Children with XP should avoid sun exposure because the acceleration of skin changes leads to the formation of neoplasms.

The avoidance of the intense or prolonged, regular use of tanning beds may help in preventing tanning-bed lentigines.

Medication

Medication Summary
The goal of pharmacotherapy is to reduce morbidity and prevent complications.

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Retinoids

Class Summary
Retinoids decrease the cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for
malignant degeneration. These agents modulate keratinocyte differentiation. They have been shown to reduce the risk of
skin cancer in patients who have undergone renal transplantation.

Tretinoin 0.025 to 0.1% (Retin-A, Avita)

Tretinoin is a keratolytic agent. It acts by increasing epidermal cell mitosis and turnover while suppressing keratin synthesis.
An important side effect of interest is hypopigmentation, which reduces the appearance of lentigines.

Bleaching creams

Class Summary
These agents lighten hyperpigmented skin by inhibiting enzymatic oxidation of tyrosine and by suppressing other
melanocyte metabolic processes, thereby further inhibiting melanin production.

Hydroquinone (Eldopaque-Forte, Solaquin Forte, Lustra)

Hydroquinone suppresses melanocyte metabolic processes, especially enzymatic oxidation of tyrosine to 3,4-
dihydroxyphenylamine. Exposure to sun reverses the effects and causes repigmentation.

Questions & Answers

Overview

What is lentigo?

What is the pathophysiology of lentigo?

What causes lentigo?

What is the prevalence of lentigo in the US?

What is the global prevalence of lentigo?

What are the racial predilections of lentigo?

What are the sexual predilections of lentigo?

Which age groups have the highest prevalence of lentigo?

What is the prognosis of lentigo?

What is included in patient education about lentigo?

Presentation

Which factors affect the appearance of lentigo?

Which physical findings are characteristic of xeroderma pigmentosum (XP)?

Which physical findings are characteristic of LEOPARD syndrome (lentigines, electrocardiographic conduction defects,
ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness syndrome)?

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Which physical findings are characteristic of Peutz-Jeghers syndrome?

Which physical findings are characteristic of Laugier-Hunziker syndrome?

Which physical findings are characteristic of inherited patterned lentiginosis?

Which physical findings are characteristic of lentigo simplex?

Which physical findings are characteristic of solar lentigo?

Which physical findings are characteristic of ink-spot lentigo?

Which physical findings are characteristic of psoralen and ultraviolet A (PUVA) lentigo?

Which physical findings are characteristic of radiation lentigo?

Which physical findings are characteristic of tanning-bed lentigines?

Which physical findings are characteristic of oral and labial melanotic macules in lentigo?

How are Laugier-Hunziker syndrome and Peutz-Jeghers syndrome differentiated from oral and labial melanotic macules in
lentigo?

Which physical findings are characteristic of vulvar and penile lentigo?

Which physical findings are characteristic of lentigines profusa?

What are the physical exam findings of agminated lentiginosis?

Which physical findings are characteristic of myxoma syndrome in relation to lentigo?

Which physical findings are characteristic of LAMB (lentigines, atrial myxomas, mucocutaneous myxomas, and blue nevi)
syndrome?

Which physical findings are characteristic of NAME (nevi, atrial myxoma, myxoid neurofibroma, and ephelides) syndrome?

Which physical findings are characteristic of Carney syndrome?

Which physical findings are characteristic of nevus spilus?

What are the possible complications of lentigo?

DDX

Which conditions should be included in the differential diagnoses of lentigo?

What are the differential diagnoses for Lentigo?

Workup

What is the role of dermoscopy in the diagnosis of lentigo?

Which histologic findings are characteristic of lentigo?

Treatment

Which medications are used in the treatment of lentigo?

What is the role of surgery in the treatment of lentigo?

How is lentigo prevented?

Medications

What is the goal of drug treatment for lentigo?

Which medications in the drug class Bleaching creams are used in the treatment of Lentigo?

Which medications in the drug class Retinoids are used in the treatment of Lentigo?

Contributor Information and Disclosures

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics,
Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of
Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Jason F Okulicz, MD, FACP, FIDSA Director, HIV Medical Evaluation Unit, Infectious Disease Service, San Antonio Military
Medical Center; Associate Professor of Medicine, F Edward Hebert School of Medicine, Uniformed Services University of
the Health Sciences; Clinical Associate Professor of Medicine, University of Texas Health Science Center at San Antonio;
Adjunct Clinical Instructor, Feik School of Pharmacy, University of the Incarnate Word

Jason F Okulicz, MD, FACP, FIDSA is a member of the following medical societies: Alpha Omega Alpha, American College
of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Gilead Sciences.

Sergiusz Jozwiak, MD, PhD Professor and Head of Pediatric Neurology, Warsaw Medical University, Poland

Sergiusz Jozwiak, MD, PhD is a member of the following medical societies: Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of
Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

John G Albertini, MD Private Practice, The Skin Surgery Center; Clinical Associate Professor (Volunteer), Department of
Plastic and Reconstructive Surgery, Wake Forest University School of Medicine; Past President, American College of Mohs
Surgery

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology, American College
of Mohs Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: QualDerm Partners;
Novascan<br/>Have a 5% or greater equity interest in: QualDerm Partners - North Carolina.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of
Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for
Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Additional Contributors

Neil Shear, MD Professor and Chief of Dermatology, Professor of Medicine, Pediatrics and Pharmacology, University of
Toronto Faculty of Medicine; Head of Dermatology, Sunnybrook Women's College Health Sciences Center and Women's
College Hospital, Canada

Neil Shear, MD is a member of the following medical societies: Canadian Medical Association, Ontario Medical Association,
Royal College of Physicians and Surgeons of Canada, Canadian Dermatology Association, American Academy of
Dermatology, American Society for Clinical Pharmacology and Therapeutics

Disclosure: Nothing to disclose.

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