Pigmented Neoplasms and Nevi
Ka Yee Kung
Henry Hin Lee Chan
BACKGROUND
Pigmented neoplasms and nevi are common dermatological conditions that dermatologists encounter frequently in daily practice. Although some patients are concerned about the associated health risk, most request the removal of these lesions for cosmetic purposes. Lasers have been used successfully for the treatment of pigmentary conditions, and although some lesions such as nevi of Ota respond very well to laser treatment, others such as café au lait macules are much less responsive. The use of lasers in the treatment of congenital melanocytic nevi is more controversial.
CAFÉ AU LAIT MACULES
PRESENTATION
Café au lait macules (CALMs) present as sharply demarcated light to dark brown hyperpigmented patches, often presenting in early infancy. The presence of multiple
CALMs should signal a workup for neurofibromatosis (NF) 1. In the newborn period, NF1 presents with pseudoarthroses, congenital glaucoma, and sphenoid wing dysplasia. In early childhood, NF1 presents with embryonal tumors, compression injuries characterized by back pain in the presence of CALMs, and optical gliomas by the age of 3 years. NF2 typically presents in middle age with acoustic neuromas, although CALMs may also be present.
CALMs should signal a workup for neurofibromatosis (NF) 1. In the newborn period, NF1 presents with pseudoarthroses, congenital glaucoma, and sphenoid wing dysplasia. In early childhood, NF1 presents with embryonal tumors, compression injuries characterized by back pain in the presence of CALMs, and optical gliomas by the age of 3 years. NF2 typically presents in middle age with acoustic neuromas, although CALMs may also be present.
DIAGNOSIS
Clinical Diagnosis
CALMs are light to dark brown sharply demarcated hyperpigmented patches found anywhere on the body. They range in size from a few millimeters to up to 20 to 30 cm and are very uniform in color. CALMs can be associated with genetic conditions such as NF1 and NF2, but they also affect 0.4% to 2.7% of the general population.1 The presence of >6 CALM should trigger a systemic workup for underlying genetic disease such as NF1 or NF2; the presence of a giant, segmental, or blaschkoid CALM should raise suspicion for McCune-Albright syndrome.2 Other inherited syndromes associated with one or more CALMs include Noonan syndrome, Legius syndrome, cardiofaciocutaneous syndrome, Watson syndrome, LEOPARD syndrome, Cowden disease, piebaldism, and ataxia-telangiectasia.
Histopathology
Subtypes
Sporadic CALM and the CALM of neurofibromatosis typically are smaller, ranging from 2 to 5 cm, with regular smooth borders. In NF1, the CALMs are found in higher numbers, whereas the CALM in McCune-Albright syndrome are fewer, larger, or segmental and have an irregular jagged border.2
Neurofibromatosis
CALMs are observed in 95% of patients with neurofibromatosis type 1 (NF1) (Table 12.1.1). CALMs may also be present in NF2, which may be diagnosed in the presence of acoustic neuromas.
TABLE 12.1.1 Diagnostic Criteria for NF1 | ||
|---|---|---|
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McCune-Albright Syndrome
A single, large, and asymmetric CALM has a “coast of Maine” appearance. They are associated with precocious puberty, polyostotic fibrous dysplasia, and endocrinopathies.
Tuberous Sclerosus
CALMs are accompanied by ash leaf spots, angiofibromas, hemangiomas, cardiac rhabdomyomas, and shagreen patches.
Fanconi Anemia
CALMs are accompanied by aplastic anemia, mental retardation, and malignancy.
Coffin-Siris Syndrome
CALMs are accompanied by developmental delay, speech impairment, coarse facial features, hypertrichosis, hypoplasia of the fifth digit distal phalanx, neurologic abnormalities, and a variety of other multisystem findings.
PATHOGENESIS
The etiology of CALMs is not known; however, Ras pathway disturbances seem to underlie the pathogenesis of CALMs. In NF1, an autosomal dominant disorder, the mutation is in the neurofibromin gene, which encodes a GTPase activating protein that downregulates p21-ras expression. In half of the cases, the mutation is spontaneous. NF2 is also autosomal dominant and due to a mutation in neurofibromin 2 or merlin, which encodes a cytoskeletal protein and acts as a tumor suppressor protein. Studies have shown that the neurofibromin tumor suppressor is involved in regulating melanogenesis via protein kinase A-ERK signaling, which in turn regulates MITF and other melanogenesis signaling pathways.2
TREATMENT
CALMs are benign and never undergo malignant transformation; however, their appearance can be associated with significant psychosocial impact, particularly when found on the face.
Medical
Medical treatment of CALMs include sunscreen use and monitoring for associated conditions when NF or other associated genetic conditions are diagnosed.
Cosmetic
Lasers
Lasers have been used to remove these lesions with inconsistent treatment results.
Q-Switched Lasers. Of all of the laser modalities, Q-switched (QS) lasers yield the most variable results, with high rates of recurrence, and even paradoxical darkening has been reported. One possible explanation is that QS lasers fail to remove the follicular melanocytic component of the CALM. A retrospective study of the treatment of CALM in Chinese patients with a QS 755-nm alexandrite laser showed that after an average of 3.2 treatments, 54.1% of the patients experienced a good to excellent response, 16.7% experienced a poor response, and 10.4% experienced recurrence.3 A similar study using a QS 694-nm ruby laser and QS 532-nm Nd:YAG laser found that the degree of improvement varied across the lesions.4
Most recently, it has been proposed that CALMs with a smooth edge rather than an irregular edge are more resistance to QS nanosecond or picosecond (PS) laser treatment, and although this is just a clinical observation, it does at least allow some degree of predictability in informing patients and their relatives of the potential outcome of laser treatment.5
Long-Pulsed Lasers. Long-pulsed (LP) pigment lasers such as the normal-mode ruby laser (NMRL) or LP Alex laser without cooling have also been used. The objective with these systems is to target not only epidermal melanocytes but also follicular melanocytes. The NMRL was shown to result in a lower risk of recurrence (42.4%) compared with the QS ruby laser (81.8%) 3 months after a single treatment in a study of 33 patients with CALM.6
Picosecond Lasers. Recently, the use of new laser devices operating at pulse durations in the subnanosecond range, such as the PS alexandrite (755 nm) laser for the treatment of CALM, has been explored. Some patients who were previously resistant to treatment appear to be responsive (parameters: 1.26-3.49 J/cm2 fluence, 2.7-4.5 mm spot size, 2.5 Hz), although further study is needed (Figure 12.1.1).
General Algorithm. Our approach to the laser treatment of CALM is to divide the lesions into 4 parts and test each area with 4 different lasers, namely, the LP alexandrite (755 nm), QS ruby (694 nm), PS alexandrite (755 nm), and PS 532. Algorithm 12.1.1 illustrates treatments for CALMs. Assessing the treatment response at each of the 4 areas will help guide the choice of the proper laser modality. If the lesion persists after 4 treatment sessions, discussion with the patient is warranted before commencing. The appropriate end point for LP alexandrite (755 nm) is slate-gray appearance (starting parameters: 25-30 J/cm2 fluence, 8-10 mm spot size, pulse duration 3 ms). For QS or PS lasers, immediate whitening is the appropriate end point (starting parameters for QS ruby laser are 3 J/cm2 fluence, 4 mm spot size; for PS 532, 0.4 J/cm2 fluence, 5 mm spot size).
 FIGURE 12.1.1 Café au lait macule before (A) and 1 mo after (B) 3 treatments with a picosecond alexandrite laser (1.26-3.49 J/cm2, 2.7-4.5 mm, 2.5 Hz, 4 wk apart). |
Surgical
Surgical treatment of CALMs is not indicated, as no reports describe malignant transformation.
BECKER NEVUS
PRESENTATION
Becker nevus is a pigmented hematoma that appears as a unilateral hyperpigmented plaque with increased hair growth usually located on the shoulder of male patients.
DIAGNOSIS
Clinical Diagnosis
Becker nevi typically become apparent after puberty and are more common in male patients. They are well circumscribed, irregular, hyperpigmented plaques with associated hypertrichosis, most often found on the shoulder or upper chest but have been described in other areas. There may be associated ipsilateral hypoplasia of internal structures such as muscle, fatty tissue, or bony abnormalities.2
Histopathology
Histology demonstrates increased pigmentation in basal epidermis, variably normal to increased number of melanocytes with overlying epidermal papillomatosis, acanthosis, and hyperkeratosis, and often a dermal smooth muscle hamartoma can be found.7
Subtypes
Solitary lesion Becker melanosis
Multiple lesions Becker melanosis
Becker nevus syndrome: Becker melanosis with associated abnormalities (ipsilateral hypoplasia including hypoplasia of breast, arm, foot, spina bifida, scoliosis, pectus carinatum, accessory scrotum, accessory nipple)
Differential Diagnosis
Smooth-muscle hamartoma
Congenital melanocytic nevus
Plexiform neurofibroma
CALM
 ALGORITHM 12.1.1 Treatments for pigmented neoplasms and nevi including café au lait macules, Becker melanosis, nevus of Ota, and melanocytic nevi. LP, long-pulsed laser; PS, picosecond laser; QS, Q-switched laser. (Courtesy of Macrene Alexiades, MD, PhD.) |
PATHOGENESIS
The pathogenetic mechanism of Becker nevi is poorly characterized, but they are thought to represent hamartomas that are derived from ectodermal and mesodermal tissue during embryogenesis. The hyperpigmentation in Becker nevus is due to the increased melanin content in the keratinocytes of the nevus.
TREATMENT
Becker nevus is treated predominantly because of the cosmetic disfigurement that may be experienced as a result of the rapid hyperpigmentation and hypertrichosis that occur during adolescence. Rarely, melanoma has been reported to arise in a Becker nevus.
Medical
Cosmetic camouflage using concealers and sunscreen comprise the primary medical treatment of Becker nevus. Skin check surveillance for the development of melanoma is indicated.
 FIGURE 12.1.2 Becker nevus before (A) and 1 mo after (B) 5 treatments with a long-pulsed alexandrite laser (20-30 J/cm2, 10 mm, 1.5 Hz, 3 ms) and nonablative fractional laser (1927 nm, 10-20 mJ, level 11, 82-164 MTZ/cm2); 4 wk apart). |
Cosmetic
The hyperpigmentation and hypertrichosis of Becker nevi have been treated with lasers and the latter with electrolysis. The results are variable but may yield acceptable cosmetic improvements for cosmetically sensitive anatomic sites (Figure 12.1.2).
Lasers
A recent review article examining the use of lasers for the treatment of Becker nevi was disappointing and showed inconsistent results with LP, QS, ablative, and fractional lasers having all been used with some, but a limited, degree of success.8 Algorithm 12.1.1 illustrates treatments for Becker nevi.
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