EPHELIDES AND LENTIGINES
Ephelides, also known as freckles,
are common benign findings. They typically manifest in childhood in fair-skinned individuals, especially those with red or blonde hair color. Ephelides
tend to be passed down from generation to generation in an autosomal dominant
inheritance pattern.
Lentigines are sun-induced proliferations of melanocytes. They tend to
occur in older people, but they may be seen in individuals at a young age after
repetitive sun exposure. They can be almost impossible to differentiate from
ephelides. Solar lentigines have many synonyms, including sun spots, liver
spots, and lentigo senilis.
Clinical Findings: Ephelides occur at a very young age and
tend to show an autosomal dominant inheritance pattern. They are accentuated in
sun-exposed regions, particularly the head, neck, and forearms. Exposure to the
sun or other ultraviolet source causes the ephelides to become darker and
clinically more noticeable. They do not occur within the oral mucosa. They are
usually uniform in coloration but can have many different sizes and shapes.
Some are round or oval; others are angulated or have a bizarre shape. Their
color is usually a uniform light to dark brown; they are never black. They have
no malignant potential. Patients with multiple ephelides may have a higher risk
for skin cancer, because their presence may be an indication of increased
exposure to ultraviolet radiation. The differential diagnosis is usually very
narrow and includes lentigines and common acquired nevi. The clinical location,
age at onset, family history, and skin type usually make the diagnosis
straightforward. The difficulty can occur when trying to differentiate a
solitary lentigo from an ephelide in an adult patient.
Solar lentigines most often arise in the adult population and are
distributed evenly among males and females. They can occur in anyone but are
much more common in light-skinned persons. The number of lentigines typically
increases with the age of the patient. Lentigines are induced by ultraviolet
radiation, the most common source being chronic sun exposure. Lentigines tend
to get darker with ultraviolet light exposure and lighten over time when
removed from the expo- sure. Unlike ephelides, they never completely fade away.
They are clinically highly uniform in color and size within an individual
patient. They can be small (1-5 mm), but some are much larger (2-3 cm in diameter).
They are most commonly located in sun-exposed areas but in some syndromes can
be located anywhere on the human body, including the mucosal regions. Over
time, some lentigines merge together to form rather large lentigines.
There are some important variants of lentigines. Lentigo simplex and the
ink spot lentigo are two very common versions. Lentigo simplex is believed to
occur at any age and to have no or minimal relationship to sun exposure. The
lesions are found anywhere on the body. Ink spot lentigines are variants of
lentigo simplex that are differentiated by their characteristic dark brown to
almost black coloration. Under dermatoscopic evaluation, they have a characteristic
uniform pigment network, with accentuation of pigment in the rete ridge
regions. They are so named because they have the appearance of a tiny drop of
dark ink dropped on the skin. Neither of these two forms of lentigines has malignant potential.
One of the more important and unique variants of lentigines are the
psoralen + ultraviolet A light (PUVA) lentigines. PUVA lentigines are iatrogenic
in nature and occur after medical therapy with PUVA treatment. Patients who
have undergone long-term therapy with PUVA have a high risk of developing PUVA
lentigines. These lentigines are darkly pigmented macules that occur across the
entire body except in the areas that were not exposed to the PUVA therapy. More
than half of patients who have
undergone prolonged PUVA treatment will develop PUVA lentigines. They are more
common in patients with fair skin types and rarely occur in darker-skinned individuals.
The lentigines induced by PUVA therapy are permanent and can have disastrous
cosmetic consequences. Like all patients undergoing ultraviolet phototherapy,
these patients must be routinely monitored for their entire lives, because they
are at increased risk for melanoma and non-melanoma
skin cancer due to their chronic use of PUVA treatment.
Patients with Peutz-Jeghers syndrome have clinical findings of multiple
lentigines of the oral mucosa and lips and of the hands. These patients are at
increased risk for gastrointestinal carcinomas, particularly colon cancer.
Peutz-Jeghers syndrome is inherited in an autosomal dominant fashion and is
caused by a defect in the STK11/LKB1 tumor suppressor gene.
LEOPARD syndrome is another of the well-described genetic syndromes
associated with lentigines. This syndrome is composed of lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary
stenosis, abnormal genitalia, retardation of growth, and deafness.
It is caused by a genetic mutation in PTPN11, which encodes a tyrosine
phosphatase protein.
Histology: Histopathological evaluation is one method to
differentiate a lentigo from an ephelide. This is rarely done. The most common
use of histology is to differentiate the benign lentigo from its malignant
counterpart, lentigo maligna (melanoma in situ).
On histopathologic evaluation, ephelides show no change in the epidermis.
There is no increase in the number of melanocytes. The only finding is an
increase in the amount of melanin and an increased rate of transfer of
melanosomes from melanocytes to keratinocytes.
Lentigines, on the other hand, show an increased number of melanocytes
within the area of involvement. The hyperpigmentation is obvious along the
club-like configuration of the rete ridges. The increase in the number of
melanocytes is not associated with any nesting of those melanocytes, as is seen
in melanocytic nevi. In solar lentigines, the dermis often shows signs of
chronic sun damage, with a thinning of the dermis and solar elastosis. The
epidermis is also thinned in some cases.
Lentigo maligna shows many more melanocytes, some large and bizarre
appearing. There is pagetoid spread of the melanocytes and an asymmetry to the
lesion. Lentigo simplex has also been shown to lack defects in the BRAF gene,
in contrast to melanoma, and this may be one way to differentiate the two.
Pathogenesis: Ephelides are thought to be genetically
inherited, most likely in a dominant pattern. They become more prominent with
sun exposure and fade during times with less exposure to ultraviolet radiation.
The increase in pigment is caused by an increase in the production of melanin
and an increase in the transfer of melanosomes from melanocytes to keratinocytes.
There is no increase in the number of melanocytes in ephelides. The exact
reason for this has not been determined.
Lentigines are caused by an increased proliferation of melanocytes
locally within the skin. The cause of this proliferation is most likely
ultraviolet light in the case of solar lentigines. In the case of lentigo
simplex, the cause is unknown. The increased number of melanocytes ultimately
leads to an increase in the amount of melanin produced, resulting in the
overlying hyperpigmentation.
The cause of lentigines in some of the genetic disorders is probably the
underlying genetic defect. The exact
mechanism of how the various gene defects lead to an increase in lentigines is under investigation. A better
understanding of how lentigines form in certain genetic syndromes may lead to
discovery of the true pathogenesis of solar lentigines and lentigo simplex.
Treatment: No therapy is needed other than to recommend sun
protection, sunscreen use, and routine skin examinations in the future. For
cosmetic reasons, lentigines can be removed in a myriad of ways. Light
cryotherapy is effective and easy to perform. This treatment can leave hypopigmented areas and should be used with
caution in darker-skinned individuals. Many different chemical peels and
dermabrasion techniques have been used to help decrease the appearance of
lentigines. With the proliferation of medical laser devices in dermatology,
lasers with unique wavelengths have been developed to target the melanin in
lentigines. These laser devices have show promise in lightening and removing solar lentigines.
